Presentazione di PowerPoint - siditalia.it · • major congenital abnormalities Adverse outcome. ... Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic

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Il parto nella donna con diabeteFederico Mecacci

Prenatal Medicine High Risk Pregnancy Unit

Careggi Universitary Hospital Newbornrsquos and Womens Health Department

0

1

2

3

4

5

6

7

madri obese

48

Del 20 delle madri obese dal 2008 al 2016Dati regione Toscana

57

Nascere in Toscana 2015

MATERNAL AGE DELAYED CHILDBEARING AND METASBOLIC SYNDROME

2016

Prevalence of metabolic syndrome(NCEP ATP III) in the NHANES III survey Ford ES JAMA 2002 287356

Balkau B Diabet Metabol 2002

36 of Europeans were observed at the ageof 40-55 years with metabolic syndrome

Prevalence of hyperglycaemia in pregnancy by age

Global estimates of the prevalence of hyperglycaemia in pregnancy L Guariguata et al Diabettesresearch and clinical practice 2014

Global prevalence of hyperglycaemia in pregnancy 169

The prevalence of HIP increases sharply with age with a prevalenceof 392 in women40ndash44 and up to 479 in women 45ndash59 years

IN CHE MODO IL DIABETE INFLUENZAIL TIMING LA MODALITAgrave E LrsquoOUTCOME DEL

PARTO

THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

FFA(fat mobilization)

Glucose

leptina

INSULIN RESISTANCE

OBESITY

GESTATIONAL DIABETES

IGF1

Adiponectina

insulin

FETAL NUTRIENT AVAILABILITY

PLACENTAL TRASPORT OF NUTRIENTS

mTOR+

ldquoadaptive regulationrdquo

FETAL OVERNUTRITION-MACROSOMIALGA

Romero Am J Obstet Gynecol 2017

Brett KE Int J Mol Sci 2014

MACROSOMIAL

MACROSOMIALG

DISTOCIA STILLBIRTH

Macrosomia e rischio di distocia

Birth weight distribution in diabetic pregnancies

Persson et al Diab Care 2011341145-1149

ldquoDIABESITYrdquo and MACROSOMIA

MACROSOMIA ASIMMETRICA

OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

Fetal growth profiles in diabetic pregnancies

08

085

09

095

1

105

11

115

12

125

13

100 120 140 160 180 200 220 240 260 280

Gestational age in days

Hea

d to

abd

omin

al c

ircu

mfe

renc

e ra

tio

(HC

AC

rati

o)

IDDM non-macrosomia

IDDM macrosomia

DM2 non-macrosomia

DM2 macrosomia

GDM non-macrosomia

GDM macrosomia

Birthweightgt90th

Type-1-diabetes LGA

Type-1 AGA

N Hammoud et al UOG 2012

Type-2-diabetes LGA

GDM LGA

Grafiek3

Fetal growth profiles in diabetic pregnancies

IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

Gestational age in days

Head to abdominal circumference ratio (HCAC ratio)

iddm gdm 977

IDDM

IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

Gestational age in days

Fetal abdominal circumference (mm)

GDM

GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

Gestational age in days

Fetal abdominal circumference (mm)

FAC 6 groups

Fetal growth profiles in diabetic pregnancies

IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631131321413511492848268500001116724824021185211653550000112031750669122113848025000011239101893612570653069512750287203000001129299213365000011310955547000000113289189603513468823737000002136484578704999991382809200400000114007726137500001141873602711436699440450000214546628537999999147262626715000011490589680515085530938515265165072000002154447992054999991562443333900000115804067472515983701606161633357395000021634296987300000116522604006500001167022381416881872273499999170615064070000021724114054050000117420774674176004088075177800429409999991795967707450000118139311208000001183189453415184985794750000031867821360850000218857847742000001190374818755000011921711600919396750142500002195763842760000021975601840950000119935652543201152866765202949208100000022047455494350000220654189077000001208338232105210134573442119309147750000221372725611000001215523597445000012173199387821911628011500002220912621450000022227089627850000122450530412000001226301645455000032280979867900000222989432812500002231690669460000012334870107952352833521300000323707969346500002238876034800000012406723761350000124246871747244265058805000022460614001400000224785774147500001249654082810000012514504241452532467654800000225504310681500002256839448150000012586357894850000326043213082262228472155000022640248134900000426582115482500001267617496160000032694138374952712101788300000227300652016500004274802861500000012765992028350000327839554416999999280191885505000022819882268400000428378456817528558090951000003287377250845000052891735921800000129096993351500004292766274852945626161850000229635895751999999298155298855000012999516401900000330174798152530354432286000002305340664195000043071370055300000130893334686500003310729688200000063125260295350000231432237086999999316118712205000013179150535400000331971139487532150773621000002323304077545000043251004188800000132689676021500003328693101550000053304894428850000233228578422000004334082125555335878466890000033376748082249999933947114956000001341267490895000043430638322334486017356500003346656514900000053484528562350000135024919757000004352045538905000063538418802400000235563822157499999357434562910000013592309042450000336102724558362823586915000023646199282500000436641626958500001368212610920000033700089522550000537180529359000002DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263117561169644999991191476615939999812073415354299999122320645491999981239071374409999912549362938999998127080121338999991286666132880000113025310523713183959718599999133426089134999981350125810839999813659907303299997138185564981999991397720569309999814135854888142945040828999991445315327779999814611802472699998147704516675999971492910086249999915087750057399998152463992523154050484471999991556369764209999915722346836999998158809960318999971603964522679999916198294421699998163569436166165155928114999991667424200639999916832891201299998169915403961999971715018959109999917308838785999998174674879809176261371758177847863706999991794343556559999818102084760499997182607339553999991841938315029999818578032345218736681540118895330734999999190539799298999981921262912479999719371278319699999195299275145999991968857670949999819847225904420005875099299999201645242941999982032317348909999720481822683999999206404718788999992079912107379999820957770268721116419463599999212750686584999982143371785339999721592367048321751016243199999219096654380999982206831463322226963827899999223856130227999982254426221769999822702911412622861560607499999230202098023999982317885899732333750819219999923496157387099998236548065819999982381345577692397210497179999924130754166699998242894033616244480525564999992460670175139999924765350946299998249240001412250826493360999992524129853099999825399947725925558596920799999257172461156999992587589531059999826034544505499997261931937004000022635184289530000126510492090226669141285126827790479999999269864396748999982714508886979999727303738064699996274623872596000012762103645452777968564942793833484429999928096984039199998282556332340999972841428242899999628572931623900001287315808188000012889023001372904887920859999929207528403499998293661775983999972952482679329999729683475988199996298421251831000013000077437830159423572899999303180727677999983047672196269999730635371157600002307940203525000023095266954740000131111318742331269967937199999314286171320999983158726632699999831745915521899997319045647167999963206321391170000132221863106632380512301499999325391614963999983269781069129999832856459886199997330151090811000023317375827600000133332407470933491056665799999336497058606999993380835505559999833967004250499997341256534453999963428430264029999534442951835234601601030099999DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

Gestational age in days

Fetal abdominal circumference (mm)

HC 6 groups

Fetal growth profiles in diabetic pregnancies

IDDM 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non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263141936936246000021434432504890000114494956473214645587897500002147962193218000011494685074611509748217040000215248113594700001153987450191554937644330000215700007867599999158506392919000011600127071620000316151902140499999163025335648000011645316498911660379641339999916754427837700001169050592621705569068629999917206322110600001173569535349000011750758495921765821638350000217808847807800001179594792321181101106564000021826074208070000118411373505185620049293000021871263635360000118863267777900001190138992022000021916453062650000219315162050800001194657934751196164248994000021976705632370000119917687748200683191722999992021895059660000120369582020920520213445220670844869500002208214762938000012097210771812112273914240000221273370566700001214240019912157463341530000221725264839600001218758962639220265276882000022217715911250000122327790536800001224784219611226290533854000022277968480970000122930316234230809476583000022323157908260000123382210506923532841931200002236834733555000012383410477980000123984736204124135367628400002242859990527000012443663047724587261901300002247378933256000012488852474992503915617420000225189787598500001253404190228254910504471000022564168187139999925792313295700001259429447200000032609357614429999926244207568600001263948389929000032654547041719999926696101841500001268467332658000032699736469012714799611440000127298627538700003274492589632759989038730000227750521811600004279011532359280517846602000022820241608449999828353047508828503678933100002286543103574000042880494178170000128955573206000003291062046302999992925683605460000129407467478900003295580989031999992970873032750000129859361751800003300099931760999993016062460040000130311256024700003304618874493061251887330000230763150297600004309137817219310644131462000023121504457050000431365675994831516307419100002316669388433999983181757026773196820169200000232118833116300004322694645406000013242009596490000332570727389199999327213588135000013287199023780000333022621662100005331732530864000013332388451070000333474515934999999336251473593000013377577878360000333926410207934077041632200002342276730564999983437830448083452893590510000234679567329400004348301987537349808301780000023513146160229999935282093026635432724450900002355833558752000043573398729950000135884618723800003DM2 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

Gestational age in days

Head circumference (mm)

HCAC 6 groups

Fetal growth profiles in diabetic pregnancies

IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

Gestational age in days

Head to abdominal circumference ratio (HCAC ratio)

Model

Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

Iperglicemia e rischio di morte fetale a termine di gravidanza

Estimated rate of stillbirth in diabetic women 1920-2000

Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

4 of all stillbirths remain attributable to diabetes

Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

Adverse outcome

HbA1C gt7

1 increase in A1Ccorresponded to 55 increased

risk of adverse outcome

The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

gestation particularly in the presence of fetal macrosomia

fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

Langer O 1995

100 mgdLfor stillbirth

Diabetic patients n = 271691

Am J Obstet Gynecol 2002

The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

4873 diabetic women

pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

GDMbull dysglycemia was more difficult to manage

2016

Differences in placental pathologyaccording to diabetes types

Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

GDM is associated with a greater rate of villous immaturity

0102030405060708090

100GDMDMIDMII

o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

A retrospective study on 175 placentas with DVM vs 175 controls

Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

Pathophysiology of fetal compromise in diabetic pregnancy

The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

Bjork 1984Nylund 1982Siddiqui 2003

A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

STILLBIRTH RISK

BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

OBESITArsquo E MORTE FETALE

6-7 per unit BMI for BMI gt 23

Tennant PWG Am J Obstet Gynecol 2007

HYPERINSULINISMHYPERANDROGENISM

IMPAIRED PLACENTATION

THE EFFECTS OF OBESITYMETABOLIC SYNDROME

Cakmak and Taylor Hum Reprod Update 2011

Makieva S Hum Reprod Update 2014

Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

Hotamisligil GS Nature 2006

LeptinCRH

Urocortin 3IL-6

INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

Adiponectina Insulin LeptinTNFα IL-6

PLACENTAL ALTERATIONIN GENE EXPRESSION

PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

CollagenaseCervical ripening

FFA

OXIDATIVE STRESS

PREVENZIONE STILLBIRTH

PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

MORBIDITAgrave NEONATALE

AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

TIMING E MODALITArsquo DEL PARTO

Induzione o attesa

INDUZIONE DEL TRAVAGLIO

Quando fare un TC elettivo

gt 4000 grgt 4500 gr gt 5000 gr

ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

No differenza in TC e outcome perinatale

200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

No differenza in TC gt di LGA e peso medio nel gruppo di attesa

RCT INDUZIONE VS ATTESA in GDM

RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

2014

1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

2 Patients well controlled on insulin should probably be delivered by the due date

3 Poorly controlled GDMrsquos using insulin require individual judgment

Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

cesarean delivery when the estimated fetal weight is ge 4500 g

MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

MODALITAgrave E TIMING DEL PARTO nel GDM

GMD in terapia insulinicaBen controllato

+Condizioni fetali rassicuranti

MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

GDM in terapia nutrizionalecon profili glicemici ottimali

+Feto AGA

MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

EFW lt 4000g LGAControllo metabolico non

ottimale

4000g lt EFW gt 4500g EFW ge 4500g

Programmare TC elettivo

Parto vaginale indotto a 38-39 sett

Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

MODALITAgrave E TIMING DEL PARTO nel GDM

IN BASE AL PESO FETALE STIMATO

- Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

- Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

- Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

GDM and the Use of Betamethasone

bull administration of betamethasone in the late preterm period should be limited to women with GDM only

bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

Society of Obstetricians and Gynaecologists of Canada

The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

late preterm delivery between 24 to 36 weeksrsquo gestation

ASSISTENZA IN TRAVAGLIO

- MONITORAGGIO FETALE CONTINUO

- Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

MANTENERE GLICEMIA gt70 E lt 126

(Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

GDM

- Intravenous infusion of regular insulin titrated and glucose

- Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

(ACOG 2005)

ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

Venere di Willendorf

Thank you for your attention

Pathophysiology of fetal compromise in diabetic pregnancy

Islet cell hyperplasia common in stillborn IDMs

There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

Salvesen 1993Hay 1989Chukwuma 2001

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  • Birth weight distribution in diabetic pregnancies
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  • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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  • Differences in placental pathology according to diabetes types
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  • Pathophysiology of fetal compromise in diabetic pregnancy
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  • GDM and the Use of Betamethasone
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  • Pathophysiology of fetal compromise in diabetic pregnancy
    Intercepting Curves Random Effects are intercept and ctime (=slope)
    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
    17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
    120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
    121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
    122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
    123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
    124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
    125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
    18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
    127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
    128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
    129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
    130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
    131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
    132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
    19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
    134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
    135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
    136-5328091174390921119170838111405379131153817241115039368311728882411124487
    137-5227041172850541118937155111396122561152048811114915830911711801311125128
    138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
    139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
    20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
    141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
    142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
    143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
    144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
    145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
    146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
    21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
    148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
    149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
    150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
    151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
    152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
    153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
    22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
    155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
    156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
    157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
    158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
    159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
    160-298411137421801113562446111183221451111374921112074470711318936011132695
    23161-287841135881421113328763111173964881109606491111950933311301854911132712
    162-277291134341041113095080111164708311107838061111827395911284773811132703
    163-266761132800661112861397111155451741106069631111703858511267692711132668
    164-256251131260281112627714111146195171104301201111580321111250611611132607
    165-2457611297199011123940311111369386110253277111145678371123353051113252
    166-235291128179521112160348111127682031100764341111333246311216449411132407
    167-224841126639141111926665111118425461098995911111209708911199368311132268
    24168-214411125098761111692982111109168891097227481111086171511182287211132103
    169-204001123558381111459299111099912321095459051110962634111165206111131912
    170-193611122018001111225616111090655751093690621110839096711148125011131695
    171-183241120477621110991933111081399181091922191110715559311131043911131452
    172-172891118937241110758250111072142611090153761110592021911113962811131183
    173-162561117396861110524567111062886041088385331110468484511096881711130888
    174-152251115856481110290884111053629471086616901110344947111079800611130567
    25175-1419611143161011100572011110443729108484847111022140971106271951113022
    176-131691112775721109823518111035116331083080041110097872311045638411129847
    177-121441111235341109589835111025859761081311611109974334911028557311129448
    178-111211109694961109356152111016603191079543181109850797511011476211129023
    179-101001108154581109122469111007346621077774751109727260110994395111128572
    180-9811106614201108888786110998090051076006321109603722710977314011128095
    181-8641105073821108655103110988833481074237891109480185310960232911127592
    26182-7491103533441108421420110979576911072469461109356647910943151811127063
    183-6361101993061108187737110970320341070701031109233110510926070711126508
    184-5251100452681107954054110961063771068932601109109573110908989611125927
    185-41610989123011077203711109518072106716417110898603571089190851112532
    186-391097371921107486688110942550631065395741108862498310874827411124687
    187-241095831541107253005110933294061063627311108738960910857746311124028
    188-111094291161107019322110924037491061858881108615423510840665211123343
    27189001092750781106785639110914780921060090451108491886110823584111122632
    190111091210401106551956110905524351058322021108368348710806503011121895
    191241089670021106318273110896267781056553591108244811310789421911121132
    192391088129641106084590110887011211054785161108121273910772340811120343
    1934161086589261105850907110877754641053016731107997736510755259711119528
    1945251085048881105617224110868498071051248301107874199110738178611118687
    19563610835085011053835411108592415104947987110775066171072109751111782
    281967491081968121105149858110849984931047711441107627124310704016411116927
    1978641080427741104916175110840728361045943011107503586910686935311116008
    1989811078887361104682492110831471791044174581107380049510669854211115063
    199101001077346981104448809110822215221042406151107256512110652773111114092
    200111211075806601104215126110812958651040637721107132974710635692011113095
    201121441074266221103981443110803702081038869291107009437310618610911112072
    202131691072725841103747760110794445511037100861106885899910601529811111023
    29203141961071185461103514077110785188941035332431106762362510584448711109948
    204152251069645081103280394110775932371033564001106638825110567367611108847
    2051625610681047011030467111107666758103179557110651528771055028651110772
    206172891066564321102813028110757419231030027141106391750310533205411106567
    207183241065023941102579345110748162661028258711106268212910516124311105388
    208193611063483561102345662110738906091026490281106144675510499043211104183
    209204001061943181102111979110729649521024721851106021138110481962111102952
    30210214411060402801101878296110720392951022953421105897600710464881011101695
    211224841058862421101644613110711136381021184991105774063310447799911100412
    212235291057322041101410930110701879811019416561105650525910430718811099103
    213245761055781661101177247110692623241017648131105526988510413637711097768
    214256251054241281100943564110683366671015879701105403451110396556611096407
    2152667610527009011007098811106741101101411127110527991371037947551109502
    216277291051160521100476198110664853531012342841105156376310362394411093607
    31217287841049620141100242515110655596961010574411105032838910345313311092168
    218298411048079761100008832110646340391008805981104909301510328232211090703
    219309001046539381099775149110637083821007037551104785764110311151111089212
    220319611044999001099541466110627827251005269121104662226710294070011087695
    2213210241043458621099307783110618570681003500691104538689310276988911086152
    2223310891041918241099074100110609314111001732261104415151910259907811084583
    2233411561040377861098840417110600057540999963831104291614510242826711082988
    322243512251038837481098606734110590800970998195401104168077110225745611081367
    22536129610372971010983730511105815444099642697110404453971020866451107972
    2263713691035756721098139368110572287830994658541103921002310191583411078047
    2273814441034216341097905685110563031260992890111103797464910174502311076348
    2283915211032675961097672002110553774690991121681103673927510157421211074623
    2294016001031135581097438319110544518120989353251103550390110140340111072872
    2304116811029595201097204636110535261550987584821103426852710123259011071095
    332314217641028054821096970953110526004980985816391103303315310106177911069292
    2324318491026514441096737270110516748410984047961103179777910089096811067463
    2334419361024974061096503587110507491840982279531103056240510072015711065608
    2344520251023433681096269904110498235270980511101102932703110054934611063727
    23546211610218933010960362211104889787097874267110280916571003785351106182
    2364722091020352921095802538110479722130976974241102685628310020772411059887
    2374823041018812541095568855110470465560975205811102562090910003691311057928
    342384924011017272161095335172110461208990973437381102438553509986610211055943
    2395025001015731781095101489110451952420971668951102315016109969529111053932
    2405126011014191401094867806110442695850969900521102191478709952448011051895
    2415227041012651021094634123110433439280968132091102067941309935366911049832
    2425328091011110641094400440110424182710966363661101944403909918285811047743
    2435429161009570261094166757110414926140964595231101820866509901204711045628
    2445530251008029881093933074110405669570962826801101697329109884123611043487
    352455631361006489501093699391110396413096105837110157379170986704251104132
    2465732491004949121093465708110387156430959289941101450254309849961411039127
    2475833641003408741093232025110377899860957521511101326716909832880311036908
    2485934811001868361092998342110368643290955753081101203179509815799211034663
    2496036001000327981092764659110359386720953984651101079642109798718111032392
    2506137210998787601092530976110350130150952216221100956104709781637011030095
    2516238440997247221092297293110340873580950447791100832567309764555911027772
    362526339690995706841092063610110331617010948679361100709029909747474811025423
    2536440960994166461091829927110322360440946910931100585492509730393711023048
    2546542250992626081091596244110313103870945142501100461955109713312611020647
    25566435609910857010913625611103038473094337407110033841770969623151101822
    2566744890989545321091128878110294590730941605641100214880309679150411015767
    2576846240988004941090895195110285334160939837211100091342909662069311013288
    2586947610986464561090661512110276077590938068781099967805509644988211010783
    372597049000984924181090427829110266821020936300351099844268109627907111008252
    2607150410983383801090194146110257564450934531921099720730709610826011005695
    2617251840981843421089960463110248307880932763491099597193309593744911003112
    2627353290980303041089726780110239051310930995061099473655909576663811000503
    2637454760978762661089493097110229794740929226631099350118509559582710997868
    PDM1
    PDM 2
    GDM
    Intercepting Curves Random Effects are intercept and ctime (=slope)
    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
    17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
    120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
    121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
    122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
    123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
    124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
    125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
    18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
    127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
    128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
    129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
    130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
    131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
    132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
    19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
    134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
    135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
    136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
    137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
    138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
    139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
    20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
    141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
    142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
    143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
    144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
    145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
    146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
    21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
    148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
    149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
    150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
    151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
    152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
    153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
    22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
    155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
    156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
    157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
    158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
    159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
    160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
    23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
    162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
    163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
    164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
    165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
    166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
    167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
    24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
    169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
    170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
    171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
    172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
    173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
    174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
    25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
    176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
    177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
    178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
    179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
    180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
    181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
    26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
    183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
    184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
    185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
    186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
    187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
    188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
    27189002414769727245863358855247378933256248771281205245293918283252156109031122632
    19011242848834431247298968107248885247499250207813572466295047242534796182011121895
    191242442206961622487345773592503915617422516443459352479650911652548031273721121132
    1923924559255789325017018661125189787598525308087832493006776062561266365431120343
    1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
    194525248336281355253041405115254910504471255953943032519718504882587736548851118687
    195636249708143086254477014367256416818714257390475395253307436929260097164056111782
    2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
    19786425245186654825734823287125942944722602635401252559786098112627441823981116008
    198981253823728279258783842123260935761443261700072492573141962522640676915691115063
    1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
    20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
    201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
    20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
    29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
    20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
    20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
    2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
    20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
    20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
    2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
    3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
    211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
    2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
    213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
    21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
    21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
    2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
    3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
    21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
    2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
    22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
    2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
    222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
    2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
    32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
    225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
    2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
    227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
    228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
    22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
    230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
    332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
    23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
    2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
    234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
    235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
    23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
    237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
    34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
    23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
    240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
    2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
    242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
    2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
    244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
    35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
    24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
    247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
    248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
    24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
    250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
    2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
    3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
    2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
    254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
    255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
    25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
    257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
    258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
    37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
    260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
    2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
    262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
    2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
    PDM1
    PDM 2
    GDM
    Intercepting Curves Random Effects are intercept and ctime (=slope)
    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
    17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
    120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
    121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
    122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
    123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
    124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
    125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
    18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
    127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
    128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
    129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
    130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
    131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
    132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
    19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
    134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
    135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
    136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
    137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
    138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
    139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
    20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
    141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
    142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
    143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
    144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
    145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
    146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
    21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
    148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
    149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
    150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
    151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
    152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
    153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
    22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
    155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
    156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
    157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
    158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
    159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
    160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
    23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
    162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
    163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
    164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
    165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
    166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
    167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
    24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
    169-204001942030097220294920811968857670952039875573619824233804820272617541131912
    170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
    171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
    172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
    173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
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    25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
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    177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
    178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
    179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
    180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
    181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
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    188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
    2718900226029388723887603482286156060752396057377229889735228236469967341122632
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    192392308033455472442650588052333750819222449484647512346368448052415315361311120343
    193416232394664496246061400142349615738712467293737682362192146642432187257281119528
    194525233985983445247857741475236548065822485102827852378015845232449059153251118687
    19563623557730239424965408281238134557769250291191802239383954382246593104922111782
    281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
    1978642387599402922532467654824130754166725385300983624254869412499674841161116008
    1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
    19910100241942578192568394481524448052556525741482787245713433818253341863311114092
    200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
    20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
    202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
    2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
    20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
    2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
    206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
    2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
    208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
    2092040025785576768274802861526034544505527522391804261537132408270213759281102952
    30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
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    21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
    2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
    2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
    216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
    312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
    218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
    21930900273768957172927662748527621036454529303300821277360830998287085655251089212
    220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
    221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
    2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
    223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
    32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
    22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
    2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
    22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
    2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
    22940160028968214666310729688229207528403531084209838293184529588303957551221072872
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    2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
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    23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
    2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
    23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
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    239502500305595336153286931015530794020352532865118855309008228178320829447191053932
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    241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
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    2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
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    263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
    PDM1
    PDM 2
    GDM
    Intercepting Curves Random Effects are intercept and ctime (=slope)
    AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
    17119-7049001103696581094598541182103721201826791109612CURVE
    120-6947611121270161112530551199690231216229731110695
    121-6846241138824721130489621217245381230675111111752DM1
    122-6744891156360261148475751234769171245162931112783
    123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
    124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
    125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
    18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
    127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
    128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
    129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
    130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
    131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
    132-5732491330669561329825351408282271392375331121663
    19133-563136134799588134810914142546111407329991122408109459854
    134-5530251365303181366419991442608571422327091123127GDM
    135-54291613825914613847579145972468143736663112382
    136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
    137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
    138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
    139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
    20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
    141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
    142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
    143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
    144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
    145-44193615544281615696253162916098159009623112932
    146-4318491571507221588260871645932131605602611129727
    21147-421764158856726160692351662671921621151431130108
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    22154-3512251707454981738319591778972371731181491132047
    155-34115617243628617571987179546128174706983113222
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    157-321024175812156179503811828345021778973831132488
    158-319611774972381813998391844739851794989491132583
    159-309001791804181832985741861103321811047591132652
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    170-193611975698662043632552039031731990487731131695
    171-183241992302222062944622055018882007055111131452
    172-172892008886762082283752070974672023664931131183
    173-16256202545228210164994208689912040317191130888
    174-152252041998782121043192102792172057011891130567
    25175-1419620585262621404635211865388207374903113022
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    177-12144209152416217938532150283222107350631129448
    178-111212107994582198886792166050852124215091129023
    179-101002124445982218415342181787122141121991128572
    180-9812140878362237970952197492032158071331128095
    181-8642157291722257553622213165582175063111127592
    26182-7492173686062277163352228807772192097331127063
    183-636219006138229680014224441862209173991126508
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    2465732493183362223588470873164679133370562611039127
    247583364319852026360983953178282923390355431036908
    2485934813213659283631235193191855353410190691034663
    2496036003228779283652657943205396423430068391032392
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    362526339693274025163717088553245831473489956131025423
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    372597049003378933183868373743339082323631179591008252
    2607150413393843963890094153352278433651524131005695
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    2627353293423608463933616153378576573692340531000503
    263745476343846218395541774339167863712812390997868
    PDM1
    PDM 2
    GDM

    0

    1

    2

    3

    4

    5

    6

    7

    madri obese

    48

    Del 20 delle madri obese dal 2008 al 2016Dati regione Toscana

    57

    Nascere in Toscana 2015

    MATERNAL AGE DELAYED CHILDBEARING AND METASBOLIC SYNDROME

    2016

    Prevalence of metabolic syndrome(NCEP ATP III) in the NHANES III survey Ford ES JAMA 2002 287356

    Balkau B Diabet Metabol 2002

    36 of Europeans were observed at the ageof 40-55 years with metabolic syndrome

    Prevalence of hyperglycaemia in pregnancy by age

    Global estimates of the prevalence of hyperglycaemia in pregnancy L Guariguata et al Diabettesresearch and clinical practice 2014

    Global prevalence of hyperglycaemia in pregnancy 169

    The prevalence of HIP increases sharply with age with a prevalenceof 392 in women40ndash44 and up to 479 in women 45ndash59 years

    IN CHE MODO IL DIABETE INFLUENZAIL TIMING LA MODALITAgrave E LrsquoOUTCOME DEL

    PARTO

    THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

    FFA(fat mobilization)

    Glucose

    leptina

    INSULIN RESISTANCE

    OBESITY

    GESTATIONAL DIABETES

    IGF1

    Adiponectina

    insulin

    FETAL NUTRIENT AVAILABILITY

    PLACENTAL TRASPORT OF NUTRIENTS

    mTOR+

    ldquoadaptive regulationrdquo

    FETAL OVERNUTRITION-MACROSOMIALGA

    Romero Am J Obstet Gynecol 2017

    Brett KE Int J Mol Sci 2014

    MACROSOMIAL

    MACROSOMIALG

    DISTOCIA STILLBIRTH

    Macrosomia e rischio di distocia

    Birth weight distribution in diabetic pregnancies

    Persson et al Diab Care 2011341145-1149

    ldquoDIABESITYrdquo and MACROSOMIA

    MACROSOMIA ASIMMETRICA

    OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

    Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

    Fetal growth profiles in diabetic pregnancies

    08

    085

    09

    095

    1

    105

    11

    115

    12

    125

    13

    100 120 140 160 180 200 220 240 260 280

    Gestational age in days

    Hea

    d to

    abd

    omin

    al c

    ircu

    mfe

    renc

    e ra

    tio

    (HC

    AC

    rati

    o)

    IDDM non-macrosomia

    IDDM macrosomia

    DM2 non-macrosomia

    DM2 macrosomia

    GDM non-macrosomia

    GDM macrosomia

    Birthweightgt90th

    Type-1-diabetes LGA

    Type-1 AGA

    N Hammoud et al UOG 2012

    Type-2-diabetes LGA

    GDM LGA

    Grafiek3

    Fetal growth profiles in diabetic pregnancies

    IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

    Gestational age in days

    Head to abdominal circumference ratio (HCAC ratio)

    iddm gdm 977

    IDDM

    IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

    Gestational age in days

    Fetal abdominal circumference (mm)

    GDM

    GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

    Gestational age in days

    Fetal abdominal circumference (mm)

    FAC 6 groups

    Fetal growth profiles in diabetic pregnancies

    IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

    Gestational age in days

    Fetal abdominal circumference (mm)

    HC 6 groups

    Fetal growth profiles in diabetic pregnancies

    IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263141936936246000021434432504890000114494956473214645587897500002147962193218000011494685074611509748217040000215248113594700001153987450191554937644330000215700007867599999158506392919000011600127071620000316151902140499999163025335648000011645316498911660379641339999916754427837700001169050592621705569068629999917206322110600001173569535349000011750758495921765821638350000217808847807800001179594792321181101106564000021826074208070000118411373505185620049293000021871263635360000118863267777900001190138992022000021916453062650000219315162050800001194657934751196164248994000021976705632370000119917687748200683191722999992021895059660000120369582020920520213445220670844869500002208214762938000012097210771812112273914240000221273370566700001214240019912157463341530000221725264839600001218758962639220265276882000022217715911250000122327790536800001224784219611226290533854000022277968480970000122930316234230809476583000022323157908260000123382210506923532841931200002236834733555000012383410477980000123984736204124135367628400002242859990527000012443663047724587261901300002247378933256000012488852474992503915617420000225189787598500001253404190228254910504471000022564168187139999925792313295700001259429447200000032609357614429999926244207568600001263948389929000032654547041719999926696101841500001268467332658000032699736469012714799611440000127298627538700003274492589632759989038730000227750521811600004279011532359280517846602000022820241608449999828353047508828503678933100002286543103574000042880494178170000128955573206000003291062046302999992925683605460000129407467478900003295580989031999992970873032750000129859361751800003300099931760999993016062460040000130311256024700003304618874493061251887330000230763150297600004309137817219310644131462000023121504457050000431365675994831516307419100002316669388433999983181757026773196820169200000232118833116300004322694645406000013242009596490000332570727389199999327213588135000013287199023780000333022621662100005331732530864000013332388451070000333474515934999999336251473593000013377577878360000333926410207934077041632200002342276730564999983437830448083452893590510000234679567329400004348301987537349808301780000023513146160229999935282093026635432724450900002355833558752000043573398729950000135884618723800003DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226315180286741315313845385400001154474040295000011558096267360000115714521317700002158480799617999991598163860590000216115197251624875589411638231453820000116515873182300001166494318264000011678299047049999916916549114600002170501077587171836664028000031731722504690000117450783691000001175843423351000011771790097920000217851459623300002179850182674181185769115000031825213555561838569419970000118519252843800001186528114879000011878637013200000218919928776099999190534874202000031918704606431932060470840000119454163352500001195877219966000011972128064070000219854839284800002199883979289000022012195657320255515217120389073861200001205226325053000012065619114940000120789749793500002209233084376000022105686708172119042572582132398436990000121457543014000001215911016581000012172466030220000221858218946300002219917775904221253362345222588948786223924535227000012252601216680000122659570810900001227931294550000022292668809910000223060246743223193805387323327364031423460922675500001235944813196000012372803996370000223861598607800002239951572519000022412871589624262274540124395833184200001245293918283000012466295047240000124796509116500002249300677606000022506362640472519718504882533074369292546430233700000125597860981100001257314196251999992586497826930000225998536913426132095557500003262656542016263992128457000042653277148980000126666330133899999267998887780000022693344742209999927067006066200003272005647103273341233544000032746768199850000127601240642599998277347992867000022786835793079999928001916574900002281354752192826903386310000328402592507200001285361511512999982866970979540000128803268439499999289368270836000022907038572772920394437180000329337503015929471061659999998296046203041000012973817894819999929871737592300002300052962364301388548805000033027241352463040597216870000430539530812800001306730894569000043080664810100000230940206745099999310737653892000033120732403333134088267739999831474441321500001316079999656000043174155860970000231875117253799999320086758979000023214223454232275793186100003324093518302000013254291047430000432676469118400001328100277624999993294358640660000233077145050733210703694800003333442623389334778209830000043361137962710000133744938271199999338784969153000023401205555943414561420350000334279172847634412731491700004GDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

    Gestational age in days

    Head circumference (mm)

    HCAC 6 groups

    Fetal growth profiles in diabetic pregnancies

    IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

    Gestational age in days

    Head to abdominal circumference ratio (HCAC ratio)

    Model

    Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

    Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

    LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

    Iperglicemia e rischio di morte fetale a termine di gravidanza

    Estimated rate of stillbirth in diabetic women 1920-2000

    Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

    4 of all stillbirths remain attributable to diabetes

    Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

    bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

    Adverse outcome

    HbA1C gt7

    1 increase in A1Ccorresponded to 55 increased

    risk of adverse outcome

    The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

    gestation particularly in the presence of fetal macrosomia

    fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

    Langer O 1995

    100 mgdLfor stillbirth

    Diabetic patients n = 271691

    Am J Obstet Gynecol 2002

    The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

    4873 diabetic women

    pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

    outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

    bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

    GDMbull dysglycemia was more difficult to manage

    2016

    Differences in placental pathologyaccording to diabetes types

    Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

    GDM is associated with a greater rate of villous immaturity

    0102030405060708090

    100GDMDMIDMII

    o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

    A retrospective study on 175 placentas with DVM vs 175 controls

    Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

    Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

    Pathophysiology of fetal compromise in diabetic pregnancy

    The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

    Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

    Bjork 1984Nylund 1982Siddiqui 2003

    A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

    STILLBIRTH RISK

    BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

    OBESITArsquo E MORTE FETALE

    6-7 per unit BMI for BMI gt 23

    Tennant PWG Am J Obstet Gynecol 2007

    HYPERINSULINISMHYPERANDROGENISM

    IMPAIRED PLACENTATION

    THE EFFECTS OF OBESITYMETABOLIC SYNDROME

    Cakmak and Taylor Hum Reprod Update 2011

    Makieva S Hum Reprod Update 2014

    Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

    Hotamisligil GS Nature 2006

    LeptinCRH

    Urocortin 3IL-6

    INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

    INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

    Adiponectina Insulin LeptinTNFα IL-6

    PLACENTAL ALTERATIONIN GENE EXPRESSION

    PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

    CollagenaseCervical ripening

    FFA

    OXIDATIVE STRESS

    PREVENZIONE STILLBIRTH

    PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

    MORBIDITAgrave NEONATALE

    AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

    TIMING E MODALITArsquo DEL PARTO

    Induzione o attesa

    INDUZIONE DEL TRAVAGLIO

    Quando fare un TC elettivo

    gt 4000 grgt 4500 gr gt 5000 gr

    ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

    425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

    No differenza in TC e outcome perinatale

    200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

    No differenza in TC gt di LGA e peso medio nel gruppo di attesa

    RCT INDUZIONE VS ATTESA in GDM

    RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

    2014

    1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

    2 Patients well controlled on insulin should probably be delivered by the due date

    3 Poorly controlled GDMrsquos using insulin require individual judgment

    Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

    1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

    2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

    3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

    cesarean delivery when the estimated fetal weight is ge 4500 g

    MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

    MODALITAgrave E TIMING DEL PARTO nel GDM

    GMD in terapia insulinicaBen controllato

    +Condizioni fetali rassicuranti

    MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

    GDM in terapia nutrizionalecon profili glicemici ottimali

    +Feto AGA

    MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

    Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

    EFW lt 4000g LGAControllo metabolico non

    ottimale

    4000g lt EFW gt 4500g EFW ge 4500g

    Programmare TC elettivo

    Parto vaginale indotto a 38-39 sett

    Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

    MODALITAgrave E TIMING DEL PARTO nel GDM

    IN BASE AL PESO FETALE STIMATO

    - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

    - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

    - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

    ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

    Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

    The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

    A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

    If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

    Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

    GDM and the Use of Betamethasone

    bull administration of betamethasone in the late preterm period should be limited to women with GDM only

    bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

    bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

    Society of Obstetricians and Gynaecologists of Canada

    The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

    late preterm delivery between 24 to 36 weeksrsquo gestation

    ASSISTENZA IN TRAVAGLIO

    - MONITORAGGIO FETALE CONTINUO

    - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

    MANTENERE GLICEMIA gt70 E lt 126

    (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

    GDM

    - Intravenous infusion of regular insulin titrated and glucose

    - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

    (ACOG 2005)

    ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

    Venere di Willendorf

    Thank you for your attention

    Pathophysiology of fetal compromise in diabetic pregnancy

    Islet cell hyperplasia common in stillborn IDMs

    There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

    Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

    Salvesen 1993Hay 1989Chukwuma 2001

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    • Birth weight distribution in diabetic pregnancies
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    • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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    • Differences in placental pathology according to diabetes types
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    • Pathophysiology of fetal compromise in diabetic pregnancy
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    • GDM and the Use of Betamethasone
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    • Pathophysiology of fetal compromise in diabetic pregnancy
      Intercepting Curves Random Effects are intercept and ctime (=slope)
      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
      17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
      120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
      121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
      122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
      123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
      124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
      125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
      18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
      127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
      128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
      129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
      130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
      131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
      132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
      19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
      134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
      135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
      136-5328091174390921119170838111405379131153817241115039368311728882411124487
      137-5227041172850541118937155111396122561152048811114915830911711801311125128
      138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
      139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
      20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
      141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
      142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
      143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
      144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
      145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
      146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
      21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
      148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
      149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
      150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
      151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
      152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
      153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
      22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
      155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
      156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
      157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
      158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
      159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
      160-298411137421801113562446111183221451111374921112074470711318936011132695
      23161-287841135881421113328763111173964881109606491111950933311301854911132712
      162-277291134341041113095080111164708311107838061111827395911284773811132703
      163-266761132800661112861397111155451741106069631111703858511267692711132668
      164-256251131260281112627714111146195171104301201111580321111250611611132607
      165-2457611297199011123940311111369386110253277111145678371123353051113252
      166-235291128179521112160348111127682031100764341111333246311216449411132407
      167-224841126639141111926665111118425461098995911111209708911199368311132268
      24168-214411125098761111692982111109168891097227481111086171511182287211132103
      169-204001123558381111459299111099912321095459051110962634111165206111131912
      170-193611122018001111225616111090655751093690621110839096711148125011131695
      171-183241120477621110991933111081399181091922191110715559311131043911131452
      172-172891118937241110758250111072142611090153761110592021911113962811131183
      173-162561117396861110524567111062886041088385331110468484511096881711130888
      174-152251115856481110290884111053629471086616901110344947111079800611130567
      25175-1419611143161011100572011110443729108484847111022140971106271951113022
      176-131691112775721109823518111035116331083080041110097872311045638411129847
      177-121441111235341109589835111025859761081311611109974334911028557311129448
      178-111211109694961109356152111016603191079543181109850797511011476211129023
      179-101001108154581109122469111007346621077774751109727260110994395111128572
      180-9811106614201108888786110998090051076006321109603722710977314011128095
      181-8641105073821108655103110988833481074237891109480185310960232911127592
      26182-7491103533441108421420110979576911072469461109356647910943151811127063
      183-6361101993061108187737110970320341070701031109233110510926070711126508
      184-5251100452681107954054110961063771068932601109109573110908989611125927
      185-41610989123011077203711109518072106716417110898603571089190851112532
      186-391097371921107486688110942550631065395741108862498310874827411124687
      187-241095831541107253005110933294061063627311108738960910857746311124028
      188-111094291161107019322110924037491061858881108615423510840665211123343
      27189001092750781106785639110914780921060090451108491886110823584111122632
      190111091210401106551956110905524351058322021108368348710806503011121895
      191241089670021106318273110896267781056553591108244811310789421911121132
      192391088129641106084590110887011211054785161108121273910772340811120343
      1934161086589261105850907110877754641053016731107997736510755259711119528
      1945251085048881105617224110868498071051248301107874199110738178611118687
      19563610835085011053835411108592415104947987110775066171072109751111782
      281967491081968121105149858110849984931047711441107627124310704016411116927
      1978641080427741104916175110840728361045943011107503586910686935311116008
      1989811078887361104682492110831471791044174581107380049510669854211115063
      199101001077346981104448809110822215221042406151107256512110652773111114092
      200111211075806601104215126110812958651040637721107132974710635692011113095
      201121441074266221103981443110803702081038869291107009437310618610911112072
      202131691072725841103747760110794445511037100861106885899910601529811111023
      29203141961071185461103514077110785188941035332431106762362510584448711109948
      204152251069645081103280394110775932371033564001106638825110567367611108847
      2051625610681047011030467111107666758103179557110651528771055028651110772
      206172891066564321102813028110757419231030027141106391750310533205411106567
      207183241065023941102579345110748162661028258711106268212910516124311105388
      208193611063483561102345662110738906091026490281106144675510499043211104183
      209204001061943181102111979110729649521024721851106021138110481962111102952
      30210214411060402801101878296110720392951022953421105897600710464881011101695
      211224841058862421101644613110711136381021184991105774063310447799911100412
      212235291057322041101410930110701879811019416561105650525910430718811099103
      213245761055781661101177247110692623241017648131105526988510413637711097768
      214256251054241281100943564110683366671015879701105403451110396556611096407
      2152667610527009011007098811106741101101411127110527991371037947551109502
      216277291051160521100476198110664853531012342841105156376310362394411093607
      31217287841049620141100242515110655596961010574411105032838910345313311092168
      218298411048079761100008832110646340391008805981104909301510328232211090703
      219309001046539381099775149110637083821007037551104785764110311151111089212
      220319611044999001099541466110627827251005269121104662226710294070011087695
      2213210241043458621099307783110618570681003500691104538689310276988911086152
      2223310891041918241099074100110609314111001732261104415151910259907811084583
      2233411561040377861098840417110600057540999963831104291614510242826711082988
      322243512251038837481098606734110590800970998195401104168077110225745611081367
      22536129610372971010983730511105815444099642697110404453971020866451107972
      2263713691035756721098139368110572287830994658541103921002310191583411078047
      2273814441034216341097905685110563031260992890111103797464910174502311076348
      2283915211032675961097672002110553774690991121681103673927510157421211074623
      2294016001031135581097438319110544518120989353251103550390110140340111072872
      2304116811029595201097204636110535261550987584821103426852710123259011071095
      332314217641028054821096970953110526004980985816391103303315310106177911069292
      2324318491026514441096737270110516748410984047961103179777910089096811067463
      2334419361024974061096503587110507491840982279531103056240510072015711065608
      2344520251023433681096269904110498235270980511101102932703110054934611063727
      23546211610218933010960362211104889787097874267110280916571003785351106182
      2364722091020352921095802538110479722130976974241102685628310020772411059887
      2374823041018812541095568855110470465560975205811102562090910003691311057928
      342384924011017272161095335172110461208990973437381102438553509986610211055943
      2395025001015731781095101489110451952420971668951102315016109969529111053932
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      2415227041012651021094634123110433439280968132091102067941309935366911049832
      2425328091011110641094400440110424182710966363661101944403909918285811047743
      2435429161009570261094166757110414926140964595231101820866509901204711045628
      2445530251008029881093933074110405669570962826801101697329109884123611043487
      352455631361006489501093699391110396413096105837110157379170986704251104132
      2465732491004949121093465708110387156430959289941101450254309849961411039127
      2475833641003408741093232025110377899860957521511101326716909832880311036908
      2485934811001868361092998342110368643290955753081101203179509815799211034663
      2496036001000327981092764659110359386720953984651101079642109798718111032392
      2506137210998787601092530976110350130150952216221100956104709781637011030095
      2516238440997247221092297293110340873580950447791100832567309764555911027772
      362526339690995706841092063610110331617010948679361100709029909747474811025423
      2536440960994166461091829927110322360440946910931100585492509730393711023048
      2546542250992626081091596244110313103870945142501100461955109713312611020647
      25566435609910857010913625611103038473094337407110033841770969623151101822
      2566744890989545321091128878110294590730941605641100214880309679150411015767
      2576846240988004941090895195110285334160939837211100091342909662069311013288
      2586947610986464561090661512110276077590938068781099967805509644988211010783
      372597049000984924181090427829110266821020936300351099844268109627907111008252
      2607150410983383801090194146110257564450934531921099720730709610826011005695
      2617251840981843421089960463110248307880932763491099597193309593744911003112
      2627353290980303041089726780110239051310930995061099473655909576663811000503
      2637454760978762661089493097110229794740929226631099350118509559582710997868
      PDM1
      PDM 2
      GDM
      Intercepting Curves Random Effects are intercept and ctime (=slope)
      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
      17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
      120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
      121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
      122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
      123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
      124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
      125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
      18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
      127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
      128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
      129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
      130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
      131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
      132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
      19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
      134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
      135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
      136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
      137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
      138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
      139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
      20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
      141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
      142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
      143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
      144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
      145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
      146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
      21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
      148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
      149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
      150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
      151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
      152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
      153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
      22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
      155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
      156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
      157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
      158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
      159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
      160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
      23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
      162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
      163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
      164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
      165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
      166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
      167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
      24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
      169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
      170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
      171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
      172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
      173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
      174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
      25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
      176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
      177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
      178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
      179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
      180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
      181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
      26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
      183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
      184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
      185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
      186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
      187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
      188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
      27189002414769727245863358855247378933256248771281205245293918283252156109031122632
      19011242848834431247298968107248885247499250207813572466295047242534796182011121895
      191242442206961622487345773592503915617422516443459352479650911652548031273721121132
      1923924559255789325017018661125189787598525308087832493006776062561266365431120343
      1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
      194525248336281355253041405115254910504471255953943032519718504882587736548851118687
      195636249708143086254477014367256416818714257390475395253307436929260097164056111782
      2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
      19786425245186654825734823287125942944722602635401252559786098112627441823981116008
      198981253823728279258783842123260935761443261700072492573141962522640676915691115063
      1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
      20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
      201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
      20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
      29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
      20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
      20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
      2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
      20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
      20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
      2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
      3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
      211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
      2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
      213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
      21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
      21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
      2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
      3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
      21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
      2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
      22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
      2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
      222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
      2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
      32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
      225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
      2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
      227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
      228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
      22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
      230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
      332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
      23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
      2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
      234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
      235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
      23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
      237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
      34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
      23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
      240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
      2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
      242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
      2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
      244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
      35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
      24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
      247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
      248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
      24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
      250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
      2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
      3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
      2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
      254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
      255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
      25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
      257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
      258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
      37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
      260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
      2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
      262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
      2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
      PDM1
      PDM 2
      GDM
      Intercepting Curves Random Effects are intercept and ctime (=slope)
      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
      17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
      120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
      121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
      122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
      123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
      124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
      125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
      18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
      127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
      128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
      129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
      130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
      131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
      132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
      19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
      134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
      135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
      136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
      137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
      138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
      139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
      20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
      141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
      142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
      143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
      144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
      145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
      146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
      21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
      148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
      149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
      150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
      151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
      152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
      153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
      22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
      155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
      156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
      157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
      158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
      159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
      160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
      23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
      162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
      163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
      164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
      165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
      166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
      167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
      24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
      169-204001942030097220294920811968857670952039875573619824233804820272617541131912
      170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
      171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
      172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
      173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
      174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
      25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
      176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
      177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
      178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
      179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
      180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
      181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
      26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
      183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
      184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
      185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
      186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
      187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
      188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
      2718900226029388723887603482286156060752396057377229889735228236469967341122632
      190112276207076492406723761352302020980242413866467172314721050872381571569371121895
      19124229212026598242468717472317885899732431675557342330544749462398443465341121132
      192392308033455472442650588052333750819222449484647512346368448052415315361311120343
      193416232394664496246061400142349615738712467293737682362192146642432187257281119528
      194525233985983445247857741475236548065822485102827852378015845232449059153251118687
      19563623557730239424965408281238134557769250291191802239383954382246593104922111782
      281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
      1978642387599402922532467654824130754166725385300983624254869412499674841161116008
      1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
      19910100241942578192568394481524448052556525741482787245713433818253341863311114092
      200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
      20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
      202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
      2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
      20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
      2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
      206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
      2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
      208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
      2092040025785576768274802861526034544505527522391804261537132408270213759281102952
      30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
      21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
      212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
      21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
      2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
      2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
      216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
      312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
      218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
      21930900273768957172927662748527621036454529303300821277360830998287085655251089212
      220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
      221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
      2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
      223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
      32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
      22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
      2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
      22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
      2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
      22940160028968214666310729688229207528403531084209838293184529588303957551221072872
      2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
      33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
      2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
      233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
      234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
      23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
      2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
      23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
      342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
      239502500305595336153286931015530794020352532865118855309008228178320829447191053932
      2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
      241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
      2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
      243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
      244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
      3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
      2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
      24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
      2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
      24960360032150852564346656514932380512301534646027872324831926768337701343161032392
      2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
      251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
      362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
      253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
      254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
      25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
      2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
      25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
      2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
      37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
      2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
      261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
      2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
      263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
      PDM1
      PDM 2
      GDM
      Intercepting Curves Random Effects are intercept and ctime (=slope)
      AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
      17119-7049001103696581094598541182103721201826791109612CURVE
      120-6947611121270161112530551199690231216229731110695
      121-6846241138824721130489621217245381230675111111752DM1
      122-6744891156360261148475751234769171245162931112783
      123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
      124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
      125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
      18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
      127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
      128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
      129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
      130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
      131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
      132-5732491330669561329825351408282271392375331121663
      19133-563136134799588134810914142546111407329991122408109459854
      134-5530251365303181366419991442608571422327091123127GDM
      135-54291613825914613847579145972468143736663112382
      136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
      137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
      138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
      139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
      20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
      141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
      142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
      143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
      144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
      145-44193615544281615696253162916098159009623112932
      146-4318491571507221588260871645932131605602611129727
      21147-421764158856726160692351662671921621151431130108
      148-4116811605608281625613191679380351636742691130463
      149-4016001622630281644329941696057421652376391130792
      150-3915211639633261663073751712703131668052531131095
      151-3814441656617221681844621729317481683771111131372
      152-3713691673582161700642551745900471699532131131623
      153-361296169052808171946754176245211715335591131848
      22154-3512251707454981738319591778972371731181491132047
      155-34115617243628617571987179546128174706983113222
      156-3310891741251721776104871811918831763000611132367
      157-321024175812156179503811828345021778973831132488
      158-319611774972381813998391844739851794989491132583
      159-309001791804181832985741861103321811047591132652
      160-298411808616961852000151877435431827148131132695
      23161-287841825410721871041621893736181843291111132712
      162-277291842185461890110151910005571859476531132703
      163-26676185894118190920574192624361875704391132668
      164-256251875677881928328391942450271891974691132607
      165-2457618923955619474781195862558190828743113252
      166-235291909094221966654871974769531924642611132407
      167-22484192577386198585871990882121941040231132268
      24168-214411942434482005089592006963351957480291132103
      169-204001959076082024347542023013221973962791131912
      170-193611975698662043632552039031731990487731131695
      171-183241992302222062944622055018882007055111131452
      172-172892008886762082283752070974672023664931131183
      173-16256202545228210164994208689912040317191130888
      174-152252041998782121043192102792172057011891130567
      25175-1419620585262621404635211865388207374903113022
      176-131692075034722159910872134484232090528611129847
      177-12144209152416217938532150283222107350631129448
      178-111212107994582198886792166050852124215091129023
      179-101002124445982218415342181787122141121991128572
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      193416235276848249465634239880212382274791119528
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      2051625625455063627356557257992278259559783110772
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      30210214412625005462837222152654056932686286131101695
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      21324576267247668289848674269816112741208391097768
      214256252688262382918962392712799772759600691096407
      2152667627040290629394651272740708277803543109502
      216277292719776722959994872741983032796512611093607
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      218298412751214983001135592771040852833594291090703
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      220319612782577163042384552799973232870845731087695
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      2395025003076723383439648143068574523233201191053932
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      2445530253152989083545814793137377473331104291043487
      3524556313631681851635671293315104398335081223104132
      2465732493183362223588470873164679133370562611039127
      247583364319852026360983953178282923390355431036908
      2485934813213659283631235193191855353410190691034663
      2496036003228779283652657943205396423430068391032392
      2506137213243880263674107753218906133449988531030095
      2516238443258962223695584623232384483469951111027772
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      372597049003378933183868373743339082323631179591008252
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      2617251843408735723911841623365443183671911111003112
      2627353293423608463933616153378576573692340531000503
      263745476343846218395541774339167863712812390997868
      PDM1
      PDM 2
      GDM

      MATERNAL AGE DELAYED CHILDBEARING AND METASBOLIC SYNDROME

      2016

      Prevalence of metabolic syndrome(NCEP ATP III) in the NHANES III survey Ford ES JAMA 2002 287356

      Balkau B Diabet Metabol 2002

      36 of Europeans were observed at the ageof 40-55 years with metabolic syndrome

      Prevalence of hyperglycaemia in pregnancy by age

      Global estimates of the prevalence of hyperglycaemia in pregnancy L Guariguata et al Diabettesresearch and clinical practice 2014

      Global prevalence of hyperglycaemia in pregnancy 169

      The prevalence of HIP increases sharply with age with a prevalenceof 392 in women40ndash44 and up to 479 in women 45ndash59 years

      IN CHE MODO IL DIABETE INFLUENZAIL TIMING LA MODALITAgrave E LrsquoOUTCOME DEL

      PARTO

      THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

      FFA(fat mobilization)

      Glucose

      leptina

      INSULIN RESISTANCE

      OBESITY

      GESTATIONAL DIABETES

      IGF1

      Adiponectina

      insulin

      FETAL NUTRIENT AVAILABILITY

      PLACENTAL TRASPORT OF NUTRIENTS

      mTOR+

      ldquoadaptive regulationrdquo

      FETAL OVERNUTRITION-MACROSOMIALGA

      Romero Am J Obstet Gynecol 2017

      Brett KE Int J Mol Sci 2014

      MACROSOMIAL

      MACROSOMIALG

      DISTOCIA STILLBIRTH

      Macrosomia e rischio di distocia

      Birth weight distribution in diabetic pregnancies

      Persson et al Diab Care 2011341145-1149

      ldquoDIABESITYrdquo and MACROSOMIA

      MACROSOMIA ASIMMETRICA

      OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

      Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

      Fetal growth profiles in diabetic pregnancies

      08

      085

      09

      095

      1

      105

      11

      115

      12

      125

      13

      100 120 140 160 180 200 220 240 260 280

      Gestational age in days

      Hea

      d to

      abd

      omin

      al c

      ircu

      mfe

      renc

      e ra

      tio

      (HC

      AC

      rati

      o)

      IDDM non-macrosomia

      IDDM macrosomia

      DM2 non-macrosomia

      DM2 macrosomia

      GDM non-macrosomia

      GDM macrosomia

      Birthweightgt90th

      Type-1-diabetes LGA

      Type-1 AGA

      N Hammoud et al UOG 2012

      Type-2-diabetes LGA

      GDM LGA

      Grafiek3

      Fetal growth profiles in diabetic pregnancies

      IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

      Gestational age in days

      Head to abdominal circumference ratio (HCAC ratio)

      iddm gdm 977

      IDDM

      IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

      Gestational age in days

      Fetal abdominal circumference (mm)

      GDM

      GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

      Gestational age in days

      Fetal abdominal circumference (mm)

      FAC 6 groups

      Fetal growth profiles in diabetic pregnancies

      IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631131321413511492848268500001116724824021185211653550000112031750669122113848025000011239101893612570653069512750287203000001129299213365000011310955547000000113289189603513468823737000002136484578704999991382809200400000114007726137500001141873602711436699440450000214546628537999999147262626715000011490589680515085530938515265165072000002154447992054999991562443333900000115804067472515983701606161633357395000021634296987300000116522604006500001167022381416881872273499999170615064070000021724114054050000117420774674176004088075177800429409999991795967707450000118139311208000001183189453415184985794750000031867821360850000218857847742000001190374818755000011921711600919396750142500002195763842760000021975601840950000119935652543201152866765202949208100000022047455494350000220654189077000001208338232105210134573442119309147750000221372725611000001215523597445000012173199387821911628011500002220912621450000022227089627850000122450530412000001226301645455000032280979867900000222989432812500002231690669460000012334870107952352833521300000323707969346500002238876034800000012406723761350000124246871747244265058805000022460614001400000224785774147500001249654082810000012514504241452532467654800000225504310681500002256839448150000012586357894850000326043213082262228472155000022640248134900000426582115482500001267617496160000032694138374952712101788300000227300652016500004274802861500000012765992028350000327839554416999999280191885505000022819882268400000428378456817528558090951000003287377250845000052891735921800000129096993351500004292766274852945626161850000229635895751999999298155298855000012999516401900000330174798152530354432286000002305340664195000043071370055300000130893334686500003310729688200000063125260295350000231432237086999999316118712205000013179150535400000331971139487532150773621000002323304077545000043251004188800000132689676021500003328693101550000053304894428850000233228578422000004334082125555335878466890000033376748082249999933947114956000001341267490895000043430638322334486017356500003346656514900000053484528562350000135024919757000004352045538905000063538418802400000235563822157499999357434562910000013592309042450000336102724558362823586915000023646199282500000436641626958500001368212610920000033700089522550000537180529359000002DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263117561169644999991191476615939999812073415354299999122320645491999981239071374409999912549362938999998127080121338999991286666132880000113025310523713183959718599999133426089134999981350125810839999813659907303299997138185564981999991397720569309999814135854888142945040828999991445315327779999814611802472699998147704516675999971492910086249999915087750057399998152463992523154050484471999991556369764209999915722346836999998158809960318999971603964522679999916198294421699998163569436166165155928114999991667424200639999916832891201299998169915403961999971715018959109999917308838785999998174674879809176261371758177847863706999991794343556559999818102084760499997182607339553999991841938315029999818578032345218736681540118895330734999999190539799298999981921262912479999719371278319699999195299275145999991968857670949999819847225904420005875099299999201645242941999982032317348909999720481822683999999206404718788999992079912107379999820957770268721116419463599999212750686584999982143371785339999721592367048321751016243199999219096654380999982206831463322226963827899999223856130227999982254426221769999822702911412622861560607499999230202098023999982317885899732333750819219999923496157387099998236548065819999982381345577692397210497179999924130754166699998242894033616244480525564999992460670175139999924765350946299998249240001412250826493360999992524129853099999825399947725925558596920799999257172461156999992587589531059999826034544505499997261931937004000022635184289530000126510492090226669141285126827790479999999269864396748999982714508886979999727303738064699996274623872596000012762103645452777968564942793833484429999928096984039199998282556332340999972841428242899999628572931623900001287315808188000012889023001372904887920859999929207528403499998293661775983999972952482679329999729683475988199996298421251831000013000077437830159423572899999303180727677999983047672196269999730635371157600002307940203525000023095266954740000131111318742331269967937199999314286171320999983158726632699999831745915521899997319045647167999963206321391170000132221863106632380512301499999325391614963999983269781069129999832856459886199997330151090811000023317375827600000133332407470933491056665799999336497058606999993380835505559999833967004250499997341256534453999963428430264029999534442951835234601601030099999DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

      Gestational age in days

      Fetal abdominal circumference (mm)

      HC 6 groups

      Fetal growth profiles in diabetic pregnancies

      IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631454466515314681851326099999148190374991999991495622367230000115093409845399998152305960185153677821916155049683646999991564215453780000215779340710899999159165268840000011605371305710000116190899230216328085403316465271576399999166024577495000021673964392259999816876830095700001170140162688171512024419172883886151742557478809999917562760961200001176999471342999981783713330740000117974319480518111505653618248691826699999183858779997999991852306417290000118660250346000001187974365191189346226922190718088653192089950384000021934618121149999919483367384600001196205535577000011975773973081989492590392003211207699999920169298250100002203064844231999982044367059630000120580856769420718042942520855229115620992415288699999211296014618000022126678763490000121403973808000001215411599811216783461542218155323272999992195271850039999922089904673500001222270908466000012236427701972250146319282263864936592277583553899999922913021712100002230502078852000012318739405830000123324580231423461766404523598952577599999237361387507000022387332492380000124010511096900001241476972724284883443124422069616224559255789299999246964419624000022483362813550000124970814308600001251080004817252451866548253823728278999992551955900100000225656745174100001257939313471999982593111752032606830369340000326205489866526342676039600002264798622126999992661704838580000126754234558899998268914207322702860690510000327165793078199999273029792513000022744016542439999927577351597500001277145377705999982785172394372798891011680000228126096289899999282632824630000022840046863609999828537654809200001286748409823000032881202715542894921332850000229086399501599999292235856747000012936077184780000429497958020900001296351441940000032977233036712990951654020000230046702713299999301838888864000013032107505950000430458261232630595447405700003307326335787999993086981975190000231007005924999999311441920981000013128137827120000331418564444331555750617400003316929367904999993183012296360000231967309136699998321044953098000013224168148290000332378867656325160538291000023265324000219999932790426175300001329276123483999983306479852150000133201984694600003333391708677334763570408000023361354321390000533750729387000001338879155600999983402510173323416228790630000334299474079399999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226315180286741315313845385400001154474040295000011558096267360000115714521317700002158480799617999991598163860590000216115197251624875589411638231453820000116515873182300001166494318264000011678299047049999916916549114600002170501077587171836664028000031731722504690000117450783691000001175843423351000011771790097920000217851459623300002179850182674181185769115000031825213555561838569419970000118519252843800001186528114879000011878637013200000218919928776099999190534874202000031918704606431932060470840000119454163352500001195877219966000011972128064070000219854839284800002199883979289000022012195657320255515217120389073861200001205226325053000012065619114940000120789749793500002209233084376000022105686708172119042572582132398436990000121457543014000001215911016581000012172466030220000221858218946300002219917775904221253362345222588948786223924535227000012252601216680000122659570810900001227931294550000022292668809910000223060246743223193805387323327364031423460922675500001235944813196000012372803996370000223861598607800002239951572519000022412871589624262274540124395833184200001245293918283000012466295047240000124796509116500002249300677606000022506362640472519718504882533074369292546430233700000125597860981100001257314196251999992586497826930000225998536913426132095557500003262656542016263992128457000042653277148980000126666330133899999267998887780000022693344742209999927067006066200003272005647103273341233544000032746768199850000127601240642599998277347992867000022786835793079999928001916574900002281354752192826903386310000328402592507200001285361511512999982866970979540000128803268439499999289368270836000022907038572772920394437180000329337503015929471061659999998296046203041000012973817894819999929871737592300002300052962364301388548805000033027241352463040597216870000430539530812800001306730894569000043080664810100000230940206745099999310737653892000033120732403333134088267739999831474441321500001316079999656000043174155860970000231875117253799999320086758979000023214223454232275793186100003324093518302000013254291047430000432676469118400001328100277624999993294358640660000233077145050733210703694800003333442623389334778209830000043361137962710000133744938271199999338784969153000023401205555943414561420350000334279172847634412731491700004GDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

      Gestational age in days

      Head circumference (mm)

      HCAC 6 groups

      Fetal growth profiles in diabetic pregnancies

      IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

      Gestational age in days

      Head to abdominal circumference ratio (HCAC ratio)

      Model

      Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

      Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

      LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

      Iperglicemia e rischio di morte fetale a termine di gravidanza

      Estimated rate of stillbirth in diabetic women 1920-2000

      Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

      4 of all stillbirths remain attributable to diabetes

      Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

      bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

      Adverse outcome

      HbA1C gt7

      1 increase in A1Ccorresponded to 55 increased

      risk of adverse outcome

      The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

      gestation particularly in the presence of fetal macrosomia

      fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

      Langer O 1995

      100 mgdLfor stillbirth

      Diabetic patients n = 271691

      Am J Obstet Gynecol 2002

      The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

      4873 diabetic women

      pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

      outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

      bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

      GDMbull dysglycemia was more difficult to manage

      2016

      Differences in placental pathologyaccording to diabetes types

      Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

      GDM is associated with a greater rate of villous immaturity

      0102030405060708090

      100GDMDMIDMII

      o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

      A retrospective study on 175 placentas with DVM vs 175 controls

      Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

      Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

      Pathophysiology of fetal compromise in diabetic pregnancy

      The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

      Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

      Bjork 1984Nylund 1982Siddiqui 2003

      A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

      STILLBIRTH RISK

      BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

      OBESITArsquo E MORTE FETALE

      6-7 per unit BMI for BMI gt 23

      Tennant PWG Am J Obstet Gynecol 2007

      HYPERINSULINISMHYPERANDROGENISM

      IMPAIRED PLACENTATION

      THE EFFECTS OF OBESITYMETABOLIC SYNDROME

      Cakmak and Taylor Hum Reprod Update 2011

      Makieva S Hum Reprod Update 2014

      Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

      Hotamisligil GS Nature 2006

      LeptinCRH

      Urocortin 3IL-6

      INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

      INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

      Adiponectina Insulin LeptinTNFα IL-6

      PLACENTAL ALTERATIONIN GENE EXPRESSION

      PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

      CollagenaseCervical ripening

      FFA

      OXIDATIVE STRESS

      PREVENZIONE STILLBIRTH

      PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

      MORBIDITAgrave NEONATALE

      AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

      TIMING E MODALITArsquo DEL PARTO

      Induzione o attesa

      INDUZIONE DEL TRAVAGLIO

      Quando fare un TC elettivo

      gt 4000 grgt 4500 gr gt 5000 gr

      ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

      425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

      No differenza in TC e outcome perinatale

      200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

      No differenza in TC gt di LGA e peso medio nel gruppo di attesa

      RCT INDUZIONE VS ATTESA in GDM

      RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

      2014

      1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

      2 Patients well controlled on insulin should probably be delivered by the due date

      3 Poorly controlled GDMrsquos using insulin require individual judgment

      Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

      1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

      2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

      3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

      cesarean delivery when the estimated fetal weight is ge 4500 g

      MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

      MODALITAgrave E TIMING DEL PARTO nel GDM

      GMD in terapia insulinicaBen controllato

      +Condizioni fetali rassicuranti

      MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

      GDM in terapia nutrizionalecon profili glicemici ottimali

      +Feto AGA

      MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

      Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

      EFW lt 4000g LGAControllo metabolico non

      ottimale

      4000g lt EFW gt 4500g EFW ge 4500g

      Programmare TC elettivo

      Parto vaginale indotto a 38-39 sett

      Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

      MODALITAgrave E TIMING DEL PARTO nel GDM

      IN BASE AL PESO FETALE STIMATO

      - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

      - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

      - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

      ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

      Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

      The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

      A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

      If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

      Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

      GDM and the Use of Betamethasone

      bull administration of betamethasone in the late preterm period should be limited to women with GDM only

      bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

      bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

      Society of Obstetricians and Gynaecologists of Canada

      The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

      late preterm delivery between 24 to 36 weeksrsquo gestation

      ASSISTENZA IN TRAVAGLIO

      - MONITORAGGIO FETALE CONTINUO

      - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

      MANTENERE GLICEMIA gt70 E lt 126

      (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

      GDM

      - Intravenous infusion of regular insulin titrated and glucose

      - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

      (ACOG 2005)

      ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

      Venere di Willendorf

      Thank you for your attention

      Pathophysiology of fetal compromise in diabetic pregnancy

      Islet cell hyperplasia common in stillborn IDMs

      There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

      Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

      Salvesen 1993Hay 1989Chukwuma 2001

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      • Birth weight distribution in diabetic pregnancies
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      • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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      • Differences in placental pathology according to diabetes types
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      • Pathophysiology of fetal compromise in diabetic pregnancy
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      • GDM and the Use of Betamethasone
      • Diapositiva numero 38
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      • Pathophysiology of fetal compromise in diabetic pregnancy
        Intercepting Curves Random Effects are intercept and ctime (=slope)
        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
        17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
        120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
        121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
        122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
        123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
        124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
        125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
        18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
        127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
        128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
        129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
        130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
        131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
        132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
        19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
        134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
        135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
        136-5328091174390921119170838111405379131153817241115039368311728882411124487
        137-5227041172850541118937155111396122561152048811114915830911711801311125128
        138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
        139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
        20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
        141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
        142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
        143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
        144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
        145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
        146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
        21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
        148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
        149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
        150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
        151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
        152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
        153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
        22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
        155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
        156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
        157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
        158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
        159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
        160-298411137421801113562446111183221451111374921112074470711318936011132695
        23161-287841135881421113328763111173964881109606491111950933311301854911132712
        162-277291134341041113095080111164708311107838061111827395911284773811132703
        163-266761132800661112861397111155451741106069631111703858511267692711132668
        164-256251131260281112627714111146195171104301201111580321111250611611132607
        165-2457611297199011123940311111369386110253277111145678371123353051113252
        166-235291128179521112160348111127682031100764341111333246311216449411132407
        167-224841126639141111926665111118425461098995911111209708911199368311132268
        24168-214411125098761111692982111109168891097227481111086171511182287211132103
        169-204001123558381111459299111099912321095459051110962634111165206111131912
        170-193611122018001111225616111090655751093690621110839096711148125011131695
        171-183241120477621110991933111081399181091922191110715559311131043911131452
        172-172891118937241110758250111072142611090153761110592021911113962811131183
        173-162561117396861110524567111062886041088385331110468484511096881711130888
        174-152251115856481110290884111053629471086616901110344947111079800611130567
        25175-1419611143161011100572011110443729108484847111022140971106271951113022
        176-131691112775721109823518111035116331083080041110097872311045638411129847
        177-121441111235341109589835111025859761081311611109974334911028557311129448
        178-111211109694961109356152111016603191079543181109850797511011476211129023
        179-101001108154581109122469111007346621077774751109727260110994395111128572
        180-9811106614201108888786110998090051076006321109603722710977314011128095
        181-8641105073821108655103110988833481074237891109480185310960232911127592
        26182-7491103533441108421420110979576911072469461109356647910943151811127063
        183-6361101993061108187737110970320341070701031109233110510926070711126508
        184-5251100452681107954054110961063771068932601109109573110908989611125927
        185-41610989123011077203711109518072106716417110898603571089190851112532
        186-391097371921107486688110942550631065395741108862498310874827411124687
        187-241095831541107253005110933294061063627311108738960910857746311124028
        188-111094291161107019322110924037491061858881108615423510840665211123343
        27189001092750781106785639110914780921060090451108491886110823584111122632
        190111091210401106551956110905524351058322021108368348710806503011121895
        191241089670021106318273110896267781056553591108244811310789421911121132
        192391088129641106084590110887011211054785161108121273910772340811120343
        1934161086589261105850907110877754641053016731107997736510755259711119528
        1945251085048881105617224110868498071051248301107874199110738178611118687
        19563610835085011053835411108592415104947987110775066171072109751111782
        281967491081968121105149858110849984931047711441107627124310704016411116927
        1978641080427741104916175110840728361045943011107503586910686935311116008
        1989811078887361104682492110831471791044174581107380049510669854211115063
        199101001077346981104448809110822215221042406151107256512110652773111114092
        200111211075806601104215126110812958651040637721107132974710635692011113095
        201121441074266221103981443110803702081038869291107009437310618610911112072
        202131691072725841103747760110794445511037100861106885899910601529811111023
        29203141961071185461103514077110785188941035332431106762362510584448711109948
        204152251069645081103280394110775932371033564001106638825110567367611108847
        2051625610681047011030467111107666758103179557110651528771055028651110772
        206172891066564321102813028110757419231030027141106391750310533205411106567
        207183241065023941102579345110748162661028258711106268212910516124311105388
        208193611063483561102345662110738906091026490281106144675510499043211104183
        209204001061943181102111979110729649521024721851106021138110481962111102952
        30210214411060402801101878296110720392951022953421105897600710464881011101695
        211224841058862421101644613110711136381021184991105774063310447799911100412
        212235291057322041101410930110701879811019416561105650525910430718811099103
        213245761055781661101177247110692623241017648131105526988510413637711097768
        214256251054241281100943564110683366671015879701105403451110396556611096407
        2152667610527009011007098811106741101101411127110527991371037947551109502
        216277291051160521100476198110664853531012342841105156376310362394411093607
        31217287841049620141100242515110655596961010574411105032838910345313311092168
        218298411048079761100008832110646340391008805981104909301510328232211090703
        219309001046539381099775149110637083821007037551104785764110311151111089212
        220319611044999001099541466110627827251005269121104662226710294070011087695
        2213210241043458621099307783110618570681003500691104538689310276988911086152
        2223310891041918241099074100110609314111001732261104415151910259907811084583
        2233411561040377861098840417110600057540999963831104291614510242826711082988
        322243512251038837481098606734110590800970998195401104168077110225745611081367
        22536129610372971010983730511105815444099642697110404453971020866451107972
        2263713691035756721098139368110572287830994658541103921002310191583411078047
        2273814441034216341097905685110563031260992890111103797464910174502311076348
        2283915211032675961097672002110553774690991121681103673927510157421211074623
        2294016001031135581097438319110544518120989353251103550390110140340111072872
        2304116811029595201097204636110535261550987584821103426852710123259011071095
        332314217641028054821096970953110526004980985816391103303315310106177911069292
        2324318491026514441096737270110516748410984047961103179777910089096811067463
        2334419361024974061096503587110507491840982279531103056240510072015711065608
        2344520251023433681096269904110498235270980511101102932703110054934611063727
        23546211610218933010960362211104889787097874267110280916571003785351106182
        2364722091020352921095802538110479722130976974241102685628310020772411059887
        2374823041018812541095568855110470465560975205811102562090910003691311057928
        342384924011017272161095335172110461208990973437381102438553509986610211055943
        2395025001015731781095101489110451952420971668951102315016109969529111053932
        2405126011014191401094867806110442695850969900521102191478709952448011051895
        2415227041012651021094634123110433439280968132091102067941309935366911049832
        2425328091011110641094400440110424182710966363661101944403909918285811047743
        2435429161009570261094166757110414926140964595231101820866509901204711045628
        2445530251008029881093933074110405669570962826801101697329109884123611043487
        352455631361006489501093699391110396413096105837110157379170986704251104132
        2465732491004949121093465708110387156430959289941101450254309849961411039127
        2475833641003408741093232025110377899860957521511101326716909832880311036908
        2485934811001868361092998342110368643290955753081101203179509815799211034663
        2496036001000327981092764659110359386720953984651101079642109798718111032392
        2506137210998787601092530976110350130150952216221100956104709781637011030095
        2516238440997247221092297293110340873580950447791100832567309764555911027772
        362526339690995706841092063610110331617010948679361100709029909747474811025423
        2536440960994166461091829927110322360440946910931100585492509730393711023048
        2546542250992626081091596244110313103870945142501100461955109713312611020647
        25566435609910857010913625611103038473094337407110033841770969623151101822
        2566744890989545321091128878110294590730941605641100214880309679150411015767
        2576846240988004941090895195110285334160939837211100091342909662069311013288
        2586947610986464561090661512110276077590938068781099967805509644988211010783
        372597049000984924181090427829110266821020936300351099844268109627907111008252
        2607150410983383801090194146110257564450934531921099720730709610826011005695
        2617251840981843421089960463110248307880932763491099597193309593744911003112
        2627353290980303041089726780110239051310930995061099473655909576663811000503
        2637454760978762661089493097110229794740929226631099350118509559582710997868
        PDM1
        PDM 2
        GDM
        Intercepting Curves Random Effects are intercept and ctime (=slope)
        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
        17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
        120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
        121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
        122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
        123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
        124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
        125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
        18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
        127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
        128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
        129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
        130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
        131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
        132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
        19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
        134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
        135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
        136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
        137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
        138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
        139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
        20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
        141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
        142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
        143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
        144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
        145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
        146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
        21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
        148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
        149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
        150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
        151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
        152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
        153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
        22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
        155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
        156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
        157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
        158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
        159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
        160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
        23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
        162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
        163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
        164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
        165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
        166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
        167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
        24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
        169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
        170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
        171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
        172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
        173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
        174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
        25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
        176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
        177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
        178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
        179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
        180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
        181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
        26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
        183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
        184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
        185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
        186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
        187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
        188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
        27189002414769727245863358855247378933256248771281205245293918283252156109031122632
        19011242848834431247298968107248885247499250207813572466295047242534796182011121895
        191242442206961622487345773592503915617422516443459352479650911652548031273721121132
        1923924559255789325017018661125189787598525308087832493006776062561266365431120343
        1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
        194525248336281355253041405115254910504471255953943032519718504882587736548851118687
        195636249708143086254477014367256416818714257390475395253307436929260097164056111782
        2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
        19786425245186654825734823287125942944722602635401252559786098112627441823981116008
        198981253823728279258783842123260935761443261700072492573141962522640676915691115063
        1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
        20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
        201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
        20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
        29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
        20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
        20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
        2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
        20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
        20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
        2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
        3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
        211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
        2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
        213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
        21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
        21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
        2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
        3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
        21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
        2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
        22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
        2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
        222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
        2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
        32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
        225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
        2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
        227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
        228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
        22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
        230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
        332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
        23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
        2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
        234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
        235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
        23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
        237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
        34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
        23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
        240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
        2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
        242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
        2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
        244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
        35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
        24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
        247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
        248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
        24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
        250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
        2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
        3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
        2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
        254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
        255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
        25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
        257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
        258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
        37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
        260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
        2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
        262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
        2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
        PDM1
        PDM 2
        GDM
        Intercepting Curves Random Effects are intercept and ctime (=slope)
        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
        17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
        120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
        121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
        122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
        123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
        124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
        125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
        18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
        127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
        128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
        129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
        130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
        131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
        132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
        19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
        134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
        135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
        136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
        137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
        138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
        139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
        20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
        141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
        142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
        143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
        144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
        145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
        146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
        21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
        148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
        149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
        150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
        151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
        152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
        153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
        22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
        155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
        156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
        157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
        158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
        159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
        160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
        23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
        162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
        163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
        164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
        165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
        166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
        167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
        24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
        169-204001942030097220294920811968857670952039875573619824233804820272617541131912
        170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
        171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
        172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
        173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
        174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
        25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
        176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
        177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
        178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
        179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
        180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
        181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
        26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
        183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
        184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
        185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
        186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
        187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
        188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
        2718900226029388723887603482286156060752396057377229889735228236469967341122632
        190112276207076492406723761352302020980242413866467172314721050872381571569371121895
        19124229212026598242468717472317885899732431675557342330544749462398443465341121132
        192392308033455472442650588052333750819222449484647512346368448052415315361311120343
        193416232394664496246061400142349615738712467293737682362192146642432187257281119528
        194525233985983445247857741475236548065822485102827852378015845232449059153251118687
        19563623557730239424965408281238134557769250291191802239383954382246593104922111782
        281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
        1978642387599402922532467654824130754166725385300983624254869412499674841161116008
        1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
        19910100241942578192568394481524448052556525741482787245713433818253341863311114092
        200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
        20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
        202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
        2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
        20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
        2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
        206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
        2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
        208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
        2092040025785576768274802861526034544505527522391804261537132408270213759281102952
        30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
        21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
        212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
        21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
        2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
        2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
        216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
        312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
        218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
        21930900273768957172927662748527621036454529303300821277360830998287085655251089212
        220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
        221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
        2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
        223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
        32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
        22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
        2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
        22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
        2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
        22940160028968214666310729688229207528403531084209838293184529588303957551221072872
        2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
        33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
        2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
        233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
        234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
        23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
        2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
        23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
        342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
        239502500305595336153286931015530794020352532865118855309008228178320829447191053932
        2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
        241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
        2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
        243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
        244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
        3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
        2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
        24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
        2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
        24960360032150852564346656514932380512301534646027872324831926768337701343161032392
        2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
        251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
        362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
        253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
        254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
        25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
        2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
        25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
        2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
        37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
        2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
        261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
        2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
        263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
        PDM1
        PDM 2
        GDM
        Intercepting Curves Random Effects are intercept and ctime (=slope)
        AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
        17119-7049001103696581094598541182103721201826791109612CURVE
        120-6947611121270161112530551199690231216229731110695
        121-6846241138824721130489621217245381230675111111752DM1
        122-6744891156360261148475751234769171245162931112783
        123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
        124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
        125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
        18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
        127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
        128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
        129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
        130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
        131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
        132-5732491330669561329825351408282271392375331121663
        19133-563136134799588134810914142546111407329991122408109459854
        134-5530251365303181366419991442608571422327091123127GDM
        135-54291613825914613847579145972468143736663112382
        136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
        137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
        138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
        139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
        20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
        141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
        142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
        143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
        144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
        145-44193615544281615696253162916098159009623112932
        146-4318491571507221588260871645932131605602611129727
        21147-421764158856726160692351662671921621151431130108
        148-4116811605608281625613191679380351636742691130463
        149-4016001622630281644329941696057421652376391130792
        150-3915211639633261663073751712703131668052531131095
        151-3814441656617221681844621729317481683771111131372
        152-3713691673582161700642551745900471699532131131623
        153-361296169052808171946754176245211715335591131848
        22154-3512251707454981738319591778972371731181491132047
        155-34115617243628617571987179546128174706983113222
        156-3310891741251721776104871811918831763000611132367
        157-321024175812156179503811828345021778973831132488
        158-319611774972381813998391844739851794989491132583
        159-309001791804181832985741861103321811047591132652
        160-298411808616961852000151877435431827148131132695
        23161-287841825410721871041621893736181843291111132712
        162-277291842185461890110151910005571859476531132703
        163-26676185894118190920574192624361875704391132668
        164-256251875677881928328391942450271891974691132607
        165-2457618923955619474781195862558190828743113252
        166-235291909094221966654871974769531924642611132407
        167-22484192577386198585871990882121941040231132268
        24168-214411942434482005089592006963351957480291132103
        169-204001959076082024347542023013221973962791131912
        170-193611975698662043632552039031731990487731131695
        171-183241992302222062944622055018882007055111131452
        172-172892008886762082283752070974672023664931131183
        173-16256202545228210164994208689912040317191130888
        174-152252041998782121043192102792172057011891130567
        25175-1419620585262621404635211865388207374903113022
        176-131692075034722159910872134484232090528611129847
        177-12144209152416217938532150283222107350631129448
        178-111212107994582198886792166050852124215091129023
        179-101002124445982218415342181787122141121991128572
        180-9812140878362237970952197492032158071331128095
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        192392336583362474748952383504872364773731120343
        193416235276848249465634239880212382274791119528
        1945252368934582514590792414067972399818291118687
        19563623850816625345523242930248241740423111782
        281967492401209722554540872444505632435032611116927
        197864241731876257455652459677422452703431116008
        1989812433408782594599192474817852470416691115063
        199101002449479782614668942489926922488172391114092
        200111212465531762634765752505004632505970531113095
        201121442481564722654889622520050982523811111112072
        202131692497578662675040552535065972541694131111023
        2920314196251357358269521854255004962559619591109948
        204152252529549482715423592565001872577587491108847
        2051625625455063627356557257992278259559783110772
        206172892561444222755914872594812332613650611106567
        20718324257736306277620112609670522631745831105388
        208193612593262882796514392624497352649883491104183
        209204002609143682816854742639292822668063591102952
        30210214412625005462837222152654056932686286131101695
        211224842640848222857616622668789682704551111100412
        212235292656671962878038152683491072722858531099103
        21324576267247668289848674269816112741208391097768
        214256252688262382918962392712799772759600691096407
        2152667627040290629394651272740708277803543109502
        216277292719776722959994872741983032796512611093607
        3121728784273550536298055172756527622815032231092168
        218298412751214983001135592771040852833594291090703
        219309002766905583021746542785522722852198791089212
        220319612782577163042384552799973232870845731087695
        2213210242798229723063049622814392382889535111086152
        2223310892813863263083741752828780172908266931084583
        223341156282947778310446094284313662927041191082988
        322243512252845073283125207192857461672945857891081367
        22536129628606497631459805287175538296471703107972
        2263713692876207223166780872886017732983618611078047
        227381444289174566318760832900248723002562631076348
        2283915212907265083208462792914448353021549091074623
        2294016002922765483229344342928616623040577991072872
        2304116812938246863250252952942753533059649331071095
        332314217642953709223271188622956859083078763111069292
        2324318492969152563292151352970933273097919331067463
        233441936298457688331314114298497613117117991065608
        2344520252999982183334157992998987573136359091063727
        23546211630153684633552019301296768315564263106182
        2364722093030735723376272873026916433174968611059887
        237482304304608396339737093040833823194337031057928
        342384924013061413183418495993054719853213747891055943
        2395025003076723383439648143068574523233201191053932
        2405126013092014563460827353082397833252696931051895
        2415227043107286723482033623096189783272235111049832
        2425328093122539863503266953109950373291815731047743
        243542916313777398352452734312367963311438791045628
        2445530253152989083545814793137377473331104291043487
        3524556313631681851635671293315104398335081223104132
        2465732493183362223588470873164679133370562611039127
        247583364319852026360983953178282923390355431036908
        2485934813213659283631235193191855353410190691034663
        2496036003228779283652657943205396423430068391032392
        2506137213243880263674107753218906133449988531030095
        2516238443258962223695584623232384483469951111027772
        362526339693274025163717088553245831473489956131025423
        253644096328906908373861954325924713510003591023048
        2546542253304093983760177593272631373530093491020647
        25566435633190998637817627328598428355022583101822
        2566744893334086723803374873299305833570400611015767
        257684624334905456382501413312596023590617831013288
        2586947613364003383846680393325854853610877491010783
        372597049003378933183868373743339082323631179591008252
        2607150413393843963890094153352278433651524131005695
        2617251843408735723911841623365443183671911111003112
        2627353293423608463933616153378576573692340531000503
        263745476343846218395541774339167863712812390997868
        PDM1
        PDM 2
        GDM

        Prevalence of hyperglycaemia in pregnancy by age

        Global estimates of the prevalence of hyperglycaemia in pregnancy L Guariguata et al Diabettesresearch and clinical practice 2014

        Global prevalence of hyperglycaemia in pregnancy 169

        The prevalence of HIP increases sharply with age with a prevalenceof 392 in women40ndash44 and up to 479 in women 45ndash59 years

        IN CHE MODO IL DIABETE INFLUENZAIL TIMING LA MODALITAgrave E LrsquoOUTCOME DEL

        PARTO

        THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

        FFA(fat mobilization)

        Glucose

        leptina

        INSULIN RESISTANCE

        OBESITY

        GESTATIONAL DIABETES

        IGF1

        Adiponectina

        insulin

        FETAL NUTRIENT AVAILABILITY

        PLACENTAL TRASPORT OF NUTRIENTS

        mTOR+

        ldquoadaptive regulationrdquo

        FETAL OVERNUTRITION-MACROSOMIALGA

        Romero Am J Obstet Gynecol 2017

        Brett KE Int J Mol Sci 2014

        MACROSOMIAL

        MACROSOMIALG

        DISTOCIA STILLBIRTH

        Macrosomia e rischio di distocia

        Birth weight distribution in diabetic pregnancies

        Persson et al Diab Care 2011341145-1149

        ldquoDIABESITYrdquo and MACROSOMIA

        MACROSOMIA ASIMMETRICA

        OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

        Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

        Fetal growth profiles in diabetic pregnancies

        08

        085

        09

        095

        1

        105

        11

        115

        12

        125

        13

        100 120 140 160 180 200 220 240 260 280

        Gestational age in days

        Hea

        d to

        abd

        omin

        al c

        ircu

        mfe

        renc

        e ra

        tio

        (HC

        AC

        rati

        o)

        IDDM non-macrosomia

        IDDM macrosomia

        DM2 non-macrosomia

        DM2 macrosomia

        GDM non-macrosomia

        GDM macrosomia

        Birthweightgt90th

        Type-1-diabetes LGA

        Type-1 AGA

        N Hammoud et al UOG 2012

        Type-2-diabetes LGA

        GDM LGA

        Grafiek3

        Fetal growth profiles in diabetic pregnancies

        IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

        Gestational age in days

        Head to abdominal circumference ratio (HCAC ratio)

        iddm gdm 977

        IDDM

        IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

        Gestational age in days

        Fetal abdominal circumference (mm)

        GDM

        GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

        Gestational age in days

        Fetal abdominal circumference (mm)

        FAC 6 groups

        Fetal growth profiles in diabetic pregnancies

        IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

        Gestational age in days

        Fetal abdominal circumference (mm)

        HC 6 groups

        Fetal growth profiles in diabetic pregnancies

        IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263141936936246000021434432504890000114494956473214645587897500002147962193218000011494685074611509748217040000215248113594700001153987450191554937644330000215700007867599999158506392919000011600127071620000316151902140499999163025335648000011645316498911660379641339999916754427837700001169050592621705569068629999917206322110600001173569535349000011750758495921765821638350000217808847807800001179594792321181101106564000021826074208070000118411373505185620049293000021871263635360000118863267777900001190138992022000021916453062650000219315162050800001194657934751196164248994000021976705632370000119917687748200683191722999992021895059660000120369582020920520213445220670844869500002208214762938000012097210771812112273914240000221273370566700001214240019912157463341530000221725264839600001218758962639220265276882000022217715911250000122327790536800001224784219611226290533854000022277968480970000122930316234230809476583000022323157908260000123382210506923532841931200002236834733555000012383410477980000123984736204124135367628400002242859990527000012443663047724587261901300002247378933256000012488852474992503915617420000225189787598500001253404190228254910504471000022564168187139999925792313295700001259429447200000032609357614429999926244207568600001263948389929000032654547041719999926696101841500001268467332658000032699736469012714799611440000127298627538700003274492589632759989038730000227750521811600004279011532359280517846602000022820241608449999828353047508828503678933100002286543103574000042880494178170000128955573206000003291062046302999992925683605460000129407467478900003295580989031999992970873032750000129859361751800003300099931760999993016062460040000130311256024700003304618874493061251887330000230763150297600004309137817219310644131462000023121504457050000431365675994831516307419100002316669388433999983181757026773196820169200000232118833116300004322694645406000013242009596490000332570727389199999327213588135000013287199023780000333022621662100005331732530864000013332388451070000333474515934999999336251473593000013377577878360000333926410207934077041632200002342276730564999983437830448083452893590510000234679567329400004348301987537349808301780000023513146160229999935282093026635432724450900002355833558752000043573398729950000135884618723800003DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226315180286741315313845385400001154474040295000011558096267360000115714521317700002158480799617999991598163860590000216115197251624875589411638231453820000116515873182300001166494318264000011678299047049999916916549114600002170501077587171836664028000031731722504690000117450783691000001175843423351000011771790097920000217851459623300002179850182674181185769115000031825213555561838569419970000118519252843800001186528114879000011878637013200000218919928776099999190534874202000031918704606431932060470840000119454163352500001195877219966000011972128064070000219854839284800002199883979289000022012195657320255515217120389073861200001205226325053000012065619114940000120789749793500002209233084376000022105686708172119042572582132398436990000121457543014000001215911016581000012172466030220000221858218946300002219917775904221253362345222588948786223924535227000012252601216680000122659570810900001227931294550000022292668809910000223060246743223193805387323327364031423460922675500001235944813196000012372803996370000223861598607800002239951572519000022412871589624262274540124395833184200001245293918283000012466295047240000124796509116500002249300677606000022506362640472519718504882533074369292546430233700000125597860981100001257314196251999992586497826930000225998536913426132095557500003262656542016263992128457000042653277148980000126666330133899999267998887780000022693344742209999927067006066200003272005647103273341233544000032746768199850000127601240642599998277347992867000022786835793079999928001916574900002281354752192826903386310000328402592507200001285361511512999982866970979540000128803268439499999289368270836000022907038572772920394437180000329337503015929471061659999998296046203041000012973817894819999929871737592300002300052962364301388548805000033027241352463040597216870000430539530812800001306730894569000043080664810100000230940206745099999310737653892000033120732403333134088267739999831474441321500001316079999656000043174155860970000231875117253799999320086758979000023214223454232275793186100003324093518302000013254291047430000432676469118400001328100277624999993294358640660000233077145050733210703694800003333442623389334778209830000043361137962710000133744938271199999338784969153000023401205555943414561420350000334279172847634412731491700004GDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

        Gestational age in days

        Head circumference (mm)

        HCAC 6 groups

        Fetal growth profiles in diabetic pregnancies

        IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

        Gestational age in days

        Head to abdominal circumference ratio (HCAC ratio)

        Model

        Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

        Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

        LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

        Iperglicemia e rischio di morte fetale a termine di gravidanza

        Estimated rate of stillbirth in diabetic women 1920-2000

        Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

        4 of all stillbirths remain attributable to diabetes

        Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

        bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

        Adverse outcome

        HbA1C gt7

        1 increase in A1Ccorresponded to 55 increased

        risk of adverse outcome

        The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

        gestation particularly in the presence of fetal macrosomia

        fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

        Langer O 1995

        100 mgdLfor stillbirth

        Diabetic patients n = 271691

        Am J Obstet Gynecol 2002

        The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

        4873 diabetic women

        pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

        outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

        bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

        GDMbull dysglycemia was more difficult to manage

        2016

        Differences in placental pathologyaccording to diabetes types

        Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

        GDM is associated with a greater rate of villous immaturity

        0102030405060708090

        100GDMDMIDMII

        o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

        A retrospective study on 175 placentas with DVM vs 175 controls

        Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

        Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

        Pathophysiology of fetal compromise in diabetic pregnancy

        The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

        Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

        Bjork 1984Nylund 1982Siddiqui 2003

        A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

        STILLBIRTH RISK

        BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

        OBESITArsquo E MORTE FETALE

        6-7 per unit BMI for BMI gt 23

        Tennant PWG Am J Obstet Gynecol 2007

        HYPERINSULINISMHYPERANDROGENISM

        IMPAIRED PLACENTATION

        THE EFFECTS OF OBESITYMETABOLIC SYNDROME

        Cakmak and Taylor Hum Reprod Update 2011

        Makieva S Hum Reprod Update 2014

        Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

        Hotamisligil GS Nature 2006

        LeptinCRH

        Urocortin 3IL-6

        INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

        INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

        Adiponectina Insulin LeptinTNFα IL-6

        PLACENTAL ALTERATIONIN GENE EXPRESSION

        PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

        CollagenaseCervical ripening

        FFA

        OXIDATIVE STRESS

        PREVENZIONE STILLBIRTH

        PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

        MORBIDITAgrave NEONATALE

        AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

        TIMING E MODALITArsquo DEL PARTO

        Induzione o attesa

        INDUZIONE DEL TRAVAGLIO

        Quando fare un TC elettivo

        gt 4000 grgt 4500 gr gt 5000 gr

        ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

        425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

        No differenza in TC e outcome perinatale

        200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

        No differenza in TC gt di LGA e peso medio nel gruppo di attesa

        RCT INDUZIONE VS ATTESA in GDM

        RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

        2014

        1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

        2 Patients well controlled on insulin should probably be delivered by the due date

        3 Poorly controlled GDMrsquos using insulin require individual judgment

        Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

        1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

        2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

        3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

        cesarean delivery when the estimated fetal weight is ge 4500 g

        MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

        MODALITAgrave E TIMING DEL PARTO nel GDM

        GMD in terapia insulinicaBen controllato

        +Condizioni fetali rassicuranti

        MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

        GDM in terapia nutrizionalecon profili glicemici ottimali

        +Feto AGA

        MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

        Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

        EFW lt 4000g LGAControllo metabolico non

        ottimale

        4000g lt EFW gt 4500g EFW ge 4500g

        Programmare TC elettivo

        Parto vaginale indotto a 38-39 sett

        Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

        MODALITAgrave E TIMING DEL PARTO nel GDM

        IN BASE AL PESO FETALE STIMATO

        - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

        - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

        - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

        ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

        Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

        The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

        A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

        If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

        Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

        GDM and the Use of Betamethasone

        bull administration of betamethasone in the late preterm period should be limited to women with GDM only

        bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

        bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

        Society of Obstetricians and Gynaecologists of Canada

        The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

        late preterm delivery between 24 to 36 weeksrsquo gestation

        ASSISTENZA IN TRAVAGLIO

        - MONITORAGGIO FETALE CONTINUO

        - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

        MANTENERE GLICEMIA gt70 E lt 126

        (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

        GDM

        - Intravenous infusion of regular insulin titrated and glucose

        - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

        (ACOG 2005)

        ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

        Venere di Willendorf

        Thank you for your attention

        Pathophysiology of fetal compromise in diabetic pregnancy

        Islet cell hyperplasia common in stillborn IDMs

        There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

        Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

        Salvesen 1993Hay 1989Chukwuma 2001

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        • Birth weight distribution in diabetic pregnancies
        • Diapositiva numero 9
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        • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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        • Differences in placental pathology according to diabetes types
        • Diapositiva numero 21
        • Pathophysiology of fetal compromise in diabetic pregnancy
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        • Diapositiva numero 35
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        • GDM and the Use of Betamethasone
        • Diapositiva numero 38
        • Diapositiva numero 39
        • Diapositiva numero 40
        • Pathophysiology of fetal compromise in diabetic pregnancy
          Intercepting Curves Random Effects are intercept and ctime (=slope)
          AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
          17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
          120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
          121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
          122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
          123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
          124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
          125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
          18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
          127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
          128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
          129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
          130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
          131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
          132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
          19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
          134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
          135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
          136-5328091174390921119170838111405379131153817241115039368311728882411124487
          137-5227041172850541118937155111396122561152048811114915830911711801311125128
          138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
          139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
          20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
          141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
          142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
          143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
          144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
          145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
          146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
          21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
          148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
          149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
          150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
          151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
          152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
          153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
          22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
          155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
          156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
          157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
          158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
          159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
          160-298411137421801113562446111183221451111374921112074470711318936011132695
          23161-287841135881421113328763111173964881109606491111950933311301854911132712
          162-277291134341041113095080111164708311107838061111827395911284773811132703
          163-266761132800661112861397111155451741106069631111703858511267692711132668
          164-256251131260281112627714111146195171104301201111580321111250611611132607
          165-2457611297199011123940311111369386110253277111145678371123353051113252
          166-235291128179521112160348111127682031100764341111333246311216449411132407
          167-224841126639141111926665111118425461098995911111209708911199368311132268
          24168-214411125098761111692982111109168891097227481111086171511182287211132103
          169-204001123558381111459299111099912321095459051110962634111165206111131912
          170-193611122018001111225616111090655751093690621110839096711148125011131695
          171-183241120477621110991933111081399181091922191110715559311131043911131452
          172-172891118937241110758250111072142611090153761110592021911113962811131183
          173-162561117396861110524567111062886041088385331110468484511096881711130888
          174-152251115856481110290884111053629471086616901110344947111079800611130567
          25175-1419611143161011100572011110443729108484847111022140971106271951113022
          176-131691112775721109823518111035116331083080041110097872311045638411129847
          177-121441111235341109589835111025859761081311611109974334911028557311129448
          178-111211109694961109356152111016603191079543181109850797511011476211129023
          179-101001108154581109122469111007346621077774751109727260110994395111128572
          180-9811106614201108888786110998090051076006321109603722710977314011128095
          181-8641105073821108655103110988833481074237891109480185310960232911127592
          26182-7491103533441108421420110979576911072469461109356647910943151811127063
          183-6361101993061108187737110970320341070701031109233110510926070711126508
          184-5251100452681107954054110961063771068932601109109573110908989611125927
          185-41610989123011077203711109518072106716417110898603571089190851112532
          186-391097371921107486688110942550631065395741108862498310874827411124687
          187-241095831541107253005110933294061063627311108738960910857746311124028
          188-111094291161107019322110924037491061858881108615423510840665211123343
          27189001092750781106785639110914780921060090451108491886110823584111122632
          190111091210401106551956110905524351058322021108368348710806503011121895
          191241089670021106318273110896267781056553591108244811310789421911121132
          192391088129641106084590110887011211054785161108121273910772340811120343
          1934161086589261105850907110877754641053016731107997736510755259711119528
          1945251085048881105617224110868498071051248301107874199110738178611118687
          19563610835085011053835411108592415104947987110775066171072109751111782
          281967491081968121105149858110849984931047711441107627124310704016411116927
          1978641080427741104916175110840728361045943011107503586910686935311116008
          1989811078887361104682492110831471791044174581107380049510669854211115063
          199101001077346981104448809110822215221042406151107256512110652773111114092
          200111211075806601104215126110812958651040637721107132974710635692011113095
          201121441074266221103981443110803702081038869291107009437310618610911112072
          202131691072725841103747760110794445511037100861106885899910601529811111023
          29203141961071185461103514077110785188941035332431106762362510584448711109948
          204152251069645081103280394110775932371033564001106638825110567367611108847
          2051625610681047011030467111107666758103179557110651528771055028651110772
          206172891066564321102813028110757419231030027141106391750310533205411106567
          207183241065023941102579345110748162661028258711106268212910516124311105388
          208193611063483561102345662110738906091026490281106144675510499043211104183
          209204001061943181102111979110729649521024721851106021138110481962111102952
          30210214411060402801101878296110720392951022953421105897600710464881011101695
          211224841058862421101644613110711136381021184991105774063310447799911100412
          212235291057322041101410930110701879811019416561105650525910430718811099103
          213245761055781661101177247110692623241017648131105526988510413637711097768
          214256251054241281100943564110683366671015879701105403451110396556611096407
          2152667610527009011007098811106741101101411127110527991371037947551109502
          216277291051160521100476198110664853531012342841105156376310362394411093607
          31217287841049620141100242515110655596961010574411105032838910345313311092168
          218298411048079761100008832110646340391008805981104909301510328232211090703
          219309001046539381099775149110637083821007037551104785764110311151111089212
          220319611044999001099541466110627827251005269121104662226710294070011087695
          2213210241043458621099307783110618570681003500691104538689310276988911086152
          2223310891041918241099074100110609314111001732261104415151910259907811084583
          2233411561040377861098840417110600057540999963831104291614510242826711082988
          322243512251038837481098606734110590800970998195401104168077110225745611081367
          22536129610372971010983730511105815444099642697110404453971020866451107972
          2263713691035756721098139368110572287830994658541103921002310191583411078047
          2273814441034216341097905685110563031260992890111103797464910174502311076348
          2283915211032675961097672002110553774690991121681103673927510157421211074623
          2294016001031135581097438319110544518120989353251103550390110140340111072872
          2304116811029595201097204636110535261550987584821103426852710123259011071095
          332314217641028054821096970953110526004980985816391103303315310106177911069292
          2324318491026514441096737270110516748410984047961103179777910089096811067463
          2334419361024974061096503587110507491840982279531103056240510072015711065608
          2344520251023433681096269904110498235270980511101102932703110054934611063727
          23546211610218933010960362211104889787097874267110280916571003785351106182
          2364722091020352921095802538110479722130976974241102685628310020772411059887
          2374823041018812541095568855110470465560975205811102562090910003691311057928
          342384924011017272161095335172110461208990973437381102438553509986610211055943
          2395025001015731781095101489110451952420971668951102315016109969529111053932
          2405126011014191401094867806110442695850969900521102191478709952448011051895
          2415227041012651021094634123110433439280968132091102067941309935366911049832
          2425328091011110641094400440110424182710966363661101944403909918285811047743
          2435429161009570261094166757110414926140964595231101820866509901204711045628
          2445530251008029881093933074110405669570962826801101697329109884123611043487
          352455631361006489501093699391110396413096105837110157379170986704251104132
          2465732491004949121093465708110387156430959289941101450254309849961411039127
          2475833641003408741093232025110377899860957521511101326716909832880311036908
          2485934811001868361092998342110368643290955753081101203179509815799211034663
          2496036001000327981092764659110359386720953984651101079642109798718111032392
          2506137210998787601092530976110350130150952216221100956104709781637011030095
          2516238440997247221092297293110340873580950447791100832567309764555911027772
          362526339690995706841092063610110331617010948679361100709029909747474811025423
          2536440960994166461091829927110322360440946910931100585492509730393711023048
          2546542250992626081091596244110313103870945142501100461955109713312611020647
          25566435609910857010913625611103038473094337407110033841770969623151101822
          2566744890989545321091128878110294590730941605641100214880309679150411015767
          2576846240988004941090895195110285334160939837211100091342909662069311013288
          2586947610986464561090661512110276077590938068781099967805509644988211010783
          372597049000984924181090427829110266821020936300351099844268109627907111008252
          2607150410983383801090194146110257564450934531921099720730709610826011005695
          2617251840981843421089960463110248307880932763491099597193309593744911003112
          2627353290980303041089726780110239051310930995061099473655909576663811000503
          2637454760978762661089493097110229794740929226631099350118509559582710997868
          PDM1
          PDM 2
          GDM
          Intercepting Curves Random Effects are intercept and ctime (=slope)
          AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
          17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
          120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
          121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
          122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
          123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
          124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
          125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
          18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
          127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
          128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
          129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
          130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
          131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
          132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
          19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
          134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
          135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
          136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
          137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
          138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
          139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
          20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
          141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
          142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
          143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
          144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
          145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
          146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
          21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
          148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
          149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
          150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
          151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
          152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
          153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
          22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
          155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
          156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
          157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
          158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
          159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
          160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
          23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
          162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
          163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
          164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
          165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
          166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
          167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
          24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
          169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
          170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
          171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
          172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
          173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
          174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
          25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
          176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
          177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
          178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
          179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
          180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
          181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
          26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
          183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
          184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
          185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
          186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
          187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
          188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
          27189002414769727245863358855247378933256248771281205245293918283252156109031122632
          19011242848834431247298968107248885247499250207813572466295047242534796182011121895
          191242442206961622487345773592503915617422516443459352479650911652548031273721121132
          1923924559255789325017018661125189787598525308087832493006776062561266365431120343
          1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
          194525248336281355253041405115254910504471255953943032519718504882587736548851118687
          195636249708143086254477014367256416818714257390475395253307436929260097164056111782
          2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
          19786425245186654825734823287125942944722602635401252559786098112627441823981116008
          198981253823728279258783842123260935761443261700072492573141962522640676915691115063
          1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
          20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
          201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
          20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
          29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
          20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
          20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
          2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
          20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
          20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
          2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
          3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
          211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
          2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
          213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
          21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
          21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
          2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
          3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
          21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
          2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
          22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
          2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
          222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
          2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
          32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
          225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
          2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
          227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
          228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
          22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
          230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
          332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
          23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
          2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
          234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
          235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
          23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
          237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
          34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
          23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
          240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
          2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
          242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
          2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
          244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
          35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
          24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
          247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
          248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
          24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
          250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
          2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
          3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
          2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
          254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
          255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
          25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
          257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
          258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
          37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
          260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
          2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
          262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
          2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
          PDM1
          PDM 2
          GDM
          Intercepting Curves Random Effects are intercept and ctime (=slope)
          AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
          17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
          120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
          121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
          122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
          123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
          124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
          125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
          18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
          127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
          128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
          129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
          130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
          131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
          132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
          19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
          134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
          135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
          136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
          137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
          138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
          139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
          20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
          141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
          142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
          143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
          144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
          145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
          146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
          21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
          148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
          149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
          150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
          151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
          152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
          153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
          22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
          155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
          156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
          157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
          158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
          159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
          160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
          23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
          162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
          163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
          164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
          165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
          166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
          167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
          24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
          169-204001942030097220294920811968857670952039875573619824233804820272617541131912
          170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
          171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
          172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
          173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
          174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
          25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
          176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
          177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
          178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
          179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
          180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
          181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
          26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
          183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
          184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
          185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
          186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
          187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
          188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
          2718900226029388723887603482286156060752396057377229889735228236469967341122632
          190112276207076492406723761352302020980242413866467172314721050872381571569371121895
          19124229212026598242468717472317885899732431675557342330544749462398443465341121132
          192392308033455472442650588052333750819222449484647512346368448052415315361311120343
          193416232394664496246061400142349615738712467293737682362192146642432187257281119528
          194525233985983445247857741475236548065822485102827852378015845232449059153251118687
          19563623557730239424965408281238134557769250291191802239383954382246593104922111782
          281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
          1978642387599402922532467654824130754166725385300983624254869412499674841161116008
          1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
          19910100241942578192568394481524448052556525741482787245713433818253341863311114092
          200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
          20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
          202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
          2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
          20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
          2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
          206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
          2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
          208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
          2092040025785576768274802861526034544505527522391804261537132408270213759281102952
          30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
          21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
          212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
          21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
          2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
          2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
          216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
          312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
          218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
          21930900273768957172927662748527621036454529303300821277360830998287085655251089212
          220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
          221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
          2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
          223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
          32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
          22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
          2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
          22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
          2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
          22940160028968214666310729688229207528403531084209838293184529588303957551221072872
          2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
          33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
          2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
          233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
          234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
          23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
          2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
          23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
          342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
          239502500305595336153286931015530794020352532865118855309008228178320829447191053932
          2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
          241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
          2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
          243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
          244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
          3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
          2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
          24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
          2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
          24960360032150852564346656514932380512301534646027872324831926768337701343161032392
          2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
          251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
          362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
          253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
          254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
          25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
          2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
          25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
          2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
          37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
          2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
          261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
          2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
          263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
          PDM1
          PDM 2
          GDM
          Intercepting Curves Random Effects are intercept and ctime (=slope)
          AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
          17119-7049001103696581094598541182103721201826791109612CURVE
          120-6947611121270161112530551199690231216229731110695
          121-6846241138824721130489621217245381230675111111752DM1
          122-6744891156360261148475751234769171245162931112783
          123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
          124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
          125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
          18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
          127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
          128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
          129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
          130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
          131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
          132-5732491330669561329825351408282271392375331121663
          19133-563136134799588134810914142546111407329991122408109459854
          134-5530251365303181366419991442608571422327091123127GDM
          135-54291613825914613847579145972468143736663112382
          136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
          137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
          138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
          139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
          20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
          141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
          142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
          143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
          144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
          145-44193615544281615696253162916098159009623112932
          146-4318491571507221588260871645932131605602611129727
          21147-421764158856726160692351662671921621151431130108
          148-4116811605608281625613191679380351636742691130463
          149-4016001622630281644329941696057421652376391130792
          150-3915211639633261663073751712703131668052531131095
          151-3814441656617221681844621729317481683771111131372
          152-3713691673582161700642551745900471699532131131623
          153-361296169052808171946754176245211715335591131848
          22154-3512251707454981738319591778972371731181491132047
          155-34115617243628617571987179546128174706983113222
          156-3310891741251721776104871811918831763000611132367
          157-321024175812156179503811828345021778973831132488
          158-319611774972381813998391844739851794989491132583
          159-309001791804181832985741861103321811047591132652
          160-298411808616961852000151877435431827148131132695
          23161-287841825410721871041621893736181843291111132712
          162-277291842185461890110151910005571859476531132703
          163-26676185894118190920574192624361875704391132668
          164-256251875677881928328391942450271891974691132607
          165-2457618923955619474781195862558190828743113252
          166-235291909094221966654871974769531924642611132407
          167-22484192577386198585871990882121941040231132268
          24168-214411942434482005089592006963351957480291132103
          169-204001959076082024347542023013221973962791131912
          170-193611975698662043632552039031731990487731131695
          171-183241992302222062944622055018882007055111131452
          172-172892008886762082283752070974672023664931131183
          173-16256202545228210164994208689912040317191130888
          174-152252041998782121043192102792172057011891130567
          25175-1419620585262621404635211865388207374903113022
          176-131692075034722159910872134484232090528611129847
          177-12144209152416217938532150283222107350631129448
          178-111212107994582198886792166050852124215091129023
          179-101002124445982218415342181787122141121991128572
          180-9812140878362237970952197492032158071331128095
          181-8642157291722257553622213165582175063111127592
          26182-7492173686062277163352228807772192097331127063
          183-636219006138229680014224441862209173991126508
          184-5252206417682316463992259998072226293091125927
          185-41622227549623361549227554618224345463112532
          186-392239073222355872872291062932260658611124687
          187-24225537246237561792306548322277905031124028
          188-112271652682395389992322002352295193891123343
          27189002287913882415189142337425022312525191122632
          190112304156062435015352352816332329898931121895
          191242320379222454868622368176282347315111121132
          192392336583362474748952383504872364773731120343
          193416235276848249465634239880212382274791119528
          1945252368934582514590792414067972399818291118687
          19563623850816625345523242930248241740423111782
          281967492401209722554540872444505632435032611116927
          197864241731876257455652459677422452703431116008
          1989812433408782594599192474817852470416691115063
          199101002449479782614668942489926922488172391114092
          200111212465531762634765752505004632505970531113095
          201121442481564722654889622520050982523811111112072
          202131692497578662675040552535065972541694131111023
          2920314196251357358269521854255004962559619591109948
          204152252529549482715423592565001872577587491108847
          2051625625455063627356557257992278259559783110772
          206172892561444222755914872594812332613650611106567
          20718324257736306277620112609670522631745831105388
          208193612593262882796514392624497352649883491104183
          209204002609143682816854742639292822668063591102952
          30210214412625005462837222152654056932686286131101695
          211224842640848222857616622668789682704551111100412
          212235292656671962878038152683491072722858531099103
          21324576267247668289848674269816112741208391097768
          214256252688262382918962392712799772759600691096407
          2152667627040290629394651272740708277803543109502
          216277292719776722959994872741983032796512611093607
          3121728784273550536298055172756527622815032231092168
          218298412751214983001135592771040852833594291090703
          219309002766905583021746542785522722852198791089212
          220319612782577163042384552799973232870845731087695
          2213210242798229723063049622814392382889535111086152
          2223310892813863263083741752828780172908266931084583
          223341156282947778310446094284313662927041191082988
          322243512252845073283125207192857461672945857891081367
          22536129628606497631459805287175538296471703107972
          2263713692876207223166780872886017732983618611078047
          227381444289174566318760832900248723002562631076348
          2283915212907265083208462792914448353021549091074623
          2294016002922765483229344342928616623040577991072872
          2304116812938246863250252952942753533059649331071095
          332314217642953709223271188622956859083078763111069292
          2324318492969152563292151352970933273097919331067463
          233441936298457688331314114298497613117117991065608
          2344520252999982183334157992998987573136359091063727
          23546211630153684633552019301296768315564263106182
          2364722093030735723376272873026916433174968611059887
          237482304304608396339737093040833823194337031057928
          342384924013061413183418495993054719853213747891055943
          2395025003076723383439648143068574523233201191053932
          2405126013092014563460827353082397833252696931051895
          2415227043107286723482033623096189783272235111049832
          2425328093122539863503266953109950373291815731047743
          243542916313777398352452734312367963311438791045628
          2445530253152989083545814793137377473331104291043487
          3524556313631681851635671293315104398335081223104132
          2465732493183362223588470873164679133370562611039127
          247583364319852026360983953178282923390355431036908
          2485934813213659283631235193191855353410190691034663
          2496036003228779283652657943205396423430068391032392
          2506137213243880263674107753218906133449988531030095
          2516238443258962223695584623232384483469951111027772
          362526339693274025163717088553245831473489956131025423
          253644096328906908373861954325924713510003591023048
          2546542253304093983760177593272631373530093491020647
          25566435633190998637817627328598428355022583101822
          2566744893334086723803374873299305833570400611015767
          257684624334905456382501413312596023590617831013288
          2586947613364003383846680393325854853610877491010783
          372597049003378933183868373743339082323631179591008252
          2607150413393843963890094153352278433651524131005695
          2617251843408735723911841623365443183671911111003112
          2627353293423608463933616153378576573692340531000503
          263745476343846218395541774339167863712812390997868
          PDM1
          PDM 2
          GDM

          IN CHE MODO IL DIABETE INFLUENZAIL TIMING LA MODALITAgrave E LrsquoOUTCOME DEL

          PARTO

          THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

          FFA(fat mobilization)

          Glucose

          leptina

          INSULIN RESISTANCE

          OBESITY

          GESTATIONAL DIABETES

          IGF1

          Adiponectina

          insulin

          FETAL NUTRIENT AVAILABILITY

          PLACENTAL TRASPORT OF NUTRIENTS

          mTOR+

          ldquoadaptive regulationrdquo

          FETAL OVERNUTRITION-MACROSOMIALGA

          Romero Am J Obstet Gynecol 2017

          Brett KE Int J Mol Sci 2014

          MACROSOMIAL

          MACROSOMIALG

          DISTOCIA STILLBIRTH

          Macrosomia e rischio di distocia

          Birth weight distribution in diabetic pregnancies

          Persson et al Diab Care 2011341145-1149

          ldquoDIABESITYrdquo and MACROSOMIA

          MACROSOMIA ASIMMETRICA

          OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

          Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

          Fetal growth profiles in diabetic pregnancies

          08

          085

          09

          095

          1

          105

          11

          115

          12

          125

          13

          100 120 140 160 180 200 220 240 260 280

          Gestational age in days

          Hea

          d to

          abd

          omin

          al c

          ircu

          mfe

          renc

          e ra

          tio

          (HC

          AC

          rati

          o)

          IDDM non-macrosomia

          IDDM macrosomia

          DM2 non-macrosomia

          DM2 macrosomia

          GDM non-macrosomia

          GDM macrosomia

          Birthweightgt90th

          Type-1-diabetes LGA

          Type-1 AGA

          N Hammoud et al UOG 2012

          Type-2-diabetes LGA

          GDM LGA

          Grafiek3

          Fetal growth profiles in diabetic pregnancies

          IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

          Gestational age in days

          Head to abdominal circumference ratio (HCAC ratio)

          iddm gdm 977

          IDDM

          IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

          Gestational age in days

          Fetal abdominal circumference (mm)

          GDM

          GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

          Gestational age in days

          Fetal abdominal circumference (mm)

          FAC 6 groups

          Fetal growth profiles in diabetic pregnancies

          IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM 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          Gestational age in days

          Fetal abdominal circumference (mm)

          HC 6 groups

          Fetal growth profiles in diabetic pregnancies

          IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

          Gestational age in days

          Head circumference (mm)

          HCAC 6 groups

          Fetal growth profiles in diabetic pregnancies

          IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

          Gestational age in days

          Head to abdominal circumference ratio (HCAC ratio)

          Model

          Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

          Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

          LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

          Iperglicemia e rischio di morte fetale a termine di gravidanza

          Estimated rate of stillbirth in diabetic women 1920-2000

          Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

          4 of all stillbirths remain attributable to diabetes

          Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

          bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

          Adverse outcome

          HbA1C gt7

          1 increase in A1Ccorresponded to 55 increased

          risk of adverse outcome

          The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

          gestation particularly in the presence of fetal macrosomia

          fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

          Langer O 1995

          100 mgdLfor stillbirth

          Diabetic patients n = 271691

          Am J Obstet Gynecol 2002

          The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

          4873 diabetic women

          pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

          outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

          bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

          GDMbull dysglycemia was more difficult to manage

          2016

          Differences in placental pathologyaccording to diabetes types

          Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

          GDM is associated with a greater rate of villous immaturity

          0102030405060708090

          100GDMDMIDMII

          o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

          A retrospective study on 175 placentas with DVM vs 175 controls

          Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

          Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

          Pathophysiology of fetal compromise in diabetic pregnancy

          The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

          Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

          Bjork 1984Nylund 1982Siddiqui 2003

          A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

          STILLBIRTH RISK

          BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

          OBESITArsquo E MORTE FETALE

          6-7 per unit BMI for BMI gt 23

          Tennant PWG Am J Obstet Gynecol 2007

          HYPERINSULINISMHYPERANDROGENISM

          IMPAIRED PLACENTATION

          THE EFFECTS OF OBESITYMETABOLIC SYNDROME

          Cakmak and Taylor Hum Reprod Update 2011

          Makieva S Hum Reprod Update 2014

          Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

          Hotamisligil GS Nature 2006

          LeptinCRH

          Urocortin 3IL-6

          INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

          INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

          Adiponectina Insulin LeptinTNFα IL-6

          PLACENTAL ALTERATIONIN GENE EXPRESSION

          PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

          CollagenaseCervical ripening

          FFA

          OXIDATIVE STRESS

          PREVENZIONE STILLBIRTH

          PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

          MORBIDITAgrave NEONATALE

          AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

          TIMING E MODALITArsquo DEL PARTO

          Induzione o attesa

          INDUZIONE DEL TRAVAGLIO

          Quando fare un TC elettivo

          gt 4000 grgt 4500 gr gt 5000 gr

          ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

          425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

          No differenza in TC e outcome perinatale

          200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

          No differenza in TC gt di LGA e peso medio nel gruppo di attesa

          RCT INDUZIONE VS ATTESA in GDM

          RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

          2014

          1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

          2 Patients well controlled on insulin should probably be delivered by the due date

          3 Poorly controlled GDMrsquos using insulin require individual judgment

          Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

          1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

          2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

          3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

          cesarean delivery when the estimated fetal weight is ge 4500 g

          MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

          MODALITAgrave E TIMING DEL PARTO nel GDM

          GMD in terapia insulinicaBen controllato

          +Condizioni fetali rassicuranti

          MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

          GDM in terapia nutrizionalecon profili glicemici ottimali

          +Feto AGA

          MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

          Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

          EFW lt 4000g LGAControllo metabolico non

          ottimale

          4000g lt EFW gt 4500g EFW ge 4500g

          Programmare TC elettivo

          Parto vaginale indotto a 38-39 sett

          Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

          MODALITAgrave E TIMING DEL PARTO nel GDM

          IN BASE AL PESO FETALE STIMATO

          - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

          - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

          - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

          ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

          Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

          The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

          A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

          If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

          Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

          GDM and the Use of Betamethasone

          bull administration of betamethasone in the late preterm period should be limited to women with GDM only

          bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

          bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

          Society of Obstetricians and Gynaecologists of Canada

          The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

          late preterm delivery between 24 to 36 weeksrsquo gestation

          ASSISTENZA IN TRAVAGLIO

          - MONITORAGGIO FETALE CONTINUO

          - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

          MANTENERE GLICEMIA gt70 E lt 126

          (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

          GDM

          - Intravenous infusion of regular insulin titrated and glucose

          - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

          (ACOG 2005)

          ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

          Venere di Willendorf

          Thank you for your attention

          Pathophysiology of fetal compromise in diabetic pregnancy

          Islet cell hyperplasia common in stillborn IDMs

          There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

          Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

          Salvesen 1993Hay 1989Chukwuma 2001

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          • Birth weight distribution in diabetic pregnancies
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          • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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          • Differences in placental pathology according to diabetes types
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          • Pathophysiology of fetal compromise in diabetic pregnancy
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          • GDM and the Use of Betamethasone
          • Diapositiva numero 38
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          • Pathophysiology of fetal compromise in diabetic pregnancy
            Intercepting Curves Random Effects are intercept and ctime (=slope)
            AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
            17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
            120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
            121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
            122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
            123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
            124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
            125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
            18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
            127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
            128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
            129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
            130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
            131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
            132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
            19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
            134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
            135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
            136-5328091174390921119170838111405379131153817241115039368311728882411124487
            137-5227041172850541118937155111396122561152048811114915830911711801311125128
            138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
            139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
            20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
            141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
            142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
            143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
            144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
            145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
            146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
            21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
            148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
            149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
            150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
            151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
            152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
            153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
            22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
            155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
            156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
            157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
            158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
            159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
            160-298411137421801113562446111183221451111374921112074470711318936011132695
            23161-287841135881421113328763111173964881109606491111950933311301854911132712
            162-277291134341041113095080111164708311107838061111827395911284773811132703
            163-266761132800661112861397111155451741106069631111703858511267692711132668
            164-256251131260281112627714111146195171104301201111580321111250611611132607
            165-2457611297199011123940311111369386110253277111145678371123353051113252
            166-235291128179521112160348111127682031100764341111333246311216449411132407
            167-224841126639141111926665111118425461098995911111209708911199368311132268
            24168-214411125098761111692982111109168891097227481111086171511182287211132103
            169-204001123558381111459299111099912321095459051110962634111165206111131912
            170-193611122018001111225616111090655751093690621110839096711148125011131695
            171-183241120477621110991933111081399181091922191110715559311131043911131452
            172-172891118937241110758250111072142611090153761110592021911113962811131183
            173-162561117396861110524567111062886041088385331110468484511096881711130888
            174-152251115856481110290884111053629471086616901110344947111079800611130567
            25175-1419611143161011100572011110443729108484847111022140971106271951113022
            176-131691112775721109823518111035116331083080041110097872311045638411129847
            177-121441111235341109589835111025859761081311611109974334911028557311129448
            178-111211109694961109356152111016603191079543181109850797511011476211129023
            179-101001108154581109122469111007346621077774751109727260110994395111128572
            180-9811106614201108888786110998090051076006321109603722710977314011128095
            181-8641105073821108655103110988833481074237891109480185310960232911127592
            26182-7491103533441108421420110979576911072469461109356647910943151811127063
            183-6361101993061108187737110970320341070701031109233110510926070711126508
            184-5251100452681107954054110961063771068932601109109573110908989611125927
            185-41610989123011077203711109518072106716417110898603571089190851112532
            186-391097371921107486688110942550631065395741108862498310874827411124687
            187-241095831541107253005110933294061063627311108738960910857746311124028
            188-111094291161107019322110924037491061858881108615423510840665211123343
            27189001092750781106785639110914780921060090451108491886110823584111122632
            190111091210401106551956110905524351058322021108368348710806503011121895
            191241089670021106318273110896267781056553591108244811310789421911121132
            192391088129641106084590110887011211054785161108121273910772340811120343
            1934161086589261105850907110877754641053016731107997736510755259711119528
            1945251085048881105617224110868498071051248301107874199110738178611118687
            19563610835085011053835411108592415104947987110775066171072109751111782
            281967491081968121105149858110849984931047711441107627124310704016411116927
            1978641080427741104916175110840728361045943011107503586910686935311116008
            1989811078887361104682492110831471791044174581107380049510669854211115063
            199101001077346981104448809110822215221042406151107256512110652773111114092
            200111211075806601104215126110812958651040637721107132974710635692011113095
            201121441074266221103981443110803702081038869291107009437310618610911112072
            202131691072725841103747760110794445511037100861106885899910601529811111023
            29203141961071185461103514077110785188941035332431106762362510584448711109948
            204152251069645081103280394110775932371033564001106638825110567367611108847
            2051625610681047011030467111107666758103179557110651528771055028651110772
            206172891066564321102813028110757419231030027141106391750310533205411106567
            207183241065023941102579345110748162661028258711106268212910516124311105388
            208193611063483561102345662110738906091026490281106144675510499043211104183
            209204001061943181102111979110729649521024721851106021138110481962111102952
            30210214411060402801101878296110720392951022953421105897600710464881011101695
            211224841058862421101644613110711136381021184991105774063310447799911100412
            212235291057322041101410930110701879811019416561105650525910430718811099103
            213245761055781661101177247110692623241017648131105526988510413637711097768
            214256251054241281100943564110683366671015879701105403451110396556611096407
            2152667610527009011007098811106741101101411127110527991371037947551109502
            216277291051160521100476198110664853531012342841105156376310362394411093607
            31217287841049620141100242515110655596961010574411105032838910345313311092168
            218298411048079761100008832110646340391008805981104909301510328232211090703
            219309001046539381099775149110637083821007037551104785764110311151111089212
            220319611044999001099541466110627827251005269121104662226710294070011087695
            2213210241043458621099307783110618570681003500691104538689310276988911086152
            2223310891041918241099074100110609314111001732261104415151910259907811084583
            2233411561040377861098840417110600057540999963831104291614510242826711082988
            322243512251038837481098606734110590800970998195401104168077110225745611081367
            22536129610372971010983730511105815444099642697110404453971020866451107972
            2263713691035756721098139368110572287830994658541103921002310191583411078047
            2273814441034216341097905685110563031260992890111103797464910174502311076348
            2283915211032675961097672002110553774690991121681103673927510157421211074623
            2294016001031135581097438319110544518120989353251103550390110140340111072872
            2304116811029595201097204636110535261550987584821103426852710123259011071095
            332314217641028054821096970953110526004980985816391103303315310106177911069292
            2324318491026514441096737270110516748410984047961103179777910089096811067463
            2334419361024974061096503587110507491840982279531103056240510072015711065608
            2344520251023433681096269904110498235270980511101102932703110054934611063727
            23546211610218933010960362211104889787097874267110280916571003785351106182
            2364722091020352921095802538110479722130976974241102685628310020772411059887
            2374823041018812541095568855110470465560975205811102562090910003691311057928
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            2395025001015731781095101489110451952420971668951102315016109969529111053932
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            2415227041012651021094634123110433439280968132091102067941309935366911049832
            2425328091011110641094400440110424182710966363661101944403909918285811047743
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            352455631361006489501093699391110396413096105837110157379170986704251104132
            2465732491004949121093465708110387156430959289941101450254309849961411039127
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            2496036001000327981092764659110359386720953984651101079642109798718111032392
            2506137210998787601092530976110350130150952216221100956104709781637011030095
            2516238440997247221092297293110340873580950447791100832567309764555911027772
            362526339690995706841092063610110331617010948679361100709029909747474811025423
            2536440960994166461091829927110322360440946910931100585492509730393711023048
            2546542250992626081091596244110313103870945142501100461955109713312611020647
            25566435609910857010913625611103038473094337407110033841770969623151101822
            2566744890989545321091128878110294590730941605641100214880309679150411015767
            2576846240988004941090895195110285334160939837211100091342909662069311013288
            2586947610986464561090661512110276077590938068781099967805509644988211010783
            372597049000984924181090427829110266821020936300351099844268109627907111008252
            2607150410983383801090194146110257564450934531921099720730709610826011005695
            2617251840981843421089960463110248307880932763491099597193309593744911003112
            2627353290980303041089726780110239051310930995061099473655909576663811000503
            2637454760978762661089493097110229794740929226631099350118509559582710997868
            PDM1
            PDM 2
            GDM
            Intercepting Curves Random Effects are intercept and ctime (=slope)
            AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
            17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
            120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
            121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
            122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
            123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
            124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
            125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
            18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
            127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
            128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
            129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
            130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
            131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
            132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
            19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
            134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
            135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
            136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
            137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
            138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
            139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
            20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
            141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
            142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
            143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
            144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
            145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
            146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
            21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
            148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
            149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
            150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
            151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
            152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
            153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
            22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
            155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
            156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
            157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
            158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
            159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
            160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
            23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
            162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
            163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
            164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
            165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
            166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
            167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
            24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
            169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
            170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
            171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
            172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
            173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
            174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
            25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
            176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
            177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
            178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
            179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
            180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
            181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
            26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
            183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
            184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
            185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
            186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
            187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
            188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
            27189002414769727245863358855247378933256248771281205245293918283252156109031122632
            19011242848834431247298968107248885247499250207813572466295047242534796182011121895
            191242442206961622487345773592503915617422516443459352479650911652548031273721121132
            1923924559255789325017018661125189787598525308087832493006776062561266365431120343
            1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
            194525248336281355253041405115254910504471255953943032519718504882587736548851118687
            195636249708143086254477014367256416818714257390475395253307436929260097164056111782
            2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
            19786425245186654825734823287125942944722602635401252559786098112627441823981116008
            198981253823728279258783842123260935761443261700072492573141962522640676915691115063
            1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
            20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
            201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
            20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
            29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
            20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
            20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
            2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
            20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
            20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
            2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
            3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
            211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
            2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
            213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
            21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
            21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
            2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
            3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
            21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
            2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
            22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
            2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
            222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
            2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
            32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
            225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
            2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
            227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
            228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
            22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
            230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
            332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
            23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
            2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
            234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
            235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
            23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
            237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
            34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
            23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
            240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
            2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
            242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
            2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
            244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
            35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
            24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
            247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
            248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
            24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
            250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
            2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
            3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
            2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
            254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
            255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
            25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
            257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
            258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
            37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
            260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
            2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
            262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
            2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
            PDM1
            PDM 2
            GDM
            Intercepting Curves Random Effects are intercept and ctime (=slope)
            AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
            17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
            120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
            121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
            122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
            123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
            124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
            125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
            18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
            127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
            128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
            129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
            130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
            131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
            132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
            19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
            134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
            135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
            136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
            137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
            138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
            139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
            20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
            141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
            142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
            143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
            144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
            145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
            146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
            21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
            148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
            149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
            150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
            151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
            152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
            153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
            22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
            155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
            156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
            157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
            158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
            159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
            160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
            23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
            162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
            163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
            164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
            165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
            166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
            167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
            24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
            169-204001942030097220294920811968857670952039875573619824233804820272617541131912
            170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
            171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
            172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
            173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
            174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
            25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
            176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
            177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
            178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
            179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
            180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
            181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
            26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
            183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
            184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
            185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
            186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
            187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
            188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
            2718900226029388723887603482286156060752396057377229889735228236469967341122632
            190112276207076492406723761352302020980242413866467172314721050872381571569371121895
            19124229212026598242468717472317885899732431675557342330544749462398443465341121132
            192392308033455472442650588052333750819222449484647512346368448052415315361311120343
            193416232394664496246061400142349615738712467293737682362192146642432187257281119528
            194525233985983445247857741475236548065822485102827852378015845232449059153251118687
            19563623557730239424965408281238134557769250291191802239383954382246593104922111782
            281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
            1978642387599402922532467654824130754166725385300983624254869412499674841161116008
            1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
            19910100241942578192568394481524448052556525741482787245713433818253341863311114092
            200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
            20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
            202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
            2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
            20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
            2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
            206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
            2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
            208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
            2092040025785576768274802861526034544505527522391804261537132408270213759281102952
            30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
            21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
            212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
            21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
            2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
            2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
            216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
            312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
            218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
            21930900273768957172927662748527621036454529303300821277360830998287085655251089212
            220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
            221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
            2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
            223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
            32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
            22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
            2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
            22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
            2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
            22940160028968214666310729688229207528403531084209838293184529588303957551221072872
            2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
            33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
            2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
            233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
            234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
            23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
            2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
            23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
            342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
            239502500305595336153286931015530794020352532865118855309008228178320829447191053932
            2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
            241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
            2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
            243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
            244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
            3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
            2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
            24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
            2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
            24960360032150852564346656514932380512301534646027872324831926768337701343161032392
            2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
            251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
            362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
            253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
            254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
            25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
            2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
            25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
            2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
            37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
            2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
            261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
            2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
            263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
            PDM1
            PDM 2
            GDM
            Intercepting Curves Random Effects are intercept and ctime (=slope)
            AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
            17119-7049001103696581094598541182103721201826791109612CURVE
            120-6947611121270161112530551199690231216229731110695
            121-6846241138824721130489621217245381230675111111752DM1
            122-6744891156360261148475751234769171245162931112783
            123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
            124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
            125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
            18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
            127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
            128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
            129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
            130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
            131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
            132-5732491330669561329825351408282271392375331121663
            19133-563136134799588134810914142546111407329991122408109459854
            134-5530251365303181366419991442608571422327091123127GDM
            135-54291613825914613847579145972468143736663112382
            136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
            137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
            138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
            139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
            20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
            141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
            142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
            143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
            144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
            145-44193615544281615696253162916098159009623112932
            146-4318491571507221588260871645932131605602611129727
            21147-421764158856726160692351662671921621151431130108
            148-4116811605608281625613191679380351636742691130463
            149-4016001622630281644329941696057421652376391130792
            150-3915211639633261663073751712703131668052531131095
            151-3814441656617221681844621729317481683771111131372
            152-3713691673582161700642551745900471699532131131623
            153-361296169052808171946754176245211715335591131848
            22154-3512251707454981738319591778972371731181491132047
            155-34115617243628617571987179546128174706983113222
            156-3310891741251721776104871811918831763000611132367
            157-321024175812156179503811828345021778973831132488
            158-319611774972381813998391844739851794989491132583
            159-309001791804181832985741861103321811047591132652
            160-298411808616961852000151877435431827148131132695
            23161-287841825410721871041621893736181843291111132712
            162-277291842185461890110151910005571859476531132703
            163-26676185894118190920574192624361875704391132668
            164-256251875677881928328391942450271891974691132607
            165-2457618923955619474781195862558190828743113252
            166-235291909094221966654871974769531924642611132407
            167-22484192577386198585871990882121941040231132268
            24168-214411942434482005089592006963351957480291132103
            169-204001959076082024347542023013221973962791131912
            170-193611975698662043632552039031731990487731131695
            171-183241992302222062944622055018882007055111131452
            172-172892008886762082283752070974672023664931131183
            173-16256202545228210164994208689912040317191130888
            174-152252041998782121043192102792172057011891130567
            25175-1419620585262621404635211865388207374903113022
            176-131692075034722159910872134484232090528611129847
            177-12144209152416217938532150283222107350631129448
            178-111212107994582198886792166050852124215091129023
            179-101002124445982218415342181787122141121991128572
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            2051625625455063627356557257992278259559783110772
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            208193612593262882796514392624497352649883491104183
            209204002609143682816854742639292822668063591102952
            30210214412625005462837222152654056932686286131101695
            211224842640848222857616622668789682704551111100412
            212235292656671962878038152683491072722858531099103
            21324576267247668289848674269816112741208391097768
            214256252688262382918962392712799772759600691096407
            2152667627040290629394651272740708277803543109502
            216277292719776722959994872741983032796512611093607
            3121728784273550536298055172756527622815032231092168
            218298412751214983001135592771040852833594291090703
            219309002766905583021746542785522722852198791089212
            220319612782577163042384552799973232870845731087695
            2213210242798229723063049622814392382889535111086152
            2223310892813863263083741752828780172908266931084583
            223341156282947778310446094284313662927041191082988
            322243512252845073283125207192857461672945857891081367
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            23546211630153684633552019301296768315564263106182
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            3524556313631681851635671293315104398335081223104132
            2465732493183362223588470873164679133370562611039127
            247583364319852026360983953178282923390355431036908
            2485934813213659283631235193191855353410190691034663
            2496036003228779283652657943205396423430068391032392
            2506137213243880263674107753218906133449988531030095
            2516238443258962223695584623232384483469951111027772
            362526339693274025163717088553245831473489956131025423
            253644096328906908373861954325924713510003591023048
            2546542253304093983760177593272631373530093491020647
            25566435633190998637817627328598428355022583101822
            2566744893334086723803374873299305833570400611015767
            257684624334905456382501413312596023590617831013288
            2586947613364003383846680393325854853610877491010783
            372597049003378933183868373743339082323631179591008252
            2607150413393843963890094153352278433651524131005695
            2617251843408735723911841623365443183671911111003112
            2627353293423608463933616153378576573692340531000503
            263745476343846218395541774339167863712812390997868
            PDM1
            PDM 2
            GDM

            THE EFFECTS OF HYPERGLYCEMIAMETABOLIC SYNDROME

            FFA(fat mobilization)

            Glucose

            leptina

            INSULIN RESISTANCE

            OBESITY

            GESTATIONAL DIABETES

            IGF1

            Adiponectina

            insulin

            FETAL NUTRIENT AVAILABILITY

            PLACENTAL TRASPORT OF NUTRIENTS

            mTOR+

            ldquoadaptive regulationrdquo

            FETAL OVERNUTRITION-MACROSOMIALGA

            Romero Am J Obstet Gynecol 2017

            Brett KE Int J Mol Sci 2014

            MACROSOMIAL

            MACROSOMIALG

            DISTOCIA STILLBIRTH

            Macrosomia e rischio di distocia

            Birth weight distribution in diabetic pregnancies

            Persson et al Diab Care 2011341145-1149

            ldquoDIABESITYrdquo and MACROSOMIA

            MACROSOMIA ASIMMETRICA

            OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

            Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

            Fetal growth profiles in diabetic pregnancies

            08

            085

            09

            095

            1

            105

            11

            115

            12

            125

            13

            100 120 140 160 180 200 220 240 260 280

            Gestational age in days

            Hea

            d to

            abd

            omin

            al c

            ircu

            mfe

            renc

            e ra

            tio

            (HC

            AC

            rati

            o)

            IDDM non-macrosomia

            IDDM macrosomia

            DM2 non-macrosomia

            DM2 macrosomia

            GDM non-macrosomia

            GDM macrosomia

            Birthweightgt90th

            Type-1-diabetes LGA

            Type-1 AGA

            N Hammoud et al UOG 2012

            Type-2-diabetes LGA

            GDM LGA

            Grafiek3

            Fetal growth profiles in diabetic pregnancies

            IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

            Gestational age in days

            Head to abdominal circumference ratio (HCAC ratio)

            iddm gdm 977

            IDDM

            IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

            Gestational age in days

            Fetal abdominal circumference (mm)

            GDM

            GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

            Gestational age in days

            Fetal abdominal circumference (mm)

            FAC 6 groups

            Fetal growth profiles in diabetic pregnancies

            IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM 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            Gestational age in days

            Fetal abdominal circumference (mm)

            HC 6 groups

            Fetal growth profiles in diabetic pregnancies

            IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

            Gestational age in days

            Head circumference (mm)

            HCAC 6 groups

            Fetal growth profiles in diabetic pregnancies

            IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

            Gestational age in days

            Head to abdominal circumference ratio (HCAC ratio)

            Model

            Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

            Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

            LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

            Iperglicemia e rischio di morte fetale a termine di gravidanza

            Estimated rate of stillbirth in diabetic women 1920-2000

            Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

            4 of all stillbirths remain attributable to diabetes

            Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

            bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

            Adverse outcome

            HbA1C gt7

            1 increase in A1Ccorresponded to 55 increased

            risk of adverse outcome

            The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

            gestation particularly in the presence of fetal macrosomia

            fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

            Langer O 1995

            100 mgdLfor stillbirth

            Diabetic patients n = 271691

            Am J Obstet Gynecol 2002

            The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

            4873 diabetic women

            pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

            outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

            bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

            GDMbull dysglycemia was more difficult to manage

            2016

            Differences in placental pathologyaccording to diabetes types

            Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

            GDM is associated with a greater rate of villous immaturity

            0102030405060708090

            100GDMDMIDMII

            o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

            A retrospective study on 175 placentas with DVM vs 175 controls

            Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

            Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

            Pathophysiology of fetal compromise in diabetic pregnancy

            The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

            Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

            Bjork 1984Nylund 1982Siddiqui 2003

            A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

            STILLBIRTH RISK

            BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

            OBESITArsquo E MORTE FETALE

            6-7 per unit BMI for BMI gt 23

            Tennant PWG Am J Obstet Gynecol 2007

            HYPERINSULINISMHYPERANDROGENISM

            IMPAIRED PLACENTATION

            THE EFFECTS OF OBESITYMETABOLIC SYNDROME

            Cakmak and Taylor Hum Reprod Update 2011

            Makieva S Hum Reprod Update 2014

            Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

            Hotamisligil GS Nature 2006

            LeptinCRH

            Urocortin 3IL-6

            INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

            INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

            Adiponectina Insulin LeptinTNFα IL-6

            PLACENTAL ALTERATIONIN GENE EXPRESSION

            PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

            CollagenaseCervical ripening

            FFA

            OXIDATIVE STRESS

            PREVENZIONE STILLBIRTH

            PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

            MORBIDITAgrave NEONATALE

            AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

            TIMING E MODALITArsquo DEL PARTO

            Induzione o attesa

            INDUZIONE DEL TRAVAGLIO

            Quando fare un TC elettivo

            gt 4000 grgt 4500 gr gt 5000 gr

            ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

            425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

            No differenza in TC e outcome perinatale

            200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

            No differenza in TC gt di LGA e peso medio nel gruppo di attesa

            RCT INDUZIONE VS ATTESA in GDM

            RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

            2014

            1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

            2 Patients well controlled on insulin should probably be delivered by the due date

            3 Poorly controlled GDMrsquos using insulin require individual judgment

            Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

            1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

            2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

            3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

            cesarean delivery when the estimated fetal weight is ge 4500 g

            MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

            MODALITAgrave E TIMING DEL PARTO nel GDM

            GMD in terapia insulinicaBen controllato

            +Condizioni fetali rassicuranti

            MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

            GDM in terapia nutrizionalecon profili glicemici ottimali

            +Feto AGA

            MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

            Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

            EFW lt 4000g LGAControllo metabolico non

            ottimale

            4000g lt EFW gt 4500g EFW ge 4500g

            Programmare TC elettivo

            Parto vaginale indotto a 38-39 sett

            Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

            MODALITAgrave E TIMING DEL PARTO nel GDM

            IN BASE AL PESO FETALE STIMATO

            - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

            - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

            - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

            ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

            Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

            The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

            A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

            If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

            Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

            GDM and the Use of Betamethasone

            bull administration of betamethasone in the late preterm period should be limited to women with GDM only

            bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

            bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

            Society of Obstetricians and Gynaecologists of Canada

            The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

            late preterm delivery between 24 to 36 weeksrsquo gestation

            ASSISTENZA IN TRAVAGLIO

            - MONITORAGGIO FETALE CONTINUO

            - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

            MANTENERE GLICEMIA gt70 E lt 126

            (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

            GDM

            - Intravenous infusion of regular insulin titrated and glucose

            - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

            (ACOG 2005)

            ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

            Venere di Willendorf

            Thank you for your attention

            Pathophysiology of fetal compromise in diabetic pregnancy

            Islet cell hyperplasia common in stillborn IDMs

            There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

            Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

            Salvesen 1993Hay 1989Chukwuma 2001

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            • Birth weight distribution in diabetic pregnancies
            • Diapositiva numero 9
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            • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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            • Differences in placental pathology according to diabetes types
            • Diapositiva numero 21
            • Pathophysiology of fetal compromise in diabetic pregnancy
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            • Diapositiva numero 34
            • Diapositiva numero 35
            • Diapositiva numero 36
            • GDM and the Use of Betamethasone
            • Diapositiva numero 38
            • Diapositiva numero 39
            • Diapositiva numero 40
            • Pathophysiology of fetal compromise in diabetic pregnancy
              Intercepting Curves Random Effects are intercept and ctime (=slope)
              AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
              17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
              120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
              121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
              122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
              123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
              124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
              125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
              18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
              127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
              128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
              129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
              130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
              131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
              132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
              19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
              134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
              135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
              136-5328091174390921119170838111405379131153817241115039368311728882411124487
              137-5227041172850541118937155111396122561152048811114915830911711801311125128
              138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
              139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
              20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
              141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
              142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
              143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
              144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
              145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
              146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
              21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
              148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
              149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
              150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
              151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
              152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
              153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
              22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
              155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
              156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
              157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
              158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
              159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
              160-298411137421801113562446111183221451111374921112074470711318936011132695
              23161-287841135881421113328763111173964881109606491111950933311301854911132712
              162-277291134341041113095080111164708311107838061111827395911284773811132703
              163-266761132800661112861397111155451741106069631111703858511267692711132668
              164-256251131260281112627714111146195171104301201111580321111250611611132607
              165-2457611297199011123940311111369386110253277111145678371123353051113252
              166-235291128179521112160348111127682031100764341111333246311216449411132407
              167-224841126639141111926665111118425461098995911111209708911199368311132268
              24168-214411125098761111692982111109168891097227481111086171511182287211132103
              169-204001123558381111459299111099912321095459051110962634111165206111131912
              170-193611122018001111225616111090655751093690621110839096711148125011131695
              171-183241120477621110991933111081399181091922191110715559311131043911131452
              172-172891118937241110758250111072142611090153761110592021911113962811131183
              173-162561117396861110524567111062886041088385331110468484511096881711130888
              174-152251115856481110290884111053629471086616901110344947111079800611130567
              25175-1419611143161011100572011110443729108484847111022140971106271951113022
              176-131691112775721109823518111035116331083080041110097872311045638411129847
              177-121441111235341109589835111025859761081311611109974334911028557311129448
              178-111211109694961109356152111016603191079543181109850797511011476211129023
              179-101001108154581109122469111007346621077774751109727260110994395111128572
              180-9811106614201108888786110998090051076006321109603722710977314011128095
              181-8641105073821108655103110988833481074237891109480185310960232911127592
              26182-7491103533441108421420110979576911072469461109356647910943151811127063
              183-6361101993061108187737110970320341070701031109233110510926070711126508
              184-5251100452681107954054110961063771068932601109109573110908989611125927
              185-41610989123011077203711109518072106716417110898603571089190851112532
              186-391097371921107486688110942550631065395741108862498310874827411124687
              187-241095831541107253005110933294061063627311108738960910857746311124028
              188-111094291161107019322110924037491061858881108615423510840665211123343
              27189001092750781106785639110914780921060090451108491886110823584111122632
              190111091210401106551956110905524351058322021108368348710806503011121895
              191241089670021106318273110896267781056553591108244811310789421911121132
              192391088129641106084590110887011211054785161108121273910772340811120343
              1934161086589261105850907110877754641053016731107997736510755259711119528
              1945251085048881105617224110868498071051248301107874199110738178611118687
              19563610835085011053835411108592415104947987110775066171072109751111782
              281967491081968121105149858110849984931047711441107627124310704016411116927
              1978641080427741104916175110840728361045943011107503586910686935311116008
              1989811078887361104682492110831471791044174581107380049510669854211115063
              199101001077346981104448809110822215221042406151107256512110652773111114092
              200111211075806601104215126110812958651040637721107132974710635692011113095
              201121441074266221103981443110803702081038869291107009437310618610911112072
              202131691072725841103747760110794445511037100861106885899910601529811111023
              29203141961071185461103514077110785188941035332431106762362510584448711109948
              204152251069645081103280394110775932371033564001106638825110567367611108847
              2051625610681047011030467111107666758103179557110651528771055028651110772
              206172891066564321102813028110757419231030027141106391750310533205411106567
              207183241065023941102579345110748162661028258711106268212910516124311105388
              208193611063483561102345662110738906091026490281106144675510499043211104183
              209204001061943181102111979110729649521024721851106021138110481962111102952
              30210214411060402801101878296110720392951022953421105897600710464881011101695
              211224841058862421101644613110711136381021184991105774063310447799911100412
              212235291057322041101410930110701879811019416561105650525910430718811099103
              213245761055781661101177247110692623241017648131105526988510413637711097768
              214256251054241281100943564110683366671015879701105403451110396556611096407
              2152667610527009011007098811106741101101411127110527991371037947551109502
              216277291051160521100476198110664853531012342841105156376310362394411093607
              31217287841049620141100242515110655596961010574411105032838910345313311092168
              218298411048079761100008832110646340391008805981104909301510328232211090703
              219309001046539381099775149110637083821007037551104785764110311151111089212
              220319611044999001099541466110627827251005269121104662226710294070011087695
              2213210241043458621099307783110618570681003500691104538689310276988911086152
              2223310891041918241099074100110609314111001732261104415151910259907811084583
              2233411561040377861098840417110600057540999963831104291614510242826711082988
              322243512251038837481098606734110590800970998195401104168077110225745611081367
              22536129610372971010983730511105815444099642697110404453971020866451107972
              2263713691035756721098139368110572287830994658541103921002310191583411078047
              2273814441034216341097905685110563031260992890111103797464910174502311076348
              2283915211032675961097672002110553774690991121681103673927510157421211074623
              2294016001031135581097438319110544518120989353251103550390110140340111072872
              2304116811029595201097204636110535261550987584821103426852710123259011071095
              332314217641028054821096970953110526004980985816391103303315310106177911069292
              2324318491026514441096737270110516748410984047961103179777910089096811067463
              2334419361024974061096503587110507491840982279531103056240510072015711065608
              2344520251023433681096269904110498235270980511101102932703110054934611063727
              23546211610218933010960362211104889787097874267110280916571003785351106182
              2364722091020352921095802538110479722130976974241102685628310020772411059887
              2374823041018812541095568855110470465560975205811102562090910003691311057928
              342384924011017272161095335172110461208990973437381102438553509986610211055943
              2395025001015731781095101489110451952420971668951102315016109969529111053932
              2405126011014191401094867806110442695850969900521102191478709952448011051895
              2415227041012651021094634123110433439280968132091102067941309935366911049832
              2425328091011110641094400440110424182710966363661101944403909918285811047743
              2435429161009570261094166757110414926140964595231101820866509901204711045628
              2445530251008029881093933074110405669570962826801101697329109884123611043487
              352455631361006489501093699391110396413096105837110157379170986704251104132
              2465732491004949121093465708110387156430959289941101450254309849961411039127
              2475833641003408741093232025110377899860957521511101326716909832880311036908
              2485934811001868361092998342110368643290955753081101203179509815799211034663
              2496036001000327981092764659110359386720953984651101079642109798718111032392
              2506137210998787601092530976110350130150952216221100956104709781637011030095
              2516238440997247221092297293110340873580950447791100832567309764555911027772
              362526339690995706841092063610110331617010948679361100709029909747474811025423
              2536440960994166461091829927110322360440946910931100585492509730393711023048
              2546542250992626081091596244110313103870945142501100461955109713312611020647
              25566435609910857010913625611103038473094337407110033841770969623151101822
              2566744890989545321091128878110294590730941605641100214880309679150411015767
              2576846240988004941090895195110285334160939837211100091342909662069311013288
              2586947610986464561090661512110276077590938068781099967805509644988211010783
              372597049000984924181090427829110266821020936300351099844268109627907111008252
              2607150410983383801090194146110257564450934531921099720730709610826011005695
              2617251840981843421089960463110248307880932763491099597193309593744911003112
              2627353290980303041089726780110239051310930995061099473655909576663811000503
              2637454760978762661089493097110229794740929226631099350118509559582710997868
              PDM1
              PDM 2
              GDM
              Intercepting Curves Random Effects are intercept and ctime (=slope)
              AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
              17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
              120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
              121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
              122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
              123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
              124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
              125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
              18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
              127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
              128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
              129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
              130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
              131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
              132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
              19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
              134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
              135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
              136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
              137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
              138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
              139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
              20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
              141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
              142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
              143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
              144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
              145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
              146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
              21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
              148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
              149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
              150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
              151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
              152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
              153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
              22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
              155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
              156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
              157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
              158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
              159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
              160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
              23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
              162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
              163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
              164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
              165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
              166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
              167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
              24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
              169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
              170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
              171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
              172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
              173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
              174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
              25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
              176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
              177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
              178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
              179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
              180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
              181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
              26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
              183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
              184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
              185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
              186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
              187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
              188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
              27189002414769727245863358855247378933256248771281205245293918283252156109031122632
              19011242848834431247298968107248885247499250207813572466295047242534796182011121895
              191242442206961622487345773592503915617422516443459352479650911652548031273721121132
              1923924559255789325017018661125189787598525308087832493006776062561266365431120343
              1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
              194525248336281355253041405115254910504471255953943032519718504882587736548851118687
              195636249708143086254477014367256416818714257390475395253307436929260097164056111782
              2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
              19786425245186654825734823287125942944722602635401252559786098112627441823981116008
              198981253823728279258783842123260935761443261700072492573141962522640676915691115063
              1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
              20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
              201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
              20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
              29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
              20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
              20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
              2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
              20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
              20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
              2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
              3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
              211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
              2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
              213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
              21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
              21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
              2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
              3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
              21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
              2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
              22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
              2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
              222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
              2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
              32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
              225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
              2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
              227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
              228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
              22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
              230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
              332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
              23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
              2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
              234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
              235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
              23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
              237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
              34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
              23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
              240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
              2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
              242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
              2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
              244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
              35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
              24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
              247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
              248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
              24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
              250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
              2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
              3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
              2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
              254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
              255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
              25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
              257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
              258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
              37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
              260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
              2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
              262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
              2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
              PDM1
              PDM 2
              GDM
              Intercepting Curves Random Effects are intercept and ctime (=slope)
              AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
              17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
              120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
              121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
              122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
              123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
              124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
              125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
              18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
              127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
              128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
              129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
              130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
              131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
              132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
              19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
              134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
              135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
              136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
              137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
              138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
              139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
              20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
              141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
              142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
              143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
              144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
              145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
              146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
              21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
              148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
              149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
              150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
              151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
              152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
              153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
              22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
              155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
              156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
              157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
              158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
              159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
              160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
              23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
              162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
              163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
              164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
              165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
              166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
              167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
              24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
              169-204001942030097220294920811968857670952039875573619824233804820272617541131912
              170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
              171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
              172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
              173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
              174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
              25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
              176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
              177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
              178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
              179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
              180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
              181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
              26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
              183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
              184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
              185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
              186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
              187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
              188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
              2718900226029388723887603482286156060752396057377229889735228236469967341122632
              190112276207076492406723761352302020980242413866467172314721050872381571569371121895
              19124229212026598242468717472317885899732431675557342330544749462398443465341121132
              192392308033455472442650588052333750819222449484647512346368448052415315361311120343
              193416232394664496246061400142349615738712467293737682362192146642432187257281119528
              194525233985983445247857741475236548065822485102827852378015845232449059153251118687
              19563623557730239424965408281238134557769250291191802239383954382246593104922111782
              281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
              1978642387599402922532467654824130754166725385300983624254869412499674841161116008
              1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
              19910100241942578192568394481524448052556525741482787245713433818253341863311114092
              200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
              20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
              202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
              2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
              20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
              2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
              206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
              2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
              208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
              2092040025785576768274802861526034544505527522391804261537132408270213759281102952
              30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
              21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
              212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
              21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
              2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
              2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
              216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
              312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
              218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
              21930900273768957172927662748527621036454529303300821277360830998287085655251089212
              220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
              221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
              2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
              223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
              32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
              22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
              2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
              22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
              2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
              22940160028968214666310729688229207528403531084209838293184529588303957551221072872
              2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
              33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
              2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
              233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
              234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
              23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
              2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
              23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
              342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
              239502500305595336153286931015530794020352532865118855309008228178320829447191053932
              2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
              241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
              2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
              243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
              244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
              3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
              2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
              24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
              2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
              24960360032150852564346656514932380512301534646027872324831926768337701343161032392
              2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
              251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
              362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
              253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
              254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
              25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
              2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
              25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
              2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
              37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
              2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
              261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
              2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
              263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
              PDM1
              PDM 2
              GDM
              Intercepting Curves Random Effects are intercept and ctime (=slope)
              AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
              17119-7049001103696581094598541182103721201826791109612CURVE
              120-6947611121270161112530551199690231216229731110695
              121-6846241138824721130489621217245381230675111111752DM1
              122-6744891156360261148475751234769171245162931112783
              123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
              124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
              125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
              18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
              127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
              128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
              129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
              130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
              131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
              132-5732491330669561329825351408282271392375331121663
              19133-563136134799588134810914142546111407329991122408109459854
              134-5530251365303181366419991442608571422327091123127GDM
              135-54291613825914613847579145972468143736663112382
              136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
              137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
              138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
              139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
              20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
              141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
              142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
              143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
              144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
              145-44193615544281615696253162916098159009623112932
              146-4318491571507221588260871645932131605602611129727
              21147-421764158856726160692351662671921621151431130108
              148-4116811605608281625613191679380351636742691130463
              149-4016001622630281644329941696057421652376391130792
              150-3915211639633261663073751712703131668052531131095
              151-3814441656617221681844621729317481683771111131372
              152-3713691673582161700642551745900471699532131131623
              153-361296169052808171946754176245211715335591131848
              22154-3512251707454981738319591778972371731181491132047
              155-34115617243628617571987179546128174706983113222
              156-3310891741251721776104871811918831763000611132367
              157-321024175812156179503811828345021778973831132488
              158-319611774972381813998391844739851794989491132583
              159-309001791804181832985741861103321811047591132652
              160-298411808616961852000151877435431827148131132695
              23161-287841825410721871041621893736181843291111132712
              162-277291842185461890110151910005571859476531132703
              163-26676185894118190920574192624361875704391132668
              164-256251875677881928328391942450271891974691132607
              165-2457618923955619474781195862558190828743113252
              166-235291909094221966654871974769531924642611132407
              167-22484192577386198585871990882121941040231132268
              24168-214411942434482005089592006963351957480291132103
              169-204001959076082024347542023013221973962791131912
              170-193611975698662043632552039031731990487731131695
              171-183241992302222062944622055018882007055111131452
              172-172892008886762082283752070974672023664931131183
              173-16256202545228210164994208689912040317191130888
              174-152252041998782121043192102792172057011891130567
              25175-1419620585262621404635211865388207374903113022
              176-131692075034722159910872134484232090528611129847
              177-12144209152416217938532150283222107350631129448
              178-111212107994582198886792166050852124215091129023
              179-101002124445982218415342181787122141121991128572
              180-9812140878362237970952197492032158071331128095
              181-8642157291722257553622213165582175063111127592
              26182-7492173686062277163352228807772192097331127063
              183-636219006138229680014224441862209173991126508
              184-5252206417682316463992259998072226293091125927
              185-41622227549623361549227554618224345463112532
              186-392239073222355872872291062932260658611124687
              187-24225537246237561792306548322277905031124028
              188-112271652682395389992322002352295193891123343
              27189002287913882415189142337425022312525191122632
              190112304156062435015352352816332329898931121895
              191242320379222454868622368176282347315111121132
              192392336583362474748952383504872364773731120343
              193416235276848249465634239880212382274791119528
              1945252368934582514590792414067972399818291118687
              19563623850816625345523242930248241740423111782
              281967492401209722554540872444505632435032611116927
              197864241731876257455652459677422452703431116008
              1989812433408782594599192474817852470416691115063
              199101002449479782614668942489926922488172391114092
              200111212465531762634765752505004632505970531113095
              201121442481564722654889622520050982523811111112072
              202131692497578662675040552535065972541694131111023
              2920314196251357358269521854255004962559619591109948
              204152252529549482715423592565001872577587491108847
              2051625625455063627356557257992278259559783110772
              206172892561444222755914872594812332613650611106567
              20718324257736306277620112609670522631745831105388
              208193612593262882796514392624497352649883491104183
              209204002609143682816854742639292822668063591102952
              30210214412625005462837222152654056932686286131101695
              211224842640848222857616622668789682704551111100412
              212235292656671962878038152683491072722858531099103
              21324576267247668289848674269816112741208391097768
              214256252688262382918962392712799772759600691096407
              2152667627040290629394651272740708277803543109502
              216277292719776722959994872741983032796512611093607
              3121728784273550536298055172756527622815032231092168
              218298412751214983001135592771040852833594291090703
              219309002766905583021746542785522722852198791089212
              220319612782577163042384552799973232870845731087695
              2213210242798229723063049622814392382889535111086152
              2223310892813863263083741752828780172908266931084583
              223341156282947778310446094284313662927041191082988
              322243512252845073283125207192857461672945857891081367
              22536129628606497631459805287175538296471703107972
              2263713692876207223166780872886017732983618611078047
              227381444289174566318760832900248723002562631076348
              2283915212907265083208462792914448353021549091074623
              2294016002922765483229344342928616623040577991072872
              2304116812938246863250252952942753533059649331071095
              332314217642953709223271188622956859083078763111069292
              2324318492969152563292151352970933273097919331067463
              233441936298457688331314114298497613117117991065608
              2344520252999982183334157992998987573136359091063727
              23546211630153684633552019301296768315564263106182
              2364722093030735723376272873026916433174968611059887
              237482304304608396339737093040833823194337031057928
              342384924013061413183418495993054719853213747891055943
              2395025003076723383439648143068574523233201191053932
              2405126013092014563460827353082397833252696931051895
              2415227043107286723482033623096189783272235111049832
              2425328093122539863503266953109950373291815731047743
              243542916313777398352452734312367963311438791045628
              2445530253152989083545814793137377473331104291043487
              3524556313631681851635671293315104398335081223104132
              2465732493183362223588470873164679133370562611039127
              247583364319852026360983953178282923390355431036908
              2485934813213659283631235193191855353410190691034663
              2496036003228779283652657943205396423430068391032392
              2506137213243880263674107753218906133449988531030095
              2516238443258962223695584623232384483469951111027772
              362526339693274025163717088553245831473489956131025423
              253644096328906908373861954325924713510003591023048
              2546542253304093983760177593272631373530093491020647
              25566435633190998637817627328598428355022583101822
              2566744893334086723803374873299305833570400611015767
              257684624334905456382501413312596023590617831013288
              2586947613364003383846680393325854853610877491010783
              372597049003378933183868373743339082323631179591008252
              2607150413393843963890094153352278433651524131005695
              2617251843408735723911841623365443183671911111003112
              2627353293423608463933616153378576573692340531000503
              263745476343846218395541774339167863712812390997868
              PDM1
              PDM 2
              GDM

              Macrosomia e rischio di distocia

              Birth weight distribution in diabetic pregnancies

              Persson et al Diab Care 2011341145-1149

              ldquoDIABESITYrdquo and MACROSOMIA

              MACROSOMIA ASIMMETRICA

              OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

              Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

              Fetal growth profiles in diabetic pregnancies

              08

              085

              09

              095

              1

              105

              11

              115

              12

              125

              13

              100 120 140 160 180 200 220 240 260 280

              Gestational age in days

              Hea

              d to

              abd

              omin

              al c

              ircu

              mfe

              renc

              e ra

              tio

              (HC

              AC

              rati

              o)

              IDDM non-macrosomia

              IDDM macrosomia

              DM2 non-macrosomia

              DM2 macrosomia

              GDM non-macrosomia

              GDM macrosomia

              Birthweightgt90th

              Type-1-diabetes LGA

              Type-1 AGA

              N Hammoud et al UOG 2012

              Type-2-diabetes LGA

              GDM LGA

              Grafiek3

              Fetal growth profiles in diabetic pregnancies

              IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

              Gestational age in days

              Head to abdominal circumference ratio (HCAC ratio)

              iddm gdm 977

              IDDM

              IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

              Gestational age in days

              Fetal abdominal circumference (mm)

              GDM

              GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

              Gestational age in days

              Fetal abdominal circumference (mm)

              FAC 6 groups

              Fetal growth profiles in diabetic pregnancies

              IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

              Gestational age in days

              Fetal abdominal circumference (mm)

              HC 6 groups

              Fetal growth profiles in diabetic pregnancies

              IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263141936936246000021434432504890000114494956473214645587897500002147962193218000011494685074611509748217040000215248113594700001153987450191554937644330000215700007867599999158506392919000011600127071620000316151902140499999163025335648000011645316498911660379641339999916754427837700001169050592621705569068629999917206322110600001173569535349000011750758495921765821638350000217808847807800001179594792321181101106564000021826074208070000118411373505185620049293000021871263635360000118863267777900001190138992022000021916453062650000219315162050800001194657934751196164248994000021976705632370000119917687748200683191722999992021895059660000120369582020920520213445220670844869500002208214762938000012097210771812112273914240000221273370566700001214240019912157463341530000221725264839600001218758962639220265276882000022217715911250000122327790536800001224784219611226290533854000022277968480970000122930316234230809476583000022323157908260000123382210506923532841931200002236834733555000012383410477980000123984736204124135367628400002242859990527000012443663047724587261901300002247378933256000012488852474992503915617420000225189787598500001253404190228254910504471000022564168187139999925792313295700001259429447200000032609357614429999926244207568600001263948389929000032654547041719999926696101841500001268467332658000032699736469012714799611440000127298627538700003274492589632759989038730000227750521811600004279011532359280517846602000022820241608449999828353047508828503678933100002286543103574000042880494178170000128955573206000003291062046302999992925683605460000129407467478900003295580989031999992970873032750000129859361751800003300099931760999993016062460040000130311256024700003304618874493061251887330000230763150297600004309137817219310644131462000023121504457050000431365675994831516307419100002316669388433999983181757026773196820169200000232118833116300004322694645406000013242009596490000332570727389199999327213588135000013287199023780000333022621662100005331732530864000013332388451070000333474515934999999336251473593000013377577878360000333926410207934077041632200002342276730564999983437830448083452893590510000234679567329400004348301987537349808301780000023513146160229999935282093026635432724450900002355833558752000043573398729950000135884618723800003DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226315180286741315313845385400001154474040295000011558096267360000115714521317700002158480799617999991598163860590000216115197251624875589411638231453820000116515873182300001166494318264000011678299047049999916916549114600002170501077587171836664028000031731722504690000117450783691000001175843423351000011771790097920000217851459623300002179850182674181185769115000031825213555561838569419970000118519252843800001186528114879000011878637013200000218919928776099999190534874202000031918704606431932060470840000119454163352500001195877219966000011972128064070000219854839284800002199883979289000022012195657320255515217120389073861200001205226325053000012065619114940000120789749793500002209233084376000022105686708172119042572582132398436990000121457543014000001215911016581000012172466030220000221858218946300002219917775904221253362345222588948786223924535227000012252601216680000122659570810900001227931294550000022292668809910000223060246743223193805387323327364031423460922675500001235944813196000012372803996370000223861598607800002239951572519000022412871589624262274540124395833184200001245293918283000012466295047240000124796509116500002249300677606000022506362640472519718504882533074369292546430233700000125597860981100001257314196251999992586497826930000225998536913426132095557500003262656542016263992128457000042653277148980000126666330133899999267998887780000022693344742209999927067006066200003272005647103273341233544000032746768199850000127601240642599998277347992867000022786835793079999928001916574900002281354752192826903386310000328402592507200001285361511512999982866970979540000128803268439499999289368270836000022907038572772920394437180000329337503015929471061659999998296046203041000012973817894819999929871737592300002300052962364301388548805000033027241352463040597216870000430539530812800001306730894569000043080664810100000230940206745099999310737653892000033120732403333134088267739999831474441321500001316079999656000043174155860970000231875117253799999320086758979000023214223454232275793186100003324093518302000013254291047430000432676469118400001328100277624999993294358640660000233077145050733210703694800003333442623389334778209830000043361137962710000133744938271199999338784969153000023401205555943414561420350000334279172847634412731491700004GDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

              Gestational age in days

              Head circumference (mm)

              HCAC 6 groups

              Fetal growth profiles in diabetic pregnancies

              IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

              Gestational age in days

              Head to abdominal circumference ratio (HCAC ratio)

              Model

              Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

              Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

              LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

              Iperglicemia e rischio di morte fetale a termine di gravidanza

              Estimated rate of stillbirth in diabetic women 1920-2000

              Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

              4 of all stillbirths remain attributable to diabetes

              Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

              bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

              Adverse outcome

              HbA1C gt7

              1 increase in A1Ccorresponded to 55 increased

              risk of adverse outcome

              The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

              gestation particularly in the presence of fetal macrosomia

              fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

              Langer O 1995

              100 mgdLfor stillbirth

              Diabetic patients n = 271691

              Am J Obstet Gynecol 2002

              The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

              4873 diabetic women

              pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

              outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

              bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

              GDMbull dysglycemia was more difficult to manage

              2016

              Differences in placental pathologyaccording to diabetes types

              Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

              GDM is associated with a greater rate of villous immaturity

              0102030405060708090

              100GDMDMIDMII

              o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

              A retrospective study on 175 placentas with DVM vs 175 controls

              Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

              Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

              Pathophysiology of fetal compromise in diabetic pregnancy

              The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

              Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

              Bjork 1984Nylund 1982Siddiqui 2003

              A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

              STILLBIRTH RISK

              BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

              OBESITArsquo E MORTE FETALE

              6-7 per unit BMI for BMI gt 23

              Tennant PWG Am J Obstet Gynecol 2007

              HYPERINSULINISMHYPERANDROGENISM

              IMPAIRED PLACENTATION

              THE EFFECTS OF OBESITYMETABOLIC SYNDROME

              Cakmak and Taylor Hum Reprod Update 2011

              Makieva S Hum Reprod Update 2014

              Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

              Hotamisligil GS Nature 2006

              LeptinCRH

              Urocortin 3IL-6

              INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

              INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

              Adiponectina Insulin LeptinTNFα IL-6

              PLACENTAL ALTERATIONIN GENE EXPRESSION

              PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

              CollagenaseCervical ripening

              FFA

              OXIDATIVE STRESS

              PREVENZIONE STILLBIRTH

              PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

              MORBIDITAgrave NEONATALE

              AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

              TIMING E MODALITArsquo DEL PARTO

              Induzione o attesa

              INDUZIONE DEL TRAVAGLIO

              Quando fare un TC elettivo

              gt 4000 grgt 4500 gr gt 5000 gr

              ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

              425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

              No differenza in TC e outcome perinatale

              200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

              No differenza in TC gt di LGA e peso medio nel gruppo di attesa

              RCT INDUZIONE VS ATTESA in GDM

              RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

              2014

              1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

              2 Patients well controlled on insulin should probably be delivered by the due date

              3 Poorly controlled GDMrsquos using insulin require individual judgment

              Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

              1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

              2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

              3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

              cesarean delivery when the estimated fetal weight is ge 4500 g

              MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

              MODALITAgrave E TIMING DEL PARTO nel GDM

              GMD in terapia insulinicaBen controllato

              +Condizioni fetali rassicuranti

              MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

              GDM in terapia nutrizionalecon profili glicemici ottimali

              +Feto AGA

              MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

              Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

              EFW lt 4000g LGAControllo metabolico non

              ottimale

              4000g lt EFW gt 4500g EFW ge 4500g

              Programmare TC elettivo

              Parto vaginale indotto a 38-39 sett

              Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

              MODALITAgrave E TIMING DEL PARTO nel GDM

              IN BASE AL PESO FETALE STIMATO

              - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

              - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

              - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

              ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

              Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

              The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

              A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

              If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

              Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

              GDM and the Use of Betamethasone

              bull administration of betamethasone in the late preterm period should be limited to women with GDM only

              bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

              bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

              Society of Obstetricians and Gynaecologists of Canada

              The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

              late preterm delivery between 24 to 36 weeksrsquo gestation

              ASSISTENZA IN TRAVAGLIO

              - MONITORAGGIO FETALE CONTINUO

              - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

              MANTENERE GLICEMIA gt70 E lt 126

              (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

              GDM

              - Intravenous infusion of regular insulin titrated and glucose

              - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

              (ACOG 2005)

              ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

              Venere di Willendorf

              Thank you for your attention

              Pathophysiology of fetal compromise in diabetic pregnancy

              Islet cell hyperplasia common in stillborn IDMs

              There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

              Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

              Salvesen 1993Hay 1989Chukwuma 2001

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              • Birth weight distribution in diabetic pregnancies
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              • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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              • Differences in placental pathology according to diabetes types
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              • Pathophysiology of fetal compromise in diabetic pregnancy
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              • GDM and the Use of Betamethasone
              • Diapositiva numero 38
              • Diapositiva numero 39
              • Diapositiva numero 40
              • Pathophysiology of fetal compromise in diabetic pregnancy
                Intercepting Curves Random Effects are intercept and ctime (=slope)
                AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
                120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
                121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
                123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
                124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
                125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
                18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
                127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
                128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
                129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
                130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
                131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
                132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
                19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
                134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
                135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
                136-5328091174390921119170838111405379131153817241115039368311728882411124487
                137-5227041172850541118937155111396122561152048811114915830911711801311125128
                138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
                139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
                141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
                142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
                143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
                144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
                145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
                146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
                21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
                148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
                149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
                150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
                151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
                152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
                153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
                22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
                155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
                156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
                157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
                158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
                159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
                160-298411137421801113562446111183221451111374921112074470711318936011132695
                23161-287841135881421113328763111173964881109606491111950933311301854911132712
                162-277291134341041113095080111164708311107838061111827395911284773811132703
                163-266761132800661112861397111155451741106069631111703858511267692711132668
                164-256251131260281112627714111146195171104301201111580321111250611611132607
                165-2457611297199011123940311111369386110253277111145678371123353051113252
                166-235291128179521112160348111127682031100764341111333246311216449411132407
                167-224841126639141111926665111118425461098995911111209708911199368311132268
                24168-214411125098761111692982111109168891097227481111086171511182287211132103
                169-204001123558381111459299111099912321095459051110962634111165206111131912
                170-193611122018001111225616111090655751093690621110839096711148125011131695
                171-183241120477621110991933111081399181091922191110715559311131043911131452
                172-172891118937241110758250111072142611090153761110592021911113962811131183
                173-162561117396861110524567111062886041088385331110468484511096881711130888
                174-152251115856481110290884111053629471086616901110344947111079800611130567
                25175-1419611143161011100572011110443729108484847111022140971106271951113022
                176-131691112775721109823518111035116331083080041110097872311045638411129847
                177-121441111235341109589835111025859761081311611109974334911028557311129448
                178-111211109694961109356152111016603191079543181109850797511011476211129023
                179-101001108154581109122469111007346621077774751109727260110994395111128572
                180-9811106614201108888786110998090051076006321109603722710977314011128095
                181-8641105073821108655103110988833481074237891109480185310960232911127592
                26182-7491103533441108421420110979576911072469461109356647910943151811127063
                183-6361101993061108187737110970320341070701031109233110510926070711126508
                184-5251100452681107954054110961063771068932601109109573110908989611125927
                185-41610989123011077203711109518072106716417110898603571089190851112532
                186-391097371921107486688110942550631065395741108862498310874827411124687
                187-241095831541107253005110933294061063627311108738960910857746311124028
                188-111094291161107019322110924037491061858881108615423510840665211123343
                27189001092750781106785639110914780921060090451108491886110823584111122632
                190111091210401106551956110905524351058322021108368348710806503011121895
                191241089670021106318273110896267781056553591108244811310789421911121132
                192391088129641106084590110887011211054785161108121273910772340811120343
                1934161086589261105850907110877754641053016731107997736510755259711119528
                1945251085048881105617224110868498071051248301107874199110738178611118687
                19563610835085011053835411108592415104947987110775066171072109751111782
                281967491081968121105149858110849984931047711441107627124310704016411116927
                1978641080427741104916175110840728361045943011107503586910686935311116008
                1989811078887361104682492110831471791044174581107380049510669854211115063
                199101001077346981104448809110822215221042406151107256512110652773111114092
                200111211075806601104215126110812958651040637721107132974710635692011113095
                201121441074266221103981443110803702081038869291107009437310618610911112072
                202131691072725841103747760110794445511037100861106885899910601529811111023
                29203141961071185461103514077110785188941035332431106762362510584448711109948
                204152251069645081103280394110775932371033564001106638825110567367611108847
                2051625610681047011030467111107666758103179557110651528771055028651110772
                206172891066564321102813028110757419231030027141106391750310533205411106567
                207183241065023941102579345110748162661028258711106268212910516124311105388
                208193611063483561102345662110738906091026490281106144675510499043211104183
                209204001061943181102111979110729649521024721851106021138110481962111102952
                30210214411060402801101878296110720392951022953421105897600710464881011101695
                211224841058862421101644613110711136381021184991105774063310447799911100412
                212235291057322041101410930110701879811019416561105650525910430718811099103
                213245761055781661101177247110692623241017648131105526988510413637711097768
                214256251054241281100943564110683366671015879701105403451110396556611096407
                2152667610527009011007098811106741101101411127110527991371037947551109502
                216277291051160521100476198110664853531012342841105156376310362394411093607
                31217287841049620141100242515110655596961010574411105032838910345313311092168
                218298411048079761100008832110646340391008805981104909301510328232211090703
                219309001046539381099775149110637083821007037551104785764110311151111089212
                220319611044999001099541466110627827251005269121104662226710294070011087695
                2213210241043458621099307783110618570681003500691104538689310276988911086152
                2223310891041918241099074100110609314111001732261104415151910259907811084583
                2233411561040377861098840417110600057540999963831104291614510242826711082988
                322243512251038837481098606734110590800970998195401104168077110225745611081367
                22536129610372971010983730511105815444099642697110404453971020866451107972
                2263713691035756721098139368110572287830994658541103921002310191583411078047
                2273814441034216341097905685110563031260992890111103797464910174502311076348
                2283915211032675961097672002110553774690991121681103673927510157421211074623
                2294016001031135581097438319110544518120989353251103550390110140340111072872
                2304116811029595201097204636110535261550987584821103426852710123259011071095
                332314217641028054821096970953110526004980985816391103303315310106177911069292
                2324318491026514441096737270110516748410984047961103179777910089096811067463
                2334419361024974061096503587110507491840982279531103056240510072015711065608
                2344520251023433681096269904110498235270980511101102932703110054934611063727
                23546211610218933010960362211104889787097874267110280916571003785351106182
                2364722091020352921095802538110479722130976974241102685628310020772411059887
                2374823041018812541095568855110470465560975205811102562090910003691311057928
                342384924011017272161095335172110461208990973437381102438553509986610211055943
                2395025001015731781095101489110451952420971668951102315016109969529111053932
                2405126011014191401094867806110442695850969900521102191478709952448011051895
                2415227041012651021094634123110433439280968132091102067941309935366911049832
                2425328091011110641094400440110424182710966363661101944403909918285811047743
                2435429161009570261094166757110414926140964595231101820866509901204711045628
                2445530251008029881093933074110405669570962826801101697329109884123611043487
                352455631361006489501093699391110396413096105837110157379170986704251104132
                2465732491004949121093465708110387156430959289941101450254309849961411039127
                2475833641003408741093232025110377899860957521511101326716909832880311036908
                2485934811001868361092998342110368643290955753081101203179509815799211034663
                2496036001000327981092764659110359386720953984651101079642109798718111032392
                2506137210998787601092530976110350130150952216221100956104709781637011030095
                2516238440997247221092297293110340873580950447791100832567309764555911027772
                362526339690995706841092063610110331617010948679361100709029909747474811025423
                2536440960994166461091829927110322360440946910931100585492509730393711023048
                2546542250992626081091596244110313103870945142501100461955109713312611020647
                25566435609910857010913625611103038473094337407110033841770969623151101822
                2566744890989545321091128878110294590730941605641100214880309679150411015767
                2576846240988004941090895195110285334160939837211100091342909662069311013288
                2586947610986464561090661512110276077590938068781099967805509644988211010783
                372597049000984924181090427829110266821020936300351099844268109627907111008252
                2607150410983383801090194146110257564450934531921099720730709610826011005695
                2617251840981843421089960463110248307880932763491099597193309593744911003112
                2627353290980303041089726780110239051310930995061099473655909576663811000503
                2637454760978762661089493097110229794740929226631099350118509559582710997868
                PDM1
                PDM 2
                GDM
                Intercepting Curves Random Effects are intercept and ctime (=slope)
                AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
                120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
                121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
                123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
                124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
                125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
                18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
                127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
                128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
                129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
                130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
                131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
                132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
                19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
                134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
                135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
                136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
                137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
                138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
                139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
                141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
                142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
                143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
                144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
                145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
                146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
                21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
                148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
                149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
                150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
                151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
                152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
                153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
                22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
                155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
                156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
                157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
                158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
                159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
                160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
                23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
                162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
                163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
                164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
                165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
                166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
                167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
                24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
                169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
                170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
                171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
                172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
                173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
                174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
                25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
                176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
                177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
                178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
                179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
                180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
                181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
                26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
                183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
                184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
                185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
                186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
                187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
                188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
                27189002414769727245863358855247378933256248771281205245293918283252156109031122632
                19011242848834431247298968107248885247499250207813572466295047242534796182011121895
                191242442206961622487345773592503915617422516443459352479650911652548031273721121132
                1923924559255789325017018661125189787598525308087832493006776062561266365431120343
                1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
                194525248336281355253041405115254910504471255953943032519718504882587736548851118687
                195636249708143086254477014367256416818714257390475395253307436929260097164056111782
                2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
                19786425245186654825734823287125942944722602635401252559786098112627441823981116008
                198981253823728279258783842123260935761443261700072492573141962522640676915691115063
                1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
                20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
                201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
                20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
                29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
                20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
                20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
                2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
                20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
                20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
                2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
                3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
                211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
                2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
                213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
                21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
                21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
                2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
                3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
                21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
                2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
                22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
                2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
                222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
                2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
                32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
                225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
                2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
                227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
                228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
                22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
                230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
                332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
                23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
                2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
                234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
                235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
                23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
                237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
                34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
                23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
                240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
                2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
                242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
                2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
                244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
                35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
                24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
                247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
                248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
                24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
                250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
                2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
                3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
                2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
                254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
                255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
                25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
                257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
                258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
                37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
                260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
                2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
                262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
                2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
                PDM1
                PDM 2
                GDM
                Intercepting Curves Random Effects are intercept and ctime (=slope)
                AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
                120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
                121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
                123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
                124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
                125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
                18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
                127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
                128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
                129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
                130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
                131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
                132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
                19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
                134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
                135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
                136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
                137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
                138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
                139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
                20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
                141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
                142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
                143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
                144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
                145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
                146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
                21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
                148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
                149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
                150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
                151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
                152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
                153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
                22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
                155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
                156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
                157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
                158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
                159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
                160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
                23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
                162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
                163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
                164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
                165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
                166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
                167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
                24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
                169-204001942030097220294920811968857670952039875573619824233804820272617541131912
                170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
                171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
                172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
                173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
                174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
                25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
                176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
                177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
                178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
                179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
                180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
                181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
                26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
                183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
                184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
                185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
                186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
                187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
                188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
                2718900226029388723887603482286156060752396057377229889735228236469967341122632
                190112276207076492406723761352302020980242413866467172314721050872381571569371121895
                19124229212026598242468717472317885899732431675557342330544749462398443465341121132
                192392308033455472442650588052333750819222449484647512346368448052415315361311120343
                193416232394664496246061400142349615738712467293737682362192146642432187257281119528
                194525233985983445247857741475236548065822485102827852378015845232449059153251118687
                19563623557730239424965408281238134557769250291191802239383954382246593104922111782
                281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
                1978642387599402922532467654824130754166725385300983624254869412499674841161116008
                1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
                19910100241942578192568394481524448052556525741482787245713433818253341863311114092
                200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
                20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
                202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
                2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
                20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
                2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
                206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
                2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
                208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
                2092040025785576768274802861526034544505527522391804261537132408270213759281102952
                30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
                21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
                212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
                21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
                2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
                2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
                216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
                312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
                218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
                21930900273768957172927662748527621036454529303300821277360830998287085655251089212
                220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
                221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
                2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
                223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
                32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
                22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
                2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
                22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
                2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
                22940160028968214666310729688229207528403531084209838293184529588303957551221072872
                2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
                33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
                2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
                233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
                234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
                23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
                2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
                23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
                342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
                239502500305595336153286931015530794020352532865118855309008228178320829447191053932
                2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
                241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
                2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
                243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
                244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
                3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
                2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
                24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
                2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
                24960360032150852564346656514932380512301534646027872324831926768337701343161032392
                2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
                251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
                362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
                253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
                254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
                25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
                2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
                25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
                2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
                37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
                2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
                261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
                2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
                263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
                PDM1
                PDM 2
                GDM
                Intercepting Curves Random Effects are intercept and ctime (=slope)
                AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
                17119-7049001103696581094598541182103721201826791109612CURVE
                120-6947611121270161112530551199690231216229731110695
                121-6846241138824721130489621217245381230675111111752DM1
                122-6744891156360261148475751234769171245162931112783
                123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
                124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
                125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
                18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
                127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
                128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
                129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
                130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
                131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
                132-5732491330669561329825351408282271392375331121663
                19133-563136134799588134810914142546111407329991122408109459854
                134-5530251365303181366419991442608571422327091123127GDM
                135-54291613825914613847579145972468143736663112382
                136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
                137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
                138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
                139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
                20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
                141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
                142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
                143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
                144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
                145-44193615544281615696253162916098159009623112932
                146-4318491571507221588260871645932131605602611129727
                21147-421764158856726160692351662671921621151431130108
                148-4116811605608281625613191679380351636742691130463
                149-4016001622630281644329941696057421652376391130792
                150-3915211639633261663073751712703131668052531131095
                151-3814441656617221681844621729317481683771111131372
                152-3713691673582161700642551745900471699532131131623
                153-361296169052808171946754176245211715335591131848
                22154-3512251707454981738319591778972371731181491132047
                155-34115617243628617571987179546128174706983113222
                156-3310891741251721776104871811918831763000611132367
                157-321024175812156179503811828345021778973831132488
                158-319611774972381813998391844739851794989491132583
                159-309001791804181832985741861103321811047591132652
                160-298411808616961852000151877435431827148131132695
                23161-287841825410721871041621893736181843291111132712
                162-277291842185461890110151910005571859476531132703
                163-26676185894118190920574192624361875704391132668
                164-256251875677881928328391942450271891974691132607
                165-2457618923955619474781195862558190828743113252
                166-235291909094221966654871974769531924642611132407
                167-22484192577386198585871990882121941040231132268
                24168-214411942434482005089592006963351957480291132103
                169-204001959076082024347542023013221973962791131912
                170-193611975698662043632552039031731990487731131695
                171-183241992302222062944622055018882007055111131452
                172-172892008886762082283752070974672023664931131183
                173-16256202545228210164994208689912040317191130888
                174-152252041998782121043192102792172057011891130567
                25175-1419620585262621404635211865388207374903113022
                176-131692075034722159910872134484232090528611129847
                177-12144209152416217938532150283222107350631129448
                178-111212107994582198886792166050852124215091129023
                179-101002124445982218415342181787122141121991128572
                180-9812140878362237970952197492032158071331128095
                181-8642157291722257553622213165582175063111127592
                26182-7492173686062277163352228807772192097331127063
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                187-24225537246237561792306548322277905031124028
                188-112271652682395389992322002352295193891123343
                27189002287913882415189142337425022312525191122632
                190112304156062435015352352816332329898931121895
                191242320379222454868622368176282347315111121132
                192392336583362474748952383504872364773731120343
                193416235276848249465634239880212382274791119528
                1945252368934582514590792414067972399818291118687
                19563623850816625345523242930248241740423111782
                281967492401209722554540872444505632435032611116927
                197864241731876257455652459677422452703431116008
                1989812433408782594599192474817852470416691115063
                199101002449479782614668942489926922488172391114092
                200111212465531762634765752505004632505970531113095
                201121442481564722654889622520050982523811111112072
                202131692497578662675040552535065972541694131111023
                2920314196251357358269521854255004962559619591109948
                204152252529549482715423592565001872577587491108847
                2051625625455063627356557257992278259559783110772
                206172892561444222755914872594812332613650611106567
                20718324257736306277620112609670522631745831105388
                208193612593262882796514392624497352649883491104183
                209204002609143682816854742639292822668063591102952
                30210214412625005462837222152654056932686286131101695
                211224842640848222857616622668789682704551111100412
                212235292656671962878038152683491072722858531099103
                21324576267247668289848674269816112741208391097768
                214256252688262382918962392712799772759600691096407
                2152667627040290629394651272740708277803543109502
                216277292719776722959994872741983032796512611093607
                3121728784273550536298055172756527622815032231092168
                218298412751214983001135592771040852833594291090703
                219309002766905583021746542785522722852198791089212
                220319612782577163042384552799973232870845731087695
                2213210242798229723063049622814392382889535111086152
                2223310892813863263083741752828780172908266931084583
                223341156282947778310446094284313662927041191082988
                322243512252845073283125207192857461672945857891081367
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                332314217642953709223271188622956859083078763111069292
                2324318492969152563292151352970933273097919331067463
                233441936298457688331314114298497613117117991065608
                2344520252999982183334157992998987573136359091063727
                23546211630153684633552019301296768315564263106182
                2364722093030735723376272873026916433174968611059887
                237482304304608396339737093040833823194337031057928
                342384924013061413183418495993054719853213747891055943
                2395025003076723383439648143068574523233201191053932
                2405126013092014563460827353082397833252696931051895
                2415227043107286723482033623096189783272235111049832
                2425328093122539863503266953109950373291815731047743
                243542916313777398352452734312367963311438791045628
                2445530253152989083545814793137377473331104291043487
                3524556313631681851635671293315104398335081223104132
                2465732493183362223588470873164679133370562611039127
                247583364319852026360983953178282923390355431036908
                2485934813213659283631235193191855353410190691034663
                2496036003228779283652657943205396423430068391032392
                2506137213243880263674107753218906133449988531030095
                2516238443258962223695584623232384483469951111027772
                362526339693274025163717088553245831473489956131025423
                253644096328906908373861954325924713510003591023048
                2546542253304093983760177593272631373530093491020647
                25566435633190998637817627328598428355022583101822
                2566744893334086723803374873299305833570400611015767
                257684624334905456382501413312596023590617831013288
                2586947613364003383846680393325854853610877491010783
                372597049003378933183868373743339082323631179591008252
                2607150413393843963890094153352278433651524131005695
                2617251843408735723911841623365443183671911111003112
                2627353293423608463933616153378576573692340531000503
                263745476343846218395541774339167863712812390997868
                PDM1
                PDM 2
                GDM

                Birth weight distribution in diabetic pregnancies

                Persson et al Diab Care 2011341145-1149

                ldquoDIABESITYrdquo and MACROSOMIA

                MACROSOMIA ASIMMETRICA

                OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

                Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

                Fetal growth profiles in diabetic pregnancies

                08

                085

                09

                095

                1

                105

                11

                115

                12

                125

                13

                100 120 140 160 180 200 220 240 260 280

                Gestational age in days

                Hea

                d to

                abd

                omin

                al c

                ircu

                mfe

                renc

                e ra

                tio

                (HC

                AC

                rati

                o)

                IDDM non-macrosomia

                IDDM macrosomia

                DM2 non-macrosomia

                DM2 macrosomia

                GDM non-macrosomia

                GDM macrosomia

                Birthweightgt90th

                Type-1-diabetes LGA

                Type-1 AGA

                N Hammoud et al UOG 2012

                Type-2-diabetes LGA

                GDM LGA

                Grafiek3

                Fetal growth profiles in diabetic pregnancies

                IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                Gestational age in days

                Head to abdominal circumference ratio (HCAC ratio)

                iddm gdm 977

                IDDM

                IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

                Gestational age in days

                Fetal abdominal circumference (mm)

                GDM

                GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

                Gestational age in days

                Fetal abdominal circumference (mm)

                FAC 6 groups

                Fetal growth profiles in diabetic pregnancies

                IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

                Gestational age in days

                Fetal abdominal circumference (mm)

                HC 6 groups

                Fetal growth profiles in diabetic pregnancies

                IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263141936936246000021434432504890000114494956473214645587897500002147962193218000011494685074611509748217040000215248113594700001153987450191554937644330000215700007867599999158506392919000011600127071620000316151902140499999163025335648000011645316498911660379641339999916754427837700001169050592621705569068629999917206322110600001173569535349000011750758495921765821638350000217808847807800001179594792321181101106564000021826074208070000118411373505185620049293000021871263635360000118863267777900001190138992022000021916453062650000219315162050800001194657934751196164248994000021976705632370000119917687748200683191722999992021895059660000120369582020920520213445220670844869500002208214762938000012097210771812112273914240000221273370566700001214240019912157463341530000221725264839600001218758962639220265276882000022217715911250000122327790536800001224784219611226290533854000022277968480970000122930316234230809476583000022323157908260000123382210506923532841931200002236834733555000012383410477980000123984736204124135367628400002242859990527000012443663047724587261901300002247378933256000012488852474992503915617420000225189787598500001253404190228254910504471000022564168187139999925792313295700001259429447200000032609357614429999926244207568600001263948389929000032654547041719999926696101841500001268467332658000032699736469012714799611440000127298627538700003274492589632759989038730000227750521811600004279011532359280517846602000022820241608449999828353047508828503678933100002286543103574000042880494178170000128955573206000003291062046302999992925683605460000129407467478900003295580989031999992970873032750000129859361751800003300099931760999993016062460040000130311256024700003304618874493061251887330000230763150297600004309137817219310644131462000023121504457050000431365675994831516307419100002316669388433999983181757026773196820169200000232118833116300004322694645406000013242009596490000332570727389199999327213588135000013287199023780000333022621662100005331732530864000013332388451070000333474515934999999336251473593000013377577878360000333926410207934077041632200002342276730564999983437830448083452893590510000234679567329400004348301987537349808301780000023513146160229999935282093026635432724450900002355833558752000043573398729950000135884618723800003DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

                Gestational age in days

                Head circumference (mm)

                HCAC 6 groups

                Fetal growth profiles in diabetic pregnancies

                IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                Gestational age in days

                Head to abdominal circumference ratio (HCAC ratio)

                Model

                Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

                Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

                LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

                Iperglicemia e rischio di morte fetale a termine di gravidanza

                Estimated rate of stillbirth in diabetic women 1920-2000

                Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                4 of all stillbirths remain attributable to diabetes

                Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                Adverse outcome

                HbA1C gt7

                1 increase in A1Ccorresponded to 55 increased

                risk of adverse outcome

                The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                gestation particularly in the presence of fetal macrosomia

                fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                Langer O 1995

                100 mgdLfor stillbirth

                Diabetic patients n = 271691

                Am J Obstet Gynecol 2002

                The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                4873 diabetic women

                pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                GDMbull dysglycemia was more difficult to manage

                2016

                Differences in placental pathologyaccording to diabetes types

                Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                GDM is associated with a greater rate of villous immaturity

                0102030405060708090

                100GDMDMIDMII

                o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                A retrospective study on 175 placentas with DVM vs 175 controls

                Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                Pathophysiology of fetal compromise in diabetic pregnancy

                The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                Bjork 1984Nylund 1982Siddiqui 2003

                A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                STILLBIRTH RISK

                BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                OBESITArsquo E MORTE FETALE

                6-7 per unit BMI for BMI gt 23

                Tennant PWG Am J Obstet Gynecol 2007

                HYPERINSULINISMHYPERANDROGENISM

                IMPAIRED PLACENTATION

                THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                Cakmak and Taylor Hum Reprod Update 2011

                Makieva S Hum Reprod Update 2014

                Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                Hotamisligil GS Nature 2006

                LeptinCRH

                Urocortin 3IL-6

                INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                Adiponectina Insulin LeptinTNFα IL-6

                PLACENTAL ALTERATIONIN GENE EXPRESSION

                PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                CollagenaseCervical ripening

                FFA

                OXIDATIVE STRESS

                PREVENZIONE STILLBIRTH

                PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                MORBIDITAgrave NEONATALE

                AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                TIMING E MODALITArsquo DEL PARTO

                Induzione o attesa

                INDUZIONE DEL TRAVAGLIO

                Quando fare un TC elettivo

                gt 4000 grgt 4500 gr gt 5000 gr

                ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                No differenza in TC e outcome perinatale

                200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                RCT INDUZIONE VS ATTESA in GDM

                RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                2014

                1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                2 Patients well controlled on insulin should probably be delivered by the due date

                3 Poorly controlled GDMrsquos using insulin require individual judgment

                Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                cesarean delivery when the estimated fetal weight is ge 4500 g

                MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                MODALITAgrave E TIMING DEL PARTO nel GDM

                GMD in terapia insulinicaBen controllato

                +Condizioni fetali rassicuranti

                MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                GDM in terapia nutrizionalecon profili glicemici ottimali

                +Feto AGA

                MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                EFW lt 4000g LGAControllo metabolico non

                ottimale

                4000g lt EFW gt 4500g EFW ge 4500g

                Programmare TC elettivo

                Parto vaginale indotto a 38-39 sett

                Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                MODALITAgrave E TIMING DEL PARTO nel GDM

                IN BASE AL PESO FETALE STIMATO

                - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                GDM and the Use of Betamethasone

                bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                Society of Obstetricians and Gynaecologists of Canada

                The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                late preterm delivery between 24 to 36 weeksrsquo gestation

                ASSISTENZA IN TRAVAGLIO

                - MONITORAGGIO FETALE CONTINUO

                - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                MANTENERE GLICEMIA gt70 E lt 126

                (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                GDM

                - Intravenous infusion of regular insulin titrated and glucose

                - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                (ACOG 2005)

                ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                Venere di Willendorf

                Thank you for your attention

                Pathophysiology of fetal compromise in diabetic pregnancy

                Islet cell hyperplasia common in stillborn IDMs

                There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                Salvesen 1993Hay 1989Chukwuma 2001

                • Diapositiva numero 1
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                • Diapositiva numero 3
                • Diapositiva numero 4
                • Diapositiva numero 5
                • Diapositiva numero 6
                • Diapositiva numero 7
                • Birth weight distribution in diabetic pregnancies
                • Diapositiva numero 9
                • Diapositiva numero 10
                • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                • Diapositiva numero 12
                • Diapositiva numero 13
                • Diapositiva numero 14
                • Diapositiva numero 15
                • Diapositiva numero 16
                • Diapositiva numero 17
                • Diapositiva numero 18
                • Diapositiva numero 19
                • Differences in placental pathology according to diabetes types
                • Diapositiva numero 21
                • Pathophysiology of fetal compromise in diabetic pregnancy
                • Diapositiva numero 23
                • Diapositiva numero 24
                • Diapositiva numero 25
                • Diapositiva numero 26
                • Diapositiva numero 27
                • Diapositiva numero 28
                • Diapositiva numero 29
                • Diapositiva numero 30
                • Diapositiva numero 31
                • Diapositiva numero 32
                • Diapositiva numero 33
                • Diapositiva numero 34
                • Diapositiva numero 35
                • Diapositiva numero 36
                • GDM and the Use of Betamethasone
                • Diapositiva numero 38
                • Diapositiva numero 39
                • Diapositiva numero 40
                • Pathophysiology of fetal compromise in diabetic pregnancy
                  Intercepting Curves Random Effects are intercept and ctime (=slope)
                  AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                  17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
                  120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
                  121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                  122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
                  123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
                  124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
                  125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
                  18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
                  127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
                  128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
                  129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
                  130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
                  131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
                  132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
                  19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
                  134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
                  135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
                  136-5328091174390921119170838111405379131153817241115039368311728882411124487
                  137-5227041172850541118937155111396122561152048811114915830911711801311125128
                  138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
                  139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                  20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
                  141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
                  142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
                  143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
                  144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
                  145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
                  146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
                  21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
                  148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
                  149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
                  150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
                  151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
                  152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
                  153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
                  22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
                  155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
                  156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
                  157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
                  158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
                  159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
                  160-298411137421801113562446111183221451111374921112074470711318936011132695
                  23161-287841135881421113328763111173964881109606491111950933311301854911132712
                  162-277291134341041113095080111164708311107838061111827395911284773811132703
                  163-266761132800661112861397111155451741106069631111703858511267692711132668
                  164-256251131260281112627714111146195171104301201111580321111250611611132607
                  165-2457611297199011123940311111369386110253277111145678371123353051113252
                  166-235291128179521112160348111127682031100764341111333246311216449411132407
                  167-224841126639141111926665111118425461098995911111209708911199368311132268
                  24168-214411125098761111692982111109168891097227481111086171511182287211132103
                  169-204001123558381111459299111099912321095459051110962634111165206111131912
                  170-193611122018001111225616111090655751093690621110839096711148125011131695
                  171-183241120477621110991933111081399181091922191110715559311131043911131452
                  172-172891118937241110758250111072142611090153761110592021911113962811131183
                  173-162561117396861110524567111062886041088385331110468484511096881711130888
                  174-152251115856481110290884111053629471086616901110344947111079800611130567
                  25175-1419611143161011100572011110443729108484847111022140971106271951113022
                  176-131691112775721109823518111035116331083080041110097872311045638411129847
                  177-121441111235341109589835111025859761081311611109974334911028557311129448
                  178-111211109694961109356152111016603191079543181109850797511011476211129023
                  179-101001108154581109122469111007346621077774751109727260110994395111128572
                  180-9811106614201108888786110998090051076006321109603722710977314011128095
                  181-8641105073821108655103110988833481074237891109480185310960232911127592
                  26182-7491103533441108421420110979576911072469461109356647910943151811127063
                  183-6361101993061108187737110970320341070701031109233110510926070711126508
                  184-5251100452681107954054110961063771068932601109109573110908989611125927
                  185-41610989123011077203711109518072106716417110898603571089190851112532
                  186-391097371921107486688110942550631065395741108862498310874827411124687
                  187-241095831541107253005110933294061063627311108738960910857746311124028
                  188-111094291161107019322110924037491061858881108615423510840665211123343
                  27189001092750781106785639110914780921060090451108491886110823584111122632
                  190111091210401106551956110905524351058322021108368348710806503011121895
                  191241089670021106318273110896267781056553591108244811310789421911121132
                  192391088129641106084590110887011211054785161108121273910772340811120343
                  1934161086589261105850907110877754641053016731107997736510755259711119528
                  1945251085048881105617224110868498071051248301107874199110738178611118687
                  19563610835085011053835411108592415104947987110775066171072109751111782
                  281967491081968121105149858110849984931047711441107627124310704016411116927
                  1978641080427741104916175110840728361045943011107503586910686935311116008
                  1989811078887361104682492110831471791044174581107380049510669854211115063
                  199101001077346981104448809110822215221042406151107256512110652773111114092
                  200111211075806601104215126110812958651040637721107132974710635692011113095
                  201121441074266221103981443110803702081038869291107009437310618610911112072
                  202131691072725841103747760110794445511037100861106885899910601529811111023
                  29203141961071185461103514077110785188941035332431106762362510584448711109948
                  204152251069645081103280394110775932371033564001106638825110567367611108847
                  2051625610681047011030467111107666758103179557110651528771055028651110772
                  206172891066564321102813028110757419231030027141106391750310533205411106567
                  207183241065023941102579345110748162661028258711106268212910516124311105388
                  208193611063483561102345662110738906091026490281106144675510499043211104183
                  209204001061943181102111979110729649521024721851106021138110481962111102952
                  30210214411060402801101878296110720392951022953421105897600710464881011101695
                  211224841058862421101644613110711136381021184991105774063310447799911100412
                  212235291057322041101410930110701879811019416561105650525910430718811099103
                  213245761055781661101177247110692623241017648131105526988510413637711097768
                  214256251054241281100943564110683366671015879701105403451110396556611096407
                  2152667610527009011007098811106741101101411127110527991371037947551109502
                  216277291051160521100476198110664853531012342841105156376310362394411093607
                  31217287841049620141100242515110655596961010574411105032838910345313311092168
                  218298411048079761100008832110646340391008805981104909301510328232211090703
                  219309001046539381099775149110637083821007037551104785764110311151111089212
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                  2223310891041918241099074100110609314111001732261104415151910259907811084583
                  2233411561040377861098840417110600057540999963831104291614510242826711082988
                  322243512251038837481098606734110590800970998195401104168077110225745611081367
                  22536129610372971010983730511105815444099642697110404453971020866451107972
                  2263713691035756721098139368110572287830994658541103921002310191583411078047
                  2273814441034216341097905685110563031260992890111103797464910174502311076348
                  2283915211032675961097672002110553774690991121681103673927510157421211074623
                  2294016001031135581097438319110544518120989353251103550390110140340111072872
                  2304116811029595201097204636110535261550987584821103426852710123259011071095
                  332314217641028054821096970953110526004980985816391103303315310106177911069292
                  2324318491026514441096737270110516748410984047961103179777910089096811067463
                  2334419361024974061096503587110507491840982279531103056240510072015711065608
                  2344520251023433681096269904110498235270980511101102932703110054934611063727
                  23546211610218933010960362211104889787097874267110280916571003785351106182
                  2364722091020352921095802538110479722130976974241102685628310020772411059887
                  2374823041018812541095568855110470465560975205811102562090910003691311057928
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                  2425328091011110641094400440110424182710966363661101944403909918285811047743
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                  2496036001000327981092764659110359386720953984651101079642109798718111032392
                  2506137210998787601092530976110350130150952216221100956104709781637011030095
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                  362526339690995706841092063610110331617010948679361100709029909747474811025423
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                  25566435609910857010913625611103038473094337407110033841770969623151101822
                  2566744890989545321091128878110294590730941605641100214880309679150411015767
                  2576846240988004941090895195110285334160939837211100091342909662069311013288
                  2586947610986464561090661512110276077590938068781099967805509644988211010783
                  372597049000984924181090427829110266821020936300351099844268109627907111008252
                  2607150410983383801090194146110257564450934531921099720730709610826011005695
                  2617251840981843421089960463110248307880932763491099597193309593744911003112
                  2627353290980303041089726780110239051310930995061099473655909576663811000503
                  2637454760978762661089493097110229794740929226631099350118509559582710997868
                  PDM1
                  PDM 2
                  GDM
                  Intercepting Curves Random Effects are intercept and ctime (=slope)
                  AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                  17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
                  120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
                  121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                  122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
                  123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
                  124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
                  125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
                  18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
                  127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
                  128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
                  129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
                  130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
                  131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
                  132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
                  19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
                  134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
                  135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
                  136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
                  137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
                  138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
                  139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                  20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
                  141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
                  142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
                  143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
                  144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
                  145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
                  146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
                  21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
                  148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
                  149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
                  150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
                  151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
                  152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
                  153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
                  22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
                  155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
                  156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
                  157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
                  158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
                  159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
                  160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
                  23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
                  162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
                  163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
                  164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
                  165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
                  166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
                  167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
                  24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
                  169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
                  170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
                  171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
                  172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
                  173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
                  174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
                  25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
                  176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
                  177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
                  178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
                  179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
                  180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
                  181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
                  26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
                  183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
                  184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
                  185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
                  186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
                  187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
                  188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
                  27189002414769727245863358855247378933256248771281205245293918283252156109031122632
                  19011242848834431247298968107248885247499250207813572466295047242534796182011121895
                  191242442206961622487345773592503915617422516443459352479650911652548031273721121132
                  1923924559255789325017018661125189787598525308087832493006776062561266365431120343
                  1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
                  194525248336281355253041405115254910504471255953943032519718504882587736548851118687
                  195636249708143086254477014367256416818714257390475395253307436929260097164056111782
                  2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
                  19786425245186654825734823287125942944722602635401252559786098112627441823981116008
                  198981253823728279258783842123260935761443261700072492573141962522640676915691115063
                  1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
                  20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
                  201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
                  20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
                  29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
                  20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
                  20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
                  2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
                  20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
                  20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
                  2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
                  3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
                  211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
                  2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
                  213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
                  21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
                  21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
                  2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
                  3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
                  21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
                  2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
                  22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
                  2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
                  222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
                  2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
                  32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
                  225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
                  2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
                  227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
                  228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
                  22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
                  230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
                  332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
                  23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
                  2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
                  234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
                  235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
                  23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
                  237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
                  34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
                  23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
                  240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
                  2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
                  242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
                  2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
                  244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
                  35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
                  24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
                  247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
                  248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
                  24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
                  250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
                  2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
                  3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
                  2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
                  254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
                  255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
                  25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
                  257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
                  258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
                  37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
                  260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
                  2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
                  262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
                  2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
                  PDM1
                  PDM 2
                  GDM
                  Intercepting Curves Random Effects are intercept and ctime (=slope)
                  AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                  17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
                  120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
                  121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                  122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
                  123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
                  124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
                  125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
                  18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
                  127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
                  128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
                  129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
                  130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
                  131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
                  132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
                  19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
                  134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
                  135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
                  136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
                  137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
                  138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
                  139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
                  20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
                  141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
                  142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
                  143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
                  144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
                  145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
                  146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
                  21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
                  148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
                  149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
                  150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
                  151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
                  152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
                  153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
                  22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
                  155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
                  156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
                  157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
                  158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
                  159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
                  160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
                  23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
                  162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
                  163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
                  164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
                  165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
                  166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
                  167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
                  24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
                  169-204001942030097220294920811968857670952039875573619824233804820272617541131912
                  170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
                  171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
                  172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
                  173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
                  174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
                  25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
                  176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
                  177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
                  178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
                  179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
                  180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
                  181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
                  26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
                  183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
                  184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
                  185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
                  186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
                  187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
                  188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
                  2718900226029388723887603482286156060752396057377229889735228236469967341122632
                  190112276207076492406723761352302020980242413866467172314721050872381571569371121895
                  19124229212026598242468717472317885899732431675557342330544749462398443465341121132
                  192392308033455472442650588052333750819222449484647512346368448052415315361311120343
                  193416232394664496246061400142349615738712467293737682362192146642432187257281119528
                  194525233985983445247857741475236548065822485102827852378015845232449059153251118687
                  19563623557730239424965408281238134557769250291191802239383954382246593104922111782
                  281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
                  1978642387599402922532467654824130754166725385300983624254869412499674841161116008
                  1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
                  19910100241942578192568394481524448052556525741482787245713433818253341863311114092
                  200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
                  20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
                  202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
                  2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
                  20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
                  2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
                  206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
                  2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
                  208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
                  2092040025785576768274802861526034544505527522391804261537132408270213759281102952
                  30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
                  21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
                  212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
                  21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
                  2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
                  2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
                  216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
                  312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
                  218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
                  21930900273768957172927662748527621036454529303300821277360830998287085655251089212
                  220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
                  221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
                  2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
                  223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
                  32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
                  22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
                  2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
                  22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
                  2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
                  22940160028968214666310729688229207528403531084209838293184529588303957551221072872
                  2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
                  33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
                  2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
                  233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
                  234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
                  23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
                  2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
                  23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
                  342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
                  239502500305595336153286931015530794020352532865118855309008228178320829447191053932
                  2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
                  241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
                  2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
                  243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
                  244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
                  3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
                  2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
                  24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
                  2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
                  24960360032150852564346656514932380512301534646027872324831926768337701343161032392
                  2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
                  251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
                  362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
                  253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
                  254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
                  25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
                  2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
                  25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
                  2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
                  37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
                  2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
                  261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
                  2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
                  263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
                  PDM1
                  PDM 2
                  GDM
                  Intercepting Curves Random Effects are intercept and ctime (=slope)
                  AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
                  17119-7049001103696581094598541182103721201826791109612CURVE
                  120-6947611121270161112530551199690231216229731110695
                  121-6846241138824721130489621217245381230675111111752DM1
                  122-6744891156360261148475751234769171245162931112783
                  123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
                  124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
                  125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
                  18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
                  127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
                  128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
                  129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
                  130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
                  131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
                  132-5732491330669561329825351408282271392375331121663
                  19133-563136134799588134810914142546111407329991122408109459854
                  134-5530251365303181366419991442608571422327091123127GDM
                  135-54291613825914613847579145972468143736663112382
                  136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
                  137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
                  138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
                  139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
                  20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
                  141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
                  142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
                  143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
                  144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
                  145-44193615544281615696253162916098159009623112932
                  146-4318491571507221588260871645932131605602611129727
                  21147-421764158856726160692351662671921621151431130108
                  148-4116811605608281625613191679380351636742691130463
                  149-4016001622630281644329941696057421652376391130792
                  150-3915211639633261663073751712703131668052531131095
                  151-3814441656617221681844621729317481683771111131372
                  152-3713691673582161700642551745900471699532131131623
                  153-361296169052808171946754176245211715335591131848
                  22154-3512251707454981738319591778972371731181491132047
                  155-34115617243628617571987179546128174706983113222
                  156-3310891741251721776104871811918831763000611132367
                  157-321024175812156179503811828345021778973831132488
                  158-319611774972381813998391844739851794989491132583
                  159-309001791804181832985741861103321811047591132652
                  160-298411808616961852000151877435431827148131132695
                  23161-287841825410721871041621893736181843291111132712
                  162-277291842185461890110151910005571859476531132703
                  163-26676185894118190920574192624361875704391132668
                  164-256251875677881928328391942450271891974691132607
                  165-2457618923955619474781195862558190828743113252
                  166-235291909094221966654871974769531924642611132407
                  167-22484192577386198585871990882121941040231132268
                  24168-214411942434482005089592006963351957480291132103
                  169-204001959076082024347542023013221973962791131912
                  170-193611975698662043632552039031731990487731131695
                  171-183241992302222062944622055018882007055111131452
                  172-172892008886762082283752070974672023664931131183
                  173-16256202545228210164994208689912040317191130888
                  174-152252041998782121043192102792172057011891130567
                  25175-1419620585262621404635211865388207374903113022
                  176-131692075034722159910872134484232090528611129847
                  177-12144209152416217938532150283222107350631129448
                  178-111212107994582198886792166050852124215091129023
                  179-101002124445982218415342181787122141121991128572
                  180-9812140878362237970952197492032158071331128095
                  181-8642157291722257553622213165582175063111127592
                  26182-7492173686062277163352228807772192097331127063
                  183-636219006138229680014224441862209173991126508
                  184-5252206417682316463992259998072226293091125927
                  185-41622227549623361549227554618224345463112532
                  186-392239073222355872872291062932260658611124687
                  187-24225537246237561792306548322277905031124028
                  188-112271652682395389992322002352295193891123343
                  27189002287913882415189142337425022312525191122632
                  190112304156062435015352352816332329898931121895
                  191242320379222454868622368176282347315111121132
                  192392336583362474748952383504872364773731120343
                  193416235276848249465634239880212382274791119528
                  1945252368934582514590792414067972399818291118687
                  19563623850816625345523242930248241740423111782
                  281967492401209722554540872444505632435032611116927
                  197864241731876257455652459677422452703431116008
                  1989812433408782594599192474817852470416691115063
                  199101002449479782614668942489926922488172391114092
                  200111212465531762634765752505004632505970531113095
                  201121442481564722654889622520050982523811111112072
                  202131692497578662675040552535065972541694131111023
                  2920314196251357358269521854255004962559619591109948
                  204152252529549482715423592565001872577587491108847
                  2051625625455063627356557257992278259559783110772
                  206172892561444222755914872594812332613650611106567
                  20718324257736306277620112609670522631745831105388
                  208193612593262882796514392624497352649883491104183
                  209204002609143682816854742639292822668063591102952
                  30210214412625005462837222152654056932686286131101695
                  211224842640848222857616622668789682704551111100412
                  212235292656671962878038152683491072722858531099103
                  21324576267247668289848674269816112741208391097768
                  214256252688262382918962392712799772759600691096407
                  2152667627040290629394651272740708277803543109502
                  216277292719776722959994872741983032796512611093607
                  3121728784273550536298055172756527622815032231092168
                  218298412751214983001135592771040852833594291090703
                  219309002766905583021746542785522722852198791089212
                  220319612782577163042384552799973232870845731087695
                  2213210242798229723063049622814392382889535111086152
                  2223310892813863263083741752828780172908266931084583
                  223341156282947778310446094284313662927041191082988
                  322243512252845073283125207192857461672945857891081367
                  22536129628606497631459805287175538296471703107972
                  2263713692876207223166780872886017732983618611078047
                  227381444289174566318760832900248723002562631076348
                  2283915212907265083208462792914448353021549091074623
                  2294016002922765483229344342928616623040577991072872
                  2304116812938246863250252952942753533059649331071095
                  332314217642953709223271188622956859083078763111069292
                  2324318492969152563292151352970933273097919331067463
                  233441936298457688331314114298497613117117991065608
                  2344520252999982183334157992998987573136359091063727
                  23546211630153684633552019301296768315564263106182
                  2364722093030735723376272873026916433174968611059887
                  237482304304608396339737093040833823194337031057928
                  342384924013061413183418495993054719853213747891055943
                  2395025003076723383439648143068574523233201191053932
                  2405126013092014563460827353082397833252696931051895
                  2415227043107286723482033623096189783272235111049832
                  2425328093122539863503266953109950373291815731047743
                  243542916313777398352452734312367963311438791045628
                  2445530253152989083545814793137377473331104291043487
                  3524556313631681851635671293315104398335081223104132
                  2465732493183362223588470873164679133370562611039127
                  247583364319852026360983953178282923390355431036908
                  2485934813213659283631235193191855353410190691034663
                  2496036003228779283652657943205396423430068391032392
                  2506137213243880263674107753218906133449988531030095
                  2516238443258962223695584623232384483469951111027772
                  362526339693274025163717088553245831473489956131025423
                  253644096328906908373861954325924713510003591023048
                  2546542253304093983760177593272631373530093491020647
                  25566435633190998637817627328598428355022583101822
                  2566744893334086723803374873299305833570400611015767
                  257684624334905456382501413312596023590617831013288
                  2586947613364003383846680393325854853610877491010783
                  372597049003378933183868373743339082323631179591008252
                  2607150413393843963890094153352278433651524131005695
                  2617251843408735723911841623365443183671911111003112
                  2627353293423608463933616153378576573692340531000503
                  263745476343846218395541774339167863712812390997868
                  PDM1
                  PDM 2
                  GDM

                  ldquoDIABESITYrdquo and MACROSOMIA

                  MACROSOMIA ASIMMETRICA

                  OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

                  Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

                  Fetal growth profiles in diabetic pregnancies

                  08

                  085

                  09

                  095

                  1

                  105

                  11

                  115

                  12

                  125

                  13

                  100 120 140 160 180 200 220 240 260 280

                  Gestational age in days

                  Hea

                  d to

                  abd

                  omin

                  al c

                  ircu

                  mfe

                  renc

                  e ra

                  tio

                  (HC

                  AC

                  rati

                  o)

                  IDDM non-macrosomia

                  IDDM macrosomia

                  DM2 non-macrosomia

                  DM2 macrosomia

                  GDM non-macrosomia

                  GDM macrosomia

                  Birthweightgt90th

                  Type-1-diabetes LGA

                  Type-1 AGA

                  N Hammoud et al UOG 2012

                  Type-2-diabetes LGA

                  GDM LGA

                  Grafiek3

                  Fetal growth profiles in diabetic pregnancies

                  IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                  Gestational age in days

                  Head to abdominal circumference ratio (HCAC ratio)

                  iddm gdm 977

                  IDDM

                  IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

                  Gestational age in days

                  Fetal abdominal circumference (mm)

                  GDM

                  GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

                  Gestational age in days

                  Fetal abdominal circumference (mm)

                  FAC 6 groups

                  Fetal growth profiles in diabetic pregnancies

                  IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

                  Gestational age in days

                  Fetal abdominal circumference (mm)

                  HC 6 groups

                  Fetal growth profiles in diabetic pregnancies

                  IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226315180286741315313845385400001154474040295000011558096267360000115714521317700002158480799617999991598163860590000216115197251624875589411638231453820000116515873182300001166494318264000011678299047049999916916549114600002170501077587171836664028000031731722504690000117450783691000001175843423351000011771790097920000217851459623300002179850182674181185769115000031825213555561838569419970000118519252843800001186528114879000011878637013200000218919928776099999190534874202000031918704606431932060470840000119454163352500001195877219966000011972128064070000219854839284800002199883979289000022012195657320255515217120389073861200001205226325053000012065619114940000120789749793500002209233084376000022105686708172119042572582132398436990000121457543014000001215911016581000012172466030220000221858218946300002219917775904221253362345222588948786223924535227000012252601216680000122659570810900001227931294550000022292668809910000223060246743223193805387323327364031423460922675500001235944813196000012372803996370000223861598607800002239951572519000022412871589624262274540124395833184200001245293918283000012466295047240000124796509116500002249300677606000022506362640472519718504882533074369292546430233700000125597860981100001257314196251999992586497826930000225998536913426132095557500003262656542016263992128457000042653277148980000126666330133899999267998887780000022693344742209999927067006066200003272005647103273341233544000032746768199850000127601240642599998277347992867000022786835793079999928001916574900002281354752192826903386310000328402592507200001285361511512999982866970979540000128803268439499999289368270836000022907038572772920394437180000329337503015929471061659999998296046203041000012973817894819999929871737592300002300052962364301388548805000033027241352463040597216870000430539530812800001306730894569000043080664810100000230940206745099999310737653892000033120732403333134088267739999831474441321500001316079999656000043174155860970000231875117253799999320086758979000023214223454232275793186100003324093518302000013254291047430000432676469118400001328100277624999993294358640660000233077145050733210703694800003333442623389334778209830000043361137962710000133744938271199999338784969153000023401205555943414561420350000334279172847634412731491700004GDM macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

                  Gestational age in days

                  Head circumference (mm)

                  HCAC 6 groups

                  Fetal growth profiles in diabetic pregnancies

                  IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                  Gestational age in days

                  Head to abdominal circumference ratio (HCAC ratio)

                  Model

                  Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

                  Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

                  LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

                  Iperglicemia e rischio di morte fetale a termine di gravidanza

                  Estimated rate of stillbirth in diabetic women 1920-2000

                  Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                  4 of all stillbirths remain attributable to diabetes

                  Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                  bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                  Adverse outcome

                  HbA1C gt7

                  1 increase in A1Ccorresponded to 55 increased

                  risk of adverse outcome

                  The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                  gestation particularly in the presence of fetal macrosomia

                  fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                  Langer O 1995

                  100 mgdLfor stillbirth

                  Diabetic patients n = 271691

                  Am J Obstet Gynecol 2002

                  The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                  4873 diabetic women

                  pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                  outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                  bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                  GDMbull dysglycemia was more difficult to manage

                  2016

                  Differences in placental pathologyaccording to diabetes types

                  Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                  GDM is associated with a greater rate of villous immaturity

                  0102030405060708090

                  100GDMDMIDMII

                  o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                  A retrospective study on 175 placentas with DVM vs 175 controls

                  Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                  Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                  Pathophysiology of fetal compromise in diabetic pregnancy

                  The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                  Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                  Bjork 1984Nylund 1982Siddiqui 2003

                  A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                  STILLBIRTH RISK

                  BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                  OBESITArsquo E MORTE FETALE

                  6-7 per unit BMI for BMI gt 23

                  Tennant PWG Am J Obstet Gynecol 2007

                  HYPERINSULINISMHYPERANDROGENISM

                  IMPAIRED PLACENTATION

                  THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                  Cakmak and Taylor Hum Reprod Update 2011

                  Makieva S Hum Reprod Update 2014

                  Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                  Hotamisligil GS Nature 2006

                  LeptinCRH

                  Urocortin 3IL-6

                  INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                  INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                  Adiponectina Insulin LeptinTNFα IL-6

                  PLACENTAL ALTERATIONIN GENE EXPRESSION

                  PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                  CollagenaseCervical ripening

                  FFA

                  OXIDATIVE STRESS

                  PREVENZIONE STILLBIRTH

                  PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                  MORBIDITAgrave NEONATALE

                  AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                  TIMING E MODALITArsquo DEL PARTO

                  Induzione o attesa

                  INDUZIONE DEL TRAVAGLIO

                  Quando fare un TC elettivo

                  gt 4000 grgt 4500 gr gt 5000 gr

                  ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                  425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                  No differenza in TC e outcome perinatale

                  200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                  No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                  RCT INDUZIONE VS ATTESA in GDM

                  RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                  2014

                  1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                  2 Patients well controlled on insulin should probably be delivered by the due date

                  3 Poorly controlled GDMrsquos using insulin require individual judgment

                  Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                  1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                  2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                  3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                  cesarean delivery when the estimated fetal weight is ge 4500 g

                  MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                  MODALITAgrave E TIMING DEL PARTO nel GDM

                  GMD in terapia insulinicaBen controllato

                  +Condizioni fetali rassicuranti

                  MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                  GDM in terapia nutrizionalecon profili glicemici ottimali

                  +Feto AGA

                  MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                  Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                  EFW lt 4000g LGAControllo metabolico non

                  ottimale

                  4000g lt EFW gt 4500g EFW ge 4500g

                  Programmare TC elettivo

                  Parto vaginale indotto a 38-39 sett

                  Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                  MODALITAgrave E TIMING DEL PARTO nel GDM

                  IN BASE AL PESO FETALE STIMATO

                  - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                  - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                  - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                  ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                  Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                  The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                  A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                  If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                  Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                  GDM and the Use of Betamethasone

                  bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                  bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                  bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                  Society of Obstetricians and Gynaecologists of Canada

                  The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                  late preterm delivery between 24 to 36 weeksrsquo gestation

                  ASSISTENZA IN TRAVAGLIO

                  - MONITORAGGIO FETALE CONTINUO

                  - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                  MANTENERE GLICEMIA gt70 E lt 126

                  (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                  GDM

                  - Intravenous infusion of regular insulin titrated and glucose

                  - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                  (ACOG 2005)

                  ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                  Venere di Willendorf

                  Thank you for your attention

                  Pathophysiology of fetal compromise in diabetic pregnancy

                  Islet cell hyperplasia common in stillborn IDMs

                  There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                  Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                  Salvesen 1993Hay 1989Chukwuma 2001

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                  • Diapositiva numero 7
                  • Birth weight distribution in diabetic pregnancies
                  • Diapositiva numero 9
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                  • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                  • Diapositiva numero 12
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                  • Diapositiva numero 15
                  • Diapositiva numero 16
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                  • Differences in placental pathology according to diabetes types
                  • Diapositiva numero 21
                  • Pathophysiology of fetal compromise in diabetic pregnancy
                  • Diapositiva numero 23
                  • Diapositiva numero 24
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                  • Diapositiva numero 26
                  • Diapositiva numero 27
                  • Diapositiva numero 28
                  • Diapositiva numero 29
                  • Diapositiva numero 30
                  • Diapositiva numero 31
                  • Diapositiva numero 32
                  • Diapositiva numero 33
                  • Diapositiva numero 34
                  • Diapositiva numero 35
                  • Diapositiva numero 36
                  • GDM and the Use of Betamethasone
                  • Diapositiva numero 38
                  • Diapositiva numero 39
                  • Diapositiva numero 40
                  • Pathophysiology of fetal compromise in diabetic pregnancy
                    Intercepting Curves Random Effects are intercept and ctime (=slope)
                    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                    17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
                    120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
                    121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                    122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
                    123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
                    124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
                    125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
                    18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
                    127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
                    128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
                    129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
                    130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
                    131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
                    132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
                    19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
                    134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
                    135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
                    136-5328091174390921119170838111405379131153817241115039368311728882411124487
                    137-5227041172850541118937155111396122561152048811114915830911711801311125128
                    138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
                    139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                    20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
                    141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
                    142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
                    143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
                    144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
                    145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
                    146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
                    21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
                    148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
                    149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
                    150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
                    151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
                    152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
                    153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
                    22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
                    155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
                    156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
                    157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
                    158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
                    159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
                    160-298411137421801113562446111183221451111374921112074470711318936011132695
                    23161-287841135881421113328763111173964881109606491111950933311301854911132712
                    162-277291134341041113095080111164708311107838061111827395911284773811132703
                    163-266761132800661112861397111155451741106069631111703858511267692711132668
                    164-256251131260281112627714111146195171104301201111580321111250611611132607
                    165-2457611297199011123940311111369386110253277111145678371123353051113252
                    166-235291128179521112160348111127682031100764341111333246311216449411132407
                    167-224841126639141111926665111118425461098995911111209708911199368311132268
                    24168-214411125098761111692982111109168891097227481111086171511182287211132103
                    169-204001123558381111459299111099912321095459051110962634111165206111131912
                    170-193611122018001111225616111090655751093690621110839096711148125011131695
                    171-183241120477621110991933111081399181091922191110715559311131043911131452
                    172-172891118937241110758250111072142611090153761110592021911113962811131183
                    173-162561117396861110524567111062886041088385331110468484511096881711130888
                    174-152251115856481110290884111053629471086616901110344947111079800611130567
                    25175-1419611143161011100572011110443729108484847111022140971106271951113022
                    176-131691112775721109823518111035116331083080041110097872311045638411129847
                    177-121441111235341109589835111025859761081311611109974334911028557311129448
                    178-111211109694961109356152111016603191079543181109850797511011476211129023
                    179-101001108154581109122469111007346621077774751109727260110994395111128572
                    180-9811106614201108888786110998090051076006321109603722710977314011128095
                    181-8641105073821108655103110988833481074237891109480185310960232911127592
                    26182-7491103533441108421420110979576911072469461109356647910943151811127063
                    183-6361101993061108187737110970320341070701031109233110510926070711126508
                    184-5251100452681107954054110961063771068932601109109573110908989611125927
                    185-41610989123011077203711109518072106716417110898603571089190851112532
                    186-391097371921107486688110942550631065395741108862498310874827411124687
                    187-241095831541107253005110933294061063627311108738960910857746311124028
                    188-111094291161107019322110924037491061858881108615423510840665211123343
                    27189001092750781106785639110914780921060090451108491886110823584111122632
                    190111091210401106551956110905524351058322021108368348710806503011121895
                    191241089670021106318273110896267781056553591108244811310789421911121132
                    192391088129641106084590110887011211054785161108121273910772340811120343
                    1934161086589261105850907110877754641053016731107997736510755259711119528
                    1945251085048881105617224110868498071051248301107874199110738178611118687
                    19563610835085011053835411108592415104947987110775066171072109751111782
                    281967491081968121105149858110849984931047711441107627124310704016411116927
                    1978641080427741104916175110840728361045943011107503586910686935311116008
                    1989811078887361104682492110831471791044174581107380049510669854211115063
                    199101001077346981104448809110822215221042406151107256512110652773111114092
                    200111211075806601104215126110812958651040637721107132974710635692011113095
                    201121441074266221103981443110803702081038869291107009437310618610911112072
                    202131691072725841103747760110794445511037100861106885899910601529811111023
                    29203141961071185461103514077110785188941035332431106762362510584448711109948
                    204152251069645081103280394110775932371033564001106638825110567367611108847
                    2051625610681047011030467111107666758103179557110651528771055028651110772
                    206172891066564321102813028110757419231030027141106391750310533205411106567
                    207183241065023941102579345110748162661028258711106268212910516124311105388
                    208193611063483561102345662110738906091026490281106144675510499043211104183
                    209204001061943181102111979110729649521024721851106021138110481962111102952
                    30210214411060402801101878296110720392951022953421105897600710464881011101695
                    211224841058862421101644613110711136381021184991105774063310447799911100412
                    212235291057322041101410930110701879811019416561105650525910430718811099103
                    213245761055781661101177247110692623241017648131105526988510413637711097768
                    214256251054241281100943564110683366671015879701105403451110396556611096407
                    2152667610527009011007098811106741101101411127110527991371037947551109502
                    216277291051160521100476198110664853531012342841105156376310362394411093607
                    31217287841049620141100242515110655596961010574411105032838910345313311092168
                    218298411048079761100008832110646340391008805981104909301510328232211090703
                    219309001046539381099775149110637083821007037551104785764110311151111089212
                    220319611044999001099541466110627827251005269121104662226710294070011087695
                    2213210241043458621099307783110618570681003500691104538689310276988911086152
                    2223310891041918241099074100110609314111001732261104415151910259907811084583
                    2233411561040377861098840417110600057540999963831104291614510242826711082988
                    322243512251038837481098606734110590800970998195401104168077110225745611081367
                    22536129610372971010983730511105815444099642697110404453971020866451107972
                    2263713691035756721098139368110572287830994658541103921002310191583411078047
                    2273814441034216341097905685110563031260992890111103797464910174502311076348
                    2283915211032675961097672002110553774690991121681103673927510157421211074623
                    2294016001031135581097438319110544518120989353251103550390110140340111072872
                    2304116811029595201097204636110535261550987584821103426852710123259011071095
                    332314217641028054821096970953110526004980985816391103303315310106177911069292
                    2324318491026514441096737270110516748410984047961103179777910089096811067463
                    2334419361024974061096503587110507491840982279531103056240510072015711065608
                    2344520251023433681096269904110498235270980511101102932703110054934611063727
                    23546211610218933010960362211104889787097874267110280916571003785351106182
                    2364722091020352921095802538110479722130976974241102685628310020772411059887
                    2374823041018812541095568855110470465560975205811102562090910003691311057928
                    342384924011017272161095335172110461208990973437381102438553509986610211055943
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                    2425328091011110641094400440110424182710966363661101944403909918285811047743
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                    2465732491004949121093465708110387156430959289941101450254309849961411039127
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                    362526339690995706841092063610110331617010948679361100709029909747474811025423
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                    25566435609910857010913625611103038473094337407110033841770969623151101822
                    2566744890989545321091128878110294590730941605641100214880309679150411015767
                    2576846240988004941090895195110285334160939837211100091342909662069311013288
                    2586947610986464561090661512110276077590938068781099967805509644988211010783
                    372597049000984924181090427829110266821020936300351099844268109627907111008252
                    2607150410983383801090194146110257564450934531921099720730709610826011005695
                    2617251840981843421089960463110248307880932763491099597193309593744911003112
                    2627353290980303041089726780110239051310930995061099473655909576663811000503
                    2637454760978762661089493097110229794740929226631099350118509559582710997868
                    PDM1
                    PDM 2
                    GDM
                    Intercepting Curves Random Effects are intercept and ctime (=slope)
                    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                    17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
                    120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
                    121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                    122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
                    123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
                    124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
                    125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
                    18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
                    127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
                    128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
                    129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
                    130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
                    131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
                    132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
                    19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
                    134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
                    135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
                    136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
                    137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
                    138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
                    139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                    20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
                    141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
                    142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
                    143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
                    144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
                    145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
                    146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
                    21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
                    148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
                    149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
                    150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
                    151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
                    152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
                    153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
                    22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
                    155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
                    156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
                    157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
                    158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
                    159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
                    160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
                    23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
                    162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
                    163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
                    164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
                    165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
                    166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
                    167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
                    24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
                    169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
                    170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
                    171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
                    172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
                    173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
                    174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
                    25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
                    176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
                    177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
                    178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
                    179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
                    180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
                    181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
                    26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
                    183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
                    184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
                    185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
                    186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
                    187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
                    188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
                    27189002414769727245863358855247378933256248771281205245293918283252156109031122632
                    19011242848834431247298968107248885247499250207813572466295047242534796182011121895
                    191242442206961622487345773592503915617422516443459352479650911652548031273721121132
                    1923924559255789325017018661125189787598525308087832493006776062561266365431120343
                    1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
                    194525248336281355253041405115254910504471255953943032519718504882587736548851118687
                    195636249708143086254477014367256416818714257390475395253307436929260097164056111782
                    2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
                    19786425245186654825734823287125942944722602635401252559786098112627441823981116008
                    198981253823728279258783842123260935761443261700072492573141962522640676915691115063
                    1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
                    20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
                    201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
                    20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
                    29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
                    20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
                    20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
                    2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
                    20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
                    20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
                    2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
                    3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
                    211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
                    2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
                    213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
                    21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
                    21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
                    2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
                    3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
                    21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
                    2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
                    22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
                    2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
                    222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
                    2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
                    32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
                    225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
                    2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
                    227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
                    228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
                    22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
                    230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
                    332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
                    23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
                    2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
                    234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
                    235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
                    23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
                    237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
                    34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
                    23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
                    240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
                    2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
                    242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
                    2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
                    244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
                    35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
                    24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
                    247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
                    248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
                    24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
                    250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
                    2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
                    3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
                    2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
                    254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
                    255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
                    25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
                    257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
                    258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
                    37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
                    260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
                    2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
                    262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
                    2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
                    PDM1
                    PDM 2
                    GDM
                    Intercepting Curves Random Effects are intercept and ctime (=slope)
                    AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                    17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
                    120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
                    121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                    122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
                    123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
                    124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
                    125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
                    18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
                    127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
                    128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
                    129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
                    130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
                    131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
                    132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
                    19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
                    134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
                    135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
                    136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
                    137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
                    138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
                    139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
                    20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
                    141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
                    142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
                    143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
                    144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
                    145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
                    146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
                    21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
                    148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
                    149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
                    150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
                    151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
                    152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
                    153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
                    22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
                    155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
                    156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
                    157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
                    158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
                    159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
                    160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
                    23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
                    162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
                    163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
                    164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
                    165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
                    166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
                    167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
                    24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
                    169-204001942030097220294920811968857670952039875573619824233804820272617541131912
                    170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
                    171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
                    172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
                    173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
                    174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
                    25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
                    176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
                    177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
                    178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
                    179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
                    180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
                    181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
                    26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
                    183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
                    184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
                    185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
                    186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
                    187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
                    188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
                    2718900226029388723887603482286156060752396057377229889735228236469967341122632
                    190112276207076492406723761352302020980242413866467172314721050872381571569371121895
                    19124229212026598242468717472317885899732431675557342330544749462398443465341121132
                    192392308033455472442650588052333750819222449484647512346368448052415315361311120343
                    193416232394664496246061400142349615738712467293737682362192146642432187257281119528
                    194525233985983445247857741475236548065822485102827852378015845232449059153251118687
                    19563623557730239424965408281238134557769250291191802239383954382246593104922111782
                    281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
                    1978642387599402922532467654824130754166725385300983624254869412499674841161116008
                    1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
                    19910100241942578192568394481524448052556525741482787245713433818253341863311114092
                    200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
                    20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
                    202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
                    2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
                    20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
                    2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
                    206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
                    2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
                    208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
                    2092040025785576768274802861526034544505527522391804261537132408270213759281102952
                    30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
                    21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
                    212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
                    21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
                    2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
                    2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
                    216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
                    312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
                    218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
                    21930900273768957172927662748527621036454529303300821277360830998287085655251089212
                    220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
                    221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
                    2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
                    223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
                    32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
                    22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
                    2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
                    22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
                    2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
                    22940160028968214666310729688229207528403531084209838293184529588303957551221072872
                    2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
                    33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
                    2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
                    233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
                    234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
                    23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
                    2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
                    23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
                    342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
                    239502500305595336153286931015530794020352532865118855309008228178320829447191053932
                    2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
                    241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
                    2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
                    243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
                    244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
                    3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
                    2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
                    24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
                    2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
                    24960360032150852564346656514932380512301534646027872324831926768337701343161032392
                    2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
                    251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
                    362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
                    253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
                    254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
                    25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
                    2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
                    25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
                    2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
                    37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
                    2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
                    261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
                    2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
                    263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
                    PDM1
                    PDM 2
                    GDM
                    Intercepting Curves Random Effects are intercept and ctime (=slope)
                    AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
                    17119-7049001103696581094598541182103721201826791109612CURVE
                    120-6947611121270161112530551199690231216229731110695
                    121-6846241138824721130489621217245381230675111111752DM1
                    122-6744891156360261148475751234769171245162931112783
                    123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
                    124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
                    125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
                    18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
                    127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
                    128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
                    129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
                    130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
                    131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
                    132-5732491330669561329825351408282271392375331121663
                    19133-563136134799588134810914142546111407329991122408109459854
                    134-5530251365303181366419991442608571422327091123127GDM
                    135-54291613825914613847579145972468143736663112382
                    136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
                    137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
                    138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
                    139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
                    20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
                    141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
                    142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
                    143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
                    144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
                    145-44193615544281615696253162916098159009623112932
                    146-4318491571507221588260871645932131605602611129727
                    21147-421764158856726160692351662671921621151431130108
                    148-4116811605608281625613191679380351636742691130463
                    149-4016001622630281644329941696057421652376391130792
                    150-3915211639633261663073751712703131668052531131095
                    151-3814441656617221681844621729317481683771111131372
                    152-3713691673582161700642551745900471699532131131623
                    153-361296169052808171946754176245211715335591131848
                    22154-3512251707454981738319591778972371731181491132047
                    155-34115617243628617571987179546128174706983113222
                    156-3310891741251721776104871811918831763000611132367
                    157-321024175812156179503811828345021778973831132488
                    158-319611774972381813998391844739851794989491132583
                    159-309001791804181832985741861103321811047591132652
                    160-298411808616961852000151877435431827148131132695
                    23161-287841825410721871041621893736181843291111132712
                    162-277291842185461890110151910005571859476531132703
                    163-26676185894118190920574192624361875704391132668
                    164-256251875677881928328391942450271891974691132607
                    165-2457618923955619474781195862558190828743113252
                    166-235291909094221966654871974769531924642611132407
                    167-22484192577386198585871990882121941040231132268
                    24168-214411942434482005089592006963351957480291132103
                    169-204001959076082024347542023013221973962791131912
                    170-193611975698662043632552039031731990487731131695
                    171-183241992302222062944622055018882007055111131452
                    172-172892008886762082283752070974672023664931131183
                    173-16256202545228210164994208689912040317191130888
                    174-152252041998782121043192102792172057011891130567
                    25175-1419620585262621404635211865388207374903113022
                    176-131692075034722159910872134484232090528611129847
                    177-12144209152416217938532150283222107350631129448
                    178-111212107994582198886792166050852124215091129023
                    179-101002124445982218415342181787122141121991128572
                    180-9812140878362237970952197492032158071331128095
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                    188-112271652682395389992322002352295193891123343
                    27189002287913882415189142337425022312525191122632
                    190112304156062435015352352816332329898931121895
                    191242320379222454868622368176282347315111121132
                    192392336583362474748952383504872364773731120343
                    193416235276848249465634239880212382274791119528
                    1945252368934582514590792414067972399818291118687
                    19563623850816625345523242930248241740423111782
                    281967492401209722554540872444505632435032611116927
                    197864241731876257455652459677422452703431116008
                    1989812433408782594599192474817852470416691115063
                    199101002449479782614668942489926922488172391114092
                    200111212465531762634765752505004632505970531113095
                    201121442481564722654889622520050982523811111112072
                    202131692497578662675040552535065972541694131111023
                    2920314196251357358269521854255004962559619591109948
                    204152252529549482715423592565001872577587491108847
                    2051625625455063627356557257992278259559783110772
                    206172892561444222755914872594812332613650611106567
                    20718324257736306277620112609670522631745831105388
                    208193612593262882796514392624497352649883491104183
                    209204002609143682816854742639292822668063591102952
                    30210214412625005462837222152654056932686286131101695
                    211224842640848222857616622668789682704551111100412
                    212235292656671962878038152683491072722858531099103
                    21324576267247668289848674269816112741208391097768
                    214256252688262382918962392712799772759600691096407
                    2152667627040290629394651272740708277803543109502
                    216277292719776722959994872741983032796512611093607
                    3121728784273550536298055172756527622815032231092168
                    218298412751214983001135592771040852833594291090703
                    219309002766905583021746542785522722852198791089212
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                    2213210242798229723063049622814392382889535111086152
                    2223310892813863263083741752828780172908266931084583
                    223341156282947778310446094284313662927041191082988
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                    22536129628606497631459805287175538296471703107972
                    2263713692876207223166780872886017732983618611078047
                    227381444289174566318760832900248723002562631076348
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                    2294016002922765483229344342928616623040577991072872
                    2304116812938246863250252952942753533059649331071095
                    332314217642953709223271188622956859083078763111069292
                    2324318492969152563292151352970933273097919331067463
                    233441936298457688331314114298497613117117991065608
                    2344520252999982183334157992998987573136359091063727
                    23546211630153684633552019301296768315564263106182
                    2364722093030735723376272873026916433174968611059887
                    237482304304608396339737093040833823194337031057928
                    342384924013061413183418495993054719853213747891055943
                    2395025003076723383439648143068574523233201191053932
                    2405126013092014563460827353082397833252696931051895
                    2415227043107286723482033623096189783272235111049832
                    2425328093122539863503266953109950373291815731047743
                    243542916313777398352452734312367963311438791045628
                    2445530253152989083545814793137377473331104291043487
                    3524556313631681851635671293315104398335081223104132
                    2465732493183362223588470873164679133370562611039127
                    247583364319852026360983953178282923390355431036908
                    2485934813213659283631235193191855353410190691034663
                    2496036003228779283652657943205396423430068391032392
                    2506137213243880263674107753218906133449988531030095
                    2516238443258962223695584623232384483469951111027772
                    362526339693274025163717088553245831473489956131025423
                    253644096328906908373861954325924713510003591023048
                    2546542253304093983760177593272631373530093491020647
                    25566435633190998637817627328598428355022583101822
                    2566744893334086723803374873299305833570400611015767
                    257684624334905456382501413312596023590617831013288
                    2586947613364003383846680393325854853610877491010783
                    372597049003378933183868373743339082323631179591008252
                    2607150413393843963890094153352278433651524131005695
                    2617251843408735723911841623365443183671911111003112
                    2627353293423608463933616153378576573692340531000503
                    263745476343846218395541774339167863712812390997868
                    PDM1
                    PDM 2
                    GDM

                    MACROSOMIA ASIMMETRICA

                    OBESITY IS INDEPENDENTLY ASSOCIATED WITH FETAL HYPERINSULINEMIABIRTH WEIGHT AND NEWBORN ADIPOSITY

                    Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

                    Fetal growth profiles in diabetic pregnancies

                    08

                    085

                    09

                    095

                    1

                    105

                    11

                    115

                    12

                    125

                    13

                    100 120 140 160 180 200 220 240 260 280

                    Gestational age in days

                    Hea

                    d to

                    abd

                    omin

                    al c

                    ircu

                    mfe

                    renc

                    e ra

                    tio

                    (HC

                    AC

                    rati

                    o)

                    IDDM non-macrosomia

                    IDDM macrosomia

                    DM2 non-macrosomia

                    DM2 macrosomia

                    GDM non-macrosomia

                    GDM macrosomia

                    Birthweightgt90th

                    Type-1-diabetes LGA

                    Type-1 AGA

                    N Hammoud et al UOG 2012

                    Type-2-diabetes LGA

                    GDM LGA

                    Grafiek3

                    Fetal growth profiles in diabetic pregnancies

                    IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                    Gestational age in days

                    Head to abdominal circumference ratio (HCAC ratio)

                    iddm gdm 977

                    IDDM

                    IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

                    Gestational age in days

                    Fetal abdominal circumference (mm)

                    GDM

                    GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

                    Gestational age in days

                    Fetal abdominal circumference (mm)

                    FAC 6 groups

                    Fetal growth profiles in diabetic pregnancies

                    IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM 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macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

                    Gestational age in days

                    Fetal abdominal circumference (mm)

                    HC 6 groups

                    Fetal growth profiles in diabetic pregnancies

                    IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

                    Gestational age in days

                    Head circumference (mm)

                    HCAC 6 groups

                    Fetal growth profiles in diabetic pregnancies

                    IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                    Gestational age in days

                    Head to abdominal circumference ratio (HCAC ratio)

                    Model

                    Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

                    Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

                    LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

                    Iperglicemia e rischio di morte fetale a termine di gravidanza

                    Estimated rate of stillbirth in diabetic women 1920-2000

                    Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                    4 of all stillbirths remain attributable to diabetes

                    Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                    bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                    Adverse outcome

                    HbA1C gt7

                    1 increase in A1Ccorresponded to 55 increased

                    risk of adverse outcome

                    The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                    gestation particularly in the presence of fetal macrosomia

                    fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                    Langer O 1995

                    100 mgdLfor stillbirth

                    Diabetic patients n = 271691

                    Am J Obstet Gynecol 2002

                    The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                    4873 diabetic women

                    pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                    outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                    bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                    GDMbull dysglycemia was more difficult to manage

                    2016

                    Differences in placental pathologyaccording to diabetes types

                    Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                    GDM is associated with a greater rate of villous immaturity

                    0102030405060708090

                    100GDMDMIDMII

                    o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                    A retrospective study on 175 placentas with DVM vs 175 controls

                    Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                    Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                    Pathophysiology of fetal compromise in diabetic pregnancy

                    The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                    Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                    Bjork 1984Nylund 1982Siddiqui 2003

                    A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                    STILLBIRTH RISK

                    BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                    OBESITArsquo E MORTE FETALE

                    6-7 per unit BMI for BMI gt 23

                    Tennant PWG Am J Obstet Gynecol 2007

                    HYPERINSULINISMHYPERANDROGENISM

                    IMPAIRED PLACENTATION

                    THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                    Cakmak and Taylor Hum Reprod Update 2011

                    Makieva S Hum Reprod Update 2014

                    Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                    Hotamisligil GS Nature 2006

                    LeptinCRH

                    Urocortin 3IL-6

                    INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                    INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                    Adiponectina Insulin LeptinTNFα IL-6

                    PLACENTAL ALTERATIONIN GENE EXPRESSION

                    PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                    CollagenaseCervical ripening

                    FFA

                    OXIDATIVE STRESS

                    PREVENZIONE STILLBIRTH

                    PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                    MORBIDITAgrave NEONATALE

                    AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                    TIMING E MODALITArsquo DEL PARTO

                    Induzione o attesa

                    INDUZIONE DEL TRAVAGLIO

                    Quando fare un TC elettivo

                    gt 4000 grgt 4500 gr gt 5000 gr

                    ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                    425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                    No differenza in TC e outcome perinatale

                    200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                    No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                    RCT INDUZIONE VS ATTESA in GDM

                    RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                    2014

                    1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                    2 Patients well controlled on insulin should probably be delivered by the due date

                    3 Poorly controlled GDMrsquos using insulin require individual judgment

                    Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                    1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                    2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                    3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                    cesarean delivery when the estimated fetal weight is ge 4500 g

                    MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                    MODALITAgrave E TIMING DEL PARTO nel GDM

                    GMD in terapia insulinicaBen controllato

                    +Condizioni fetali rassicuranti

                    MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                    GDM in terapia nutrizionalecon profili glicemici ottimali

                    +Feto AGA

                    MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                    Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                    EFW lt 4000g LGAControllo metabolico non

                    ottimale

                    4000g lt EFW gt 4500g EFW ge 4500g

                    Programmare TC elettivo

                    Parto vaginale indotto a 38-39 sett

                    Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                    MODALITAgrave E TIMING DEL PARTO nel GDM

                    IN BASE AL PESO FETALE STIMATO

                    - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                    - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                    - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                    ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                    Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                    The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                    A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                    If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                    Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                    GDM and the Use of Betamethasone

                    bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                    bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                    bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                    Society of Obstetricians and Gynaecologists of Canada

                    The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                    late preterm delivery between 24 to 36 weeksrsquo gestation

                    ASSISTENZA IN TRAVAGLIO

                    - MONITORAGGIO FETALE CONTINUO

                    - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                    MANTENERE GLICEMIA gt70 E lt 126

                    (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                    GDM

                    - Intravenous infusion of regular insulin titrated and glucose

                    - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                    (ACOG 2005)

                    ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                    Venere di Willendorf

                    Thank you for your attention

                    Pathophysiology of fetal compromise in diabetic pregnancy

                    Islet cell hyperplasia common in stillborn IDMs

                    There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                    Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                    Salvesen 1993Hay 1989Chukwuma 2001

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                    • Diapositiva numero 7
                    • Birth weight distribution in diabetic pregnancies
                    • Diapositiva numero 9
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                    • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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                    • Differences in placental pathology according to diabetes types
                    • Diapositiva numero 21
                    • Pathophysiology of fetal compromise in diabetic pregnancy
                    • Diapositiva numero 23
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                    • Diapositiva numero 32
                    • Diapositiva numero 33
                    • Diapositiva numero 34
                    • Diapositiva numero 35
                    • Diapositiva numero 36
                    • GDM and the Use of Betamethasone
                    • Diapositiva numero 38
                    • Diapositiva numero 39
                    • Diapositiva numero 40
                    • Pathophysiology of fetal compromise in diabetic pregnancy
                      Intercepting Curves Random Effects are intercept and ctime (=slope)
                      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                      17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
                      120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
                      121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                      122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
                      123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
                      124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
                      125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
                      18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
                      127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
                      128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
                      129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
                      130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
                      131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
                      132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
                      19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
                      134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
                      135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
                      136-5328091174390921119170838111405379131153817241115039368311728882411124487
                      137-5227041172850541118937155111396122561152048811114915830911711801311125128
                      138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
                      139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                      20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
                      141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
                      142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
                      143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
                      144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
                      145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
                      146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
                      21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
                      148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
                      149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
                      150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
                      151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
                      152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
                      153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
                      22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
                      155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
                      156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
                      157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
                      158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
                      159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
                      160-298411137421801113562446111183221451111374921112074470711318936011132695
                      23161-287841135881421113328763111173964881109606491111950933311301854911132712
                      162-277291134341041113095080111164708311107838061111827395911284773811132703
                      163-266761132800661112861397111155451741106069631111703858511267692711132668
                      164-256251131260281112627714111146195171104301201111580321111250611611132607
                      165-2457611297199011123940311111369386110253277111145678371123353051113252
                      166-235291128179521112160348111127682031100764341111333246311216449411132407
                      167-224841126639141111926665111118425461098995911111209708911199368311132268
                      24168-214411125098761111692982111109168891097227481111086171511182287211132103
                      169-204001123558381111459299111099912321095459051110962634111165206111131912
                      170-193611122018001111225616111090655751093690621110839096711148125011131695
                      171-183241120477621110991933111081399181091922191110715559311131043911131452
                      172-172891118937241110758250111072142611090153761110592021911113962811131183
                      173-162561117396861110524567111062886041088385331110468484511096881711130888
                      174-152251115856481110290884111053629471086616901110344947111079800611130567
                      25175-1419611143161011100572011110443729108484847111022140971106271951113022
                      176-131691112775721109823518111035116331083080041110097872311045638411129847
                      177-121441111235341109589835111025859761081311611109974334911028557311129448
                      178-111211109694961109356152111016603191079543181109850797511011476211129023
                      179-101001108154581109122469111007346621077774751109727260110994395111128572
                      180-9811106614201108888786110998090051076006321109603722710977314011128095
                      181-8641105073821108655103110988833481074237891109480185310960232911127592
                      26182-7491103533441108421420110979576911072469461109356647910943151811127063
                      183-6361101993061108187737110970320341070701031109233110510926070711126508
                      184-5251100452681107954054110961063771068932601109109573110908989611125927
                      185-41610989123011077203711109518072106716417110898603571089190851112532
                      186-391097371921107486688110942550631065395741108862498310874827411124687
                      187-241095831541107253005110933294061063627311108738960910857746311124028
                      188-111094291161107019322110924037491061858881108615423510840665211123343
                      27189001092750781106785639110914780921060090451108491886110823584111122632
                      190111091210401106551956110905524351058322021108368348710806503011121895
                      191241089670021106318273110896267781056553591108244811310789421911121132
                      192391088129641106084590110887011211054785161108121273910772340811120343
                      1934161086589261105850907110877754641053016731107997736510755259711119528
                      1945251085048881105617224110868498071051248301107874199110738178611118687
                      19563610835085011053835411108592415104947987110775066171072109751111782
                      281967491081968121105149858110849984931047711441107627124310704016411116927
                      1978641080427741104916175110840728361045943011107503586910686935311116008
                      1989811078887361104682492110831471791044174581107380049510669854211115063
                      199101001077346981104448809110822215221042406151107256512110652773111114092
                      200111211075806601104215126110812958651040637721107132974710635692011113095
                      201121441074266221103981443110803702081038869291107009437310618610911112072
                      202131691072725841103747760110794445511037100861106885899910601529811111023
                      29203141961071185461103514077110785188941035332431106762362510584448711109948
                      204152251069645081103280394110775932371033564001106638825110567367611108847
                      2051625610681047011030467111107666758103179557110651528771055028651110772
                      206172891066564321102813028110757419231030027141106391750310533205411106567
                      207183241065023941102579345110748162661028258711106268212910516124311105388
                      208193611063483561102345662110738906091026490281106144675510499043211104183
                      209204001061943181102111979110729649521024721851106021138110481962111102952
                      30210214411060402801101878296110720392951022953421105897600710464881011101695
                      211224841058862421101644613110711136381021184991105774063310447799911100412
                      212235291057322041101410930110701879811019416561105650525910430718811099103
                      213245761055781661101177247110692623241017648131105526988510413637711097768
                      214256251054241281100943564110683366671015879701105403451110396556611096407
                      2152667610527009011007098811106741101101411127110527991371037947551109502
                      216277291051160521100476198110664853531012342841105156376310362394411093607
                      31217287841049620141100242515110655596961010574411105032838910345313311092168
                      218298411048079761100008832110646340391008805981104909301510328232211090703
                      219309001046539381099775149110637083821007037551104785764110311151111089212
                      220319611044999001099541466110627827251005269121104662226710294070011087695
                      2213210241043458621099307783110618570681003500691104538689310276988911086152
                      2223310891041918241099074100110609314111001732261104415151910259907811084583
                      2233411561040377861098840417110600057540999963831104291614510242826711082988
                      322243512251038837481098606734110590800970998195401104168077110225745611081367
                      22536129610372971010983730511105815444099642697110404453971020866451107972
                      2263713691035756721098139368110572287830994658541103921002310191583411078047
                      2273814441034216341097905685110563031260992890111103797464910174502311076348
                      2283915211032675961097672002110553774690991121681103673927510157421211074623
                      2294016001031135581097438319110544518120989353251103550390110140340111072872
                      2304116811029595201097204636110535261550987584821103426852710123259011071095
                      332314217641028054821096970953110526004980985816391103303315310106177911069292
                      2324318491026514441096737270110516748410984047961103179777910089096811067463
                      2334419361024974061096503587110507491840982279531103056240510072015711065608
                      2344520251023433681096269904110498235270980511101102932703110054934611063727
                      23546211610218933010960362211104889787097874267110280916571003785351106182
                      2364722091020352921095802538110479722130976974241102685628310020772411059887
                      2374823041018812541095568855110470465560975205811102562090910003691311057928
                      342384924011017272161095335172110461208990973437381102438553509986610211055943
                      2395025001015731781095101489110451952420971668951102315016109969529111053932
                      2405126011014191401094867806110442695850969900521102191478709952448011051895
                      2415227041012651021094634123110433439280968132091102067941309935366911049832
                      2425328091011110641094400440110424182710966363661101944403909918285811047743
                      2435429161009570261094166757110414926140964595231101820866509901204711045628
                      2445530251008029881093933074110405669570962826801101697329109884123611043487
                      352455631361006489501093699391110396413096105837110157379170986704251104132
                      2465732491004949121093465708110387156430959289941101450254309849961411039127
                      2475833641003408741093232025110377899860957521511101326716909832880311036908
                      2485934811001868361092998342110368643290955753081101203179509815799211034663
                      2496036001000327981092764659110359386720953984651101079642109798718111032392
                      2506137210998787601092530976110350130150952216221100956104709781637011030095
                      2516238440997247221092297293110340873580950447791100832567309764555911027772
                      362526339690995706841092063610110331617010948679361100709029909747474811025423
                      2536440960994166461091829927110322360440946910931100585492509730393711023048
                      2546542250992626081091596244110313103870945142501100461955109713312611020647
                      25566435609910857010913625611103038473094337407110033841770969623151101822
                      2566744890989545321091128878110294590730941605641100214880309679150411015767
                      2576846240988004941090895195110285334160939837211100091342909662069311013288
                      2586947610986464561090661512110276077590938068781099967805509644988211010783
                      372597049000984924181090427829110266821020936300351099844268109627907111008252
                      2607150410983383801090194146110257564450934531921099720730709610826011005695
                      2617251840981843421089960463110248307880932763491099597193309593744911003112
                      2627353290980303041089726780110239051310930995061099473655909576663811000503
                      2637454760978762661089493097110229794740929226631099350118509559582710997868
                      PDM1
                      PDM 2
                      GDM
                      Intercepting Curves Random Effects are intercept and ctime (=slope)
                      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                      17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
                      120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
                      121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                      122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
                      123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
                      124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
                      125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
                      18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
                      127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
                      128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
                      129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
                      130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
                      131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
                      132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
                      19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
                      134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
                      135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
                      136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
                      137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
                      138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
                      139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                      20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
                      141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
                      142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
                      143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
                      144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
                      145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
                      146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
                      21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
                      148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
                      149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
                      150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
                      151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
                      152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
                      153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
                      22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
                      155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
                      156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
                      157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
                      158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
                      159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
                      160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
                      23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
                      162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
                      163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
                      164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
                      165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
                      166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
                      167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
                      24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
                      169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
                      170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
                      171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
                      172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
                      173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
                      174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
                      25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
                      176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
                      177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
                      178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
                      179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
                      180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
                      181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
                      26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
                      183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
                      184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
                      185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
                      186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
                      187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
                      188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
                      27189002414769727245863358855247378933256248771281205245293918283252156109031122632
                      19011242848834431247298968107248885247499250207813572466295047242534796182011121895
                      191242442206961622487345773592503915617422516443459352479650911652548031273721121132
                      1923924559255789325017018661125189787598525308087832493006776062561266365431120343
                      1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
                      194525248336281355253041405115254910504471255953943032519718504882587736548851118687
                      195636249708143086254477014367256416818714257390475395253307436929260097164056111782
                      2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
                      19786425245186654825734823287125942944722602635401252559786098112627441823981116008
                      198981253823728279258783842123260935761443261700072492573141962522640676915691115063
                      1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
                      20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
                      201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
                      20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
                      29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
                      20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
                      20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
                      2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
                      20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
                      20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
                      2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
                      3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
                      211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
                      2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
                      213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
                      21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
                      21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
                      2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
                      3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
                      21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
                      2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
                      22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
                      2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
                      222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
                      2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
                      32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
                      225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
                      2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
                      227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
                      228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
                      22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
                      230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
                      332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
                      23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
                      2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
                      234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
                      235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
                      23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
                      237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
                      34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
                      23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
                      240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
                      2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
                      242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
                      2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
                      244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
                      35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
                      24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
                      247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
                      248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
                      24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
                      250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
                      2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
                      3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
                      2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
                      254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
                      255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
                      25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
                      257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
                      258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
                      37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
                      260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
                      2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
                      262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
                      2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
                      PDM1
                      PDM 2
                      GDM
                      Intercepting Curves Random Effects are intercept and ctime (=slope)
                      AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                      17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
                      120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
                      121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                      122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
                      123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
                      124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
                      125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
                      18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
                      127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
                      128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
                      129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
                      130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
                      131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
                      132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
                      19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
                      134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
                      135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
                      136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
                      137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
                      138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
                      139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
                      20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
                      141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
                      142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
                      143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
                      144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
                      145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
                      146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
                      21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
                      148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
                      149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
                      150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
                      151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
                      152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
                      153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
                      22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
                      155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
                      156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
                      157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
                      158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
                      159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
                      160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
                      23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
                      162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
                      163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
                      164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
                      165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
                      166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
                      167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
                      24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
                      169-204001942030097220294920811968857670952039875573619824233804820272617541131912
                      170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
                      171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
                      172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
                      173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
                      174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
                      25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
                      176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
                      177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
                      178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
                      179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
                      180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
                      181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
                      26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
                      183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
                      184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
                      185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
                      186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
                      187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
                      188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
                      2718900226029388723887603482286156060752396057377229889735228236469967341122632
                      190112276207076492406723761352302020980242413866467172314721050872381571569371121895
                      19124229212026598242468717472317885899732431675557342330544749462398443465341121132
                      192392308033455472442650588052333750819222449484647512346368448052415315361311120343
                      193416232394664496246061400142349615738712467293737682362192146642432187257281119528
                      194525233985983445247857741475236548065822485102827852378015845232449059153251118687
                      19563623557730239424965408281238134557769250291191802239383954382246593104922111782
                      281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
                      1978642387599402922532467654824130754166725385300983624254869412499674841161116008
                      1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
                      19910100241942578192568394481524448052556525741482787245713433818253341863311114092
                      200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
                      20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
                      202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
                      2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
                      20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
                      2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
                      206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
                      2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
                      208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
                      2092040025785576768274802861526034544505527522391804261537132408270213759281102952
                      30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
                      21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
                      212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
                      21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
                      2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
                      2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
                      216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
                      312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
                      218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
                      21930900273768957172927662748527621036454529303300821277360830998287085655251089212
                      220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
                      221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
                      2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
                      223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
                      32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
                      22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
                      2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
                      22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
                      2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
                      22940160028968214666310729688229207528403531084209838293184529588303957551221072872
                      2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
                      33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
                      2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
                      233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
                      234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
                      23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
                      2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
                      23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
                      342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
                      239502500305595336153286931015530794020352532865118855309008228178320829447191053932
                      2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
                      241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
                      2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
                      243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
                      244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
                      3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
                      2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
                      24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
                      2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
                      24960360032150852564346656514932380512301534646027872324831926768337701343161032392
                      2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
                      251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
                      362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
                      253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
                      254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
                      25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
                      2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
                      25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
                      2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
                      37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
                      2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
                      261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
                      2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
                      263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
                      PDM1
                      PDM 2
                      GDM
                      Intercepting Curves Random Effects are intercept and ctime (=slope)
                      AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
                      17119-7049001103696581094598541182103721201826791109612CURVE
                      120-6947611121270161112530551199690231216229731110695
                      121-6846241138824721130489621217245381230675111111752DM1
                      122-6744891156360261148475751234769171245162931112783
                      123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
                      124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
                      125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
                      18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
                      127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
                      128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
                      129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
                      130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
                      131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
                      132-5732491330669561329825351408282271392375331121663
                      19133-563136134799588134810914142546111407329991122408109459854
                      134-5530251365303181366419991442608571422327091123127GDM
                      135-54291613825914613847579145972468143736663112382
                      136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
                      137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
                      138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
                      139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
                      20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
                      141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
                      142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
                      143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
                      144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
                      145-44193615544281615696253162916098159009623112932
                      146-4318491571507221588260871645932131605602611129727
                      21147-421764158856726160692351662671921621151431130108
                      148-4116811605608281625613191679380351636742691130463
                      149-4016001622630281644329941696057421652376391130792
                      150-3915211639633261663073751712703131668052531131095
                      151-3814441656617221681844621729317481683771111131372
                      152-3713691673582161700642551745900471699532131131623
                      153-361296169052808171946754176245211715335591131848
                      22154-3512251707454981738319591778972371731181491132047
                      155-34115617243628617571987179546128174706983113222
                      156-3310891741251721776104871811918831763000611132367
                      157-321024175812156179503811828345021778973831132488
                      158-319611774972381813998391844739851794989491132583
                      159-309001791804181832985741861103321811047591132652
                      160-298411808616961852000151877435431827148131132695
                      23161-287841825410721871041621893736181843291111132712
                      162-277291842185461890110151910005571859476531132703
                      163-26676185894118190920574192624361875704391132668
                      164-256251875677881928328391942450271891974691132607
                      165-2457618923955619474781195862558190828743113252
                      166-235291909094221966654871974769531924642611132407
                      167-22484192577386198585871990882121941040231132268
                      24168-214411942434482005089592006963351957480291132103
                      169-204001959076082024347542023013221973962791131912
                      170-193611975698662043632552039031731990487731131695
                      171-183241992302222062944622055018882007055111131452
                      172-172892008886762082283752070974672023664931131183
                      173-16256202545228210164994208689912040317191130888
                      174-152252041998782121043192102792172057011891130567
                      25175-1419620585262621404635211865388207374903113022
                      176-131692075034722159910872134484232090528611129847
                      177-12144209152416217938532150283222107350631129448
                      178-111212107994582198886792166050852124215091129023
                      179-101002124445982218415342181787122141121991128572
                      180-9812140878362237970952197492032158071331128095
                      181-8642157291722257553622213165582175063111127592
                      26182-7492173686062277163352228807772192097331127063
                      183-636219006138229680014224441862209173991126508
                      184-5252206417682316463992259998072226293091125927
                      185-41622227549623361549227554618224345463112532
                      186-392239073222355872872291062932260658611124687
                      187-24225537246237561792306548322277905031124028
                      188-112271652682395389992322002352295193891123343
                      27189002287913882415189142337425022312525191122632
                      190112304156062435015352352816332329898931121895
                      191242320379222454868622368176282347315111121132
                      192392336583362474748952383504872364773731120343
                      193416235276848249465634239880212382274791119528
                      1945252368934582514590792414067972399818291118687
                      19563623850816625345523242930248241740423111782
                      281967492401209722554540872444505632435032611116927
                      197864241731876257455652459677422452703431116008
                      1989812433408782594599192474817852470416691115063
                      199101002449479782614668942489926922488172391114092
                      200111212465531762634765752505004632505970531113095
                      201121442481564722654889622520050982523811111112072
                      202131692497578662675040552535065972541694131111023
                      2920314196251357358269521854255004962559619591109948
                      204152252529549482715423592565001872577587491108847
                      2051625625455063627356557257992278259559783110772
                      206172892561444222755914872594812332613650611106567
                      20718324257736306277620112609670522631745831105388
                      208193612593262882796514392624497352649883491104183
                      209204002609143682816854742639292822668063591102952
                      30210214412625005462837222152654056932686286131101695
                      211224842640848222857616622668789682704551111100412
                      212235292656671962878038152683491072722858531099103
                      21324576267247668289848674269816112741208391097768
                      214256252688262382918962392712799772759600691096407
                      2152667627040290629394651272740708277803543109502
                      216277292719776722959994872741983032796512611093607
                      3121728784273550536298055172756527622815032231092168
                      218298412751214983001135592771040852833594291090703
                      219309002766905583021746542785522722852198791089212
                      220319612782577163042384552799973232870845731087695
                      2213210242798229723063049622814392382889535111086152
                      2223310892813863263083741752828780172908266931084583
                      223341156282947778310446094284313662927041191082988
                      322243512252845073283125207192857461672945857891081367
                      22536129628606497631459805287175538296471703107972
                      2263713692876207223166780872886017732983618611078047
                      227381444289174566318760832900248723002562631076348
                      2283915212907265083208462792914448353021549091074623
                      2294016002922765483229344342928616623040577991072872
                      2304116812938246863250252952942753533059649331071095
                      332314217642953709223271188622956859083078763111069292
                      2324318492969152563292151352970933273097919331067463
                      233441936298457688331314114298497613117117991065608
                      2344520252999982183334157992998987573136359091063727
                      23546211630153684633552019301296768315564263106182
                      2364722093030735723376272873026916433174968611059887
                      237482304304608396339737093040833823194337031057928
                      342384924013061413183418495993054719853213747891055943
                      2395025003076723383439648143068574523233201191053932
                      2405126013092014563460827353082397833252696931051895
                      2415227043107286723482033623096189783272235111049832
                      2425328093122539863503266953109950373291815731047743
                      243542916313777398352452734312367963311438791045628
                      2445530253152989083545814793137377473331104291043487
                      3524556313631681851635671293315104398335081223104132
                      2465732493183362223588470873164679133370562611039127
                      247583364319852026360983953178282923390355431036908
                      2485934813213659283631235193191855353410190691034663
                      2496036003228779283652657943205396423430068391032392
                      2506137213243880263674107753218906133449988531030095
                      2516238443258962223695584623232384483469951111027772
                      362526339693274025163717088553245831473489956131025423
                      253644096328906908373861954325924713510003591023048
                      2546542253304093983760177593272631373530093491020647
                      25566435633190998637817627328598428355022583101822
                      2566744893334086723803374873299305833570400611015767
                      257684624334905456382501413312596023590617831013288
                      2586947613364003383846680393325854853610877491010783
                      372597049003378933183868373743339082323631179591008252
                      2607150413393843963890094153352278433651524131005695
                      2617251843408735723911841623365443183671911111003112
                      2627353293423608463933616153378576573692340531000503
                      263745476343846218395541774339167863712812390997868
                      PDM1
                      PDM 2
                      GDM

                      Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio

                      Fetal growth profiles in diabetic pregnancies

                      08

                      085

                      09

                      095

                      1

                      105

                      11

                      115

                      12

                      125

                      13

                      100 120 140 160 180 200 220 240 260 280

                      Gestational age in days

                      Hea

                      d to

                      abd

                      omin

                      al c

                      ircu

                      mfe

                      renc

                      e ra

                      tio

                      (HC

                      AC

                      rati

                      o)

                      IDDM non-macrosomia

                      IDDM macrosomia

                      DM2 non-macrosomia

                      DM2 macrosomia

                      GDM non-macrosomia

                      GDM macrosomia

                      Birthweightgt90th

                      Type-1-diabetes LGA

                      Type-1 AGA

                      N Hammoud et al UOG 2012

                      Type-2-diabetes LGA

                      GDM LGA

                      Grafiek3

                      Fetal growth profiles in diabetic pregnancies

                      IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                      Gestational age in days

                      Head to abdominal circumference ratio (HCAC ratio)

                      iddm gdm 977

                      IDDM

                      IDDM lt9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631103696580000000211212701600000001113882472000000011156360261173876780000000111913742812088527612263122200000001124375266000000011261174080000000112785764800000001129595986000000011313324220000000113306695613479958813653031799999999138259146000000021399860720000000114171109614343421800000002145155438146874755999999991485921720000000115030768600000002152021298153733008000000041554428159999999915715072200000003158856726000000011605608280000000116226302799999999163963326000000021656617221673582160000000316905280817074549800000003172436286174125172000000021758121559999999917749723800000001179180418180861696000000021825410719999999918421854600000003185894117999999991875677880000000118923955599999999190909422000000011925773860000000219424344800000003195907608000000011975698660000000219923022200000003200888676000000032025452280000000120419987800000001205852626000000012075034720000000220915241600000002210799458000000022124445980000000121408783600000001215729172000000012173686060000000321900613800000002220641768000000012222754962239073220000000222553724600000001227165268000000032287913880000000123041560600000003232037922000000012336583360000000223527684823689345800000001238508166000000022401209720000000224173187624334087824494797800000001246553176000000012481564720000000124975786600000001251357358252954948254550636256144422000000022577363060000000125932628799999998260914368000000022625005459999999926408482200000003265667195999999992672476680000000326882623799999999270402906000000032719776719999999827355053600000002275121497999999972766905580000000127825771600000002279822972000000052813863262829477780000000328450732799999997286064976287620722289174566000000032907265080000000229227654800000005293824685999999992953709220000000129691525629845768800000002299998218000000013015368460000000330307357200000001304608396000000033061413180000000130767233800000002309201456000000063107286720000000231225398631377739800000001315298908000000043168185160000000531833622199999996319852026000000023213659280000000532287792832438802599999997325896222000000023274025160000000532890690800000004330409398000000013319099863334086720000000233490545600000002336400337999999983378933180000000233938439600000004340873572000000023423608459999999834384621800000002IDDM =gt 9771191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631094598540000000211125305500000002113048962000000021148475750000000211664889400000003118452919000000021202596500000000212206908700000002123881230000000021256960790000000312751363400000002129333895000000011311568620000000213298253500000001134810914000000031366419990000000313847579000000002140312287000000031421514900000000214399339900000001145838014000000021476853350000000114953536200000002151388095000000021532435340000000115510167900000002156962530000000021588260870000000316069235000000003162561319000000031644329940000000416630737500000004168184462000000021700642550000000317194675400000003173831959000000011757198700000000117761048700000003179503810000000021813998390000000118329857400000003185200015000000041871041620000000318901101500000001190920574000000021928328390000000419474781000000002196665487000000011985858700000000320050895900000003202434754000000032043632550000000120629446200000001208228375000000032101649940000000421210431900000003214046350000000022159910870000000221793853000000001219888679000000022218415340000000222379709500000001225755362000000022277163350000000222968001400000003231646399000000032336154900000000223558728700000003237561790000000032395389990000000224151891400000002243501535000000022454868620000000324747489500000003249465634000000022514590790000000325345523000000003255454087000000022574556499999999925945991900000001261466893999999972634765749999999726548896200000001267504054999999992695218540000000227154235899999998273565569999999982755914869999999727762011000000001279651438999999982816854742837222150000000128576166228780381499999999289848674000000022918962389999999829394650999999999295999486999999992980551699999999830011355900000001302174653999999983042384549999999930630496199999999308374174999999983104460940000000231252071899999999314598053166780873187608332084627899999998322934434000000013250252949999999732711886199999998329215134999999983313141140000000233341579899999999335520190000000013376272870000000233973709000000002341849599000000013439648139999999934608273500000001348203361999999973503266949999999735245273400000002354581479356712929999999973588470869999999936098394999999999363123518999999993652657939999999736741077536955846200000002371708854999999973738619539999999737601775900000001378176269999999993803374870000000138250141000000002384668039000000023868373740000000138900941499999999391184162000000013933616149999999739554177399999998

                      Gestational age in days

                      Fetal abdominal circumference (mm)

                      GDM

                      GDM lt97711912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311821037200000001119969022999999991217245379999999812347691712522615999999999126972266999999991287152381304550730000000313219177200000001133925334999999991356557620000000113738305299999999139107207999999991408282271425461114426085699999999145972468000000021476809429999999814938628199999999151088484999999991527875520000000115448348299999998156176278157865937000000031595524616123584700000001162916098000000011645932129999999916626719199999999167938035000000011696057419999999917127031299999999172931748174590047176245209999999991778972370000000217954612799999998181191882999999991828345019999999918447398500000003186110332187743542999999991893736180000000219100055700000001192624361942450270000000219586255800000001197476952999999981990882122006963352023013222039031730000000120550188800000001207097467000000022086899121027921699999999211865388213448422999999992150283222166050852181787119999999921974920300000002221316558000000012228807769999999922444186000000002225999807227554617999999982291062929999999923065483223220023500000002233742502235281633236817628000000012383504869999999923988021000000001241406797000000012429302480000000124445056300000002245967742000000022474817852489926920000000125050046325200509799999998253506597255004959999999982565001869999999825799227825948123300000003260967051999999972624497349999999826392928226540569299999999266878967999999992683491072698161100000000427127997699999997272740707999999982741983029999999527565276227710408527855227200000002279997322999999992814392379999999928287801728431365999999997285746167000000012871755380000000228860177300000004290024872000000022914448350000000129286166199999997294275353295685907999999982970933270000000429849761000000001299898756999999993012967679999999930269164330408338200000003305471985000000023068574520000000230823978299999999309618978000000033109950369999999731236795999999998313737747000000013151043980000000631646791300000001317828292000000033191855349999999632053964200000001321890613000000033232384480000000132458314732592471327263137000000033285984279999999632993058300000001331259602000000033325854850000000633390823233522784300000001336544317999999983378576570000000233916786000000002GDM =gt 977119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120182679000000011216229731230675110000000112451629300000002125969319127426589000000011288881031303538609999999913182386300000002133298109000000011347765991362593330000000313774631100000002139237533000000011407329990000000114223270914373666299999999145244861000000011467573030000000114827398914979491899999999151320092999999991528495109999999815438317315592107899999999157463229000000011590096231605602611621151430000000216367426900000001165237639166805253000000021683771110000000116995321300000003171533559000000031731181489999999917470698300000001176300061177897383000000021794989490000000118110475918271481300000002184329110999999981859476531875704389999999918919746899999998190828743192464260999999991941040230000000119574802919739627900000002199048773000000012007055112023664930000000220403171900000001205701189207374902999999992090528610000000121073506321242150900000001214112199215807133000000022175063110000000121920973300000003220917399000000022226293090000000122434546322606586100000001227790503229519389000000022312525190000000123298989300000002234731511000000012364773730000000323822747900000002239981829000000032417404229999999924350326100000001245270343247041669000000012488172392505970530000000225238111125416941300000002255961959000000012577587489999999725955978299999998261365060999999972631745829999999826498834900000003266806358999999992686286130000000327045511099999999272285853000000032741208389999999927596006900000003277803543000000052796512610000000328150322300000005283359429000000032852198790000000528708457300000003288953510999999992908266930000000329270411899999999294585788999999982964717029999999929836186099999998300256262999999993021549089999999830405779899999999305964933000000033078763109999999930979193300000003311711798999999983136359090000000331556426300000004317496861000000023194337030000000432137478900000002323320119000000033252696929999999632722351100000003329181572999999963311438790000000333311042900000001335081223000000023370562610000000133903554300000002341019069343006839000000013449988533469951110000000134899561299999999351000359353009348999999993550225833570400610000000435906178299999999361087749000000033631179590000000436515241300000002367191110999999983692340530000000237128123899999997

                      Gestational age in days

                      Fetal abdominal circumference (mm)

                      FAC 6 groups

                      Fetal growth profiles in diabetic pregnancies

                      IDDM non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311463706227116228381219117819700168119411019117000011210023380660000112259365701500001124184975964125776294913127367613862128958932811000011305502517600000113214157070900001133732889658135324208607136915527556138506846505140098165454141689484402999991432808033520000214487212230099999146463441250000021480547601989999914964607914800001151237398096999981528287170460000115442003599500001156011354944157602673893159193992842160785311791162376630741639679496889999916555926863799999167150587587000021687419065359999917033322548500001171924544433999981735158633830000117510718233200001176698501281000011782898202317988113917918147245812818306377707718465509602618624641497499999187837733923999991894290528729999919102037182200002192611690770999991942030097200000119579432866900001197385647618000011989769665670000120056828551620215960446520375092341420534224236320693356131199999208524880260999992101161992099999921170751815899999213298837107999992148901560570000121648147500600001218072793955000012196641129040000122125543185322284675080222443806975122602938872276207076492292120265979999923080334554699999232394664495999992339859834449999923557730239399999237168621342999982387599402920000124035125924100001241942578190000012435338971392451252160882467165350372483078539862498991729352514904918839999925308181083299999254673129781999992562644487310000225785576767999999259447086629000012610384055779999826262972452700001264221043475999982658123624252674036813739999726899500032327058631927199997272177638221273768957170000022753602761189999927695159506800002278542914016999992801342329660000128172555191499998283316870864000012849081898129999828649950876228809082771099997289682146662912734656090000329286478455829445610350699997296047422455999992976387414050000229923006035399999300821379303000013024126982519999830400401720100001305595336149999983071866550990000130877797404799998310369292997311960611945999973135519308953151432498440000231673456879299999318325887741999963199172066909999932150852564000002323099844588999993246911635380000132628248248699998327873801436000013294651203849999833105643933433264775828299997334239077232335830396180999973374217151333901303407900002340604353027999993421956719769999634378699092599999IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631149421065111672301552711850392454412028483356112206574257812384665159512562756061212740846962912918937864599999130970287662999991327511966799999913453210569699999136313014713999991380939237309999913987483274799999141655741765000021434366507820000214521755979900001146998468816000011487793778330000115056028685000001152341195867000011541221048840000115590301390100001157683922918000011594648319350000116124574095200001163026649969164807558986166588468003168369377021701502860371719311950541737121040711754930130881772739221051790548311221808357401389999918261664915599999184397558172999991861784671899999918795937620699999189740285223999991915211942409999919330210325799999195083012274999991968639212919999919864483030899999200425739325999982022066483429999820398755735999998205768466376999982075493753939999820933028441099998211111193427999982128921024449999821467301146199998216453920479218234829496220015738513221796647532235775565472253584655642271393745812289202835982307011926152324821016322342630106489999923604391966599999237824828682999992396057376999999924138664671699999243167555733999992449484647509999924672937376799999248510282784999992502911918019999925207210081899998253853009835999982556339188529999825741482787000001259195736887000012609766459040000126275755492100001264538463938000012663193729550000126810028197226988119098927166210000627344300902327522391804277004827057278785736074280566645091282347554108284128463125285909372142287690281158999992894711901759999929125209919299999293033008209999992948139172269999929659482624399999298375735260999993001566442779999930193755329499999303718462311999993054993713289999830728028034599998309061189362999983108420983799999831262300739699998314403916413999983161848254309999831796573444799998319746643464999983215275524819999832330846149899997325089370515999973268702795329999732865118854999997330432097566999973322130065839999733399391560099997335774824617999973375557336349999733933664265200002341117551669000023428984606860000234467936970300002346460278720000023482411877370000235002209675400002351803005771000023535839147880000235536482380500001357145732822000013589266418390000136070755085600001362488459873000013642693688900000136605027790700001367831186924000013696120959410000137139300495800001GDM non-macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263119123845098120706214957000011222885848160000112387095467500001125453324534000021270356943930000112861806425200001130200434110999991317828039713336517382900001134947543688136529913547000011381122834060000213969465326514127702312400001142859392983000021444417628421460241327010000114760650256000002149188872419000011507712422780000215235361213700003153935981996000011555183518549999915710072171415868309157300001160265461432161847831291000011634302011500000216501257100916659494086800001168177310727000021697596805861713420504450000117292442030400002174506790163000011760891600220000217767152988100003179253899740000011808362695989999918241863945818400100931700001185583379175999991871657490351887481188940000219033048875319191285861200001193495228471000021950775983319665996818900001198242338048000021998247079072014070777660000120298944762520457181748400001206154187343000022077365572022093189270610000121090129691999999212483666779214066036638000012156484064972172307763560000121881314621500002220395516074221977885933000012235602557920000222514262565122672499551000001228307365369229889735228000012314721050870000223305447494623463684480500001236219214663999992378015845232393839543820000124096632424124254869410000001244131063959000022457134338182472958036770000124887817353600002250460543395252042913254000012536252831129999925520765297200001256790022830999992583723926900000325995476254900001261537132407999992631195022670000326470187212600001266284241984999992678666118439999826944898170300002271031351562272613721421000042741960912800000227577846113927736083099799998278943200857000022805255707162821079405749999928369031043400003285272680293000012868550501519999928843742001099997290019789870000012916021597289999929318452958800003294766899447000012963492693062979316391649999829951400902400002301096378883302678748742000043042611186010000230584348846307425858318999993090082281779999731059059803700001312172967895999993137553377550000331533770761400001316920077472999993185024473319999732008481719100001321667187053232495569090000332483192676800002326414296627327996666485999983295790363450000233116140620433274377606299998334326145922000023359085157810000133749088563999999339073255498999973406556253580000134223799521699999343820365076000033454027349350000134698510479399999GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263118366695550000021200538851470000212174107474400002123428264341000021251154539380000212680264353500002128489833132130177022729000021318642123260000313355140192300001135238591521369257811170000113861297071400003140300160311000011419873499081436745395050000114536172910200003147048918699000011487361082961504232978930000115211048749000003153797677087000011554848666841571720562810000115885924587800002160546435475000011622336250721639208146690000116560800426600002167295193863000011689823834599999917066957305700001172356762654000021740439522510000117573114184800002177418331445000011791055210420000218079271063900001182479900236000021841670898330000118585427943000002187541469027000011892286586240000219091584822119260303781800002194290227415195977417012000021976646066091993517962060000220103898580320272617540000002204413364997206100554594000022077877441912094749337880000221116212338521284931298200001214536502579216223692176000012179108817732195980713700000122128526096722297245056400001224659640161226346829758000012280340193552297212089520000123140839854923309558814600001234782777743236469967340000012381571569370000223984434653400001241531536131000022432187257280000124490591532500002246593104922000012482802945190000224996748411600001251654673713000022533418633100000125502905290700002256716242504000042584034321010000226009062169800001261777811294999992634650008920000326515219048900002266839380086000012685265696829999927021375928000003271900948877000022735881384742752753280709999927696251766800003278649707265000022803368968622820240864589999928371127605600003285398465653000022870856552528877284484699999290460034444000032921472240410000229383441363829552160323499999297208792832000032988959824290000130058317202630227036162299999303957551220000033056447408170000130733193041430901912001100004310706309608000033123934992050000131408068880231576787839899998317455067996000033191422575930000132082944719322516636787000043242038263840000232589101598100001327578205578329265395174999983309525847720000233263977436900001334326963965999993360141535630000433770134316000002339388532757000013410757223539999934276291195099998344450101548000023461372911450000134782448074199999349511670339000033511988599360000235288604953335457323912999999356260428726999983579476183240000235963480792136132199751799999

                      Gestational age in days

                      Fetal abdominal circumference (mm)

                      HC 6 groups

                      Fetal growth profiles in diabetic pregnancies

                      IDDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631453707112151468063204669999814824192971899998149677538970999991511131482231525487574751539843667270000115541997597900001156855585230999991582911944831597268037349999816116241298699998162598022238999991640336314909999916546924074316690484999500001168340459247000011697760684989999917121167775117264728700317408289625499998175518505506999991769541147589999917838972401117982533326318126094251500001182696551766999991841321610189999918556777027118700337952300001188438988774999981898745980269999919131020727919274581653119418142578300001195617035035000011970526442869999919848825353919992386279120135947204299998202795081294999992042306905469999920566629979920710190905100001208537518303000012099731275549999921140873680721284434605921427995531100001215715564562999992171511738149999921858678306722002239231900001221458001571000012228936108229999922432922007499999225764829327227200438579000012286360478309999823007165708299999231507266335232942875587234378484839000012358140940910000223724970334299999238685312595240120921847000012415565310990000124299214035099999244427749603245863358855247298968107000012487345773590000125017018661099999251605795863253041405115254477014367000012559126236189999925734823287099999258783842123260219451375000012616550606270000126309066987900002264526279131000022659618883829999726739749763499998268833106886999992702687161389999927170432539127313993464327457554389500001276011153147000022774467623990000227888237165100003280317980903000032817535901549999828318919940699999284624808659286060417911287496027163000012889316364150000129036724566700002291802854919000032932384641710000329467407342299998296109682674999992975452919269999929898090117930041651043100001301852119683000013032877289350000230472333818700002306158947439000033075945566909999830903016594299999310465775194999993119013844473133369936993147726029510000131620821220300002317643821455000023190794307070000332051503995899998321950649211000043233862584629999932482186771532625747696732769308621900001329128695471000013305643047230000233199991397500003333435523226999983348711324790000433630674173099999337742350982999993391779602353406135694870000134204917873900001343484787991000023449203972430000234635600649499997347791615747000043492272249989999935066283425099999352098443503DM2 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631482140156551496505480215108708038499998152523612749999981539601451149999915539667747999999156833209845158269742211597062745750000116114280694000001162579339305000021640158716716545240403516688893640000001168325468764999981697620011299999917119853349499999172635065861740715982251755081305900000117694466295500001178381195320000021798177276849999918125426005182690792415184127324779999981855638571449999918700038950999999188436921875189873454241913099866050000119274651897000001194183051335000021956195836999999919705611606519849264843199929180795000012013657131600000120280224552499999204238777889999992056753102552071118426220854837498500001209984907350000012114214397150000221285797208214294504445215731036810000012171675691750000121860410154000002220040633904999992214771662722291369863522435023100000001225786763365000012272232957300000222865982809499999230096360462315328928252329694251900000123440595755500001235842489920000022372790222852387155546524015208701500001241588619380000012430251517450000224446168411000002245898216475247334748842487712812050000125020781357000001251644345935000022530808782999999925451741066525595394303257390475395000012588270077600000126026354012500002261700072490000032631366048550000326457313722000004266009669584999982674462019499999926888273431499999270319266682717557990452731923314100000127462886377500001276065396140000022775019285050000227893846087000003280374993235000032818115255999999828324805796500004284684590329999992861211226952875576550628899418742500001290430719790000012918672521550000229330378452000002294740316885000032961768492500000329761338161500004299049913980000043004864463449999930192297871303359511075304796043440000013062325758050000130766910817000002309105640535000023105421729000000331197870526500003313415237630000043148517699950000431628830235999999317724834725000053191613670932059789945532203443182000001323470964185000013249074965500000232634402891500002327780561280000033292170936450000333065362601000004332090158374999993335266907400000533496322310533639975547337836287835000013392728202000000134070935256500002342145884930000023435824172950000334501894966000003346455482025000043478920143899999934932854675500005350765079123522016114853536381438500000135507467621500001GDM 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macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631595104670616083397623100001162157485402000021634809945730000316480450374400002166128012915167451522086000011687750312570000217009854042800001171422049598999991727455587717406906794100001175392577112000031767160862830000117803959545399999179363104625000011806866137960000218201012296700003183333632138000011846571413091859806504800000118730415965100002188627668822189951177993000021912746871641925981963350000119392170550600002195245214677000011965687238480000219789223301919921574219000001200539251361000032018627605320000120318626970299999204509778874000012058332880450000220715679721620848030638700001209803815558211127324729000012124508339000000221377434307121509785224200002216421361413217744870584000012190683797550000222039188892600001221715398097000022230389072682243624164390000122568592561000003227009434781000012283329439520000222965645312300001230979962294000022323034714652336269806360000123495048980723627399897800001237597508149000022389210173224024452649100002241568035662242891544833000012442150540040000224553856317500001246862072346000022481855815172495090906880000125083259985925215610903000001253479618201000022548031273720000125612663654300002257450145714000032587736548849999826009716405626142067322700001262744182398000022640676915690000326539120073999999266714709911268038219082000012693617282530000227068523742400004272008746594999992733322557662746557649370000127597927410800003277302783278999982786262924499999927994980162100001281273310792000022825968199630000328392032913399999285243838305286567347476000012878908566470000228921436581800003290537874988999992918613841629318489333100001294508402502000022958319116730000429715542084399999298478930015299802439186000023011259483570000330244945752800004303772966698999993050964758700000130641998504100002307743494212000033090670033829999931039051255431171402172500001313037530896000023143610400670000331568454923799999317008058409318331567580000013196550767510000232097858592199998322302095092999993236256042643249491134350000232627262260600003327596131776999983289196409479999933024315011900001331566659290000023328901684610000333421367763199999335537186803336860695974000013381842051450000233950771431600003340831223486999993421547326583434782418290000134480175100000002346125260171000043474487693419999934877227851335009578768400002

                      Gestational age in days

                      Head circumference (mm)

                      HCAC 6 groups

                      Fetal growth profiles in diabetic pregnancies

                      IDDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631200577381119903700111974966211195956241119441586111928754811191335101118979472099999991188254340999999911867139609999999118517358099999991183633200999999911820928209999999118055244099999991179012060999999911774716809999999117593130099999991174390920999999911728505409999999117131016099999981169769780999999811682294009999998116668902099999981165148640999999811636082609999998116206788099999981160527500999999811589871211157446740999999811559063611154365981115282560111512852211149744841114820446111466640809999999114512370099999991143583320999999911420429409999999114050256099999991138962180999999911374218009999999113588142099999991134341040999999911328006609999999113126028099999991129719900999999911281795209999999112663914099999981125098760999999811235583809999998112201800099999981120477620999999811189372409999998111739686099999981115856480999999811143161011112775721111123534111096949611108154581110661420111050738211103533440999999911019930609999999110045268099999991098912300999999910973719209999999109583154099999991094291160999999910927507809999999109121040099999991089670020999999910881296409999999108658926099999991085048880999999910835085009999998108196812099999981080427740999999810788873609999998107734698099999981075806600999999810742662209999998107272584099999981071185460999999810696450811068104701106656432110650239411063483561106194318110604028011058862420999999910573220409999999105578166099999991054241280999999910527009009999999105116052099999991049620140999999910480797609999999104653938099999991044999000999999910434586209999999104191824099999991040377860999999810388374809999998103729710099999981035756720999999810342163409999998103267596099999981031135580999999810295952009999998102805482110265144409999998102497406110234336811021893301102035292110188125411017272161101573178099999991014191400999999910126510209999999101111064099999991009570260999999910080298809999999100648950099999991004949120999999910034087409999999100186836099999991000327980999999909987876009999998609972472209999998509957068409999998409941664609999998309926260809999999409910857009999999309895453209999999209880049409999999109864645609999999109849241809999999098338380099999989098184342099999988098030304099999988097876266099999987IDDM macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226312314344909999999122909766112267608309999998122442400099999981222087170999999912197503409999999121741351099999971215076680999999812127398509999998121040302099999991208066190999999912057293609999999120339253099999981201055700999999811987188709999999119638204099999991194045210999999711917083809999998118937155099999981187034720999999811846978909999999118236106099999991180024230999999811776874009999998117535057099999981173013740999999911706769109999999116834008099999981166003250999999811636664209999998116132959099999991158992760999999911566559309999997115431910099999981151982270999999811496454409999999114730861099999991144971780999999711426349509999998114029812099999981137961290999999911356244609999999113328763111309508009999998112861397099999981126277140999999911239403109999999112160348099999971119266650999999811169298209999998111459299099999991112256160999999911099193311107582500999999811052456709999998110290884099999991100572010999999910982351809999999109589835099999981093561520999999810912246909999999108888786099999991086551030999999910842142009999998108187737099999981079540540999999910772037109999999107486688099999991072530050999999810701932209999998106785639099999981065519560999999910631827309999999106084590099999981058509070999999810561722409999998105383541099999991051498580999999910491617509999998104682492099999981044488090999999810421512609999999103981443099999991037477600999999710351407709999998103280394099999981030467110999999910281302809999999102579345099999971023456620999999810211197909999998101878296099999991016446130999999910141093011011772470999999810094356409999998100709881099999991004761980999999910024251509999997100008832099999980997751490999999820995414660999999870993077830999999910990741000999999840988404170999999890986067340999999820983730510999999860981393680999999910979056850999999840976720020999999880974383190999999820972046360999999860969709530999999909673727009999998309650358709999998809626990409999998109603622109999998509580253809999999095568855099999983095335172099999987095101489099999981094867806099999985094634123099999989094400440099999983094166757099999987093933074099999980936993910999999850934657080999999890932320250999999820929983420999999870927646590999999809253097609999998409229729309999998909206361009999999309182992709999998609159624409999997909136256109999998409112887809999998809089519509999999209066151209999998609042782909999999090194146099999983089960463099999988089726780099999992089493097099999985DM2 non-macrosomia11912012112212312412512612712812913013113213313413513613713813914014114214314414514614714814915015115215315415515615715815916016116216316416516616716816917017117217317417517617717817918018118218318418518618718818919019119219319419519619719819920020120220320420520620720820921021121221321421521621721821922022122222322422522622722822923023123223323423523623723823924024124224324424524624724824925025125225325425525625725825926026126226311562740819999997115534842499999971154422767999999911534971109999999115257145399999981151645796999999811507201399999998114979448299999981148868825999999711479431689999997114701751199999971146091854999999911451661979999999114424054099999981143314883999999811423892269999998114146356999999981140537912999999711396122559999997113868659899999971137760941999999911368352849999999113590962799999981134983970999999811340583139999998113313265699999981132206999999999711312813429999997113035568599999971129430028999999911285043719999999112757871499999981126653057999999811257274009999998112480174399999981123876086999999711229504299999997112202477299999971121099115999999911201734589999999111924780199999981118322144999999811173964879999998111647083099999981115545173999999811146195169999997111369385999999971112768202999999911118425459999999111091688899999991109991231999999811090655749999998110813991799999981107214260999999811062886039999997110536294699999971104437289999999711035116329999999110258597599999991101660318999999811007346619999998109980900499999981098883347999999810979576909999997109703203399999971096106376999999710951807199999999109425506299999991093329405999999810924037489999998109147809199999981090552434999999810896267779999997108870112099999971087775463999999710868498069999999108592414999999991084998492999999810840728359999998108314717899999981082221521999999810812958649999997108037020799999971079444550999999710785188939999999107759323699999991076667579999999810757419229999998107481626599999981073890608999999810729649519999997107203929499999971071113637999999710701879809999997106926232399999991068336666999999910674110099999998106648535299999981065559695999999810646340389999998106370838199999971062782724999999710618570679999997106093141099999991060005753999999910590800969999998105815443999999981057228782999999810563031259999998105537746899999971054451811999999710535261549999997105260049799999991051674840999999910507491839999998104982352699999981048897869999999810479722129999998104704655599999971046120898999999710451952419999997104426958499999991043343927999999910424182709999998104149261399999981040566956999999810396412999999998103871564299999971037789985999999710368643289999997103593867199999991035013014999999910340873579999998103316170099999981032236043999999810313103869999998103038472999999971029459072999999710285334159999997102760775899999991026682101999999910257564449999999102483078799999981023905130999999810229794739999998DM2 macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631183880550999999911821121210000001118034369111785752611176806830999999911750384009999999117326997100000011171501541116973311111679646809999999116619625099999991164427821000000111626593911160890961115912253111573541009999999115558567100000011153817241115204881111502803811148511950999999911467435209999999114497509100000011143206661114143823111396698009999999113790137099999991136132941000000111343645111132596081113082765099999991129059220999999911272907910000001112552236111237539311121985500999999911202170709999999111844864100000011116680211111491178111131433509999999111137492099999991109606491000000111078380611106069631110430120111025327709999999110076434100000011098995911109722748110954590511093690620999999910919221910000001109015376100000011088385331108661690110848484709999999108308004099999991081311611000000110795431811077774751107600632099999991074237890999999910724694610000001107070103110689326011067164170999999910653957409999999106362731100000011061858881106009045110583220209999999105655359099999991054785161000000110530167311051248301104947987110477114409999999104594301100000011044174581104240615110406377211038869290999999910371008610000001103533243100000011033564001103179557110300271409999999102825871099999991026490281000000110247218511022953421102118499099999991019416560999999910176481310000001101587970110141112711012342840999999910105744109999999100880598100000011007037551100526912110035006909999999100173226099999990999963830999999970998195401000000040996426970999999990994658540999999950992890111000000020991121680999999980989353251000000040987584821098581639099999996098404796100000003098227953099999998098051110099999994097874267100000001097697424099999997097520581099999992097343738099999999097166895099999995096990052100000002096813209099999997096636366099999993096459523109628268009999999509610583710000000209592899409999999809575215109999999409557530810953984650999999960952216221000000030950447790999999990948679360999999940946910931000000010945142500999999970943374071000000040941605640999999990939837210999999950938068781000000020936300350999999980934531921000000040932763491093099506099999996092922663099999991GDM non-macrosomia1191201211221231241251261271281291301311321331341351361371381391401411421431441451461471481491501511521531541551561571581591601611621631641651661671681691701711721731741751761771781791801811821831841851861871881891901911921931941951961971981992002012022032042052062072082092102112122132142152162172182192202212222232242252262272282292302312322332342352362372382392402412422432442452462472482492502512522532542552562572582592602612622631171395040999999811701596669999998116892429299999991167688918999999711664535449999998116521817099999981163982796999999811627474229999999116151204899999971160276674999999811590413009999998115780592699999981156570552999999911553351789999997115409980499999981152864430999999811516290569999998115039368299999991149158308999999711479229349999998114668756099999981145452186999999811442168129999999114298143899999971141746064999999811405106909999998113927531699999981138039942999999911368045689999997113556919499999981134333820999999811330984469999998113186307299999991130627698999999711293923249999998112815695099999981126921576999999811256862029999999112445082899999971123215454999999811219800809999998112074470699999981119509332999999911182739589999997111703858499999981115803210999999811145678369999998111333246299999991112097088999999711108617149999997110962634099999981108390966999999811071555929999999110592021899999971104684844999999711034494709999998110221409699999981100978722999999910997433489999997109850797499999971097272600999999810960372269999998109480185299999991093566478999999710923311049999997109109573099999981089860356999999810886249829999999108738960899999971086154234999999710849188609999998108368348699999981082448112999999910812127389999997107997736499999971078741990999999810775066169999998107627124299999991075035868999999710738004949999997107256512099999981071329746999999810700943729999999106885899899999971067623624999999710663882509999998106515287699999981063917502999999910626821289999997106144675499999971060211380999999810589760069999998105774063299999991056505258999999710552698849999997105403451099999981052799136999999810515637629999999105032838899999971049093014999999710478576409999998104662226699999981045386892999999910441515189999997104291614499999971041680770999999810404453969999998103921002299999991037974648999999710367392749999997103550390099999981034268526999999810330331529999999103179777899999971030562404999999710293270309999998102809165699999981026856282999999910256209089999997102438553499999971023150160999999810219147869999998102067941299999991019444038999999710182086649999997101697329099999981015737916999999810145025429999999101326716899999971012031794999999710107964209999998100956104699999981008325672999999910070902989999997100585492499999971004619550999999810033841769999998100214880299999991000913428999999709996780549999997309984426809999997809972073069999998209959719329999997509947365589999998099350118499999973GDM macrosomia119120121122123124125126127128129130131132133134135136137138139140141142143144145146147148149150151152153154155156157158159160161162163164165166167168169170171172173174175176177178179180181182183184185186187188189190191192193194195196197198199200201202203204205206207208209210211212213214215216217218219220221222223224225226227228229230231232233234235236237238239240241242243244245246247248249250251252253254255256257258259260261262263120192611099999991200218000999999911985098911196801781119509367111933855609999999119167745099999991189969341000000111882612311186553121118484501099999991183136900999999911814287909999999117972068111780125711176304461117459635099999991172888240999999911711801310000001116947202111677639111166055800999999911643476909999999116263958099999991160931471115922336111575152511155807140999999911540990309999999115239092100000011150682811114897470111472665909999999114555848099999991143850370999999911421422611140434151113872604111370179309999999113530982099999991133601711000000111318936011130185491112847738099999991126769270999999911250611609999999112335305111216449411119936831111822872099999991116520610999999911148125010000001111310439111113962811109688170999999911079800609999999110627195099999991104563841110285573111011476211099439510999999910977314009999999109602329100000011094315181109260707110908989609999999108919085099999991087482740999999910857746311084066521108235841110806503009999999107894219099999991077234081000000110755259711073817861107210975099999991070401640999999910686935309999999106698542110652773111063569201106186109099999991060152980999999910584448710000001105673676110550286511053320540999999910516124309999999104990432099999991048196211104648810110447799911043071880999999910413637709999999103965566100000011037947551103623944110345313309999999103282322099999991031115110999999910294070011027698891102599078110242826709999999102257456099999991020866451000000110191583411017450231101574212099999991014034010999999910123259009999999101061779110089096811007201571100549346099999991003785350999999910020772410000001100036913109986610209999999809969529109999999409952448009999999099353669099999997099182858099999993099012047109884123609999999609867042509999999209849961409999999909832880309999999509815799209999999109798718109999999809781637009999999409764555909999999097474748099999997097303937099999993097133126109696231509999999609679150409999999209662069309999999909644988209999999509627907109999999109610826009999999809593744909999999409576663809999999095595827099999997

                      Gestational age in days

                      Head to abdominal circumference ratio (HCAC ratio)

                      Model

                      Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

                      Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

                      LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

                      Iperglicemia e rischio di morte fetale a termine di gravidanza

                      Estimated rate of stillbirth in diabetic women 1920-2000

                      Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                      4 of all stillbirths remain attributable to diabetes

                      Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                      bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                      Adverse outcome

                      HbA1C gt7

                      1 increase in A1Ccorresponded to 55 increased

                      risk of adverse outcome

                      The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                      gestation particularly in the presence of fetal macrosomia

                      fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                      Langer O 1995

                      100 mgdLfor stillbirth

                      Diabetic patients n = 271691

                      Am J Obstet Gynecol 2002

                      The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                      4873 diabetic women

                      pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                      outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                      bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                      GDMbull dysglycemia was more difficult to manage

                      2016

                      Differences in placental pathologyaccording to diabetes types

                      Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                      GDM is associated with a greater rate of villous immaturity

                      0102030405060708090

                      100GDMDMIDMII

                      o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                      A retrospective study on 175 placentas with DVM vs 175 controls

                      Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                      Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                      Pathophysiology of fetal compromise in diabetic pregnancy

                      The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                      Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                      Bjork 1984Nylund 1982Siddiqui 2003

                      A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                      STILLBIRTH RISK

                      BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                      OBESITArsquo E MORTE FETALE

                      6-7 per unit BMI for BMI gt 23

                      Tennant PWG Am J Obstet Gynecol 2007

                      HYPERINSULINISMHYPERANDROGENISM

                      IMPAIRED PLACENTATION

                      THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                      Cakmak and Taylor Hum Reprod Update 2011

                      Makieva S Hum Reprod Update 2014

                      Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                      Hotamisligil GS Nature 2006

                      LeptinCRH

                      Urocortin 3IL-6

                      INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                      INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                      Adiponectina Insulin LeptinTNFα IL-6

                      PLACENTAL ALTERATIONIN GENE EXPRESSION

                      PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                      CollagenaseCervical ripening

                      FFA

                      OXIDATIVE STRESS

                      PREVENZIONE STILLBIRTH

                      PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                      MORBIDITAgrave NEONATALE

                      AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                      TIMING E MODALITArsquo DEL PARTO

                      Induzione o attesa

                      INDUZIONE DEL TRAVAGLIO

                      Quando fare un TC elettivo

                      gt 4000 grgt 4500 gr gt 5000 gr

                      ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                      425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                      No differenza in TC e outcome perinatale

                      200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                      No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                      RCT INDUZIONE VS ATTESA in GDM

                      RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                      2014

                      1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                      2 Patients well controlled on insulin should probably be delivered by the due date

                      3 Poorly controlled GDMrsquos using insulin require individual judgment

                      Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                      1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                      2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                      3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                      cesarean delivery when the estimated fetal weight is ge 4500 g

                      MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                      MODALITAgrave E TIMING DEL PARTO nel GDM

                      GMD in terapia insulinicaBen controllato

                      +Condizioni fetali rassicuranti

                      MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                      GDM in terapia nutrizionalecon profili glicemici ottimali

                      +Feto AGA

                      MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                      Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                      EFW lt 4000g LGAControllo metabolico non

                      ottimale

                      4000g lt EFW gt 4500g EFW ge 4500g

                      Programmare TC elettivo

                      Parto vaginale indotto a 38-39 sett

                      Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                      MODALITAgrave E TIMING DEL PARTO nel GDM

                      IN BASE AL PESO FETALE STIMATO

                      - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                      - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                      - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                      ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                      Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                      The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                      A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                      If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                      Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                      GDM and the Use of Betamethasone

                      bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                      bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                      bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                      Society of Obstetricians and Gynaecologists of Canada

                      The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                      late preterm delivery between 24 to 36 weeksrsquo gestation

                      ASSISTENZA IN TRAVAGLIO

                      - MONITORAGGIO FETALE CONTINUO

                      - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                      MANTENERE GLICEMIA gt70 E lt 126

                      (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                      GDM

                      - Intravenous infusion of regular insulin titrated and glucose

                      - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                      (ACOG 2005)

                      ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                      Venere di Willendorf

                      Thank you for your attention

                      Pathophysiology of fetal compromise in diabetic pregnancy

                      Islet cell hyperplasia common in stillborn IDMs

                      There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                      Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                      Salvesen 1993Hay 1989Chukwuma 2001

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                      • Birth weight distribution in diabetic pregnancies
                      • Diapositiva numero 9
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                      • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
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                      • Differences in placental pathology according to diabetes types
                      • Diapositiva numero 21
                      • Pathophysiology of fetal compromise in diabetic pregnancy
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                      • Diapositiva numero 32
                      • Diapositiva numero 33
                      • Diapositiva numero 34
                      • Diapositiva numero 35
                      • Diapositiva numero 36
                      • GDM and the Use of Betamethasone
                      • Diapositiva numero 38
                      • Diapositiva numero 39
                      • Diapositiva numero 40
                      • Pathophysiology of fetal compromise in diabetic pregnancy
                        Intercepting Curves Random Effects are intercept and ctime (=slope)
                        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                        17119-7049001200577381123143449111562740821183880551117139504112019261111109612LINE
                        120-6947611199037001122909766111553484251182112121117015966712002180011110695Estimates of Fixed Effectsa
                        121-6846241197496621122676083111544227681180343691116892429311985098911111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                        122-6744891195956241122442400111534971111178575261116768891911968017811112783Lower BoundUpper Bound
                        123-6643561194415861122208717111525714541176806831116645354511950936711113788Intercept109275078150007644208524838616461181429514624586156360851038611E-2401077695049411078065136
                        124-6542251192875481121975034111516457971175038401116521817111933855611114767ctime-000154038000018738132361894509163-82205637360-00019095322-00011712279
                        125-64409611913351011217413511115072014117326997111639827971191677451111572DM1M-00248943874001286083912384370237175-1935673656200540899658-0050229765400004409907
                        18126-6339691189794721121507668111497944831171501541116274742311899693411116647DM2nM-00012726893001100064332439624938932-0115692259909079916115-0022941046900203956684
                        127-6238441188254341121273985111488688261169733111116151204911882612311117548DM2M-00326603281001431972892333680597702-2280792342500234630719-00608727913-00044478648
                        128-6137211186713961121040302111479431691167964681116027667511865531211118423DM3nM-00078319191001022303492661779271785-0766105085504442926229-0027960219300122963812
                        129-6036001185173581120806619111470175121166196251115904130111848450111119272DM3M-00103923671001681213544167163320542-0618146763205368162888-0043439528600226547944
                        130-5934811183633201120572936111460918551164427821115780592711831369011120095ctime DM1M-0000796454600003133092294715100798-254207365800116788476-00014137849-00001791244
                        131-5833641182092821120339253111451661981162659391115657055311814287911120892ctime DM2nM000061472300002699383238491381681622772718510023656225300000829550001146491
                        132-5732491180552441120105570111442405411160890961115533517911797206811121663ctime DM2M-000022804640000354152299388660551-0643925960305202652078-0000925840400004697476
                        19133-5631361179012061119871887111433148841159122531115409980511780125711122408ctime DM3nM000030500620000251500225870668533341212747274402263327011-000019024200008002544
                        134-5530251177471681119638204111423892271157354101115286443111763044611123127ctime DM3M-00001677324000039261623843503141477-0427217281806694603024-000093967690000604212
                        135-54291611759313011194045211114146357115558567111516290571174596351112382a Dependent Variable HCAC ratio echo 1
                        136-5328091174390921119170838111405379131153817241115039368311728882411124487
                        137-5227041172850541118937155111396122561152048811114915830911711801311125128
                        138-5126011171310161118703472111386865991150280381114792293511694720211125743Estimates of Fixed Effectsa
                        139-5025001169769781118469789111377609421148511951114668756111677639111126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                        20140-4924011168229401118236106111368352851146743521114545218711660558011126895Lower BoundUpper Bound
                        141-4823041166689021118002423111359096281144975091114421681311643476911127432Intercept1100131329000972397355091201207314113135985998101081027275811192353823
                        142-4722091165148641117768740111349839711143206661114298143911626395811127943ctime-00015055347000018962642453458441236-793947960610-0001879038-00011320314
                        143-4621161163608261117535057111340583141141438231114174606511609314711128428ctimesq-0000004175700000034043552737663669-1226570458302205063137-0000010862700000025114
                        144-4520251162067881117301374111331326571139669801114051069111592233611128887DM1M-00337425008001673712965123546308965-2016026737500443186119-00666243475-00008606541
                        145-441936116052750111706769111132207113790137111392753171157515251112932DM2nM-00143395763001408089784950486711294-1018370881503089991569-004200526700133261143
                        146-4318491158987121116834008111312813431136132941113803994311558071411129727DM2M-00289134247001830108244962153900811-1579875120701147726649-0064870589700070437403
                        21147-4217641157446741116600325111303556861134364511113680456911540990311130108DM3nM-00092688892001313905885276671855448-07054454470480844366-003508017500165423965
                        148-4116811155906361116366642111294300291132596081113556919511523909211130463DM3M-00041390353001956390635795483919757-0211564867508325208967-0042563832900342857623
                        149-4016001154365981116132959111285043721130827651113433382111506828111130792ctime DM1M-00008318378000031480022321213468068-2642431304100087914156-00014520686-0000211607
                        150-3915211152825601115899276111275787151129059221113309844711489747011131095ctime DM2nM000054932700002737601249375683849720066000847004587185090000010150400010885037
                        151-3814441151285221115665593111266530581127290791113186307311472665911131372ctime DM2M-00002165967000035777362405317547939-0605401569205454829861-0000921366100004881728
                        152-3713691149744841115431910111257274011125522361113062769911455584811131623ctime DM3nM000030466410000255344326975443686551193150338802338588418-000019805700008073851
                        153-3612961148204461115198227111248017441123753931112939232511438503711131848ctime DM3M000023776020000471535351152172227760504225585506143199743-0000688623900011641443
                        22154-3512251146664081114964544111238760871121985501112815695111421422611132047ctimesq DM1M00000049385000000572455269246547768086269955410388695145-0000006307100000161842
                        155-34115611451237011147308611112295043112021707111269215771140434151113222ctimesq DM2nM000000753220000005089658881569245641479899762201394348201-0000002463900000175282
                        156-3310891143583321114497178111220247731118448641112568620311387260411132367ctimesq DM2M-00000022137000000652655535916331-0339205376807345832447-000001503230000010605
                        157-3210241142042941114263495111210991161116680211112445082911370179311132488ctimesq DM3nM00000005286000000486715971385213096010860080140913555607-0000009030100000100872
                        158-319611140502561114029812111201734591114911781112321545511353098211132583ctimesq DM3M-0000008534700000082276863599279549-1037395314402999169916-0000024687900000076185
                        159-309001138962181113796129111192478021113143351112198008111336017111132652a Dependent Variable HCAC ratio echo 1
                        160-298411137421801113562446111183221451111374921112074470711318936011132695
                        23161-287841135881421113328763111173964881109606491111950933311301854911132712
                        162-277291134341041113095080111164708311107838061111827395911284773811132703
                        163-266761132800661112861397111155451741106069631111703858511267692711132668
                        164-256251131260281112627714111146195171104301201111580321111250611611132607
                        165-2457611297199011123940311111369386110253277111145678371123353051113252
                        166-235291128179521112160348111127682031100764341111333246311216449411132407
                        167-224841126639141111926665111118425461098995911111209708911199368311132268
                        24168-214411125098761111692982111109168891097227481111086171511182287211132103
                        169-204001123558381111459299111099912321095459051110962634111165206111131912
                        170-193611122018001111225616111090655751093690621110839096711148125011131695
                        171-183241120477621110991933111081399181091922191110715559311131043911131452
                        172-172891118937241110758250111072142611090153761110592021911113962811131183
                        173-162561117396861110524567111062886041088385331110468484511096881711130888
                        174-152251115856481110290884111053629471086616901110344947111079800611130567
                        25175-1419611143161011100572011110443729108484847111022140971106271951113022
                        176-131691112775721109823518111035116331083080041110097872311045638411129847
                        177-121441111235341109589835111025859761081311611109974334911028557311129448
                        178-111211109694961109356152111016603191079543181109850797511011476211129023
                        179-101001108154581109122469111007346621077774751109727260110994395111128572
                        180-9811106614201108888786110998090051076006321109603722710977314011128095
                        181-8641105073821108655103110988833481074237891109480185310960232911127592
                        26182-7491103533441108421420110979576911072469461109356647910943151811127063
                        183-6361101993061108187737110970320341070701031109233110510926070711126508
                        184-5251100452681107954054110961063771068932601109109573110908989611125927
                        185-41610989123011077203711109518072106716417110898603571089190851112532
                        186-391097371921107486688110942550631065395741108862498310874827411124687
                        187-241095831541107253005110933294061063627311108738960910857746311124028
                        188-111094291161107019322110924037491061858881108615423510840665211123343
                        27189001092750781106785639110914780921060090451108491886110823584111122632
                        190111091210401106551956110905524351058322021108368348710806503011121895
                        191241089670021106318273110896267781056553591108244811310789421911121132
                        192391088129641106084590110887011211054785161108121273910772340811120343
                        1934161086589261105850907110877754641053016731107997736510755259711119528
                        1945251085048881105617224110868498071051248301107874199110738178611118687
                        19563610835085011053835411108592415104947987110775066171072109751111782
                        281967491081968121105149858110849984931047711441107627124310704016411116927
                        1978641080427741104916175110840728361045943011107503586910686935311116008
                        1989811078887361104682492110831471791044174581107380049510669854211115063
                        199101001077346981104448809110822215221042406151107256512110652773111114092
                        200111211075806601104215126110812958651040637721107132974710635692011113095
                        201121441074266221103981443110803702081038869291107009437310618610911112072
                        202131691072725841103747760110794445511037100861106885899910601529811111023
                        29203141961071185461103514077110785188941035332431106762362510584448711109948
                        204152251069645081103280394110775932371033564001106638825110567367611108847
                        2051625610681047011030467111107666758103179557110651528771055028651110772
                        206172891066564321102813028110757419231030027141106391750310533205411106567
                        207183241065023941102579345110748162661028258711106268212910516124311105388
                        208193611063483561102345662110738906091026490281106144675510499043211104183
                        209204001061943181102111979110729649521024721851106021138110481962111102952
                        30210214411060402801101878296110720392951022953421105897600710464881011101695
                        211224841058862421101644613110711136381021184991105774063310447799911100412
                        212235291057322041101410930110701879811019416561105650525910430718811099103
                        213245761055781661101177247110692623241017648131105526988510413637711097768
                        214256251054241281100943564110683366671015879701105403451110396556611096407
                        2152667610527009011007098811106741101101411127110527991371037947551109502
                        216277291051160521100476198110664853531012342841105156376310362394411093607
                        31217287841049620141100242515110655596961010574411105032838910345313311092168
                        218298411048079761100008832110646340391008805981104909301510328232211090703
                        219309001046539381099775149110637083821007037551104785764110311151111089212
                        220319611044999001099541466110627827251005269121104662226710294070011087695
                        2213210241043458621099307783110618570681003500691104538689310276988911086152
                        2223310891041918241099074100110609314111001732261104415151910259907811084583
                        2233411561040377861098840417110600057540999963831104291614510242826711082988
                        322243512251038837481098606734110590800970998195401104168077110225745611081367
                        22536129610372971010983730511105815444099642697110404453971020866451107972
                        2263713691035756721098139368110572287830994658541103921002310191583411078047
                        2273814441034216341097905685110563031260992890111103797464910174502311076348
                        2283915211032675961097672002110553774690991121681103673927510157421211074623
                        2294016001031135581097438319110544518120989353251103550390110140340111072872
                        2304116811029595201097204636110535261550987584821103426852710123259011071095
                        332314217641028054821096970953110526004980985816391103303315310106177911069292
                        2324318491026514441096737270110516748410984047961103179777910089096811067463
                        2334419361024974061096503587110507491840982279531103056240510072015711065608
                        2344520251023433681096269904110498235270980511101102932703110054934611063727
                        23546211610218933010960362211104889787097874267110280916571003785351106182
                        2364722091020352921095802538110479722130976974241102685628310020772411059887
                        2374823041018812541095568855110470465560975205811102562090910003691311057928
                        342384924011017272161095335172110461208990973437381102438553509986610211055943
                        2395025001015731781095101489110451952420971668951102315016109969529111053932
                        2405126011014191401094867806110442695850969900521102191478709952448011051895
                        2415227041012651021094634123110433439280968132091102067941309935366911049832
                        2425328091011110641094400440110424182710966363661101944403909918285811047743
                        2435429161009570261094166757110414926140964595231101820866509901204711045628
                        2445530251008029881093933074110405669570962826801101697329109884123611043487
                        352455631361006489501093699391110396413096105837110157379170986704251104132
                        2465732491004949121093465708110387156430959289941101450254309849961411039127
                        2475833641003408741093232025110377899860957521511101326716909832880311036908
                        2485934811001868361092998342110368643290955753081101203179509815799211034663
                        2496036001000327981092764659110359386720953984651101079642109798718111032392
                        2506137210998787601092530976110350130150952216221100956104709781637011030095
                        2516238440997247221092297293110340873580950447791100832567309764555911027772
                        362526339690995706841092063610110331617010948679361100709029909747474811025423
                        2536440960994166461091829927110322360440946910931100585492509730393711023048
                        2546542250992626081091596244110313103870945142501100461955109713312611020647
                        25566435609910857010913625611103038473094337407110033841770969623151101822
                        2566744890989545321091128878110294590730941605641100214880309679150411015767
                        2576846240988004941090895195110285334160939837211100091342909662069311013288
                        2586947610986464561090661512110276077590938068781099967805509644988211010783
                        372597049000984924181090427829110266821020936300351099844268109627907111008252
                        2607150410983383801090194146110257564450934531921099720730709610826011005695
                        2617251840981843421089960463110248307880932763491099597193309593744911003112
                        2627353290980303041089726780110239051310930995061099473655909576663811000503
                        2637454760978762661089493097110229794740929226631099350118509559582710997868
                        PDM1
                        PDM 2
                        GDM
                        Intercepting Curves Random Effects are intercept and ctime (=slope)
                        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                        17119-70490014544665153145370711215141936936246148214015655151802867413159510467061109612LINE
                        120-694761146818513261146806320467143443250489149650548021531384538541608339762311110695Estimates of Fixed Effectsa
                        121-6846241481903749921482419297191449495647321510870803851544740402951621574854021111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                        122-674489149562236723149677538971146455878975152523612751558096267361634809945731112783Lower BoundUpper Bound
                        123-6643561509340984541511131482231479621932181539601451151571452131771648045037441113788Intercept24147697273862091012654126140676430151154832670487245604019415608E-22623735960059812455943448792
                        124-654225152305960185152548757475149468507461155396677481584807996181661280129151114767ctime1371861731500571400378239396876075240087648764112260983751603E-651259300269114844231939
                        125-644096153677821916153984366727150974821704156833209845159816386059167451522086111572DM1M43863861553350749927232478790002161250573646602122692588-25219155524112946878629
                        18126-6339691550496836471554199759791524811359471582697422116115197251687750312571116647DM2nM59019605562997025486125513510474711969272728400500037953-0000098509118040196211
                        127-623844156421545378156855585231153987450191597062745751624875589411700985404281117548DM2M72946085053388601758324659091539861877142434200616792034-03594115822149486285928
                        128-613721157793407109158291194483155493764433161142806941638231453821714220495991118423DM3nM38169455833279767165827940396240191364329360201735618163-169024513549324136302
                        129-60360015916526884159726803735157000078676162579339305165158731823172745558771119272DM3M106791363334460093597994361065178194232107909780020742792416363715676197219010992
                        130-593481160537130571161162412987158506392919164015871671664943182641740690679411120095ctime DM1M006374752100954499537231686983180667863299905048855867-0124313312702518083548
                        131-5833641619089923021625980222391600127071621654524040351678299047051753925771121120892ctime DM2nM013445251160082022456823960556025231639215855401024806101-0027124679902960297032
                        132-57324916328085403316403363149116151902140516688893641691654911461767160862831121663ctime DM2M006467063370107176336723494264974290603404031505468220328-0146478812502758200798
                        19133-5631361646527157641654692407431630253356481683254687651705010775871780395954541122408ctime DM3nM-00362752914007615583882589784113082-0476329745906342410886-0186238804801136882221
                        134-553025166024577495166904849995164531649891169762001131718366640281793631046251123127ctime DM3M-00483525556011653227093612630049027-0414928459406784405727-0277519357501808142462
                        135-542916167396439226168340459247166037964134171198533495173172250469180686613796112382a Dependent Variable hoofdomtrek echo 1 (mm)
                        136-53280916876830095716977606849916754427837717263506586174507836911820101229671124487
                        137-522704170140162688171211677751169050592621740715982251758434233511833336321381125128Estimates of Fixed Effectsa
                        138-512601171512024419172647287003170556906863175508130591771790097921846571413091125743Estimates of Fixed Effectsa
                        139-50250017288388615174082896255172063221106176944662955178514596233185980650481126332ParameterEstimateStd ErrordftSig95 Confidence Interval
                        20140-492401174255747881175518505507173569535349178381195321798501826741873041596511126895Lower BoundUpper Bound
                        141-4823041756276096121769541147591750758495921798177276851811857691151886276688221127432Intercept249320500642326818036416544567462346592967470390702440525539212545884473637
                        142-472209176999471343178389724011176582163835181254260051825213555561899511779931127943ctime14061521215005669318852517092044335248028406738152316286832415E-691294498665715178055773
                        143-4621161783713330741798253332631780884780781826907924151838569419971912746871641128428ctimesq-00043893444000096482695486636325832-454935955630000006629-00062845511-00024941378
                        144-452025179743194805181260942515179594792321184127324781851925284381925981963351128887DM1M4389405611546160652135456102232991095089766050342077354-46780300913134568413143
                        145-441936181115056536182696551767181101106564185563857145186528114879193921705506112932DM2nM155906834513878532601252755652558260401973763106878661352-6060195922191783326124
                        146-43184918248691826718413216101918260742080718700038951187863701321952452146771129727DM2M86765461465040811736853369582541481721259709600857832245-12257196918185788119839
                        21147-421764183858779998185567770271184113735051884369218751891992877611965687238481130108DM3nM29890766743626377390455951016731680824259681804101432535-413390065810112054006
                        148-411681185230641729187003379523185620049293189873454241905348742021978922330191130463DM3M1054840924425415333515760970059840791947878041800518881117-00865609965211833794849
                        149-40160018660250346188438988775187126363536191309986605191870460643199215742191130792ctime DM1M00294596956009422748622385137605335031264439670754824023-0156164668302150840595
                        150-391521187974365191189874598027188632677779192746518971932060470842005392513611131095ctime DM2nM011746192008145212592525904242866144209765901505135651-004294990902778737491
                        151-3814441893462269221913102072791901389920221941830513351945416335252018627605321131372ctime DM2M006273249140106090242424671644263280591312546805548523969-0146225597802716905806
                        152-37136919071808865319274581653119164530626519561958371958772199662031862697031131623ctime DM3nM-0038530229900755558747270985031372-0509956771706104968317-0187281372101102209122
                        153-3612961920899503841941814257831931516205081970561160651972128064072045097788741131848ctime DM3M01049055790129760841946099982049950808453285704192466886-0150090464203599016222
                        22154-351225193461812115195617035035194657934751198492648431985483928482058332880451132047ctimesq DM1M000036621690001618201852614766676660226310988108210474432-0002812713100035451468
                        155-341156194833673846197052644287196164248994199929180795199883979289207156797216113222ctimesq DM2nM00023659357000143774965861984512081645582651201003857522-0000457831800051897033
                        156-33108919620553557719848825353919767056323720136571316201219565732084803063871132367ctimesq DM2M-0000812769000185232865638208329212-0438782307706609873692-0004451076500028255384
                        157-321024197577397308199923862791199176877482028022455252025551521712098038155581132488ctimesq DM3nM000023639010001367120959624541468290172910903308627801407-0002448567900029213481
                        158-31961198949259039201359472043200683191723204238777892038907386122111273247291132583ctimesq DM3M-00017469554000222795546974552491839-0784106958604332435648-000612125870002627348
                        159-309002003211207720279508129520218950596620567531025520522632505321245083391132652a Dependent Variable hoofdomtrek echo 1 (mm)
                        160-29841201692982501204230690547203695820209207111842622065619114942137743430711132695
                        23161-287842030648442322056662997992052021344522085483749852078974979352150978522421132712
                        162-27729204436705963207101909051206708448695209984907352092330843762164213614131132703
                        163-266762058085676942085375183032082147629382114214397152105686708172177448705841132668
                        164-25625207180429425209973127555209721077181212857972082119042572582190683797551132607
                        165-24576208552291156211408736807211227391424214294504445213239843699220391888926113252
                        166-2352920992415288721284434605921273370566721573103681214575430142217153980971132407
                        167-22484211296014618214279955311214240019912171675691752159110165812230389072681132268
                        24168-21441212667876349215715564563215746334153218604101542172466030222243624164391132103
                        169-2040021403973808217151173815217252648396220040633905218582189463225685925611131912
                        170-19361215411599811218586783067218758962639221477166272199177759042270094347811131695
                        171-183242167834615422200223923192202652768822229136986352212533623452283329439521131452
                        172-172892181553232732214580015712217715911252243502312225889487862296564531231131183
                        173-162562195271850042228936108232232779053682257867633652239245352272309799622941130888
                        174-15225220899046735224329220075224784219611227223295732252601216682323034714651130567
                        25175-14196222270908466225764829327226290533854228659828095226595708109233626980636113022
                        176-1316922364277019722720043857922779684809723009636046227931294552349504898071129847
                        177-12144225014631928228636047831229303162342315328928252292668809912362739989781129448
                        178-11121226386493659230071657083230809476583232969425192306024674322375975081491129023
                        179-1010022775835539231507266335232315790826234405957555231938053873238921017321128572
                        180-981229130217121232942875587233822105069235842489922332736403142402445264911128095
                        181-8642305020788522343784848392353284193122372790222852346092267552415680356621127592
                        26182-749231873940583235814094091236834733555238715554652359448131962428915448331127063
                        183-6362332458023142372497033432383410477982401520870152372803996372442150540041126508
                        184-525234617664045238685312595239847362041241588619382386159860782455385631751125927
                        185-416235989525776240120921847241353676284243025151745239951572519246862072346112532
                        186-3923736138750724155653109924285999052724446168411241287158962481855815171124687
                        187-24238733249238242992140351244366304772458982164752426227454012495090906881124028
                        188-11240105110969244427749603245872619013247334748842439583318422508325998591123343
                        27189002414769727245863358855247378933256248771281205245293918283252156109031122632
                        19011242848834431247298968107248885247499250207813572466295047242534796182011121895
                        191242442206961622487345773592503915617422516443459352479650911652548031273721121132
                        1923924559255789325017018661125189787598525308087832493006776062561266365431120343
                        1934162469644196242516057958632534041902282545174106652506362640472574501457141119528
                        194525248336281355253041405115254910504471255953943032519718504882587736548851118687
                        195636249708143086254477014367256416818714257390475395253307436929260097164056111782
                        2819674925108000481725591262361925792313295725882700776254643023372614206732271116927
                        19786425245186654825734823287125942944722602635401252559786098112627441823981116008
                        198981253823728279258783842123260935761443261700072492573141962522640676915691115063
                        1991010025519559001260219451375262442075686263136604855258649782693265391200741114092
                        20011121256567451741261655060627263948389929264573137222599853691342667147099111113095
                        201121442579393134722630906698792654547041722660096695852613209555752680382190821112072
                        20213169259311175203264526279131266961018415267446201952626565420162693617282531111023
                        29203141962606830369342659618883832684673326582688827343152639921284572706852374241109948
                        20415225262054898665267397497635269973646901270319266682653277148982720087465951108847
                        20516256263426760396268833106887271479961144271755799045266663301339273332255766110772
                        2061728926479862212727026871613927298627538727319233141267998887782746557649371106567
                        20718324266170483858271704325391274492589632746288637752693344742212759792741081105388
                        20819361267542345589273139934643275998903873276065396142706700606622773027832791104183
                        2092040026891420732274575543895277505218116277501928505272005647103278626292451102952
                        3021021441270286069051276011153147279011532359278938460872733412335442799498016211101695
                        211224842716579307822774467623992805178466022803749932352746768199852812733107921100412
                        2122352927302979251327888237165128202416084528181152562760124064262825968199631099103
                        213245762744016542442803179809032835304750882832480579652773479928672839203291341097768
                        21425625275773515975281753590155285036789331284684590332786835793082852438383051096407
                        21526676277145377706283189199407286543103574286121122695280019165749286567347476109502
                        2162772927851723943728462480865928804941781728755765506281354752192878908566471093607
                        3121728784279889101168286060417911289555732062889941874252826903386312892143658181092168
                        21829841281260962899287496027163291062046303290430719792840259250722905378749891090703
                        2193090028263282463288931636415292568360546291867252155285361511513291861384161089212
                        22031961284004686361290367245667294074674789293303784522866970979542931848933311087695
                        2213210242853765480922918028549192955809890322947403168852880326843952945084025021086152
                        222331089286748409823293238464171297087303275296176849252893682708362958319116731084583
                        2233411562881202715542946740734232985936175182976133816152907038572772971554208441082988
                        32224351225289492133285296109682675300099931761299049913982920394437182984789300151081367
                        225361296290863995016297545291927301606246004300486446345293375030159299802439186107972
                        2263713692922358567472989809011793031125602473019229787129471061663011259483571078047
                        227381444293607718478300416510431304618874493033595110752960462030413024494575281076348
                        228391521294979580209301852119683306125188733304796043442973817894823037729666991074623
                        22940160029635144194303287728935307631502976306232575805298717375923305096475871072872
                        230411681297723303671304723338187309137817219307669108173000529623643064199850411071095
                        332314217642990951654023061589474393106441314623091056405353013885488053077434942121069292
                        23243184930046702713330759455669131215044570531054217293027241352463090670033831067463
                        2334419363018388888643090301659433136567599483119787052653040597216873103905125541065608
                        234452025303210750595310465775195315163074191313415237633053953081283117140217251063727
                        235462116304582612326311901384447316669388434314851769995306730894569313037530896106182
                        23647220930595447405731333699369931817570267731628830236308066481013143610400671059887
                        237482304307326335788314772602951319682016923177248347253094020674513156845492381057928
                        34238492401308698197519316208212203321188331163319161367093107376538923170080584091055943
                        23950250031007005925317643821455322694645406320597899455312073240333318331567581053932
                        240512601311441920981319079430707324200959649322034431823134088267743196550767511051895
                        2415227043128137827123205150399593257072738923234709641853147444132153209785859221049832
                        242532809314185644443321950649211327213588135324907496553160799996563223020950931047743
                        2435429163155575061743233862584633287199023783263440289153174155860973236256042641045628
                        244553025316929367905324821867715330226216621327780561283187511725383249491134351043487
                        35245563136318301229636326257476967331732530864329217093645320086758979326272622606104132
                        24657324931967309136732769308621933323884510733065362601321422345423275961317771039127
                        247583364321044953098329128695471334745159353320901583753227579318613289196409481036908
                        248593481322416814829330564304723336251473593333526690743240935183023302431501191034663
                        24960360032378867656331999913975337757787836334963223105325429104743331566659291032392
                        250613721325160538291333435523227339264102079336399755473267646911843328901684611030095
                        2516238443265324000223348711324793407704163223378362878353281002776253342136776321027772
                        3625263396932790426175333630674173134227673056533927282023294358640663355371868031025423
                        2536440963292761234843377423509833437830448083407093525653307714505073368606959741023048
                        254654225330647985215339177960235345289359051342145884933321070369483381842051451020647
                        255664356332019846946340613569487346795673294343582417295333442623389339507714316101822
                        25667448933339170867734204917873934830198753734501894966334778209833408312234871015767
                        257684624334763570408343484787991349808301783464554820253361137962713421547326581013288
                        258694761336135432139344920397243351314616023347892014393374493827123434782418291010783
                        37259704900337507293873463560064953528209302663493285467553387849691533448017511008252
                        260715041338879155601347791615747354327244509350765079123401205555943461252601711005695
                        2617251843402510173323492272249993558335587523522016114853414561420353474487693421003112
                        262735329341622879063350662834251357339872995353638143853427917284763487722785131000503
                        2637454763429947407943520984435033588461872383550746762153441273149173500957876840997868
                        PDM1
                        PDM 2
                        GDM
                        Intercepting Curves Random Effects are intercept and ctime (=slope)
                        AD weekAD dagenctimectimesqDM1 non macroDM1 macroDM2 non macroDM2 macroGDM non macroGDM macrocontrole
                        17119-704900114637062271131321413511756116964511494210651119123845098118366695551109612LINE
                        120-6947611162283812191149284826851191476615941167230155271207062149571200538851471110695Estimates of Fixed Effectsa
                        121-684624117819700168116724824021207341535431185039245441222885848161217410747441111752ParameterEstimateStd ErrordftSig95 Confidence Interval
                        122-6744891194110191171185211653551223206454921202848335611238709546751234282643411112783Lower BoundUpper Bound
                        123-664356121002338066120317506691239071374411220657425781254533245341251154539381113788Intercept22602938774451583294249920751245013141427589266846388446233098433E-20922290798366992291507918191
                        124-654225122593657015122113848025125493629391238466515951270356943931268026435351114767ctime15913189487002572697571842828363543618541008714333232731447193E-125154056167116420762263
                        125-64409612418497596412391018936127080121339125627560612128618064252128489833132111572DM1M128466647132266375711672050371372228482276129180000002757175947975092180985319172
                        18126-6339691257762949131257065306951286666132881274084696291302004341111301770227291116647DM2nM258621837512292444106121203454437051128148934302605319151-1932682220671051189709
                        127-62384412736761386212750287203130253105237129189378646131782803971318642123261117548DM2M13576357083302267560592068960521546449150317560000011749476171635627195355506033
                        128-6137211289589328111292992133651318395971861309702876631333651738291335514019231118423DM3nM386034752842099197398822408656183581838963563200672437607-0276345195779970402525
                        129-60360013055025176131095554713342608913513275119668134947543688135238591521119272DM3M104405796385316560254763066137679353329813344580001087805842115250622166696342147
                        130-5934811321415707091328918960351350125810841345321056971365299135471369257811171120095ctime DM1M02831518450043271222518175004715236543652539100000000006019777329903685303911
                        131-583364133732889658134688237371365990730331363130147141381122834061386129707141120892ctime DM2nM-00048270024003765967571948296000005-012817429520898143248-007909997300694459682
                        132-5732491353242086071364845787051381855649821380939237311396946532651403001603111121663ctime DM2M0189590068400490866258176936128961238623569074000015735930092719472402864606643
                        19133-563136136915527556138280920041397720569311398748327481412770231241419873499081122408ctime DM3nM-00894909013003518407432100120618088-254350592300116941229-01588501162-00201316865
                        134-553025138506846505140077261375141358548881416557417651428593929831436745395051123127ctime DM3M009587064750055027108232757052885991742243971900824043069-0012380461402041217564
                        135-54291614009816545414187360271142945040829143436650782144441762842145361729102112382a Dependent Variable buikomtrek echo 1 (mm)
                        136-5328091416894844031436699440451445315327781452175597991460241327011470489186991124487
                        137-52270414328080335214546628538146118024727146998468816147606502561487361082961125128Estimates of Fixed Effectsa
                        138-5126011448721223011472626267151477045166761487793778331491888724191504232978931125743ParameterEstimateStd ErrordftSig95 Confidence Interval
                        139-502500146463441251490589680514929100862515056028685150771242278152110487491126332CURVELower BoundUpper Bound
                        20140-4924011480547601991508553093851508775005741523411958671523536121371537976770871126895Intercept22790836062891756309403529952775762381297654958632282728501152131E-26522445209199412313646292636
                        141-482304149646079148152651650721524639925231541221048841539359819961554848666841127432ctime15999477276002635691311888603928837607031529296763256315745845E-1261547955962916519394924
                        142-4722091512373980971544479920551540504844721559030139011555183518551571720562811127943ctimesq-00010312178000040632384962942680429-2537921447900114560307-00018295447-0000232891
                        143-462116152828717046156244333391556369764211576839229181571007217141588592458781128428DM1M10312768706229645141222995736875962347873826260000578517544788588131161466785993
                        144-452025154420035995158040674725157223468371594648319351586830915731605464354751128887DM2nM34564457141255999840873097187915991350174946301779456963-1580742656684936340847
                        145-44193615601135494415983701606158809960319161245740952160265461432162233625072112932DM2M12200555833556108055301223079811336358673598000032573475597147788918803963811
                        146-4318491576026738931616333573951603964522681630266499691618478312911639208146691129727DM3nM42962102717234631544963264884826781831045468500680049689-0319594176889120147201
                        21147-42176415919399284216342969873161982944217164807558986163430201151656080042661130108DM3M89716998107338470024993726004476445265066302720008375964923161905447156272090768
                        148-4116811607853117911652260400651635694361661665884680031650125710091672951938631130463ctime DM1M0273335641300441319342183573922502261936021292000000000380186264621403604066613
                        149-40160016237663074167022381416515592811516836937702166594940868168982383461130792ctime DM2nM-0001801609003852754341993813052744-0046761584409627500508-0077775361400741721434
                        150-3915211639679496891688187227351667424200641701502860371681773107271706695730571131095ctime DM2M018351233550050400264218527995115136410986806000035213850084080158102829445129
                        151-381444165559268638170615064071683289120131719311950541697596805861723567626541131372ctime DM3nM-00828939084003613451762154072117374-2294036668800227523171-01541164168-00116713999
                        152-3713691671505875871724114054051699154039621737121040711713420504451740439522511131623ctime DM3M01043800754006833358544289704404311527507664201273718042-002993023630238690387
                        153-361296168741906536174207746741715018959111754930130881729244203041757311418481131848ctimesq DM1M00013868456000068355948648344249722028860113900430166221000004375310002729938
                        22154-351225170333225485176004088075173088387861772739221051745067901631774183314451132047ctimesq DM2nM-00005653252000062960465273178841193-089790520203696458706-0001802166400006715159
                        155-34115617192454443417780042941174674879809179054831122176089160022179105521042113222ctimesq DM2M000075008730000765705947828891110020979602361703277776707-000075447600022546507
                        156-3310891735158633831795967707451762613717581808357401391776715298811807927106391132367ctimesq DM3nM-00004192175000060387515431674664601-0694212254504878459099-0001605434200007669992
                        157-32102417510718233218139311208177847863707182616649156179253899741824799002361132488ctimesq DM3M000059628620001088715170367914567330547697190905840735181-000154123270002733805
                        158-319611766985012811831894534151794343556561843975581731808362695991841670898331132583a Dependent Variable buikomtrek echo 1 (mm)
                        159-30900178289820231849857947518102084760518617846719182418639458185854279431132652
                        160-298411798811391791867821360851826073395541879593762071840010093171875414690271132695
                        23161-28784181472458128188578477421841938315031897402852241855833791761892286586241132712
                        162-277291830637770771903748187551857803234521915211942411871657490351909158482211132703
                        163-26676184655096026192171160091873668154011933021032581887481188941926030378181132668
                        164-25625186246414975193967501425188953307351950830122751903304887531942902274151132607
                        165-2457618783773392419576384276190539799299196863921292191912858612195977417012113252
                        166-235291894290528731975601840951921262912481986448303091934952284711976646066091132407
                        167-2248419102037182219935652543193712783197200425739326195077598331993517962061132268
                        24168-214411926116907712011528667651952992751462022066483431966599681892010389858031132103
                        169-204001942030097220294920811968857670952039875573619824233804820272617541131912
                        170-193611957943286692047455494351984722590442057684663771998247079072044133649971131695
                        171-18324197385647618206541890772000587509932075493753942014070777662061005545941131452
                        172-172891989769665672083382321052016452429422093302844112029894476252077877441911131183
                        173-16256200568285516210134573442032317348912111111934282045718174842094749337881130888
                        174-15225202159604465211930914775204818226842128921024452061541873432111621233851130567
                        25175-1419620375092341421372725611206404718789214673011462207736557202212849312982113022
                        176-131692053422423632155235974452079912107382164539204792093189270612145365025791129847
                        177-1214420693356131221731993878209577702687218234829496210901296922162236921761129448
                        178-111212085248802612191162801152111641946362200157385132124836667792179108817731129023
                        179-10100210116199212209126214521275068658522179664753214066036638219598071371128572
                        180-9812117075181592227089627852143371785342235775565472156484064972212852609671128095
                        181-864213298837108224505304122159236704832253584655642172307763562229724505641127592
                        26182-7492148901560572263016454552175101624322271393745812188131462152246596401611127063
                        183-636216481475006228097986792190966543812289202835982203955160742263468297581126508
                        184-525218072793955229894328125220683146332307011926152219778859332280340193551125927
                        185-41621966411290423169066946222269638279232482101632223560255792229721208952112532
                        186-392212554318532334870107952238561302282342630106492251426256512314083985491124687
                        187-2422284675080223528335213225442622177236043919666226724995512330955881461124028
                        188-112244380697512370796934652270291141262378248286832283073653692347827777431123343
                        2718900226029388723887603482286156060752396057377229889735228236469967341122632
                        190112276207076492406723761352302020980242413866467172314721050872381571569371121895
                        19124229212026598242468717472317885899732431675557342330544749462398443465341121132
                        192392308033455472442650588052333750819222449484647512346368448052415315361311120343
                        193416232394664496246061400142349615738712467293737682362192146642432187257281119528
                        194525233985983445247857741475236548065822485102827852378015845232449059153251118687
                        19563623557730239424965408281238134557769250291191802239383954382246593104922111782
                        281967492371686213432514504241452397210497182520721008192409663242412482802945191116927
                        1978642387599402922532467654824130754166725385300983624254869412499674841161116008
                        1989812403512592412550431068152428940336162556339188532441310639592516546737131115063
                        19910100241942578192568394481524448052556525741482787245713433818253341863311114092
                        200111212435338971392586357894852460670175142591957368872472958036772550290529071113095
                        20112144245125216088260432130822476535094632609766459042488781735362567162425041112072
                        202131692467165350372622284721552492400014122627575549212504605433952584034321011111023
                        2920314196248307853986264024813492508264933612645384639382520429132542600906216981109948
                        20415225249899172935265821154825252412985312663193729552536252831132617778112951108847
                        2051625625149049188426761749616253999477259268100281972255207652972263465000892110772
                        206172892530818108332694138374952555859692082698811909892567900228312651521904891106567
                        2071832425467312978227121017883257172461157271662100006258372392692668393800861105388
                        208193612562644487312730065201652587589531062734430090232599547625492685265696831104183
                        2092040025785576768274802861526034544505527522391804261537132408270213759281102952
                        30210214412594470866292765992028352619319370042770048270572631195022672719009488771101695
                        21122484261038405578278395544172635184289532787857360742647018721262735881384741100412
                        212235292626297245272801918855052651049209022805666450912662842419852752753280711099103
                        21324576264221043476281988226842666914128512823475541082678666118442769625176681097768
                        2142562526581236242528378456817526827790482841284631252694489817032786497072651096407
                        2152667626740368137428558090951269864396749285909372142271031351562280336896862109502
                        216277292689950003232873772508452714508886982876902811592726137214212820240864591093607
                        312172878427058631927228917359218273037380647289471190176274196091282837112760561092168
                        218298412721776382212909699335152746238725962912520991932757784611392853984656531090703
                        21930900273768957172927662748527621036454529303300821277360830998287085655251089212
                        220319612753602761192945626161852777968564942948139172272789432008572887728448471087695
                        221321024276951595068296358957522793833484432965948262442805255707162904600344441086152
                        2223310892785429140172981552988552809698403922983757352612821079405752921472240411084583
                        223341156280134232966299951640192825563323413001566442782836903104342938344136381082988
                        32224351225281725551915301747981525284142824293019375532952852726802932955216032351081367
                        22536129628331687086430354432286285729316239303718462312286855050152297208792832107972
                        2263713692849081898133053406641952873158081883054993713292884374200112988959824291078047
                        22738144428649950876230713700553288902300137307280280346290019789873005831720261076348
                        2283915212880908277113089333468652904887920863090611893632916021597293022703616231074623
                        22940160028968214666310729688229207528403531084209838293184529588303957551221072872
                        2304116812912734656093125260295352936617759843126230073972947668994473056447408171071095
                        33231421764292864784558314322370872952482679333144039164142963492693063073319304141069292
                        2324318492944561035073161187122052968347598823161848254312979316391653090191200111067463
                        233441936296047422456317915053542984212518313179657344482995140090243107063096081065608
                        234452025297638741405319711394875300007743783197466434653010963788833123934992051063727
                        23546211629923006035432150773621301594235729321527552482302678748742314080688802106182
                        2364722093008213793033233040775453031807276783233084614993042611186013157678783991059887
                        23748230430241269825232510041888304767219627325089370516305843488463174550679961057928
                        342384924013040040172013268967602153063537115763268702795333074258583193191422575931055943
                        239502500305595336153286931015530794020352532865118855309008228178320829447191053932
                        2405126013071866550993304894428853095266954743304320975673105905980373225166367871051895
                        241522704308777974048332285784223111131874233322130065843121729678963242038263841049832
                        2425328093103692929973340821255553126996793723339939156013137553377553258910159811047743
                        243542916311960611946335878466893142861713213357748246183153377076143275782055781045628
                        244553025313551930895337674808225315872663273375557336353169200774733292653951751043487
                        3524556313631514324984433947114956317459155219339336642652318502447332330952584772104132
                        2465732493167345687933412674908953190456471683411175516693200848171913326397743691039127
                        24758336431832588774234306383223320632139117342898460686321667187053343269639661036908
                        2485934813199172066913448601735653222186310663446793697033232495569093360141535631034663
                        24960360032150852564346656514932380512301534646027872324831926768337701343161032392
                        2506137213230998445893484528562353253916149643482411877373264142966273393885327571030095
                        251623844324691163538350249197573269781069133500220967543279966664863410757223541027772
                        362526339693262824824873520455389053285645988623518030057713295790363453427629119511025423
                        253644096327873801436353841880243301510908113535839147883311614062043444501015481023048
                        254654225329465120385355638221575331737582763553648238053327437760633461372911451020647
                        25566435633105643933435743456291333324074709357145732822334326145922347824480742101822
                        2566744893326477582833592309042453349105666583589266418393359085157813495116703391015767
                        25768462433423907723236102724558336497058607360707550856337490885643511988599361013288
                        2586947613358303961813628235869153380835505563624884598733390732554993528860495331010783
                        37259704900337421715133646199282533967004250536426936889340655625358354573239131008252
                        2607150413390130340793664162695853412565344543660502779073422379952173562604287271005695
                        261725184340604353028368212610923428430264033678311869243438203650763579476183241003112
                        2627353293421956719773700089522553444295183523696120959413454027349353596348079211000503
                        263745476343786990926371805293593460160103013713930049583469851047943613219975180997868
                        PDM1
                        PDM 2
                        GDM
                        Intercepting Curves Random Effects are intercept and ctime (=slope)
                        AD weekAD dagenctimectimesqDM1 lt977DM1 gt977DM2GDMlt977GDN gt977controle
                        17119-7049001103696581094598541182103721201826791109612CURVE
                        120-6947611121270161112530551199690231216229731110695
                        121-6846241138824721130489621217245381230675111111752DM1
                        122-6744891156360261148475751234769171245162931112783
                        123-664356117387678116648894125226161259693191113788Estimates of Fixed Effectsa
                        124-6542251191374281184529191269722671274265891114767ParameterEstimateStd ErrordftSig95 Confidence Interval
                        125-64409612088527612025965128715238128888103111572Lower BoundUpper Bound
                        18126-6339691226312221220690871304550731303538611116647Intercept2287913881520384108618150483000225777917231804859
                        127-623844124375266123881231321917721318238631117548ctime1625169022128710967344400015810481669290
                        128-6137211261174081256960791339253351332981091118423ctimesq-000951000354194196-2688008-001648-000253
                        129-6036001278576481275136341356557621347765991119272macro9771272752633378541089963813000611200519343047
                        130-5934811295959861293338951373830531362593331120095ctime macro977356099048599710657327000259198453001
                        131-5833641313324221311568621391072081377463111120892ctimesq macro9770023040007931887032906004000740003867
                        132-5732491330669561329825351408282271392375331121663
                        19133-563136134799588134810914142546111407329991122408109459854
                        134-5530251365303181366419991442608571422327091123127GDM
                        135-54291613825914613847579145972468143736663112382
                        136-5328091399860721403122871476809431452448611124487Estimates of Fixed Effectsa
                        137-522704141711096142151491493862821467573031125128ParameterEstimateStd ErrordftSig95 Confidence Interval
                        138-5126011434342181439933991510884851482739891125743Lower BoundUpper Bound
                        139-5025001451554381458380141527875521497949191126332Intercept2337425021590949123524146920000230593448236891556
                        20140-4924011468747561476853351544834831513200931126895ctime1540699026577949835797100014879371593462
                        141-4823041485921721495353621561762781528495111127432ctimesq-001568000409171203-3835000-002376-000761
                        142-4722091503076861513880951578659371543831731127943macro977-24899835139890126886-484629-126609847681019
                        143-462116152021298153243534159552461559210791128428ctime macro9771945531231521807261580116-048449437554
                        144-4520251537330081551016791612358471574632291128887ctimesq macro9770036900018622344051982049000022007359
                        145-44193615544281615696253162916098159009623112932
                        146-4318491571507221588260871645932131605602611129727
                        21147-421764158856726160692351662671921621151431130108
                        148-4116811605608281625613191679380351636742691130463
                        149-4016001622630281644329941696057421652376391130792
                        150-3915211639633261663073751712703131668052531131095
                        151-3814441656617221681844621729317481683771111131372
                        152-3713691673582161700642551745900471699532131131623
                        153-361296169052808171946754176245211715335591131848
                        22154-3512251707454981738319591778972371731181491132047
                        155-34115617243628617571987179546128174706983113222
                        156-3310891741251721776104871811918831763000611132367
                        157-321024175812156179503811828345021778973831132488
                        158-319611774972381813998391844739851794989491132583
                        159-309001791804181832985741861103321811047591132652
                        160-298411808616961852000151877435431827148131132695
                        23161-287841825410721871041621893736181843291111132712
                        162-277291842185461890110151910005571859476531132703
                        163-26676185894118190920574192624361875704391132668
                        164-256251875677881928328391942450271891974691132607
                        165-2457618923955619474781195862558190828743113252
                        166-235291909094221966654871974769531924642611132407
                        167-22484192577386198585871990882121941040231132268
                        24168-214411942434482005089592006963351957480291132103
                        169-204001959076082024347542023013221973962791131912
                        170-193611975698662043632552039031731990487731131695
                        171-183241992302222062944622055018882007055111131452
                        172-172892008886762082283752070974672023664931131183
                        173-16256202545228210164994208689912040317191130888
                        174-152252041998782121043192102792172057011891130567
                        25175-1419620585262621404635211865388207374903113022
                        176-131692075034722159910872134484232090528611129847
                        177-12144209152416217938532150283222107350631129448
                        178-111212107994582198886792166050852124215091129023
                        179-101002124445982218415342181787122141121991128572
                        180-9812140878362237970952197492032158071331128095
                        181-8642157291722257553622213165582175063111127592
                        26182-7492173686062277163352228807772192097331127063
                        183-636219006138229680014224441862209173991126508
                        184-5252206417682316463992259998072226293091125927
                        185-41622227549623361549227554618224345463112532
                        186-392239073222355872872291062932260658611124687
                        187-24225537246237561792306548322277905031124028
                        188-112271652682395389992322002352295193891123343
                        27189002287913882415189142337425022312525191122632
                        190112304156062435015352352816332329898931121895
                        191242320379222454868622368176282347315111121132
                        192392336583362474748952383504872364773731120343
                        193416235276848249465634239880212382274791119528
                        1945252368934582514590792414067972399818291118687
                        19563623850816625345523242930248241740423111782
                        281967492401209722554540872444505632435032611116927
                        197864241731876257455652459677422452703431116008
                        1989812433408782594599192474817852470416691115063
                        199101002449479782614668942489926922488172391114092
                        200111212465531762634765752505004632505970531113095
                        201121442481564722654889622520050982523811111112072
                        202131692497578662675040552535065972541694131111023
                        2920314196251357358269521854255004962559619591109948
                        204152252529549482715423592565001872577587491108847
                        2051625625455063627356557257992278259559783110772
                        206172892561444222755914872594812332613650611106567
                        20718324257736306277620112609670522631745831105388
                        208193612593262882796514392624497352649883491104183
                        209204002609143682816854742639292822668063591102952
                        30210214412625005462837222152654056932686286131101695
                        211224842640848222857616622668789682704551111100412
                        212235292656671962878038152683491072722858531099103
                        21324576267247668289848674269816112741208391097768
                        214256252688262382918962392712799772759600691096407
                        2152667627040290629394651272740708277803543109502
                        216277292719776722959994872741983032796512611093607
                        3121728784273550536298055172756527622815032231092168
                        218298412751214983001135592771040852833594291090703
                        219309002766905583021746542785522722852198791089212
                        220319612782577163042384552799973232870845731087695
                        2213210242798229723063049622814392382889535111086152
                        2223310892813863263083741752828780172908266931084583
                        223341156282947778310446094284313662927041191082988
                        322243512252845073283125207192857461672945857891081367
                        22536129628606497631459805287175538296471703107972
                        2263713692876207223166780872886017732983618611078047
                        227381444289174566318760832900248723002562631076348
                        2283915212907265083208462792914448353021549091074623
                        2294016002922765483229344342928616623040577991072872
                        2304116812938246863250252952942753533059649331071095
                        332314217642953709223271188622956859083078763111069292
                        2324318492969152563292151352970933273097919331067463
                        233441936298457688331314114298497613117117991065608
                        2344520252999982183334157992998987573136359091063727
                        23546211630153684633552019301296768315564263106182
                        2364722093030735723376272873026916433174968611059887
                        237482304304608396339737093040833823194337031057928
                        342384924013061413183418495993054719853213747891055943
                        2395025003076723383439648143068574523233201191053932
                        2405126013092014563460827353082397833252696931051895
                        2415227043107286723482033623096189783272235111049832
                        2425328093122539863503266953109950373291815731047743
                        243542916313777398352452734312367963311438791045628
                        2445530253152989083545814793137377473331104291043487
                        3524556313631681851635671293315104398335081223104132
                        2465732493183362223588470873164679133370562611039127
                        247583364319852026360983953178282923390355431036908
                        2485934813213659283631235193191855353410190691034663
                        2496036003228779283652657943205396423430068391032392
                        2506137213243880263674107753218906133449988531030095
                        2516238443258962223695584623232384483469951111027772
                        362526339693274025163717088553245831473489956131025423
                        253644096328906908373861954325924713510003591023048
                        2546542253304093983760177593272631373530093491020647
                        25566435633190998637817627328598428355022583101822
                        2566744893334086723803374873299305833570400611015767
                        257684624334905456382501413312596023590617831013288
                        2586947613364003383846680393325854853610877491010783
                        372597049003378933183868373743339082323631179591008252
                        2607150413393843963890094153352278433651524131005695
                        2617251843408735723911841623365443183671911111003112
                        2627353293423608463933616153378576573692340531000503
                        263745476343846218395541774339167863712812390997868
                        PDM1
                        PDM 2
                        GDM

                        Conseguenze neonataliParalisi transitoria plesso brachiale (30-168)Frattura della clavicola (17-95)Frattura dellrsquo omero (01-42)Paralisi permanente del plesso brachiale(05-16)encefalopatia ipossico-ischemica (03)morte (0-035)

                        Hoffman MK Obstet Gynecol 2011117(6)1272Gherman RB Am J Obstet Gynecol 2006195(3)657

                        LA MACROSOMIA Egrave UN IMPORTANTE FATTORE DI RISCHIO PER DISTOCIA DI SPALLA

                        Iperglicemia e rischio di morte fetale a termine di gravidanza

                        Estimated rate of stillbirth in diabetic women 1920-2000

                        Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                        4 of all stillbirths remain attributable to diabetes

                        Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                        bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                        Adverse outcome

                        HbA1C gt7

                        1 increase in A1Ccorresponded to 55 increased

                        risk of adverse outcome

                        The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                        gestation particularly in the presence of fetal macrosomia

                        fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                        Langer O 1995

                        100 mgdLfor stillbirth

                        Diabetic patients n = 271691

                        Am J Obstet Gynecol 2002

                        The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                        4873 diabetic women

                        pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                        outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                        bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                        GDMbull dysglycemia was more difficult to manage

                        2016

                        Differences in placental pathologyaccording to diabetes types

                        Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                        GDM is associated with a greater rate of villous immaturity

                        0102030405060708090

                        100GDMDMIDMII

                        o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                        A retrospective study on 175 placentas with DVM vs 175 controls

                        Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                        Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                        Pathophysiology of fetal compromise in diabetic pregnancy

                        The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                        Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                        Bjork 1984Nylund 1982Siddiqui 2003

                        A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                        STILLBIRTH RISK

                        BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                        OBESITArsquo E MORTE FETALE

                        6-7 per unit BMI for BMI gt 23

                        Tennant PWG Am J Obstet Gynecol 2007

                        HYPERINSULINISMHYPERANDROGENISM

                        IMPAIRED PLACENTATION

                        THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                        Cakmak and Taylor Hum Reprod Update 2011

                        Makieva S Hum Reprod Update 2014

                        Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                        Hotamisligil GS Nature 2006

                        LeptinCRH

                        Urocortin 3IL-6

                        INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                        INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                        Adiponectina Insulin LeptinTNFα IL-6

                        PLACENTAL ALTERATIONIN GENE EXPRESSION

                        PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                        CollagenaseCervical ripening

                        FFA

                        OXIDATIVE STRESS

                        PREVENZIONE STILLBIRTH

                        PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                        MORBIDITAgrave NEONATALE

                        AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                        TIMING E MODALITArsquo DEL PARTO

                        Induzione o attesa

                        INDUZIONE DEL TRAVAGLIO

                        Quando fare un TC elettivo

                        gt 4000 grgt 4500 gr gt 5000 gr

                        ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                        425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                        No differenza in TC e outcome perinatale

                        200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                        No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                        RCT INDUZIONE VS ATTESA in GDM

                        RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                        2014

                        1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                        2 Patients well controlled on insulin should probably be delivered by the due date

                        3 Poorly controlled GDMrsquos using insulin require individual judgment

                        Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                        1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                        2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                        3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                        cesarean delivery when the estimated fetal weight is ge 4500 g

                        MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                        MODALITAgrave E TIMING DEL PARTO nel GDM

                        GMD in terapia insulinicaBen controllato

                        +Condizioni fetali rassicuranti

                        MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                        GDM in terapia nutrizionalecon profili glicemici ottimali

                        +Feto AGA

                        MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                        Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                        EFW lt 4000g LGAControllo metabolico non

                        ottimale

                        4000g lt EFW gt 4500g EFW ge 4500g

                        Programmare TC elettivo

                        Parto vaginale indotto a 38-39 sett

                        Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                        MODALITAgrave E TIMING DEL PARTO nel GDM

                        IN BASE AL PESO FETALE STIMATO

                        - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                        - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                        - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                        ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                        Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                        The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                        A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                        If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                        Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                        GDM and the Use of Betamethasone

                        bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                        bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                        bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                        Society of Obstetricians and Gynaecologists of Canada

                        The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                        late preterm delivery between 24 to 36 weeksrsquo gestation

                        ASSISTENZA IN TRAVAGLIO

                        - MONITORAGGIO FETALE CONTINUO

                        - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                        MANTENERE GLICEMIA gt70 E lt 126

                        (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                        GDM

                        - Intravenous infusion of regular insulin titrated and glucose

                        - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                        (ACOG 2005)

                        ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                        Venere di Willendorf

                        Thank you for your attention

                        Pathophysiology of fetal compromise in diabetic pregnancy

                        Islet cell hyperplasia common in stillborn IDMs

                        There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                        Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                        Salvesen 1993Hay 1989Chukwuma 2001

                        • Diapositiva numero 1
                        • Diapositiva numero 2
                        • Diapositiva numero 3
                        • Diapositiva numero 4
                        • Diapositiva numero 5
                        • Diapositiva numero 6
                        • Diapositiva numero 7
                        • Birth weight distribution in diabetic pregnancies
                        • Diapositiva numero 9
                        • Diapositiva numero 10
                        • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                        • Diapositiva numero 12
                        • Diapositiva numero 13
                        • Diapositiva numero 14
                        • Diapositiva numero 15
                        • Diapositiva numero 16
                        • Diapositiva numero 17
                        • Diapositiva numero 18
                        • Diapositiva numero 19
                        • Differences in placental pathology according to diabetes types
                        • Diapositiva numero 21
                        • Pathophysiology of fetal compromise in diabetic pregnancy
                        • Diapositiva numero 23
                        • Diapositiva numero 24
                        • Diapositiva numero 25
                        • Diapositiva numero 26
                        • Diapositiva numero 27
                        • Diapositiva numero 28
                        • Diapositiva numero 29
                        • Diapositiva numero 30
                        • Diapositiva numero 31
                        • Diapositiva numero 32
                        • Diapositiva numero 33
                        • Diapositiva numero 34
                        • Diapositiva numero 35
                        • Diapositiva numero 36
                        • GDM and the Use of Betamethasone
                        • Diapositiva numero 38
                        • Diapositiva numero 39
                        • Diapositiva numero 40
                        • Pathophysiology of fetal compromise in diabetic pregnancy

                          Iperglicemia e rischio di morte fetale a termine di gravidanza

                          Estimated rate of stillbirth in diabetic women 1920-2000

                          Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                          4 of all stillbirths remain attributable to diabetes

                          Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                          bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                          Adverse outcome

                          HbA1C gt7

                          1 increase in A1Ccorresponded to 55 increased

                          risk of adverse outcome

                          The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                          gestation particularly in the presence of fetal macrosomia

                          fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                          Langer O 1995

                          100 mgdLfor stillbirth

                          Diabetic patients n = 271691

                          Am J Obstet Gynecol 2002

                          The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                          4873 diabetic women

                          pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                          outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                          bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                          GDMbull dysglycemia was more difficult to manage

                          2016

                          Differences in placental pathologyaccording to diabetes types

                          Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                          GDM is associated with a greater rate of villous immaturity

                          0102030405060708090

                          100GDMDMIDMII

                          o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                          A retrospective study on 175 placentas with DVM vs 175 controls

                          Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                          Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                          Pathophysiology of fetal compromise in diabetic pregnancy

                          The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                          Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                          Bjork 1984Nylund 1982Siddiqui 2003

                          A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                          STILLBIRTH RISK

                          BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                          OBESITArsquo E MORTE FETALE

                          6-7 per unit BMI for BMI gt 23

                          Tennant PWG Am J Obstet Gynecol 2007

                          HYPERINSULINISMHYPERANDROGENISM

                          IMPAIRED PLACENTATION

                          THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                          Cakmak and Taylor Hum Reprod Update 2011

                          Makieva S Hum Reprod Update 2014

                          Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                          Hotamisligil GS Nature 2006

                          LeptinCRH

                          Urocortin 3IL-6

                          INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                          INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                          Adiponectina Insulin LeptinTNFα IL-6

                          PLACENTAL ALTERATIONIN GENE EXPRESSION

                          PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                          CollagenaseCervical ripening

                          FFA

                          OXIDATIVE STRESS

                          PREVENZIONE STILLBIRTH

                          PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                          MORBIDITAgrave NEONATALE

                          AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                          TIMING E MODALITArsquo DEL PARTO

                          Induzione o attesa

                          INDUZIONE DEL TRAVAGLIO

                          Quando fare un TC elettivo

                          gt 4000 grgt 4500 gr gt 5000 gr

                          ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                          425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                          No differenza in TC e outcome perinatale

                          200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                          No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                          RCT INDUZIONE VS ATTESA in GDM

                          RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                          2014

                          1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                          2 Patients well controlled on insulin should probably be delivered by the due date

                          3 Poorly controlled GDMrsquos using insulin require individual judgment

                          Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                          1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                          2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                          3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                          cesarean delivery when the estimated fetal weight is ge 4500 g

                          MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                          MODALITAgrave E TIMING DEL PARTO nel GDM

                          GMD in terapia insulinicaBen controllato

                          +Condizioni fetali rassicuranti

                          MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                          GDM in terapia nutrizionalecon profili glicemici ottimali

                          +Feto AGA

                          MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                          Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                          EFW lt 4000g LGAControllo metabolico non

                          ottimale

                          4000g lt EFW gt 4500g EFW ge 4500g

                          Programmare TC elettivo

                          Parto vaginale indotto a 38-39 sett

                          Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                          MODALITAgrave E TIMING DEL PARTO nel GDM

                          IN BASE AL PESO FETALE STIMATO

                          - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                          - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                          - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                          ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                          Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                          The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                          A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                          If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                          Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                          GDM and the Use of Betamethasone

                          bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                          bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                          bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                          Society of Obstetricians and Gynaecologists of Canada

                          The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                          late preterm delivery between 24 to 36 weeksrsquo gestation

                          ASSISTENZA IN TRAVAGLIO

                          - MONITORAGGIO FETALE CONTINUO

                          - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                          MANTENERE GLICEMIA gt70 E lt 126

                          (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                          GDM

                          - Intravenous infusion of regular insulin titrated and glucose

                          - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                          (ACOG 2005)

                          ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                          Venere di Willendorf

                          Thank you for your attention

                          Pathophysiology of fetal compromise in diabetic pregnancy

                          Islet cell hyperplasia common in stillborn IDMs

                          There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                          Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                          Salvesen 1993Hay 1989Chukwuma 2001

                          • Diapositiva numero 1
                          • Diapositiva numero 2
                          • Diapositiva numero 3
                          • Diapositiva numero 4
                          • Diapositiva numero 5
                          • Diapositiva numero 6
                          • Diapositiva numero 7
                          • Birth weight distribution in diabetic pregnancies
                          • Diapositiva numero 9
                          • Diapositiva numero 10
                          • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                          • Diapositiva numero 12
                          • Diapositiva numero 13
                          • Diapositiva numero 14
                          • Diapositiva numero 15
                          • Diapositiva numero 16
                          • Diapositiva numero 17
                          • Diapositiva numero 18
                          • Diapositiva numero 19
                          • Differences in placental pathology according to diabetes types
                          • Diapositiva numero 21
                          • Pathophysiology of fetal compromise in diabetic pregnancy
                          • Diapositiva numero 23
                          • Diapositiva numero 24
                          • Diapositiva numero 25
                          • Diapositiva numero 26
                          • Diapositiva numero 27
                          • Diapositiva numero 28
                          • Diapositiva numero 29
                          • Diapositiva numero 30
                          • Diapositiva numero 31
                          • Diapositiva numero 32
                          • Diapositiva numero 33
                          • Diapositiva numero 34
                          • Diapositiva numero 35
                          • Diapositiva numero 36
                          • GDM and the Use of Betamethasone
                          • Diapositiva numero 38
                          • Diapositiva numero 39
                          • Diapositiva numero 40
                          • Pathophysiology of fetal compromise in diabetic pregnancy

                            Estimated rate of stillbirth in diabetic women 1920-2000

                            Diabetic-Associated Stillbirth Incidence Pathophysiology and PreventionDonald J Dudley Clin Perinatol 34 (2007)

                            4 of all stillbirths remain attributable to diabetes

                            Stillbirth rates are higher than in non diabetic pregnancies by 15 to 6-folds

                            bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                            Adverse outcome

                            HbA1C gt7

                            1 increase in A1Ccorresponded to 55 increased

                            risk of adverse outcome

                            The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                            gestation particularly in the presence of fetal macrosomia

                            fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                            Langer O 1995

                            100 mgdLfor stillbirth

                            Diabetic patients n = 271691

                            Am J Obstet Gynecol 2002

                            The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                            4873 diabetic women

                            pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                            outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                            bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                            GDMbull dysglycemia was more difficult to manage

                            2016

                            Differences in placental pathologyaccording to diabetes types

                            Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                            GDM is associated with a greater rate of villous immaturity

                            0102030405060708090

                            100GDMDMIDMII

                            o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                            A retrospective study on 175 placentas with DVM vs 175 controls

                            Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                            Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                            Pathophysiology of fetal compromise in diabetic pregnancy

                            The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                            Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                            Bjork 1984Nylund 1982Siddiqui 2003

                            A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                            STILLBIRTH RISK

                            BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                            OBESITArsquo E MORTE FETALE

                            6-7 per unit BMI for BMI gt 23

                            Tennant PWG Am J Obstet Gynecol 2007

                            HYPERINSULINISMHYPERANDROGENISM

                            IMPAIRED PLACENTATION

                            THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                            Cakmak and Taylor Hum Reprod Update 2011

                            Makieva S Hum Reprod Update 2014

                            Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                            Hotamisligil GS Nature 2006

                            LeptinCRH

                            Urocortin 3IL-6

                            INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                            INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                            Adiponectina Insulin LeptinTNFα IL-6

                            PLACENTAL ALTERATIONIN GENE EXPRESSION

                            PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                            CollagenaseCervical ripening

                            FFA

                            OXIDATIVE STRESS

                            PREVENZIONE STILLBIRTH

                            PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                            MORBIDITAgrave NEONATALE

                            AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                            TIMING E MODALITArsquo DEL PARTO

                            Induzione o attesa

                            INDUZIONE DEL TRAVAGLIO

                            Quando fare un TC elettivo

                            gt 4000 grgt 4500 gr gt 5000 gr

                            ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                            425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                            No differenza in TC e outcome perinatale

                            200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                            No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                            RCT INDUZIONE VS ATTESA in GDM

                            RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                            2014

                            1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                            2 Patients well controlled on insulin should probably be delivered by the due date

                            3 Poorly controlled GDMrsquos using insulin require individual judgment

                            Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                            1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                            2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                            3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                            cesarean delivery when the estimated fetal weight is ge 4500 g

                            MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                            MODALITAgrave E TIMING DEL PARTO nel GDM

                            GMD in terapia insulinicaBen controllato

                            +Condizioni fetali rassicuranti

                            MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                            GDM in terapia nutrizionalecon profili glicemici ottimali

                            +Feto AGA

                            MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                            Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                            EFW lt 4000g LGAControllo metabolico non

                            ottimale

                            4000g lt EFW gt 4500g EFW ge 4500g

                            Programmare TC elettivo

                            Parto vaginale indotto a 38-39 sett

                            Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                            MODALITAgrave E TIMING DEL PARTO nel GDM

                            IN BASE AL PESO FETALE STIMATO

                            - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                            - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                            - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                            ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                            Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                            The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                            A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                            If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                            Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                            GDM and the Use of Betamethasone

                            bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                            bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                            bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                            Society of Obstetricians and Gynaecologists of Canada

                            The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                            late preterm delivery between 24 to 36 weeksrsquo gestation

                            ASSISTENZA IN TRAVAGLIO

                            - MONITORAGGIO FETALE CONTINUO

                            - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                            MANTENERE GLICEMIA gt70 E lt 126

                            (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                            GDM

                            - Intravenous infusion of regular insulin titrated and glucose

                            - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                            (ACOG 2005)

                            ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                            Venere di Willendorf

                            Thank you for your attention

                            Pathophysiology of fetal compromise in diabetic pregnancy

                            Islet cell hyperplasia common in stillborn IDMs

                            There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                            Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                            Salvesen 1993Hay 1989Chukwuma 2001

                            • Diapositiva numero 1
                            • Diapositiva numero 2
                            • Diapositiva numero 3
                            • Diapositiva numero 4
                            • Diapositiva numero 5
                            • Diapositiva numero 6
                            • Diapositiva numero 7
                            • Birth weight distribution in diabetic pregnancies
                            • Diapositiva numero 9
                            • Diapositiva numero 10
                            • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                            • Diapositiva numero 12
                            • Diapositiva numero 13
                            • Diapositiva numero 14
                            • Diapositiva numero 15
                            • Diapositiva numero 16
                            • Diapositiva numero 17
                            • Diapositiva numero 18
                            • Diapositiva numero 19
                            • Differences in placental pathology according to diabetes types
                            • Diapositiva numero 21
                            • Pathophysiology of fetal compromise in diabetic pregnancy
                            • Diapositiva numero 23
                            • Diapositiva numero 24
                            • Diapositiva numero 25
                            • Diapositiva numero 26
                            • Diapositiva numero 27
                            • Diapositiva numero 28
                            • Diapositiva numero 29
                            • Diapositiva numero 30
                            • Diapositiva numero 31
                            • Diapositiva numero 32
                            • Diapositiva numero 33
                            • Diapositiva numero 34
                            • Diapositiva numero 35
                            • Diapositiva numero 36
                            • GDM and the Use of Betamethasone
                            • Diapositiva numero 38
                            • Diapositiva numero 39
                            • Diapositiva numero 40
                            • Pathophysiology of fetal compromise in diabetic pregnancy

                              bull spontaneous and therapeutic abortionbull stillbirthbull neonatal deathbull major congenital abnormalities

                              Adverse outcome

                              HbA1C gt7

                              1 increase in A1Ccorresponded to 55 increased

                              risk of adverse outcome

                              The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                              gestation particularly in the presence of fetal macrosomia

                              fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                              Langer O 1995

                              100 mgdLfor stillbirth

                              Diabetic patients n = 271691

                              Am J Obstet Gynecol 2002

                              The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                              4873 diabetic women

                              pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                              outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                              bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                              GDMbull dysglycemia was more difficult to manage

                              2016

                              Differences in placental pathologyaccording to diabetes types

                              Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                              GDM is associated with a greater rate of villous immaturity

                              0102030405060708090

                              100GDMDMIDMII

                              o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                              A retrospective study on 175 placentas with DVM vs 175 controls

                              Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                              Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                              Pathophysiology of fetal compromise in diabetic pregnancy

                              The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                              Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                              Bjork 1984Nylund 1982Siddiqui 2003

                              A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                              STILLBIRTH RISK

                              BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                              OBESITArsquo E MORTE FETALE

                              6-7 per unit BMI for BMI gt 23

                              Tennant PWG Am J Obstet Gynecol 2007

                              HYPERINSULINISMHYPERANDROGENISM

                              IMPAIRED PLACENTATION

                              THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                              Cakmak and Taylor Hum Reprod Update 2011

                              Makieva S Hum Reprod Update 2014

                              Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                              Hotamisligil GS Nature 2006

                              LeptinCRH

                              Urocortin 3IL-6

                              INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                              INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                              Adiponectina Insulin LeptinTNFα IL-6

                              PLACENTAL ALTERATIONIN GENE EXPRESSION

                              PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                              CollagenaseCervical ripening

                              FFA

                              OXIDATIVE STRESS

                              PREVENZIONE STILLBIRTH

                              PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                              MORBIDITAgrave NEONATALE

                              AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                              TIMING E MODALITArsquo DEL PARTO

                              Induzione o attesa

                              INDUZIONE DEL TRAVAGLIO

                              Quando fare un TC elettivo

                              gt 4000 grgt 4500 gr gt 5000 gr

                              ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                              425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                              No differenza in TC e outcome perinatale

                              200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                              No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                              RCT INDUZIONE VS ATTESA in GDM

                              RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                              2014

                              1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                              2 Patients well controlled on insulin should probably be delivered by the due date

                              3 Poorly controlled GDMrsquos using insulin require individual judgment

                              Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                              1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                              2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                              3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                              cesarean delivery when the estimated fetal weight is ge 4500 g

                              MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                              MODALITAgrave E TIMING DEL PARTO nel GDM

                              GMD in terapia insulinicaBen controllato

                              +Condizioni fetali rassicuranti

                              MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                              GDM in terapia nutrizionalecon profili glicemici ottimali

                              +Feto AGA

                              MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                              Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                              EFW lt 4000g LGAControllo metabolico non

                              ottimale

                              4000g lt EFW gt 4500g EFW ge 4500g

                              Programmare TC elettivo

                              Parto vaginale indotto a 38-39 sett

                              Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                              MODALITAgrave E TIMING DEL PARTO nel GDM

                              IN BASE AL PESO FETALE STIMATO

                              - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                              - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                              - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                              ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                              Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                              The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                              A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                              If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                              Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                              GDM and the Use of Betamethasone

                              bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                              bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                              bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                              Society of Obstetricians and Gynaecologists of Canada

                              The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                              late preterm delivery between 24 to 36 weeksrsquo gestation

                              ASSISTENZA IN TRAVAGLIO

                              - MONITORAGGIO FETALE CONTINUO

                              - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                              MANTENERE GLICEMIA gt70 E lt 126

                              (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                              GDM

                              - Intravenous infusion of regular insulin titrated and glucose

                              - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                              (ACOG 2005)

                              ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                              Venere di Willendorf

                              Thank you for your attention

                              Pathophysiology of fetal compromise in diabetic pregnancy

                              Islet cell hyperplasia common in stillborn IDMs

                              There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                              Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                              Salvesen 1993Hay 1989Chukwuma 2001

                              • Diapositiva numero 1
                              • Diapositiva numero 2
                              • Diapositiva numero 3
                              • Diapositiva numero 4
                              • Diapositiva numero 5
                              • Diapositiva numero 6
                              • Diapositiva numero 7
                              • Birth weight distribution in diabetic pregnancies
                              • Diapositiva numero 9
                              • Diapositiva numero 10
                              • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                              • Diapositiva numero 12
                              • Diapositiva numero 13
                              • Diapositiva numero 14
                              • Diapositiva numero 15
                              • Diapositiva numero 16
                              • Diapositiva numero 17
                              • Diapositiva numero 18
                              • Diapositiva numero 19
                              • Differences in placental pathology according to diabetes types
                              • Diapositiva numero 21
                              • Pathophysiology of fetal compromise in diabetic pregnancy
                              • Diapositiva numero 23
                              • Diapositiva numero 24
                              • Diapositiva numero 25
                              • Diapositiva numero 26
                              • Diapositiva numero 27
                              • Diapositiva numero 28
                              • Diapositiva numero 29
                              • Diapositiva numero 30
                              • Diapositiva numero 31
                              • Diapositiva numero 32
                              • Diapositiva numero 33
                              • Diapositiva numero 34
                              • Diapositiva numero 35
                              • Diapositiva numero 36
                              • GDM and the Use of Betamethasone
                              • Diapositiva numero 38
                              • Diapositiva numero 39
                              • Diapositiva numero 40
                              • Pathophysiology of fetal compromise in diabetic pregnancy

                                The risk of stillbirth appears to increase in diabetic pregnancies starting at 34 weeks

                                gestation particularly in the presence of fetal macrosomia

                                fetal and neonatal outcomes are directly correlated with the degree of maternal glycemic control

                                Langer O 1995

                                100 mgdLfor stillbirth

                                Diabetic patients n = 271691

                                Am J Obstet Gynecol 2002

                                The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                                4873 diabetic women

                                pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                                outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                                bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                                GDMbull dysglycemia was more difficult to manage

                                2016

                                Differences in placental pathologyaccording to diabetes types

                                Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                                GDM is associated with a greater rate of villous immaturity

                                0102030405060708090

                                100GDMDMIDMII

                                o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                                A retrospective study on 175 placentas with DVM vs 175 controls

                                Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                                Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                                Pathophysiology of fetal compromise in diabetic pregnancy

                                The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                Bjork 1984Nylund 1982Siddiqui 2003

                                A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                STILLBIRTH RISK

                                BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                OBESITArsquo E MORTE FETALE

                                6-7 per unit BMI for BMI gt 23

                                Tennant PWG Am J Obstet Gynecol 2007

                                HYPERINSULINISMHYPERANDROGENISM

                                IMPAIRED PLACENTATION

                                THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                Cakmak and Taylor Hum Reprod Update 2011

                                Makieva S Hum Reprod Update 2014

                                Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                Hotamisligil GS Nature 2006

                                LeptinCRH

                                Urocortin 3IL-6

                                INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                Adiponectina Insulin LeptinTNFα IL-6

                                PLACENTAL ALTERATIONIN GENE EXPRESSION

                                PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                CollagenaseCervical ripening

                                FFA

                                OXIDATIVE STRESS

                                PREVENZIONE STILLBIRTH

                                PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                MORBIDITAgrave NEONATALE

                                AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                TIMING E MODALITArsquo DEL PARTO

                                Induzione o attesa

                                INDUZIONE DEL TRAVAGLIO

                                Quando fare un TC elettivo

                                gt 4000 grgt 4500 gr gt 5000 gr

                                ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                No differenza in TC e outcome perinatale

                                200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                RCT INDUZIONE VS ATTESA in GDM

                                RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                2014

                                1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                2 Patients well controlled on insulin should probably be delivered by the due date

                                3 Poorly controlled GDMrsquos using insulin require individual judgment

                                Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                cesarean delivery when the estimated fetal weight is ge 4500 g

                                MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                MODALITAgrave E TIMING DEL PARTO nel GDM

                                GMD in terapia insulinicaBen controllato

                                +Condizioni fetali rassicuranti

                                MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                GDM in terapia nutrizionalecon profili glicemici ottimali

                                +Feto AGA

                                MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                EFW lt 4000g LGAControllo metabolico non

                                ottimale

                                4000g lt EFW gt 4500g EFW ge 4500g

                                Programmare TC elettivo

                                Parto vaginale indotto a 38-39 sett

                                Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                MODALITAgrave E TIMING DEL PARTO nel GDM

                                IN BASE AL PESO FETALE STIMATO

                                - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                GDM and the Use of Betamethasone

                                bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                Society of Obstetricians and Gynaecologists of Canada

                                The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                late preterm delivery between 24 to 36 weeksrsquo gestation

                                ASSISTENZA IN TRAVAGLIO

                                - MONITORAGGIO FETALE CONTINUO

                                - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                MANTENERE GLICEMIA gt70 E lt 126

                                (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                GDM

                                - Intravenous infusion of regular insulin titrated and glucose

                                - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                (ACOG 2005)

                                ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                Venere di Willendorf

                                Thank you for your attention

                                Pathophysiology of fetal compromise in diabetic pregnancy

                                Islet cell hyperplasia common in stillborn IDMs

                                There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                Salvesen 1993Hay 1989Chukwuma 2001

                                • Diapositiva numero 1
                                • Diapositiva numero 2
                                • Diapositiva numero 3
                                • Diapositiva numero 4
                                • Diapositiva numero 5
                                • Diapositiva numero 6
                                • Diapositiva numero 7
                                • Birth weight distribution in diabetic pregnancies
                                • Diapositiva numero 9
                                • Diapositiva numero 10
                                • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                • Diapositiva numero 12
                                • Diapositiva numero 13
                                • Diapositiva numero 14
                                • Diapositiva numero 15
                                • Diapositiva numero 16
                                • Diapositiva numero 17
                                • Diapositiva numero 18
                                • Diapositiva numero 19
                                • Differences in placental pathology according to diabetes types
                                • Diapositiva numero 21
                                • Pathophysiology of fetal compromise in diabetic pregnancy
                                • Diapositiva numero 23
                                • Diapositiva numero 24
                                • Diapositiva numero 25
                                • Diapositiva numero 26
                                • Diapositiva numero 27
                                • Diapositiva numero 28
                                • Diapositiva numero 29
                                • Diapositiva numero 30
                                • Diapositiva numero 31
                                • Diapositiva numero 32
                                • Diapositiva numero 33
                                • Diapositiva numero 34
                                • Diapositiva numero 35
                                • Diapositiva numero 36
                                • GDM and the Use of Betamethasone
                                • Diapositiva numero 38
                                • Diapositiva numero 39
                                • Diapositiva numero 40
                                • Pathophysiology of fetal compromise in diabetic pregnancy

                                  Diabetic patients n = 271691

                                  Am J Obstet Gynecol 2002

                                  The overall fetal death rates in diabetic women were increased when birth weight was 4000 g (adjusted rela- tive risk of 20 95 [CI] 18ndash22)

                                  4873 diabetic women

                                  pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                                  outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                                  bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                                  GDMbull dysglycemia was more difficult to manage

                                  2016

                                  Differences in placental pathologyaccording to diabetes types

                                  Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                                  GDM is associated with a greater rate of villous immaturity

                                  0102030405060708090

                                  100GDMDMIDMII

                                  o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                                  A retrospective study on 175 placentas with DVM vs 175 controls

                                  Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                                  Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                                  Pathophysiology of fetal compromise in diabetic pregnancy

                                  The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                  Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                  Bjork 1984Nylund 1982Siddiqui 2003

                                  A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                  STILLBIRTH RISK

                                  BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                  OBESITArsquo E MORTE FETALE

                                  6-7 per unit BMI for BMI gt 23

                                  Tennant PWG Am J Obstet Gynecol 2007

                                  HYPERINSULINISMHYPERANDROGENISM

                                  IMPAIRED PLACENTATION

                                  THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                  Cakmak and Taylor Hum Reprod Update 2011

                                  Makieva S Hum Reprod Update 2014

                                  Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                  Hotamisligil GS Nature 2006

                                  LeptinCRH

                                  Urocortin 3IL-6

                                  INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                  INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                  Adiponectina Insulin LeptinTNFα IL-6

                                  PLACENTAL ALTERATIONIN GENE EXPRESSION

                                  PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                  CollagenaseCervical ripening

                                  FFA

                                  OXIDATIVE STRESS

                                  PREVENZIONE STILLBIRTH

                                  PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                  MORBIDITAgrave NEONATALE

                                  AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                  TIMING E MODALITArsquo DEL PARTO

                                  Induzione o attesa

                                  INDUZIONE DEL TRAVAGLIO

                                  Quando fare un TC elettivo

                                  gt 4000 grgt 4500 gr gt 5000 gr

                                  ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                  425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                  No differenza in TC e outcome perinatale

                                  200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                  No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                  RCT INDUZIONE VS ATTESA in GDM

                                  RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                  2014

                                  1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                  2 Patients well controlled on insulin should probably be delivered by the due date

                                  3 Poorly controlled GDMrsquos using insulin require individual judgment

                                  Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                  1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                  2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                  3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                  cesarean delivery when the estimated fetal weight is ge 4500 g

                                  MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                  MODALITAgrave E TIMING DEL PARTO nel GDM

                                  GMD in terapia insulinicaBen controllato

                                  +Condizioni fetali rassicuranti

                                  MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                  GDM in terapia nutrizionalecon profili glicemici ottimali

                                  +Feto AGA

                                  MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                  Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                  EFW lt 4000g LGAControllo metabolico non

                                  ottimale

                                  4000g lt EFW gt 4500g EFW ge 4500g

                                  Programmare TC elettivo

                                  Parto vaginale indotto a 38-39 sett

                                  Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                  MODALITAgrave E TIMING DEL PARTO nel GDM

                                  IN BASE AL PESO FETALE STIMATO

                                  - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                  - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                  - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                  ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                  Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                  The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                  A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                  If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                  Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                  GDM and the Use of Betamethasone

                                  bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                  bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                  bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                  Society of Obstetricians and Gynaecologists of Canada

                                  The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                  late preterm delivery between 24 to 36 weeksrsquo gestation

                                  ASSISTENZA IN TRAVAGLIO

                                  - MONITORAGGIO FETALE CONTINUO

                                  - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                  MANTENERE GLICEMIA gt70 E lt 126

                                  (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                  GDM

                                  - Intravenous infusion of regular insulin titrated and glucose

                                  - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                  (ACOG 2005)

                                  ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                  Venere di Willendorf

                                  Thank you for your attention

                                  Pathophysiology of fetal compromise in diabetic pregnancy

                                  Islet cell hyperplasia common in stillborn IDMs

                                  There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                  Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                  Salvesen 1993Hay 1989Chukwuma 2001

                                  • Diapositiva numero 1
                                  • Diapositiva numero 2
                                  • Diapositiva numero 3
                                  • Diapositiva numero 4
                                  • Diapositiva numero 5
                                  • Diapositiva numero 6
                                  • Diapositiva numero 7
                                  • Birth weight distribution in diabetic pregnancies
                                  • Diapositiva numero 9
                                  • Diapositiva numero 10
                                  • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                  • Diapositiva numero 12
                                  • Diapositiva numero 13
                                  • Diapositiva numero 14
                                  • Diapositiva numero 15
                                  • Diapositiva numero 16
                                  • Diapositiva numero 17
                                  • Diapositiva numero 18
                                  • Diapositiva numero 19
                                  • Differences in placental pathology according to diabetes types
                                  • Diapositiva numero 21
                                  • Pathophysiology of fetal compromise in diabetic pregnancy
                                  • Diapositiva numero 23
                                  • Diapositiva numero 24
                                  • Diapositiva numero 25
                                  • Diapositiva numero 26
                                  • Diapositiva numero 27
                                  • Diapositiva numero 28
                                  • Diapositiva numero 29
                                  • Diapositiva numero 30
                                  • Diapositiva numero 31
                                  • Diapositiva numero 32
                                  • Diapositiva numero 33
                                  • Diapositiva numero 34
                                  • Diapositiva numero 35
                                  • Diapositiva numero 36
                                  • GDM and the Use of Betamethasone
                                  • Diapositiva numero 38
                                  • Diapositiva numero 39
                                  • Diapositiva numero 40
                                  • Pathophysiology of fetal compromise in diabetic pregnancy

                                    4873 diabetic women

                                    pre-existing diabetes (n = 65) GDM lt12 weeks (n = 68)GDM 12ndash23 weeks of gestation (n = 1247)GDM ge24 weeks of gestation (n = 3493)

                                    outcomes in GDM lt12 weeks are the worst of the GDM cohort and approximate those of women with pre-existing diabete

                                    bull higher prepregnancy BMI bull greater insulin requirementsbull higher rates of hypertensive disorders of pregnancybull more insulin-resistant phenotype compared with later

                                    GDMbull dysglycemia was more difficult to manage

                                    2016

                                    Differences in placental pathologyaccording to diabetes types

                                    Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                                    GDM is associated with a greater rate of villous immaturity

                                    0102030405060708090

                                    100GDMDMIDMII

                                    o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                                    A retrospective study on 175 placentas with DVM vs 175 controls

                                    Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                                    Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                                    Pathophysiology of fetal compromise in diabetic pregnancy

                                    The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                    Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                    Bjork 1984Nylund 1982Siddiqui 2003

                                    A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                    STILLBIRTH RISK

                                    BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                    OBESITArsquo E MORTE FETALE

                                    6-7 per unit BMI for BMI gt 23

                                    Tennant PWG Am J Obstet Gynecol 2007

                                    HYPERINSULINISMHYPERANDROGENISM

                                    IMPAIRED PLACENTATION

                                    THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                    Cakmak and Taylor Hum Reprod Update 2011

                                    Makieva S Hum Reprod Update 2014

                                    Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                    Hotamisligil GS Nature 2006

                                    LeptinCRH

                                    Urocortin 3IL-6

                                    INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                    INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                    Adiponectina Insulin LeptinTNFα IL-6

                                    PLACENTAL ALTERATIONIN GENE EXPRESSION

                                    PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                    CollagenaseCervical ripening

                                    FFA

                                    OXIDATIVE STRESS

                                    PREVENZIONE STILLBIRTH

                                    PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                    MORBIDITAgrave NEONATALE

                                    AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                    TIMING E MODALITArsquo DEL PARTO

                                    Induzione o attesa

                                    INDUZIONE DEL TRAVAGLIO

                                    Quando fare un TC elettivo

                                    gt 4000 grgt 4500 gr gt 5000 gr

                                    ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                    425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                    No differenza in TC e outcome perinatale

                                    200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                    No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                    RCT INDUZIONE VS ATTESA in GDM

                                    RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                    2014

                                    1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                    2 Patients well controlled on insulin should probably be delivered by the due date

                                    3 Poorly controlled GDMrsquos using insulin require individual judgment

                                    Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                    1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                    2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                    3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                    cesarean delivery when the estimated fetal weight is ge 4500 g

                                    MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                    MODALITAgrave E TIMING DEL PARTO nel GDM

                                    GMD in terapia insulinicaBen controllato

                                    +Condizioni fetali rassicuranti

                                    MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                    GDM in terapia nutrizionalecon profili glicemici ottimali

                                    +Feto AGA

                                    MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                    Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                    EFW lt 4000g LGAControllo metabolico non

                                    ottimale

                                    4000g lt EFW gt 4500g EFW ge 4500g

                                    Programmare TC elettivo

                                    Parto vaginale indotto a 38-39 sett

                                    Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                    MODALITAgrave E TIMING DEL PARTO nel GDM

                                    IN BASE AL PESO FETALE STIMATO

                                    - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                    - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                    - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                    ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                    Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                    The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                    A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                    If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                    Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                    GDM and the Use of Betamethasone

                                    bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                    bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                    bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                    Society of Obstetricians and Gynaecologists of Canada

                                    The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                    late preterm delivery between 24 to 36 weeksrsquo gestation

                                    ASSISTENZA IN TRAVAGLIO

                                    - MONITORAGGIO FETALE CONTINUO

                                    - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                    MANTENERE GLICEMIA gt70 E lt 126

                                    (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                    GDM

                                    - Intravenous infusion of regular insulin titrated and glucose

                                    - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                    (ACOG 2005)

                                    ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                    Venere di Willendorf

                                    Thank you for your attention

                                    Pathophysiology of fetal compromise in diabetic pregnancy

                                    Islet cell hyperplasia common in stillborn IDMs

                                    There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                    Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                    Salvesen 1993Hay 1989Chukwuma 2001

                                    • Diapositiva numero 1
                                    • Diapositiva numero 2
                                    • Diapositiva numero 3
                                    • Diapositiva numero 4
                                    • Diapositiva numero 5
                                    • Diapositiva numero 6
                                    • Diapositiva numero 7
                                    • Birth weight distribution in diabetic pregnancies
                                    • Diapositiva numero 9
                                    • Diapositiva numero 10
                                    • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                    • Diapositiva numero 12
                                    • Diapositiva numero 13
                                    • Diapositiva numero 14
                                    • Diapositiva numero 15
                                    • Diapositiva numero 16
                                    • Diapositiva numero 17
                                    • Diapositiva numero 18
                                    • Diapositiva numero 19
                                    • Differences in placental pathology according to diabetes types
                                    • Diapositiva numero 21
                                    • Pathophysiology of fetal compromise in diabetic pregnancy
                                    • Diapositiva numero 23
                                    • Diapositiva numero 24
                                    • Diapositiva numero 25
                                    • Diapositiva numero 26
                                    • Diapositiva numero 27
                                    • Diapositiva numero 28
                                    • Diapositiva numero 29
                                    • Diapositiva numero 30
                                    • Diapositiva numero 31
                                    • Diapositiva numero 32
                                    • Diapositiva numero 33
                                    • Diapositiva numero 34
                                    • Diapositiva numero 35
                                    • Diapositiva numero 36
                                    • GDM and the Use of Betamethasone
                                    • Diapositiva numero 38
                                    • Diapositiva numero 39
                                    • Diapositiva numero 40
                                    • Pathophysiology of fetal compromise in diabetic pregnancy

                                      Differences in placental pathologyaccording to diabetes types

                                      Type 1 Type 2 and Gestational Diabetes Mellitus Differentially Impact Placental Pathologic Characteristics of UteroplacentalMalperfusion Jennifer Huynh et al Placenta 2016

                                      GDM is associated with a greater rate of villous immaturity

                                      0102030405060708090

                                      100GDMDMIDMII

                                      o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                                      A retrospective study on 175 placentas with DVM vs 175 controls

                                      Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                                      Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                                      Pathophysiology of fetal compromise in diabetic pregnancy

                                      The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                      Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                      Bjork 1984Nylund 1982Siddiqui 2003

                                      A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                      STILLBIRTH RISK

                                      BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                      OBESITArsquo E MORTE FETALE

                                      6-7 per unit BMI for BMI gt 23

                                      Tennant PWG Am J Obstet Gynecol 2007

                                      HYPERINSULINISMHYPERANDROGENISM

                                      IMPAIRED PLACENTATION

                                      THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                      Cakmak and Taylor Hum Reprod Update 2011

                                      Makieva S Hum Reprod Update 2014

                                      Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                      Hotamisligil GS Nature 2006

                                      LeptinCRH

                                      Urocortin 3IL-6

                                      INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                      INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                      Adiponectina Insulin LeptinTNFα IL-6

                                      PLACENTAL ALTERATIONIN GENE EXPRESSION

                                      PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                      CollagenaseCervical ripening

                                      FFA

                                      OXIDATIVE STRESS

                                      PREVENZIONE STILLBIRTH

                                      PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                      MORBIDITAgrave NEONATALE

                                      AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                      TIMING E MODALITArsquo DEL PARTO

                                      Induzione o attesa

                                      INDUZIONE DEL TRAVAGLIO

                                      Quando fare un TC elettivo

                                      gt 4000 grgt 4500 gr gt 5000 gr

                                      ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                      425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                      No differenza in TC e outcome perinatale

                                      200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                      No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                      RCT INDUZIONE VS ATTESA in GDM

                                      RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                      2014

                                      1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                      2 Patients well controlled on insulin should probably be delivered by the due date

                                      3 Poorly controlled GDMrsquos using insulin require individual judgment

                                      Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                      1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                      2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                      3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                      cesarean delivery when the estimated fetal weight is ge 4500 g

                                      MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                      MODALITAgrave E TIMING DEL PARTO nel GDM

                                      GMD in terapia insulinicaBen controllato

                                      +Condizioni fetali rassicuranti

                                      MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                      GDM in terapia nutrizionalecon profili glicemici ottimali

                                      +Feto AGA

                                      MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                      Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                      EFW lt 4000g LGAControllo metabolico non

                                      ottimale

                                      4000g lt EFW gt 4500g EFW ge 4500g

                                      Programmare TC elettivo

                                      Parto vaginale indotto a 38-39 sett

                                      Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                      MODALITAgrave E TIMING DEL PARTO nel GDM

                                      IN BASE AL PESO FETALE STIMATO

                                      - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                      - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                      - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                      ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                      Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                      The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                      A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                      If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                      Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                      GDM and the Use of Betamethasone

                                      bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                      bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                      bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                      Society of Obstetricians and Gynaecologists of Canada

                                      The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                      late preterm delivery between 24 to 36 weeksrsquo gestation

                                      ASSISTENZA IN TRAVAGLIO

                                      - MONITORAGGIO FETALE CONTINUO

                                      - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                      MANTENERE GLICEMIA gt70 E lt 126

                                      (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                      GDM

                                      - Intravenous infusion of regular insulin titrated and glucose

                                      - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                      (ACOG 2005)

                                      ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                      Venere di Willendorf

                                      Thank you for your attention

                                      Pathophysiology of fetal compromise in diabetic pregnancy

                                      Islet cell hyperplasia common in stillborn IDMs

                                      There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                      Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                      Salvesen 1993Hay 1989Chukwuma 2001

                                      • Diapositiva numero 1
                                      • Diapositiva numero 2
                                      • Diapositiva numero 3
                                      • Diapositiva numero 4
                                      • Diapositiva numero 5
                                      • Diapositiva numero 6
                                      • Diapositiva numero 7
                                      • Birth weight distribution in diabetic pregnancies
                                      • Diapositiva numero 9
                                      • Diapositiva numero 10
                                      • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                      • Diapositiva numero 12
                                      • Diapositiva numero 13
                                      • Diapositiva numero 14
                                      • Diapositiva numero 15
                                      • Diapositiva numero 16
                                      • Diapositiva numero 17
                                      • Diapositiva numero 18
                                      • Diapositiva numero 19
                                      • Differences in placental pathology according to diabetes types
                                      • Diapositiva numero 21
                                      • Pathophysiology of fetal compromise in diabetic pregnancy
                                      • Diapositiva numero 23
                                      • Diapositiva numero 24
                                      • Diapositiva numero 25
                                      • Diapositiva numero 26
                                      • Diapositiva numero 27
                                      • Diapositiva numero 28
                                      • Diapositiva numero 29
                                      • Diapositiva numero 30
                                      • Diapositiva numero 31
                                      • Diapositiva numero 32
                                      • Diapositiva numero 33
                                      • Diapositiva numero 34
                                      • Diapositiva numero 35
                                      • Diapositiva numero 36
                                      • GDM and the Use of Betamethasone
                                      • Diapositiva numero 38
                                      • Diapositiva numero 39
                                      • Diapositiva numero 40
                                      • Pathophysiology of fetal compromise in diabetic pregnancy

                                        o decreased tertiary villus formationo reduced vasculosyncytial membrane formationo increased large bullous villi

                                        A retrospective study on 175 placentas with DVM vs 175 controls

                                        Pregestational diabetes (8 vs 28 P lt 005 relative risk 28 Gestational diabetes (86 vs 34 P lt 005 relative risk 25 Prenatal or intrapartum intrauterine death (86 vs 0 P lt 005)

                                        Delayed villous maturation (DVM)is associated with an increased risk of stillbirth in the late third trimester

                                        Pathophysiology of fetal compromise in diabetic pregnancy

                                        The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                        Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                        Bjork 1984Nylund 1982Siddiqui 2003

                                        A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                        STILLBIRTH RISK

                                        BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                        OBESITArsquo E MORTE FETALE

                                        6-7 per unit BMI for BMI gt 23

                                        Tennant PWG Am J Obstet Gynecol 2007

                                        HYPERINSULINISMHYPERANDROGENISM

                                        IMPAIRED PLACENTATION

                                        THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                        Cakmak and Taylor Hum Reprod Update 2011

                                        Makieva S Hum Reprod Update 2014

                                        Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                        Hotamisligil GS Nature 2006

                                        LeptinCRH

                                        Urocortin 3IL-6

                                        INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                        INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                        Adiponectina Insulin LeptinTNFα IL-6

                                        PLACENTAL ALTERATIONIN GENE EXPRESSION

                                        PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                        CollagenaseCervical ripening

                                        FFA

                                        OXIDATIVE STRESS

                                        PREVENZIONE STILLBIRTH

                                        PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                        MORBIDITAgrave NEONATALE

                                        AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                        TIMING E MODALITArsquo DEL PARTO

                                        Induzione o attesa

                                        INDUZIONE DEL TRAVAGLIO

                                        Quando fare un TC elettivo

                                        gt 4000 grgt 4500 gr gt 5000 gr

                                        ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                        425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                        No differenza in TC e outcome perinatale

                                        200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                        No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                        RCT INDUZIONE VS ATTESA in GDM

                                        RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                        2014

                                        1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                        2 Patients well controlled on insulin should probably be delivered by the due date

                                        3 Poorly controlled GDMrsquos using insulin require individual judgment

                                        Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                        1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                        2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                        3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                        cesarean delivery when the estimated fetal weight is ge 4500 g

                                        MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                        MODALITAgrave E TIMING DEL PARTO nel GDM

                                        GMD in terapia insulinicaBen controllato

                                        +Condizioni fetali rassicuranti

                                        MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                        GDM in terapia nutrizionalecon profili glicemici ottimali

                                        +Feto AGA

                                        MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                        Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                        EFW lt 4000g LGAControllo metabolico non

                                        ottimale

                                        4000g lt EFW gt 4500g EFW ge 4500g

                                        Programmare TC elettivo

                                        Parto vaginale indotto a 38-39 sett

                                        Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                        MODALITAgrave E TIMING DEL PARTO nel GDM

                                        IN BASE AL PESO FETALE STIMATO

                                        - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                        - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                        - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                        ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                        Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                        The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                        A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                        If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                        Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                        GDM and the Use of Betamethasone

                                        bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                        bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                        bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                        Society of Obstetricians and Gynaecologists of Canada

                                        The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                        late preterm delivery between 24 to 36 weeksrsquo gestation

                                        ASSISTENZA IN TRAVAGLIO

                                        - MONITORAGGIO FETALE CONTINUO

                                        - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                        MANTENERE GLICEMIA gt70 E lt 126

                                        (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                        GDM

                                        - Intravenous infusion of regular insulin titrated and glucose

                                        - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                        (ACOG 2005)

                                        ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                        Venere di Willendorf

                                        Thank you for your attention

                                        Pathophysiology of fetal compromise in diabetic pregnancy

                                        Islet cell hyperplasia common in stillborn IDMs

                                        There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                        Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                        Salvesen 1993Hay 1989Chukwuma 2001

                                        • Diapositiva numero 1
                                        • Diapositiva numero 2
                                        • Diapositiva numero 3
                                        • Diapositiva numero 4
                                        • Diapositiva numero 5
                                        • Diapositiva numero 6
                                        • Diapositiva numero 7
                                        • Birth weight distribution in diabetic pregnancies
                                        • Diapositiva numero 9
                                        • Diapositiva numero 10
                                        • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                        • Diapositiva numero 12
                                        • Diapositiva numero 13
                                        • Diapositiva numero 14
                                        • Diapositiva numero 15
                                        • Diapositiva numero 16
                                        • Diapositiva numero 17
                                        • Diapositiva numero 18
                                        • Diapositiva numero 19
                                        • Differences in placental pathology according to diabetes types
                                        • Diapositiva numero 21
                                        • Pathophysiology of fetal compromise in diabetic pregnancy
                                        • Diapositiva numero 23
                                        • Diapositiva numero 24
                                        • Diapositiva numero 25
                                        • Diapositiva numero 26
                                        • Diapositiva numero 27
                                        • Diapositiva numero 28
                                        • Diapositiva numero 29
                                        • Diapositiva numero 30
                                        • Diapositiva numero 31
                                        • Diapositiva numero 32
                                        • Diapositiva numero 33
                                        • Diapositiva numero 34
                                        • Diapositiva numero 35
                                        • Diapositiva numero 36
                                        • GDM and the Use of Betamethasone
                                        • Diapositiva numero 38
                                        • Diapositiva numero 39
                                        • Diapositiva numero 40
                                        • Pathophysiology of fetal compromise in diabetic pregnancy

                                          Pathophysiology of fetal compromise in diabetic pregnancy

                                          The growth factor-like effect of insulin producesplacental overgrowth as well as organomegalyand thus results in changes in vascular tone andhaemodynamic

                                          Thickening of the basement membrane of the chorionic villi in diabetic pregnancies

                                          Bjork 1984Nylund 1982Siddiqui 2003

                                          A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                          STILLBIRTH RISK

                                          BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                          OBESITArsquo E MORTE FETALE

                                          6-7 per unit BMI for BMI gt 23

                                          Tennant PWG Am J Obstet Gynecol 2007

                                          HYPERINSULINISMHYPERANDROGENISM

                                          IMPAIRED PLACENTATION

                                          THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                          Cakmak and Taylor Hum Reprod Update 2011

                                          Makieva S Hum Reprod Update 2014

                                          Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                          Hotamisligil GS Nature 2006

                                          LeptinCRH

                                          Urocortin 3IL-6

                                          INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                          INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                          Adiponectina Insulin LeptinTNFα IL-6

                                          PLACENTAL ALTERATIONIN GENE EXPRESSION

                                          PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                          CollagenaseCervical ripening

                                          FFA

                                          OXIDATIVE STRESS

                                          PREVENZIONE STILLBIRTH

                                          PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                          MORBIDITAgrave NEONATALE

                                          AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                          TIMING E MODALITArsquo DEL PARTO

                                          Induzione o attesa

                                          INDUZIONE DEL TRAVAGLIO

                                          Quando fare un TC elettivo

                                          gt 4000 grgt 4500 gr gt 5000 gr

                                          ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                          425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                          No differenza in TC e outcome perinatale

                                          200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                          No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                          RCT INDUZIONE VS ATTESA in GDM

                                          RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                          2014

                                          1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                          2 Patients well controlled on insulin should probably be delivered by the due date

                                          3 Poorly controlled GDMrsquos using insulin require individual judgment

                                          Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                          1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                          2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                          3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                          cesarean delivery when the estimated fetal weight is ge 4500 g

                                          MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                          MODALITAgrave E TIMING DEL PARTO nel GDM

                                          GMD in terapia insulinicaBen controllato

                                          +Condizioni fetali rassicuranti

                                          MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                          GDM in terapia nutrizionalecon profili glicemici ottimali

                                          +Feto AGA

                                          MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                          Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                          EFW lt 4000g LGAControllo metabolico non

                                          ottimale

                                          4000g lt EFW gt 4500g EFW ge 4500g

                                          Programmare TC elettivo

                                          Parto vaginale indotto a 38-39 sett

                                          Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                          MODALITAgrave E TIMING DEL PARTO nel GDM

                                          IN BASE AL PESO FETALE STIMATO

                                          - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                          - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                          - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                          ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                          Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                          The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                          A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                          If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                          Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                          GDM and the Use of Betamethasone

                                          bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                          bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                          bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                          Society of Obstetricians and Gynaecologists of Canada

                                          The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                          late preterm delivery between 24 to 36 weeksrsquo gestation

                                          ASSISTENZA IN TRAVAGLIO

                                          - MONITORAGGIO FETALE CONTINUO

                                          - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                          MANTENERE GLICEMIA gt70 E lt 126

                                          (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                          GDM

                                          - Intravenous infusion of regular insulin titrated and glucose

                                          - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                          (ACOG 2005)

                                          ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                          Venere di Willendorf

                                          Thank you for your attention

                                          Pathophysiology of fetal compromise in diabetic pregnancy

                                          Islet cell hyperplasia common in stillborn IDMs

                                          There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                          Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                          Salvesen 1993Hay 1989Chukwuma 2001

                                          • Diapositiva numero 1
                                          • Diapositiva numero 2
                                          • Diapositiva numero 3
                                          • Diapositiva numero 4
                                          • Diapositiva numero 5
                                          • Diapositiva numero 6
                                          • Diapositiva numero 7
                                          • Birth weight distribution in diabetic pregnancies
                                          • Diapositiva numero 9
                                          • Diapositiva numero 10
                                          • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                          • Diapositiva numero 12
                                          • Diapositiva numero 13
                                          • Diapositiva numero 14
                                          • Diapositiva numero 15
                                          • Diapositiva numero 16
                                          • Diapositiva numero 17
                                          • Diapositiva numero 18
                                          • Diapositiva numero 19
                                          • Differences in placental pathology according to diabetes types
                                          • Diapositiva numero 21
                                          • Pathophysiology of fetal compromise in diabetic pregnancy
                                          • Diapositiva numero 23
                                          • Diapositiva numero 24
                                          • Diapositiva numero 25
                                          • Diapositiva numero 26
                                          • Diapositiva numero 27
                                          • Diapositiva numero 28
                                          • Diapositiva numero 29
                                          • Diapositiva numero 30
                                          • Diapositiva numero 31
                                          • Diapositiva numero 32
                                          • Diapositiva numero 33
                                          • Diapositiva numero 34
                                          • Diapositiva numero 35
                                          • Diapositiva numero 36
                                          • GDM and the Use of Betamethasone
                                          • Diapositiva numero 38
                                          • Diapositiva numero 39
                                          • Diapositiva numero 40
                                          • Pathophysiology of fetal compromise in diabetic pregnancy

                                            A Lindam et al High maternal body mass index in early pregnancy and risks of stillbirth and infant mortality A population-based Sibling study in Sweden American Journal of Epidemiology 2016

                                            STILLBIRTH RISK

                                            BMI 25-299 OR 151 (95 CI 121-189)BMI 30-349 OR 177 (95 CI 124-25)BMI gt 35 OR 316 (95 CI 210-476)

                                            OBESITArsquo E MORTE FETALE

                                            6-7 per unit BMI for BMI gt 23

                                            Tennant PWG Am J Obstet Gynecol 2007

                                            HYPERINSULINISMHYPERANDROGENISM

                                            IMPAIRED PLACENTATION

                                            THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                            Cakmak and Taylor Hum Reprod Update 2011

                                            Makieva S Hum Reprod Update 2014

                                            Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                            Hotamisligil GS Nature 2006

                                            LeptinCRH

                                            Urocortin 3IL-6

                                            INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                            INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                            Adiponectina Insulin LeptinTNFα IL-6

                                            PLACENTAL ALTERATIONIN GENE EXPRESSION

                                            PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                            CollagenaseCervical ripening

                                            FFA

                                            OXIDATIVE STRESS

                                            PREVENZIONE STILLBIRTH

                                            PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                            MORBIDITAgrave NEONATALE

                                            AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                            TIMING E MODALITArsquo DEL PARTO

                                            Induzione o attesa

                                            INDUZIONE DEL TRAVAGLIO

                                            Quando fare un TC elettivo

                                            gt 4000 grgt 4500 gr gt 5000 gr

                                            ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                            425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                            No differenza in TC e outcome perinatale

                                            200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                            No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                            RCT INDUZIONE VS ATTESA in GDM

                                            RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                            2014

                                            1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                            2 Patients well controlled on insulin should probably be delivered by the due date

                                            3 Poorly controlled GDMrsquos using insulin require individual judgment

                                            Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                            1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                            2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                            3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                            cesarean delivery when the estimated fetal weight is ge 4500 g

                                            MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                            MODALITAgrave E TIMING DEL PARTO nel GDM

                                            GMD in terapia insulinicaBen controllato

                                            +Condizioni fetali rassicuranti

                                            MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                            GDM in terapia nutrizionalecon profili glicemici ottimali

                                            +Feto AGA

                                            MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                            Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                            EFW lt 4000g LGAControllo metabolico non

                                            ottimale

                                            4000g lt EFW gt 4500g EFW ge 4500g

                                            Programmare TC elettivo

                                            Parto vaginale indotto a 38-39 sett

                                            Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                            MODALITAgrave E TIMING DEL PARTO nel GDM

                                            IN BASE AL PESO FETALE STIMATO

                                            - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                            - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                            - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                            ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                            Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                            The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                            A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                            If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                            Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                            GDM and the Use of Betamethasone

                                            bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                            bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                            bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                            Society of Obstetricians and Gynaecologists of Canada

                                            The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                            late preterm delivery between 24 to 36 weeksrsquo gestation

                                            ASSISTENZA IN TRAVAGLIO

                                            - MONITORAGGIO FETALE CONTINUO

                                            - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                            MANTENERE GLICEMIA gt70 E lt 126

                                            (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                            GDM

                                            - Intravenous infusion of regular insulin titrated and glucose

                                            - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                            (ACOG 2005)

                                            ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                            Venere di Willendorf

                                            Thank you for your attention

                                            Pathophysiology of fetal compromise in diabetic pregnancy

                                            Islet cell hyperplasia common in stillborn IDMs

                                            There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                            Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                            Salvesen 1993Hay 1989Chukwuma 2001

                                            • Diapositiva numero 1
                                            • Diapositiva numero 2
                                            • Diapositiva numero 3
                                            • Diapositiva numero 4
                                            • Diapositiva numero 5
                                            • Diapositiva numero 6
                                            • Diapositiva numero 7
                                            • Birth weight distribution in diabetic pregnancies
                                            • Diapositiva numero 9
                                            • Diapositiva numero 10
                                            • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                            • Diapositiva numero 12
                                            • Diapositiva numero 13
                                            • Diapositiva numero 14
                                            • Diapositiva numero 15
                                            • Diapositiva numero 16
                                            • Diapositiva numero 17
                                            • Diapositiva numero 18
                                            • Diapositiva numero 19
                                            • Differences in placental pathology according to diabetes types
                                            • Diapositiva numero 21
                                            • Pathophysiology of fetal compromise in diabetic pregnancy
                                            • Diapositiva numero 23
                                            • Diapositiva numero 24
                                            • Diapositiva numero 25
                                            • Diapositiva numero 26
                                            • Diapositiva numero 27
                                            • Diapositiva numero 28
                                            • Diapositiva numero 29
                                            • Diapositiva numero 30
                                            • Diapositiva numero 31
                                            • Diapositiva numero 32
                                            • Diapositiva numero 33
                                            • Diapositiva numero 34
                                            • Diapositiva numero 35
                                            • Diapositiva numero 36
                                            • GDM and the Use of Betamethasone
                                            • Diapositiva numero 38
                                            • Diapositiva numero 39
                                            • Diapositiva numero 40
                                            • Pathophysiology of fetal compromise in diabetic pregnancy

                                              HYPERINSULINISMHYPERANDROGENISM

                                              IMPAIRED PLACENTATION

                                              THE EFFECTS OF OBESITYMETABOLIC SYNDROME

                                              Cakmak and Taylor Hum Reprod Update 2011

                                              Makieva S Hum Reprod Update 2014

                                              Piltonen TT Hum Reprod 2015 Crujeiras and Casanueva Hum Reprod Update 2015Denison FC Reproduction2010

                                              Hotamisligil GS Nature 2006

                                              LeptinCRH

                                              Urocortin 3IL-6

                                              INFLAMMATIONImpaired decidualizationImpaired trophoblast invasion

                                              INSULIN RESISTANCEDYSLIPIDEMIALOW GRADE CHRONIC INFLAMMATION

                                              Adiponectina Insulin LeptinTNFα IL-6

                                              PLACENTAL ALTERATIONIN GENE EXPRESSION

                                              PRETERM BIRTH PHIPREECLAMPSIASTILLBIRTH

                                              CollagenaseCervical ripening

                                              FFA

                                              OXIDATIVE STRESS

                                              PREVENZIONE STILLBIRTH

                                              PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                              MORBIDITAgrave NEONATALE

                                              AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                              TIMING E MODALITArsquo DEL PARTO

                                              Induzione o attesa

                                              INDUZIONE DEL TRAVAGLIO

                                              Quando fare un TC elettivo

                                              gt 4000 grgt 4500 gr gt 5000 gr

                                              ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                              425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                              No differenza in TC e outcome perinatale

                                              200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                              No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                              RCT INDUZIONE VS ATTESA in GDM

                                              RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                              2014

                                              1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                              2 Patients well controlled on insulin should probably be delivered by the due date

                                              3 Poorly controlled GDMrsquos using insulin require individual judgment

                                              Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                              1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                              2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                              3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                              cesarean delivery when the estimated fetal weight is ge 4500 g

                                              MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                              MODALITAgrave E TIMING DEL PARTO nel GDM

                                              GMD in terapia insulinicaBen controllato

                                              +Condizioni fetali rassicuranti

                                              MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                              GDM in terapia nutrizionalecon profili glicemici ottimali

                                              +Feto AGA

                                              MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                              Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                              EFW lt 4000g LGAControllo metabolico non

                                              ottimale

                                              4000g lt EFW gt 4500g EFW ge 4500g

                                              Programmare TC elettivo

                                              Parto vaginale indotto a 38-39 sett

                                              Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                              MODALITAgrave E TIMING DEL PARTO nel GDM

                                              IN BASE AL PESO FETALE STIMATO

                                              - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                              - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                              - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                              ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                              Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                              The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                              A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                              If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                              Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                              GDM and the Use of Betamethasone

                                              bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                              bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                              bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                              Society of Obstetricians and Gynaecologists of Canada

                                              The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                              late preterm delivery between 24 to 36 weeksrsquo gestation

                                              ASSISTENZA IN TRAVAGLIO

                                              - MONITORAGGIO FETALE CONTINUO

                                              - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                              MANTENERE GLICEMIA gt70 E lt 126

                                              (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                              GDM

                                              - Intravenous infusion of regular insulin titrated and glucose

                                              - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                              (ACOG 2005)

                                              ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                              Venere di Willendorf

                                              Thank you for your attention

                                              Pathophysiology of fetal compromise in diabetic pregnancy

                                              Islet cell hyperplasia common in stillborn IDMs

                                              There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                              Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                              Salvesen 1993Hay 1989Chukwuma 2001

                                              • Diapositiva numero 1
                                              • Diapositiva numero 2
                                              • Diapositiva numero 3
                                              • Diapositiva numero 4
                                              • Diapositiva numero 5
                                              • Diapositiva numero 6
                                              • Diapositiva numero 7
                                              • Birth weight distribution in diabetic pregnancies
                                              • Diapositiva numero 9
                                              • Diapositiva numero 10
                                              • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                              • Diapositiva numero 12
                                              • Diapositiva numero 13
                                              • Diapositiva numero 14
                                              • Diapositiva numero 15
                                              • Diapositiva numero 16
                                              • Diapositiva numero 17
                                              • Diapositiva numero 18
                                              • Diapositiva numero 19
                                              • Differences in placental pathology according to diabetes types
                                              • Diapositiva numero 21
                                              • Pathophysiology of fetal compromise in diabetic pregnancy
                                              • Diapositiva numero 23
                                              • Diapositiva numero 24
                                              • Diapositiva numero 25
                                              • Diapositiva numero 26
                                              • Diapositiva numero 27
                                              • Diapositiva numero 28
                                              • Diapositiva numero 29
                                              • Diapositiva numero 30
                                              • Diapositiva numero 31
                                              • Diapositiva numero 32
                                              • Diapositiva numero 33
                                              • Diapositiva numero 34
                                              • Diapositiva numero 35
                                              • Diapositiva numero 36
                                              • GDM and the Use of Betamethasone
                                              • Diapositiva numero 38
                                              • Diapositiva numero 39
                                              • Diapositiva numero 40
                                              • Pathophysiology of fetal compromise in diabetic pregnancy

                                                PREVENZIONE STILLBIRTH

                                                PREVENZIONE COMPLICANZE INTRAPARTUM DEL FETO MACROSOMA

                                                MORBIDITAgrave NEONATALE

                                                AUMENTO INCIDENZA TCCOMPLICANZE TRAVAGLIO INDOTTO

                                                TIMING E MODALITArsquo DEL PARTO

                                                Induzione o attesa

                                                INDUZIONE DEL TRAVAGLIO

                                                Quando fare un TC elettivo

                                                gt 4000 grgt 4500 gr gt 5000 gr

                                                ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                                425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                                No differenza in TC e outcome perinatale

                                                200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                                No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                                RCT INDUZIONE VS ATTESA in GDM

                                                RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                                2014

                                                1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                                2 Patients well controlled on insulin should probably be delivered by the due date

                                                3 Poorly controlled GDMrsquos using insulin require individual judgment

                                                Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                                1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                cesarean delivery when the estimated fetal weight is ge 4500 g

                                                MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                MODALITAgrave E TIMING DEL PARTO nel GDM

                                                GMD in terapia insulinicaBen controllato

                                                +Condizioni fetali rassicuranti

                                                MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                GDM in terapia nutrizionalecon profili glicemici ottimali

                                                +Feto AGA

                                                MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                EFW lt 4000g LGAControllo metabolico non

                                                ottimale

                                                4000g lt EFW gt 4500g EFW ge 4500g

                                                Programmare TC elettivo

                                                Parto vaginale indotto a 38-39 sett

                                                Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                MODALITAgrave E TIMING DEL PARTO nel GDM

                                                IN BASE AL PESO FETALE STIMATO

                                                - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                GDM and the Use of Betamethasone

                                                bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                Society of Obstetricians and Gynaecologists of Canada

                                                The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                late preterm delivery between 24 to 36 weeksrsquo gestation

                                                ASSISTENZA IN TRAVAGLIO

                                                - MONITORAGGIO FETALE CONTINUO

                                                - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                MANTENERE GLICEMIA gt70 E lt 126

                                                (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                GDM

                                                - Intravenous infusion of regular insulin titrated and glucose

                                                - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                (ACOG 2005)

                                                ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                Venere di Willendorf

                                                Thank you for your attention

                                                Pathophysiology of fetal compromise in diabetic pregnancy

                                                Islet cell hyperplasia common in stillborn IDMs

                                                There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                Salvesen 1993Hay 1989Chukwuma 2001

                                                • Diapositiva numero 1
                                                • Diapositiva numero 2
                                                • Diapositiva numero 3
                                                • Diapositiva numero 4
                                                • Diapositiva numero 5
                                                • Diapositiva numero 6
                                                • Diapositiva numero 7
                                                • Birth weight distribution in diabetic pregnancies
                                                • Diapositiva numero 9
                                                • Diapositiva numero 10
                                                • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                • Diapositiva numero 12
                                                • Diapositiva numero 13
                                                • Diapositiva numero 14
                                                • Diapositiva numero 15
                                                • Diapositiva numero 16
                                                • Diapositiva numero 17
                                                • Diapositiva numero 18
                                                • Diapositiva numero 19
                                                • Differences in placental pathology according to diabetes types
                                                • Diapositiva numero 21
                                                • Pathophysiology of fetal compromise in diabetic pregnancy
                                                • Diapositiva numero 23
                                                • Diapositiva numero 24
                                                • Diapositiva numero 25
                                                • Diapositiva numero 26
                                                • Diapositiva numero 27
                                                • Diapositiva numero 28
                                                • Diapositiva numero 29
                                                • Diapositiva numero 30
                                                • Diapositiva numero 31
                                                • Diapositiva numero 32
                                                • Diapositiva numero 33
                                                • Diapositiva numero 34
                                                • Diapositiva numero 35
                                                • Diapositiva numero 36
                                                • GDM and the Use of Betamethasone
                                                • Diapositiva numero 38
                                                • Diapositiva numero 39
                                                • Diapositiva numero 40
                                                • Pathophysiology of fetal compromise in diabetic pregnancy

                                                  ESISTONO RCT SUL TIMING E MODALITAgrave DEL PARTO NELLE GRAVIDANZE COMPLICATE DA DIABETE

                                                  425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                                  No differenza in TC e outcome perinatale

                                                  200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                                  No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                                  RCT INDUZIONE VS ATTESA in GDM

                                                  RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                                  2014

                                                  1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                                  2 Patients well controlled on insulin should probably be delivered by the due date

                                                  3 Poorly controlled GDMrsquos using insulin require individual judgment

                                                  Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                                  1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                  2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                  3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                  cesarean delivery when the estimated fetal weight is ge 4500 g

                                                  MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                  MODALITAgrave E TIMING DEL PARTO nel GDM

                                                  GMD in terapia insulinicaBen controllato

                                                  +Condizioni fetali rassicuranti

                                                  MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                  GDM in terapia nutrizionalecon profili glicemici ottimali

                                                  +Feto AGA

                                                  MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                  Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                  EFW lt 4000g LGAControllo metabolico non

                                                  ottimale

                                                  4000g lt EFW gt 4500g EFW ge 4500g

                                                  Programmare TC elettivo

                                                  Parto vaginale indotto a 38-39 sett

                                                  Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                  MODALITAgrave E TIMING DEL PARTO nel GDM

                                                  IN BASE AL PESO FETALE STIMATO

                                                  - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                  - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                  - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                  ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                  Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                  The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                  A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                  If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                  Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                  GDM and the Use of Betamethasone

                                                  bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                  bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                  bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                  Society of Obstetricians and Gynaecologists of Canada

                                                  The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                  late preterm delivery between 24 to 36 weeksrsquo gestation

                                                  ASSISTENZA IN TRAVAGLIO

                                                  - MONITORAGGIO FETALE CONTINUO

                                                  - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                  MANTENERE GLICEMIA gt70 E lt 126

                                                  (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                  GDM

                                                  - Intravenous infusion of regular insulin titrated and glucose

                                                  - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                  (ACOG 2005)

                                                  ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                  Venere di Willendorf

                                                  Thank you for your attention

                                                  Pathophysiology of fetal compromise in diabetic pregnancy

                                                  Islet cell hyperplasia common in stillborn IDMs

                                                  There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                  Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                  Salvesen 1993Hay 1989Chukwuma 2001

                                                  • Diapositiva numero 1
                                                  • Diapositiva numero 2
                                                  • Diapositiva numero 3
                                                  • Diapositiva numero 4
                                                  • Diapositiva numero 5
                                                  • Diapositiva numero 6
                                                  • Diapositiva numero 7
                                                  • Birth weight distribution in diabetic pregnancies
                                                  • Diapositiva numero 9
                                                  • Diapositiva numero 10
                                                  • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                  • Diapositiva numero 12
                                                  • Diapositiva numero 13
                                                  • Diapositiva numero 14
                                                  • Diapositiva numero 15
                                                  • Diapositiva numero 16
                                                  • Diapositiva numero 17
                                                  • Diapositiva numero 18
                                                  • Diapositiva numero 19
                                                  • Differences in placental pathology according to diabetes types
                                                  • Diapositiva numero 21
                                                  • Pathophysiology of fetal compromise in diabetic pregnancy
                                                  • Diapositiva numero 23
                                                  • Diapositiva numero 24
                                                  • Diapositiva numero 25
                                                  • Diapositiva numero 26
                                                  • Diapositiva numero 27
                                                  • Diapositiva numero 28
                                                  • Diapositiva numero 29
                                                  • Diapositiva numero 30
                                                  • Diapositiva numero 31
                                                  • Diapositiva numero 32
                                                  • Diapositiva numero 33
                                                  • Diapositiva numero 34
                                                  • Diapositiva numero 35
                                                  • Diapositiva numero 36
                                                  • GDM and the Use of Betamethasone
                                                  • Diapositiva numero 38
                                                  • Diapositiva numero 39
                                                  • Diapositiva numero 40
                                                  • Pathophysiology of fetal compromise in diabetic pregnancy

                                                    425 donne con DMG escluse se PFS gt 4000Induzione tra 38+0 e 39+0 vs attesa fino a 41

                                                    No differenza in TC e outcome perinatale

                                                    200 donne diabete insulino trattato (13 diabete preesistente)Induzione a 38 vs attesa fino a 42

                                                    No differenza in TC gt di LGA e peso medio nel gruppo di attesa

                                                    RCT INDUZIONE VS ATTESA in GDM

                                                    RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                                    2014

                                                    1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                                    2 Patients well controlled on insulin should probably be delivered by the due date

                                                    3 Poorly controlled GDMrsquos using insulin require individual judgment

                                                    Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                                    1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                    2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                    3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                    cesarean delivery when the estimated fetal weight is ge 4500 g

                                                    MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                    MODALITAgrave E TIMING DEL PARTO nel GDM

                                                    GMD in terapia insulinicaBen controllato

                                                    +Condizioni fetali rassicuranti

                                                    MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                    GDM in terapia nutrizionalecon profili glicemici ottimali

                                                    +Feto AGA

                                                    MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                    Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                    EFW lt 4000g LGAControllo metabolico non

                                                    ottimale

                                                    4000g lt EFW gt 4500g EFW ge 4500g

                                                    Programmare TC elettivo

                                                    Parto vaginale indotto a 38-39 sett

                                                    Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                    MODALITAgrave E TIMING DEL PARTO nel GDM

                                                    IN BASE AL PESO FETALE STIMATO

                                                    - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                    - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                    - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                    ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                    Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                    The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                    A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                    If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                    Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                    GDM and the Use of Betamethasone

                                                    bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                    bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                    bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                    Society of Obstetricians and Gynaecologists of Canada

                                                    The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                    late preterm delivery between 24 to 36 weeksrsquo gestation

                                                    ASSISTENZA IN TRAVAGLIO

                                                    - MONITORAGGIO FETALE CONTINUO

                                                    - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                    MANTENERE GLICEMIA gt70 E lt 126

                                                    (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                    GDM

                                                    - Intravenous infusion of regular insulin titrated and glucose

                                                    - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                    (ACOG 2005)

                                                    ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                    Venere di Willendorf

                                                    Thank you for your attention

                                                    Pathophysiology of fetal compromise in diabetic pregnancy

                                                    Islet cell hyperplasia common in stillborn IDMs

                                                    There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                    Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                    Salvesen 1993Hay 1989Chukwuma 2001

                                                    • Diapositiva numero 1
                                                    • Diapositiva numero 2
                                                    • Diapositiva numero 3
                                                    • Diapositiva numero 4
                                                    • Diapositiva numero 5
                                                    • Diapositiva numero 6
                                                    • Diapositiva numero 7
                                                    • Birth weight distribution in diabetic pregnancies
                                                    • Diapositiva numero 9
                                                    • Diapositiva numero 10
                                                    • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                    • Diapositiva numero 12
                                                    • Diapositiva numero 13
                                                    • Diapositiva numero 14
                                                    • Diapositiva numero 15
                                                    • Diapositiva numero 16
                                                    • Diapositiva numero 17
                                                    • Diapositiva numero 18
                                                    • Diapositiva numero 19
                                                    • Differences in placental pathology according to diabetes types
                                                    • Diapositiva numero 21
                                                    • Pathophysiology of fetal compromise in diabetic pregnancy
                                                    • Diapositiva numero 23
                                                    • Diapositiva numero 24
                                                    • Diapositiva numero 25
                                                    • Diapositiva numero 26
                                                    • Diapositiva numero 27
                                                    • Diapositiva numero 28
                                                    • Diapositiva numero 29
                                                    • Diapositiva numero 30
                                                    • Diapositiva numero 31
                                                    • Diapositiva numero 32
                                                    • Diapositiva numero 33
                                                    • Diapositiva numero 34
                                                    • Diapositiva numero 35
                                                    • Diapositiva numero 36
                                                    • GDM and the Use of Betamethasone
                                                    • Diapositiva numero 38
                                                    • Diapositiva numero 39
                                                    • Diapositiva numero 40
                                                    • Pathophysiology of fetal compromise in diabetic pregnancy

                                                      RACCOMANDAZIONI DELLE LINEE GUIDA INTERNAZIONALI

                                                      2014

                                                      1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                                      2 Patients well controlled on insulin should probably be delivered by the due date

                                                      3 Poorly controlled GDMrsquos using insulin require individual judgment

                                                      Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                                      1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                      2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                      3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                      cesarean delivery when the estimated fetal weight is ge 4500 g

                                                      MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                      MODALITAgrave E TIMING DEL PARTO nel GDM

                                                      GMD in terapia insulinicaBen controllato

                                                      +Condizioni fetali rassicuranti

                                                      MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                      GDM in terapia nutrizionalecon profili glicemici ottimali

                                                      +Feto AGA

                                                      MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                      Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                      EFW lt 4000g LGAControllo metabolico non

                                                      ottimale

                                                      4000g lt EFW gt 4500g EFW ge 4500g

                                                      Programmare TC elettivo

                                                      Parto vaginale indotto a 38-39 sett

                                                      Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                      MODALITAgrave E TIMING DEL PARTO nel GDM

                                                      IN BASE AL PESO FETALE STIMATO

                                                      - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                      - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                      - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                      ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                      Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                      The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                      A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                      If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                      Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                      GDM and the Use of Betamethasone

                                                      bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                      bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                      bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                      Society of Obstetricians and Gynaecologists of Canada

                                                      The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                      late preterm delivery between 24 to 36 weeksrsquo gestation

                                                      ASSISTENZA IN TRAVAGLIO

                                                      - MONITORAGGIO FETALE CONTINUO

                                                      - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                      MANTENERE GLICEMIA gt70 E lt 126

                                                      (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                      GDM

                                                      - Intravenous infusion of regular insulin titrated and glucose

                                                      - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                      (ACOG 2005)

                                                      ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                      Venere di Willendorf

                                                      Thank you for your attention

                                                      Pathophysiology of fetal compromise in diabetic pregnancy

                                                      Islet cell hyperplasia common in stillborn IDMs

                                                      There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                      Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                      Salvesen 1993Hay 1989Chukwuma 2001

                                                      • Diapositiva numero 1
                                                      • Diapositiva numero 2
                                                      • Diapositiva numero 3
                                                      • Diapositiva numero 4
                                                      • Diapositiva numero 5
                                                      • Diapositiva numero 6
                                                      • Diapositiva numero 7
                                                      • Birth weight distribution in diabetic pregnancies
                                                      • Diapositiva numero 9
                                                      • Diapositiva numero 10
                                                      • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                      • Diapositiva numero 12
                                                      • Diapositiva numero 13
                                                      • Diapositiva numero 14
                                                      • Diapositiva numero 15
                                                      • Diapositiva numero 16
                                                      • Diapositiva numero 17
                                                      • Diapositiva numero 18
                                                      • Diapositiva numero 19
                                                      • Differences in placental pathology according to diabetes types
                                                      • Diapositiva numero 21
                                                      • Pathophysiology of fetal compromise in diabetic pregnancy
                                                      • Diapositiva numero 23
                                                      • Diapositiva numero 24
                                                      • Diapositiva numero 25
                                                      • Diapositiva numero 26
                                                      • Diapositiva numero 27
                                                      • Diapositiva numero 28
                                                      • Diapositiva numero 29
                                                      • Diapositiva numero 30
                                                      • Diapositiva numero 31
                                                      • Diapositiva numero 32
                                                      • Diapositiva numero 33
                                                      • Diapositiva numero 34
                                                      • Diapositiva numero 35
                                                      • Diapositiva numero 36
                                                      • GDM and the Use of Betamethasone
                                                      • Diapositiva numero 38
                                                      • Diapositiva numero 39
                                                      • Diapositiva numero 40
                                                      • Pathophysiology of fetal compromise in diabetic pregnancy

                                                        2014

                                                        1 Diet controlled GDMrsquos may deliver post-dates if the fetal parameters are normal

                                                        2 Patients well controlled on insulin should probably be delivered by the due date

                                                        3 Poorly controlled GDMrsquos using insulin require individual judgment

                                                        Estimated weight at birth ge4500 g there is a significant increase in the risk ofshoulder dystocia so a primary section must be consideredWhen estimated weight at birth is 4000ndash4999g an informed consent aboutincreased shoulder dystocia risk

                                                        1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                        2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                        3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                        cesarean delivery when the estimated fetal weight is ge 4500 g

                                                        MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                        MODALITAgrave E TIMING DEL PARTO nel GDM

                                                        GMD in terapia insulinicaBen controllato

                                                        +Condizioni fetali rassicuranti

                                                        MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                        GDM in terapia nutrizionalecon profili glicemici ottimali

                                                        +Feto AGA

                                                        MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                        Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                        EFW lt 4000g LGAControllo metabolico non

                                                        ottimale

                                                        4000g lt EFW gt 4500g EFW ge 4500g

                                                        Programmare TC elettivo

                                                        Parto vaginale indotto a 38-39 sett

                                                        Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                        MODALITAgrave E TIMING DEL PARTO nel GDM

                                                        IN BASE AL PESO FETALE STIMATO

                                                        - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                        - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                        - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                        ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                        Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                        The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                        A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                        If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                        Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                        GDM and the Use of Betamethasone

                                                        bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                        bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                        bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                        Society of Obstetricians and Gynaecologists of Canada

                                                        The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                        late preterm delivery between 24 to 36 weeksrsquo gestation

                                                        ASSISTENZA IN TRAVAGLIO

                                                        - MONITORAGGIO FETALE CONTINUO

                                                        - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                        MANTENERE GLICEMIA gt70 E lt 126

                                                        (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                        GDM

                                                        - Intravenous infusion of regular insulin titrated and glucose

                                                        - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                        (ACOG 2005)

                                                        ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                        Venere di Willendorf

                                                        Thank you for your attention

                                                        Pathophysiology of fetal compromise in diabetic pregnancy

                                                        Islet cell hyperplasia common in stillborn IDMs

                                                        There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                        Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                        Salvesen 1993Hay 1989Chukwuma 2001

                                                        • Diapositiva numero 1
                                                        • Diapositiva numero 2
                                                        • Diapositiva numero 3
                                                        • Diapositiva numero 4
                                                        • Diapositiva numero 5
                                                        • Diapositiva numero 6
                                                        • Diapositiva numero 7
                                                        • Birth weight distribution in diabetic pregnancies
                                                        • Diapositiva numero 9
                                                        • Diapositiva numero 10
                                                        • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                        • Diapositiva numero 12
                                                        • Diapositiva numero 13
                                                        • Diapositiva numero 14
                                                        • Diapositiva numero 15
                                                        • Diapositiva numero 16
                                                        • Diapositiva numero 17
                                                        • Diapositiva numero 18
                                                        • Diapositiva numero 19
                                                        • Differences in placental pathology according to diabetes types
                                                        • Diapositiva numero 21
                                                        • Pathophysiology of fetal compromise in diabetic pregnancy
                                                        • Diapositiva numero 23
                                                        • Diapositiva numero 24
                                                        • Diapositiva numero 25
                                                        • Diapositiva numero 26
                                                        • Diapositiva numero 27
                                                        • Diapositiva numero 28
                                                        • Diapositiva numero 29
                                                        • Diapositiva numero 30
                                                        • Diapositiva numero 31
                                                        • Diapositiva numero 32
                                                        • Diapositiva numero 33
                                                        • Diapositiva numero 34
                                                        • Diapositiva numero 35
                                                        • Diapositiva numero 36
                                                        • GDM and the Use of Betamethasone
                                                        • Diapositiva numero 38
                                                        • Diapositiva numero 39
                                                        • Diapositiva numero 40
                                                        • Pathophysiology of fetal compromise in diabetic pregnancy

                                                          1 the timing of delivery in women with GDM that is controlled with only diet and exercise (A1GDM) should not be before 39 weeks of gestation unless otherwise indicatedExpectant management up to 40 67 weeks of gestation in the setting of indicated antepartum testing is generally appropriate

                                                          2 For women with GDM that is well controlled by medications (A2GDM) delivery is recommended from 39 07 weeks to 39 67 weeks of gestation

                                                          3 Earlier delivery for women with poorly controlled GDM delivery between 37 07 weeks and 38 67 weeks of gestation may be justified but delivery in the late preterm period from 34 07 weeks to 36 67 weeks of gestation should be reserved for those women who fail in-hospital attempts to improve glycemic control or who have abnormal antepartum fetal testing

                                                          cesarean delivery when the estimated fetal weight is ge 4500 g

                                                          MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                          MODALITAgrave E TIMING DEL PARTO nel GDM

                                                          GMD in terapia insulinicaBen controllato

                                                          +Condizioni fetali rassicuranti

                                                          MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                          GDM in terapia nutrizionalecon profili glicemici ottimali

                                                          +Feto AGA

                                                          MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                          Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                          EFW lt 4000g LGAControllo metabolico non

                                                          ottimale

                                                          4000g lt EFW gt 4500g EFW ge 4500g

                                                          Programmare TC elettivo

                                                          Parto vaginale indotto a 38-39 sett

                                                          Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                          MODALITAgrave E TIMING DEL PARTO nel GDM

                                                          IN BASE AL PESO FETALE STIMATO

                                                          - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                          - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                          - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                          ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                          Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                          The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                          A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                          If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                          Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                          GDM and the Use of Betamethasone

                                                          bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                          bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                          bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                          Society of Obstetricians and Gynaecologists of Canada

                                                          The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                          late preterm delivery between 24 to 36 weeksrsquo gestation

                                                          ASSISTENZA IN TRAVAGLIO

                                                          - MONITORAGGIO FETALE CONTINUO

                                                          - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                          MANTENERE GLICEMIA gt70 E lt 126

                                                          (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                          GDM

                                                          - Intravenous infusion of regular insulin titrated and glucose

                                                          - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                          (ACOG 2005)

                                                          ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                          Venere di Willendorf

                                                          Thank you for your attention

                                                          Pathophysiology of fetal compromise in diabetic pregnancy

                                                          Islet cell hyperplasia common in stillborn IDMs

                                                          There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                          Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                          Salvesen 1993Hay 1989Chukwuma 2001

                                                          • Diapositiva numero 1
                                                          • Diapositiva numero 2
                                                          • Diapositiva numero 3
                                                          • Diapositiva numero 4
                                                          • Diapositiva numero 5
                                                          • Diapositiva numero 6
                                                          • Diapositiva numero 7
                                                          • Birth weight distribution in diabetic pregnancies
                                                          • Diapositiva numero 9
                                                          • Diapositiva numero 10
                                                          • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                          • Diapositiva numero 12
                                                          • Diapositiva numero 13
                                                          • Diapositiva numero 14
                                                          • Diapositiva numero 15
                                                          • Diapositiva numero 16
                                                          • Diapositiva numero 17
                                                          • Diapositiva numero 18
                                                          • Diapositiva numero 19
                                                          • Differences in placental pathology according to diabetes types
                                                          • Diapositiva numero 21
                                                          • Pathophysiology of fetal compromise in diabetic pregnancy
                                                          • Diapositiva numero 23
                                                          • Diapositiva numero 24
                                                          • Diapositiva numero 25
                                                          • Diapositiva numero 26
                                                          • Diapositiva numero 27
                                                          • Diapositiva numero 28
                                                          • Diapositiva numero 29
                                                          • Diapositiva numero 30
                                                          • Diapositiva numero 31
                                                          • Diapositiva numero 32
                                                          • Diapositiva numero 33
                                                          • Diapositiva numero 34
                                                          • Diapositiva numero 35
                                                          • Diapositiva numero 36
                                                          • GDM and the Use of Betamethasone
                                                          • Diapositiva numero 38
                                                          • Diapositiva numero 39
                                                          • Diapositiva numero 40
                                                          • Pathophysiology of fetal compromise in diabetic pregnancy

                                                            MATERNAL DIABETES + ESTIMATED FETAL WEIGHT

                                                            MODALITAgrave E TIMING DEL PARTO nel GDM

                                                            GMD in terapia insulinicaBen controllato

                                                            +Condizioni fetali rassicuranti

                                                            MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                            GDM in terapia nutrizionalecon profili glicemici ottimali

                                                            +Feto AGA

                                                            MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                            Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                            EFW lt 4000g LGAControllo metabolico non

                                                            ottimale

                                                            4000g lt EFW gt 4500g EFW ge 4500g

                                                            Programmare TC elettivo

                                                            Parto vaginale indotto a 38-39 sett

                                                            Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                            MODALITAgrave E TIMING DEL PARTO nel GDM

                                                            IN BASE AL PESO FETALE STIMATO

                                                            - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                            - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                            - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                            ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                            Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                            The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                            A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                            If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                            Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                            GDM and the Use of Betamethasone

                                                            bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                            bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                            bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                            Society of Obstetricians and Gynaecologists of Canada

                                                            The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                            late preterm delivery between 24 to 36 weeksrsquo gestation

                                                            ASSISTENZA IN TRAVAGLIO

                                                            - MONITORAGGIO FETALE CONTINUO

                                                            - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                            MANTENERE GLICEMIA gt70 E lt 126

                                                            (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                            GDM

                                                            - Intravenous infusion of regular insulin titrated and glucose

                                                            - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                            (ACOG 2005)

                                                            ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                            Venere di Willendorf

                                                            Thank you for your attention

                                                            Pathophysiology of fetal compromise in diabetic pregnancy

                                                            Islet cell hyperplasia common in stillborn IDMs

                                                            There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                            Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                            Salvesen 1993Hay 1989Chukwuma 2001

                                                            • Diapositiva numero 1
                                                            • Diapositiva numero 2
                                                            • Diapositiva numero 3
                                                            • Diapositiva numero 4
                                                            • Diapositiva numero 5
                                                            • Diapositiva numero 6
                                                            • Diapositiva numero 7
                                                            • Birth weight distribution in diabetic pregnancies
                                                            • Diapositiva numero 9
                                                            • Diapositiva numero 10
                                                            • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                            • Diapositiva numero 12
                                                            • Diapositiva numero 13
                                                            • Diapositiva numero 14
                                                            • Diapositiva numero 15
                                                            • Diapositiva numero 16
                                                            • Diapositiva numero 17
                                                            • Diapositiva numero 18
                                                            • Diapositiva numero 19
                                                            • Differences in placental pathology according to diabetes types
                                                            • Diapositiva numero 21
                                                            • Pathophysiology of fetal compromise in diabetic pregnancy
                                                            • Diapositiva numero 23
                                                            • Diapositiva numero 24
                                                            • Diapositiva numero 25
                                                            • Diapositiva numero 26
                                                            • Diapositiva numero 27
                                                            • Diapositiva numero 28
                                                            • Diapositiva numero 29
                                                            • Diapositiva numero 30
                                                            • Diapositiva numero 31
                                                            • Diapositiva numero 32
                                                            • Diapositiva numero 33
                                                            • Diapositiva numero 34
                                                            • Diapositiva numero 35
                                                            • Diapositiva numero 36
                                                            • GDM and the Use of Betamethasone
                                                            • Diapositiva numero 38
                                                            • Diapositiva numero 39
                                                            • Diapositiva numero 40
                                                            • Pathophysiology of fetal compromise in diabetic pregnancy

                                                              MODALITAgrave E TIMING DEL PARTO nel GDM

                                                              GMD in terapia insulinicaBen controllato

                                                              +Condizioni fetali rassicuranti

                                                              MANAGEMENT DI ATTESANON OLTRE LA 40 SETTIMANAIN ASSENZA DI COMORBIDITAgrave

                                                              GDM in terapia nutrizionalecon profili glicemici ottimali

                                                              +Feto AGA

                                                              MANAGEMENT DI ATTESA FINO ALLA 41 SETTIMANA

                                                              Condotta di attesa uarr probabilitagrave di travaglio spontaneo minor rischio di parto cesareo per fallita induzione

                                                              EFW lt 4000g LGAControllo metabolico non

                                                              ottimale

                                                              4000g lt EFW gt 4500g EFW ge 4500g

                                                              Programmare TC elettivo

                                                              Parto vaginale indotto a 38-39 sett

                                                              Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                              MODALITAgrave E TIMING DEL PARTO nel GDM

                                                              IN BASE AL PESO FETALE STIMATO

                                                              - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                              - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                              - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                              ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                              Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                              The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                              A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                              If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                              Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                              GDM and the Use of Betamethasone

                                                              bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                              bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                              bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                              Society of Obstetricians and Gynaecologists of Canada

                                                              The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                              late preterm delivery between 24 to 36 weeksrsquo gestation

                                                              ASSISTENZA IN TRAVAGLIO

                                                              - MONITORAGGIO FETALE CONTINUO

                                                              - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                              MANTENERE GLICEMIA gt70 E lt 126

                                                              (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                              GDM

                                                              - Intravenous infusion of regular insulin titrated and glucose

                                                              - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                              (ACOG 2005)

                                                              ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                              Venere di Willendorf

                                                              Thank you for your attention

                                                              Pathophysiology of fetal compromise in diabetic pregnancy

                                                              Islet cell hyperplasia common in stillborn IDMs

                                                              There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                              Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                              Salvesen 1993Hay 1989Chukwuma 2001

                                                              • Diapositiva numero 1
                                                              • Diapositiva numero 2
                                                              • Diapositiva numero 3
                                                              • Diapositiva numero 4
                                                              • Diapositiva numero 5
                                                              • Diapositiva numero 6
                                                              • Diapositiva numero 7
                                                              • Birth weight distribution in diabetic pregnancies
                                                              • Diapositiva numero 9
                                                              • Diapositiva numero 10
                                                              • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                              • Diapositiva numero 12
                                                              • Diapositiva numero 13
                                                              • Diapositiva numero 14
                                                              • Diapositiva numero 15
                                                              • Diapositiva numero 16
                                                              • Diapositiva numero 17
                                                              • Diapositiva numero 18
                                                              • Diapositiva numero 19
                                                              • Differences in placental pathology according to diabetes types
                                                              • Diapositiva numero 21
                                                              • Pathophysiology of fetal compromise in diabetic pregnancy
                                                              • Diapositiva numero 23
                                                              • Diapositiva numero 24
                                                              • Diapositiva numero 25
                                                              • Diapositiva numero 26
                                                              • Diapositiva numero 27
                                                              • Diapositiva numero 28
                                                              • Diapositiva numero 29
                                                              • Diapositiva numero 30
                                                              • Diapositiva numero 31
                                                              • Diapositiva numero 32
                                                              • Diapositiva numero 33
                                                              • Diapositiva numero 34
                                                              • Diapositiva numero 35
                                                              • Diapositiva numero 36
                                                              • GDM and the Use of Betamethasone
                                                              • Diapositiva numero 38
                                                              • Diapositiva numero 39
                                                              • Diapositiva numero 40
                                                              • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                EFW lt 4000g LGAControllo metabolico non

                                                                ottimale

                                                                4000g lt EFW gt 4500g EFW ge 4500g

                                                                Programmare TC elettivo

                                                                Parto vaginale indotto a 38-39 sett

                                                                Parto vaginale o TC Considerare-caratteristiche materne (statura BMI pregravidico pelvi bishop)-anamnesi ostetrica (pregressi parti macrosomici o con distocia)

                                                                MODALITAgrave E TIMING DEL PARTO nel GDM

                                                                IN BASE AL PESO FETALE STIMATO

                                                                - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                                - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                                - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                                ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                                Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                                The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                                A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                                If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                                Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                                GDM and the Use of Betamethasone

                                                                bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                                bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                                bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                                Society of Obstetricians and Gynaecologists of Canada

                                                                The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                                late preterm delivery between 24 to 36 weeksrsquo gestation

                                                                ASSISTENZA IN TRAVAGLIO

                                                                - MONITORAGGIO FETALE CONTINUO

                                                                - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                                MANTENERE GLICEMIA gt70 E lt 126

                                                                (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                                GDM

                                                                - Intravenous infusion of regular insulin titrated and glucose

                                                                - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                (ACOG 2005)

                                                                ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                Venere di Willendorf

                                                                Thank you for your attention

                                                                Pathophysiology of fetal compromise in diabetic pregnancy

                                                                Islet cell hyperplasia common in stillborn IDMs

                                                                There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                Salvesen 1993Hay 1989Chukwuma 2001

                                                                • Diapositiva numero 1
                                                                • Diapositiva numero 2
                                                                • Diapositiva numero 3
                                                                • Diapositiva numero 4
                                                                • Diapositiva numero 5
                                                                • Diapositiva numero 6
                                                                • Diapositiva numero 7
                                                                • Birth weight distribution in diabetic pregnancies
                                                                • Diapositiva numero 9
                                                                • Diapositiva numero 10
                                                                • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                • Diapositiva numero 12
                                                                • Diapositiva numero 13
                                                                • Diapositiva numero 14
                                                                • Diapositiva numero 15
                                                                • Diapositiva numero 16
                                                                • Diapositiva numero 17
                                                                • Diapositiva numero 18
                                                                • Diapositiva numero 19
                                                                • Differences in placental pathology according to diabetes types
                                                                • Diapositiva numero 21
                                                                • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                • Diapositiva numero 23
                                                                • Diapositiva numero 24
                                                                • Diapositiva numero 25
                                                                • Diapositiva numero 26
                                                                • Diapositiva numero 27
                                                                • Diapositiva numero 28
                                                                • Diapositiva numero 29
                                                                • Diapositiva numero 30
                                                                • Diapositiva numero 31
                                                                • Diapositiva numero 32
                                                                • Diapositiva numero 33
                                                                • Diapositiva numero 34
                                                                • Diapositiva numero 35
                                                                • Diapositiva numero 36
                                                                • GDM and the Use of Betamethasone
                                                                • Diapositiva numero 38
                                                                • Diapositiva numero 39
                                                                • Diapositiva numero 40
                                                                • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                  - Patients with well-controlled diabetes may be allowed to progress to their expected date of delivery as long as antenatal testing remains reassuring - Expectant management beyond the estimated due date generally is not recommended

                                                                  - Early delivery may be indicated in some patients with vasculopathy nephropathy poor glucose control or a prior stillbirth

                                                                  - Cesarean delivery may be considered if the estimated fetal weight is greater than 4500 g

                                                                  ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                                  Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                                  The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                                  A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                                  If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                                  Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                                  GDM and the Use of Betamethasone

                                                                  bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                                  bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                                  bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                                  Society of Obstetricians and Gynaecologists of Canada

                                                                  The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                                  late preterm delivery between 24 to 36 weeksrsquo gestation

                                                                  ASSISTENZA IN TRAVAGLIO

                                                                  - MONITORAGGIO FETALE CONTINUO

                                                                  - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                                  MANTENERE GLICEMIA gt70 E lt 126

                                                                  (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                                  GDM

                                                                  - Intravenous infusion of regular insulin titrated and glucose

                                                                  - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                  (ACOG 2005)

                                                                  ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                  Venere di Willendorf

                                                                  Thank you for your attention

                                                                  Pathophysiology of fetal compromise in diabetic pregnancy

                                                                  Islet cell hyperplasia common in stillborn IDMs

                                                                  There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                  Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                  Salvesen 1993Hay 1989Chukwuma 2001

                                                                  • Diapositiva numero 1
                                                                  • Diapositiva numero 2
                                                                  • Diapositiva numero 3
                                                                  • Diapositiva numero 4
                                                                  • Diapositiva numero 5
                                                                  • Diapositiva numero 6
                                                                  • Diapositiva numero 7
                                                                  • Birth weight distribution in diabetic pregnancies
                                                                  • Diapositiva numero 9
                                                                  • Diapositiva numero 10
                                                                  • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                  • Diapositiva numero 12
                                                                  • Diapositiva numero 13
                                                                  • Diapositiva numero 14
                                                                  • Diapositiva numero 15
                                                                  • Diapositiva numero 16
                                                                  • Diapositiva numero 17
                                                                  • Diapositiva numero 18
                                                                  • Diapositiva numero 19
                                                                  • Differences in placental pathology according to diabetes types
                                                                  • Diapositiva numero 21
                                                                  • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                  • Diapositiva numero 23
                                                                  • Diapositiva numero 24
                                                                  • Diapositiva numero 25
                                                                  • Diapositiva numero 26
                                                                  • Diapositiva numero 27
                                                                  • Diapositiva numero 28
                                                                  • Diapositiva numero 29
                                                                  • Diapositiva numero 30
                                                                  • Diapositiva numero 31
                                                                  • Diapositiva numero 32
                                                                  • Diapositiva numero 33
                                                                  • Diapositiva numero 34
                                                                  • Diapositiva numero 35
                                                                  • Diapositiva numero 36
                                                                  • GDM and the Use of Betamethasone
                                                                  • Diapositiva numero 38
                                                                  • Diapositiva numero 39
                                                                  • Diapositiva numero 40
                                                                  • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                    ANTENATAL CORTICOSTEROIDS FOR IMPROVING PRETERM BIRTH OUTCOMES WITH MATERNAL DIABETES MELLITUS

                                                                    Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of WomenatRisk of Imminent PretermBirth A Systematic Review and Meta-Analysis RachelMAmiya et al Plos One 2016

                                                                    The presence of maternal diabetes in pregnancy is not a reason to withholdantenatal corticosteroids where there is an imminent RISK OF PRETERM BIRTH

                                                                    A HYPERGLYCAEMIC EFFECT of corticosteroids in pregnant women closemonitoring and treatment for glycaemic control essential at all stage

                                                                    If corticosteroids are administered to accelerate lung maturation an increased insulin requirement over the next 5 days should be anticipated (ACOG)

                                                                    Betamethasone should be prescribed for inducing fetal lung maturity (beforeWeek34) only if strictly indicated because this will also cause the blood glucose levels to rise (GERMAN DIABETES ASSOCIATION)

                                                                    GDM and the Use of Betamethasone

                                                                    bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                                    bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                                    bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                                    Society of Obstetricians and Gynaecologists of Canada

                                                                    The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                                    late preterm delivery between 24 to 36 weeksrsquo gestation

                                                                    ASSISTENZA IN TRAVAGLIO

                                                                    - MONITORAGGIO FETALE CONTINUO

                                                                    - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                                    MANTENERE GLICEMIA gt70 E lt 126

                                                                    (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                                    GDM

                                                                    - Intravenous infusion of regular insulin titrated and glucose

                                                                    - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                    (ACOG 2005)

                                                                    ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                    Venere di Willendorf

                                                                    Thank you for your attention

                                                                    Pathophysiology of fetal compromise in diabetic pregnancy

                                                                    Islet cell hyperplasia common in stillborn IDMs

                                                                    There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                    Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                    Salvesen 1993Hay 1989Chukwuma 2001

                                                                    • Diapositiva numero 1
                                                                    • Diapositiva numero 2
                                                                    • Diapositiva numero 3
                                                                    • Diapositiva numero 4
                                                                    • Diapositiva numero 5
                                                                    • Diapositiva numero 6
                                                                    • Diapositiva numero 7
                                                                    • Birth weight distribution in diabetic pregnancies
                                                                    • Diapositiva numero 9
                                                                    • Diapositiva numero 10
                                                                    • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                    • Diapositiva numero 12
                                                                    • Diapositiva numero 13
                                                                    • Diapositiva numero 14
                                                                    • Diapositiva numero 15
                                                                    • Diapositiva numero 16
                                                                    • Diapositiva numero 17
                                                                    • Diapositiva numero 18
                                                                    • Diapositiva numero 19
                                                                    • Differences in placental pathology according to diabetes types
                                                                    • Diapositiva numero 21
                                                                    • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                    • Diapositiva numero 23
                                                                    • Diapositiva numero 24
                                                                    • Diapositiva numero 25
                                                                    • Diapositiva numero 26
                                                                    • Diapositiva numero 27
                                                                    • Diapositiva numero 28
                                                                    • Diapositiva numero 29
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                                                                    • Diapositiva numero 31
                                                                    • Diapositiva numero 32
                                                                    • Diapositiva numero 33
                                                                    • Diapositiva numero 34
                                                                    • Diapositiva numero 35
                                                                    • Diapositiva numero 36
                                                                    • GDM and the Use of Betamethasone
                                                                    • Diapositiva numero 38
                                                                    • Diapositiva numero 39
                                                                    • Diapositiva numero 40
                                                                    • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                      GDM and the Use of Betamethasone

                                                                      bull administration of betamethasone in the late preterm period should be limited to women with GDM only

                                                                      bull ketoacidosis in the pregnant diabetic individual is a potential cause of fetal demise

                                                                      bull it is recommended to closely monitor maternal glycaemia after betamethasone administration in women with poorly controlled diabetes particularly during the first 12 hours

                                                                      Society of Obstetricians and Gynaecologists of Canada

                                                                      The administration of betamethasone to pregnant women with GDM should be restricted to the routine obstetric indications related to the risk of preterm and

                                                                      late preterm delivery between 24 to 36 weeksrsquo gestation

                                                                      ASSISTENZA IN TRAVAGLIO

                                                                      - MONITORAGGIO FETALE CONTINUO

                                                                      - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                                      MANTENERE GLICEMIA gt70 E lt 126

                                                                      (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                                      GDM

                                                                      - Intravenous infusion of regular insulin titrated and glucose

                                                                      - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                      (ACOG 2005)

                                                                      ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                      Venere di Willendorf

                                                                      Thank you for your attention

                                                                      Pathophysiology of fetal compromise in diabetic pregnancy

                                                                      Islet cell hyperplasia common in stillborn IDMs

                                                                      There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                      Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                      Salvesen 1993Hay 1989Chukwuma 2001

                                                                      • Diapositiva numero 1
                                                                      • Diapositiva numero 2
                                                                      • Diapositiva numero 3
                                                                      • Diapositiva numero 4
                                                                      • Diapositiva numero 5
                                                                      • Diapositiva numero 6
                                                                      • Diapositiva numero 7
                                                                      • Birth weight distribution in diabetic pregnancies
                                                                      • Diapositiva numero 9
                                                                      • Diapositiva numero 10
                                                                      • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                      • Diapositiva numero 12
                                                                      • Diapositiva numero 13
                                                                      • Diapositiva numero 14
                                                                      • Diapositiva numero 15
                                                                      • Diapositiva numero 16
                                                                      • Diapositiva numero 17
                                                                      • Diapositiva numero 18
                                                                      • Diapositiva numero 19
                                                                      • Differences in placental pathology according to diabetes types
                                                                      • Diapositiva numero 21
                                                                      • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                      • Diapositiva numero 23
                                                                      • Diapositiva numero 24
                                                                      • Diapositiva numero 25
                                                                      • Diapositiva numero 26
                                                                      • Diapositiva numero 27
                                                                      • Diapositiva numero 28
                                                                      • Diapositiva numero 29
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                                                                      • Diapositiva numero 31
                                                                      • Diapositiva numero 32
                                                                      • Diapositiva numero 33
                                                                      • Diapositiva numero 34
                                                                      • Diapositiva numero 35
                                                                      • Diapositiva numero 36
                                                                      • GDM and the Use of Betamethasone
                                                                      • Diapositiva numero 38
                                                                      • Diapositiva numero 39
                                                                      • Diapositiva numero 40
                                                                      • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                        ASSISTENZA IN TRAVAGLIO

                                                                        - MONITORAGGIO FETALE CONTINUO

                                                                        - Monitoraggio glicemie plasmatiche materne nelle pz in terapia insulinica ogni ora

                                                                        MANTENERE GLICEMIA gt70 E lt 126

                                                                        (Endocrine Society Clinical Practice Guidelines 2013ACOG 2005)

                                                                        GDM

                                                                        - Intravenous infusion of regular insulin titrated and glucose

                                                                        - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                        (ACOG 2005)

                                                                        ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                        Venere di Willendorf

                                                                        Thank you for your attention

                                                                        Pathophysiology of fetal compromise in diabetic pregnancy

                                                                        Islet cell hyperplasia common in stillborn IDMs

                                                                        There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                        Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                        Salvesen 1993Hay 1989Chukwuma 2001

                                                                        • Diapositiva numero 1
                                                                        • Diapositiva numero 2
                                                                        • Diapositiva numero 3
                                                                        • Diapositiva numero 4
                                                                        • Diapositiva numero 5
                                                                        • Diapositiva numero 6
                                                                        • Diapositiva numero 7
                                                                        • Birth weight distribution in diabetic pregnancies
                                                                        • Diapositiva numero 9
                                                                        • Diapositiva numero 10
                                                                        • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                        • Diapositiva numero 12
                                                                        • Diapositiva numero 13
                                                                        • Diapositiva numero 14
                                                                        • Diapositiva numero 15
                                                                        • Diapositiva numero 16
                                                                        • Diapositiva numero 17
                                                                        • Diapositiva numero 18
                                                                        • Diapositiva numero 19
                                                                        • Differences in placental pathology according to diabetes types
                                                                        • Diapositiva numero 21
                                                                        • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                        • Diapositiva numero 23
                                                                        • Diapositiva numero 24
                                                                        • Diapositiva numero 25
                                                                        • Diapositiva numero 26
                                                                        • Diapositiva numero 27
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                                                                        • Diapositiva numero 32
                                                                        • Diapositiva numero 33
                                                                        • Diapositiva numero 34
                                                                        • Diapositiva numero 35
                                                                        • Diapositiva numero 36
                                                                        • GDM and the Use of Betamethasone
                                                                        • Diapositiva numero 38
                                                                        • Diapositiva numero 39
                                                                        • Diapositiva numero 40
                                                                        • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                          - Intravenous infusion of regular insulin titrated and glucose

                                                                          - Maintain hourly readings of BLOOD GLUCOSE LEVELS LESS THAN 110 MGDL

                                                                          (ACOG 2005)

                                                                          ASSISTENZA IN TRAVAGLIO DIABETE PREGESTAZIONALE

                                                                          Venere di Willendorf

                                                                          Thank you for your attention

                                                                          Pathophysiology of fetal compromise in diabetic pregnancy

                                                                          Islet cell hyperplasia common in stillborn IDMs

                                                                          There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                          Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                          Salvesen 1993Hay 1989Chukwuma 2001

                                                                          • Diapositiva numero 1
                                                                          • Diapositiva numero 2
                                                                          • Diapositiva numero 3
                                                                          • Diapositiva numero 4
                                                                          • Diapositiva numero 5
                                                                          • Diapositiva numero 6
                                                                          • Diapositiva numero 7
                                                                          • Birth weight distribution in diabetic pregnancies
                                                                          • Diapositiva numero 9
                                                                          • Diapositiva numero 10
                                                                          • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                          • Diapositiva numero 12
                                                                          • Diapositiva numero 13
                                                                          • Diapositiva numero 14
                                                                          • Diapositiva numero 15
                                                                          • Diapositiva numero 16
                                                                          • Diapositiva numero 17
                                                                          • Diapositiva numero 18
                                                                          • Diapositiva numero 19
                                                                          • Differences in placental pathology according to diabetes types
                                                                          • Diapositiva numero 21
                                                                          • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                          • Diapositiva numero 23
                                                                          • Diapositiva numero 24
                                                                          • Diapositiva numero 25
                                                                          • Diapositiva numero 26
                                                                          • Diapositiva numero 27
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                                                                          • Diapositiva numero 33
                                                                          • Diapositiva numero 34
                                                                          • Diapositiva numero 35
                                                                          • Diapositiva numero 36
                                                                          • GDM and the Use of Betamethasone
                                                                          • Diapositiva numero 38
                                                                          • Diapositiva numero 39
                                                                          • Diapositiva numero 40
                                                                          • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                            Venere di Willendorf

                                                                            Thank you for your attention

                                                                            Pathophysiology of fetal compromise in diabetic pregnancy

                                                                            Islet cell hyperplasia common in stillborn IDMs

                                                                            There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                            Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                            Salvesen 1993Hay 1989Chukwuma 2001

                                                                            • Diapositiva numero 1
                                                                            • Diapositiva numero 2
                                                                            • Diapositiva numero 3
                                                                            • Diapositiva numero 4
                                                                            • Diapositiva numero 5
                                                                            • Diapositiva numero 6
                                                                            • Diapositiva numero 7
                                                                            • Birth weight distribution in diabetic pregnancies
                                                                            • Diapositiva numero 9
                                                                            • Diapositiva numero 10
                                                                            • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                            • Diapositiva numero 12
                                                                            • Diapositiva numero 13
                                                                            • Diapositiva numero 14
                                                                            • Diapositiva numero 15
                                                                            • Diapositiva numero 16
                                                                            • Diapositiva numero 17
                                                                            • Diapositiva numero 18
                                                                            • Diapositiva numero 19
                                                                            • Differences in placental pathology according to diabetes types
                                                                            • Diapositiva numero 21
                                                                            • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                            • Diapositiva numero 23
                                                                            • Diapositiva numero 24
                                                                            • Diapositiva numero 25
                                                                            • Diapositiva numero 26
                                                                            • Diapositiva numero 27
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                                                                            • Diapositiva numero 33
                                                                            • Diapositiva numero 34
                                                                            • Diapositiva numero 35
                                                                            • Diapositiva numero 36
                                                                            • GDM and the Use of Betamethasone
                                                                            • Diapositiva numero 38
                                                                            • Diapositiva numero 39
                                                                            • Diapositiva numero 40
                                                                            • Pathophysiology of fetal compromise in diabetic pregnancy

                                                                              Pathophysiology of fetal compromise in diabetic pregnancy

                                                                              Islet cell hyperplasia common in stillborn IDMs

                                                                              There is a significant association between fetalplasma insulin concentration and the degree of fetal acidemia

                                                                              Hyperglycemia (chronic) when accompanied byminimal hypoxemia may result in lactic acidosis

                                                                              Salvesen 1993Hay 1989Chukwuma 2001

                                                                              • Diapositiva numero 1
                                                                              • Diapositiva numero 2
                                                                              • Diapositiva numero 3
                                                                              • Diapositiva numero 4
                                                                              • Diapositiva numero 5
                                                                              • Diapositiva numero 6
                                                                              • Diapositiva numero 7
                                                                              • Birth weight distribution in diabetic pregnancies
                                                                              • Diapositiva numero 9
                                                                              • Diapositiva numero 10
                                                                              • Fetal growth profiles in diabetic pregnanciesHead to abdomen circumf Ratio
                                                                              • Diapositiva numero 12
                                                                              • Diapositiva numero 13
                                                                              • Diapositiva numero 14
                                                                              • Diapositiva numero 15
                                                                              • Diapositiva numero 16
                                                                              • Diapositiva numero 17
                                                                              • Diapositiva numero 18
                                                                              • Diapositiva numero 19
                                                                              • Differences in placental pathology according to diabetes types
                                                                              • Diapositiva numero 21
                                                                              • Pathophysiology of fetal compromise in diabetic pregnancy
                                                                              • Diapositiva numero 23
                                                                              • Diapositiva numero 24
                                                                              • Diapositiva numero 25
                                                                              • Diapositiva numero 26
                                                                              • Diapositiva numero 27
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                                                                              • Diapositiva numero 30
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                                                                              • Diapositiva numero 33
                                                                              • Diapositiva numero 34
                                                                              • Diapositiva numero 35
                                                                              • Diapositiva numero 36
                                                                              • GDM and the Use of Betamethasone
                                                                              • Diapositiva numero 38
                                                                              • Diapositiva numero 39
                                                                              • Diapositiva numero 40
                                                                              • Pathophysiology of fetal compromise in diabetic pregnancy

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