Research Article Mild Anemia and Pregnancy …downloads.hindawi.com/journals/jp/2014/307535.pdfgestational age at which anemia is diagnosed and adverse pregnancy outcomes is an important
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Research ArticleMild Anemia and Pregnancy Outcome in a Swiss Collective
Gabriela Bencaiova and Christian Breymann
Division of Obstetrics Department of Obstetrics and Gynecology University Hospital of Zurich Frauenklinikstrasse 108091 Zurich Switzerland
Correspondence should be addressed to Gabriela Bencaiova bencabluewinch
Received 20 August 2014 Accepted 20 October 2014 Published 13 November 2014
Academic Editor Sinuhe Hahn
Copyright copy 2014 G Bencaiova and C Breymann This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited
Background Over half of all women in the world experience anemia during their pregnancy Our aimwas to investigate the relationbetween hemoglobin and iron status examined in second trimester and pregnancy outcomeMethods In a prospective longitudinalstudy 382 pregnantwomenwere included Blood sampleswere examined for hematological status and serum ferritin between 16 and20 weeks and for hemoglobin before delivery The adverse maternal and perinatal outcomes were determined Regression analysiswas performed to establish if anemia and low serum ferritin are risk factors for pregnancy complications Results There was noincrease of complications in women with mild anemia and in women with depleted iron stores The finding showed that mild irondeficiency anemia and depleted iron stores are not risk factors for adverse outcomes in iron supplemented women ConclusionsMild anemia and depleted iron stores detected early in pregnancywere not associatedwith adversematernal and perinatal outcomesin iron supplemented women
1 Introduction
Over half of all women in the world experience anemiaduring their pregnancy [1ndash4] The association between thegestational age at which anemia is diagnosed and adversepregnancy outcomes is an important issue [5 6] Some ofthe increase in anemia and iron deficiency anemia (IDA)with gestation is a consequence of the normal physiologicalchanges of pregnancy [7] To avoid the difficulties in anemiadetection caused by plasma volume increase the examinationshould be conducted until 20 weeks of gestation
Findings from the studies on the relationship betweenanemia and adverse pregnancy outcome are contradictorySeveral studies have shown that preterm delivery small forgestational age and low birth weight are increased for womenwith anemia during the 1st trimester and risk depends onthe severity of the hemoglobin deficit [6 8ndash11] Womenwith hemoglobin between 80 and 99 gdL had significantlyhigher risk for low birth weight preterm birth and small forgestational age than women with hemoglobin between 100and 119 gdL [12] The observation by Scholl et al showedthat only iron deficiency anemia not any other anemia
was related to preterm birth which suggests that some ironspecific mechanism may be at play [12]
Severe anemia is also associated with adverse maternaloutcome and may contribute directly or indirectly to a sig-nificant proportion of maternal cardiac failure hemorrhageand infection On the other hand higher rates of placentalproblems (abnormal placentation and placental abruption)were found among the anemic women [13]
The aim of this study was to investigate the relationshipbetween hemoglobin concentration and serum ferritin andadverse outcomes The logistic regression analysis was per-formed to establish if anemia and low serum ferritin are riskfactors for well-known adverse pregnancy outcome
2 Methods
21 Study Population A prospective longitudinal study wasperformed at the Department of Obstetrics UniversityHospital of Zurich to determine the relationship betweenhemoglobin concentration and serum ferritin and adverseoutcome The study was approved by the Human ResearchEthics Committee at the Womenrsquos Hospital in Zurich
Hindawi Publishing CorporationJournal of PregnancyVolume 2014 Article ID 307535 7 pageshttpdxdoiorg1011552014307535
2 Journal of Pregnancy
The women were asked for their consent to participate in ourstudy and the informed consent was obtained before studyenrolment
The hematological status and serum ferritin were exam-ined in 382 pregnant women between 16 and 20 pregnancyweeks and hemoglobin concentration before delivery Allwomenwere presentedwith singleton pregnancies Exclusioncriteria included chronic renal disease and malignancies andhaving a blood transfusion at least 3months before enrolmentin the studyWomenwith hemoglobin (Hb) between 100 and110 gdL received oral iron supplementation Women withhemoglobinlt100 gdLwere treated directlywith intravenousiron in the anemia clinic if they agreed with intravenoustherapy
22 Study Criteria According to current guidelines basedon recommendations of the CDC anemia in pregnancy isdefined by a hemoglobin value less than 110 gdL in both thefirst and third trimesters and less than 105 gdL in the secondtrimester [14] On the basis of our experiences determiningHb (error of measurement of Hb plusmn05 gdL) and the relatedhigh intraindividual variations we chose Hb lt 110 gdL asthe cut-off Iron deficiency anemia was defined as Hb lt110 gdL and a serum ferritin le 15 120583gL Depleted iron storeswas defined as a serum ferritin lt 20120583gL Anemia forother reasons was defined as Hb lt 110 gdL and ferritin gt15 120583gL The category anemia for other reasons included thefollowing thalassemia and hemoglobinopathies vitamin B12deficiency anemia folic acid deficiency anemia and chronicinflammatory diseases (particularly HIV positive womenactive hepatitis B)
The women were divided according to hemoglobin con-centration and ferritin levels into womenwith iron deficiencyanemia (Hb lt 110 gdL and ferritin le 15 120583gL) (Group 1)women with depleted iron stores without anemia (Hb ge110 gdL and ferritin lt 20120583gL) (Group 2) women withanemia for other reasons (Hb lt 110 gdL and ferritin gt15 120583gL) (Group 3) and women with normal status (Group4 control group)
23 Laboratory Assessment Blood samples were collectedby venipuncture Hb red blood cells (RBC) hematocrit(HCT) mean corpuscular volume (MCV) percentage ofred cells microcytic macrocytic hypochromic and hyper-chromic erythrocytes hemoglobin content of reticulocytes(CHr) and red blood cell distribution width (RDW) weremeasured using an ADVIA hematology analyser system(Bayer Diagnostics Leverkusen Germany) Mean corpuscu-lar hemoglobin (MCH) was automatically calculated fromHb and RBC Ferritin was assessed by chemiluminescenceimmunoassay (ACS 190 CibaCorning Diagnostic CorpCleveland OH)
24 Maternal and Perinatal Outcomes Postpartum hemor-rhage was defined as Hb decrease of more than 30 gdLon the second day after delivery Abnormal site of placentalimplantation (placenta praevia) and abnormal placental pen-etration (placenta accretaincretapercreta) were described
as abnormal placental invasion or abnormal placentationGestational age was determined on the basis of early ultra-sound examination Low birth weight (LBW) was definedas birth weight lt2500 g Preterm birth was defined as birthbefore 37 completed weeks of gestation Preterm prematurerupture of fetal membranes (PPROM) was defined as ruptureof fetal membranes before 37 completed weeks of gestationIntrauterine growth restriction (IUGR) was defined as birthweight below the sex-specific 5th percentile of weights forgestational age decreased amniotic fluid volume or abnor-mal Doppler Macrosomia was defined as birth weight abovethe sex-specific 95th percentile of weights for gestational age
The Statistical Package for the Social Sciences (SPSS)(Version 1201 for Windows SPSS Inc) was used for alldata analyses Demographic characteristics were expressedas means (plusmnstandard deviation) and range The outcomevariables were expressed as the absolute number (percent-age) 119875 value was based on Fisherrsquos exact test for categoricaldata and the Mann-Whitney119880 test for quantitative variablesUnivariate logistic regression analysis was performed tocompute odds ratios with 95 confidence intervals of womenin Groups 1 2 and 3 versus nonanemic women (Group 4)for well-known adverse maternal and perinatal outcomesNo correction for multiple testing was performed whencomparing single groups with nonanemic women Those 119875values are only descriptive
3 Results
The demographic and clinical characteristics are shownin Table 1 Iron deficiency anemia was observed in 65depleted iron stores in 322 and anemia for other reasons in118Themean gestational age at study enrolment was 163plusmn14weeksThemean hemoglobin concentration at enrolmentwas 118 plusmn 09 gdL and serum ferritin was 335 plusmn 278 120583gLOut of 70 anemic women only mild anemia was observedat enrolment A higher parity was observed in women withiron deficiency anemia andwith depleted iron stores (Table 1)Women in Groups 1 2 and 3 came more often from formerYugoslavia and developing countries than women in Group 4(119875 = 0001)
The maternal outcomes are shown in Table 2 The meanhemoglobin level before delivery was 121 plusmn 12 gdL (79ndash154) The prevalence of anemia before delivery was 97namely mild anemia in 88 and moderate anemia in 09(Hb lt 90 gdL) Although iron therapy was given in anemicwomen a significantly lowerHb before deliverywas observedin these women (119875 = 0001) There was also a significant dif-ference of hemoglobin concentration before delivery betweenwomen with depleted iron stores and normal women (119875 =0005) There was no increase of maternal complications inwomen with anemia and in women with depleted iron stores
The mean gestational age at delivery was 387 plusmn 29weeks (25ndash42) and birth weight was 3320 plusmn 646 g (730ndash5250) (Table 3) Preterm delivery was observed in 76(29382) low birth weight in 81 (31382) and perinatalmortality in 05 (2382) There was a significant differenceof meconium stained amniotic fluid between women with
Journal of Pregnancy 3
Table 1 Demographic and clinical characteristics
(a)
Group 1 Group 2 Group 3 Group 4 All womenPregnant women 25382 (65) 123382 (322) 45382 (118) 189382 (495) 382
Origin of motherEurope + North America 225 (80) 37123 (301) 745 (156) 76189 (402) 122382 (319)Former Yugoslavia 1228 (480) 49123 (398) 1645 (356) 50189 (265) 127382 (332)Developing countries 1125 (440) 37123 (301) 2245 (489) 63189 (333) 133382 (348)
Data expressed as mean plusmn sd (range) or number ()
(b)
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Maternal age 0827 0068 0336 0082Gravidity 0121 0144 0913 0153Parity 0029lowast 0005lowastlowast 0797 0006lowast
Gestational age at delivery 0633 0687 0485 0919BMI 019 0383 0941 031Origin of mother 005 0038lowast 0008lowast 0001lowastlowastlowastP value lt 005 lowastlowastP value lt 0005Group 1 iron deficiency anemiaGroup 2 depleted iron storesGroup 3 anemia for other reasonsGroup 4 normal status
depleted iron stores and nonanemic women (1123 versus14189) (119875 = 0006) (Table 3) No difference of low birthweight IUGR pretermdelivery or PPROMbetween anaemicand nonanemic women was ascertained Macrosomia wasmore often in women with iron deficiency anemia and withdepleted iron stores (16 and 114)
The logistic regression analysis showed that anemia anddepleted iron stores are not significant risk factors for adversepregnancy outcome (Table 4) The upper limits of the 95confidence intervals of the odds ratios for preterm deliveryLBW IUGR and caesarean section showed that mild anemiaand depleted iron stores are not associated with those adverse
outcomes in iron supplemented women Placental abruptionabnormal placentation and puerperal infection were too rareto draw any conclusions
4 Discussion
The prevalence of anemia and depleted iron stores in thepresent study was 505 (193382) namely anemia in 183(70382) and depleted iron stores in 322 (123382) Ourresults are in accordance with other studies performed inEuropean countries [15] A higher parity was observed inwomen with iron deficiency anemia and depleted iron stores
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Hb at delivery 0001lowastlowastlowast 0005lowastlowast 0001lowastlowastlowast 0001lowastlowastlowast
Postpartum hemorrhage 0482 011 0613 0217Puerperal infection 1 055 1 1Subinvolution 0312 0386 1 0685lowastP value lt 005 lowastlowastP value lt 0005 lowastlowastlowastP value lt 0001
Depleted iron stores were higher in women from formerYugoslavia and anemia for other reasons in women fromdeveloping countries
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse outcomes in ironsupplemented women In our study macrosomia was moreoften in nondiabetic women with iron deficiency anemia(160) Early nonexcessive placental hyperplasia in womenwith mild anemia might lead to increased nutrition supportin later pregnancy if a stress situation is experienced Toour knowledge no studies exist observing the increasedprevalence of macrosomia in women with iron deficiencyanemia
There is a lot of controversial information about anemia inpregnancy and adverse outcomes Two points are importantfor assessment of this relationship the gestational age atwhich the determination of hemoglobin is performed and thedegree of anemia
Hemoglobin and hematocrit decline due to physiologicexpansion of the plasma volume throughout the 1st and 2ndtrimesters [7] Plasma volume expansion reaches its lowestpoint late in the second to early in the third trimester andthen rises again nearer to term It is thus becoming clearthat the best time to detect any risk associated with maternalanemia may be early in pregnancy This was also confirmedin the following current studies [10 16] Any estimation ofhemoglobin concentration taken after 20weeksrsquo gestationwillbe reasonably representative of the fall induced by pregnancy[17] The mean gestational age at enrolment in our study was16 weeks
The second important point is the degree of anemia inpregnancy This is the reason why there is a lot of con-troversial information about the relationship between anemiaand adverse outcomes The extensive literature review pre-sented strong evidence for an association between maternalhemoglobin and birth weight as well as between maternal
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Meconium in amniotic fluid 0428 0006lowast 1 012LBW 1 0211 0583 0192IUGR 0368 1 1 0666Macrosomia 025 0324 082 0717Preterm delivery 1 0287 038 0179PPROM 1 0491 0351 0216Still birth NoS NoS 0192 1Neonatal death 1 1 1 0495NICU admissions 1 1 1 0495Apgar score lt5 at 51015840 1 0281 0577 0368lowastP value lt 005NoS no statistics are computed because variable is a constant
Table 4 Logistic regression analysis of adverse outcomes among anemic women and women with depleted iron stores (Groups 1 2 and 3)versus nonanemic women (Group 4)
Adverse outcome Groups 1 2 and 3 Group 4 OR (95 CI) P value(119899 = 193) (119899 = 189)
hemoglobin and preterm delivery [18] Mild anemia whichwas present in our study was not associated with adverse out-comes in iron supplemented women Therefore we assumethat iron supplementation had a protective effect on adverseoutcome On the other hand severe maternal anemia par-ticularly in the first trimester is associated with adverse out-comes namely preterm birth low birth weight intrauterinegrowth restriction low Apgar score and operative deliveries[5 9 10 16 19 20] The association between the degree
of anemia and adverse outcome was investigated by manystudies in which this association was confirmed [5 9 1021] Extremely high maternal mortality (62) and perinatalmortality (60) were determined in the study by Patra et alin which severematernal anemia was determined in the thirdtrimester [20]
A meta-analysis of studies on the association betweenhemoglobin concentration and adverse outcome conductedbetween 1985 and 1998 showed that maternal anemia during
6 Journal of Pregnancy
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
The women were asked for their consent to participate in ourstudy and the informed consent was obtained before studyenrolment
The hematological status and serum ferritin were exam-ined in 382 pregnant women between 16 and 20 pregnancyweeks and hemoglobin concentration before delivery Allwomenwere presentedwith singleton pregnancies Exclusioncriteria included chronic renal disease and malignancies andhaving a blood transfusion at least 3months before enrolmentin the studyWomenwith hemoglobin (Hb) between 100 and110 gdL received oral iron supplementation Women withhemoglobinlt100 gdLwere treated directlywith intravenousiron in the anemia clinic if they agreed with intravenoustherapy
22 Study Criteria According to current guidelines basedon recommendations of the CDC anemia in pregnancy isdefined by a hemoglobin value less than 110 gdL in both thefirst and third trimesters and less than 105 gdL in the secondtrimester [14] On the basis of our experiences determiningHb (error of measurement of Hb plusmn05 gdL) and the relatedhigh intraindividual variations we chose Hb lt 110 gdL asthe cut-off Iron deficiency anemia was defined as Hb lt110 gdL and a serum ferritin le 15 120583gL Depleted iron storeswas defined as a serum ferritin lt 20120583gL Anemia forother reasons was defined as Hb lt 110 gdL and ferritin gt15 120583gL The category anemia for other reasons included thefollowing thalassemia and hemoglobinopathies vitamin B12deficiency anemia folic acid deficiency anemia and chronicinflammatory diseases (particularly HIV positive womenactive hepatitis B)
The women were divided according to hemoglobin con-centration and ferritin levels into womenwith iron deficiencyanemia (Hb lt 110 gdL and ferritin le 15 120583gL) (Group 1)women with depleted iron stores without anemia (Hb ge110 gdL and ferritin lt 20120583gL) (Group 2) women withanemia for other reasons (Hb lt 110 gdL and ferritin gt15 120583gL) (Group 3) and women with normal status (Group4 control group)
23 Laboratory Assessment Blood samples were collectedby venipuncture Hb red blood cells (RBC) hematocrit(HCT) mean corpuscular volume (MCV) percentage ofred cells microcytic macrocytic hypochromic and hyper-chromic erythrocytes hemoglobin content of reticulocytes(CHr) and red blood cell distribution width (RDW) weremeasured using an ADVIA hematology analyser system(Bayer Diagnostics Leverkusen Germany) Mean corpuscu-lar hemoglobin (MCH) was automatically calculated fromHb and RBC Ferritin was assessed by chemiluminescenceimmunoassay (ACS 190 CibaCorning Diagnostic CorpCleveland OH)
24 Maternal and Perinatal Outcomes Postpartum hemor-rhage was defined as Hb decrease of more than 30 gdLon the second day after delivery Abnormal site of placentalimplantation (placenta praevia) and abnormal placental pen-etration (placenta accretaincretapercreta) were described
as abnormal placental invasion or abnormal placentationGestational age was determined on the basis of early ultra-sound examination Low birth weight (LBW) was definedas birth weight lt2500 g Preterm birth was defined as birthbefore 37 completed weeks of gestation Preterm prematurerupture of fetal membranes (PPROM) was defined as ruptureof fetal membranes before 37 completed weeks of gestationIntrauterine growth restriction (IUGR) was defined as birthweight below the sex-specific 5th percentile of weights forgestational age decreased amniotic fluid volume or abnor-mal Doppler Macrosomia was defined as birth weight abovethe sex-specific 95th percentile of weights for gestational age
The Statistical Package for the Social Sciences (SPSS)(Version 1201 for Windows SPSS Inc) was used for alldata analyses Demographic characteristics were expressedas means (plusmnstandard deviation) and range The outcomevariables were expressed as the absolute number (percent-age) 119875 value was based on Fisherrsquos exact test for categoricaldata and the Mann-Whitney119880 test for quantitative variablesUnivariate logistic regression analysis was performed tocompute odds ratios with 95 confidence intervals of womenin Groups 1 2 and 3 versus nonanemic women (Group 4)for well-known adverse maternal and perinatal outcomesNo correction for multiple testing was performed whencomparing single groups with nonanemic women Those 119875values are only descriptive
3 Results
The demographic and clinical characteristics are shownin Table 1 Iron deficiency anemia was observed in 65depleted iron stores in 322 and anemia for other reasons in118Themean gestational age at study enrolment was 163plusmn14weeksThemean hemoglobin concentration at enrolmentwas 118 plusmn 09 gdL and serum ferritin was 335 plusmn 278 120583gLOut of 70 anemic women only mild anemia was observedat enrolment A higher parity was observed in women withiron deficiency anemia andwith depleted iron stores (Table 1)Women in Groups 1 2 and 3 came more often from formerYugoslavia and developing countries than women in Group 4(119875 = 0001)
The maternal outcomes are shown in Table 2 The meanhemoglobin level before delivery was 121 plusmn 12 gdL (79ndash154) The prevalence of anemia before delivery was 97namely mild anemia in 88 and moderate anemia in 09(Hb lt 90 gdL) Although iron therapy was given in anemicwomen a significantly lowerHb before deliverywas observedin these women (119875 = 0001) There was also a significant dif-ference of hemoglobin concentration before delivery betweenwomen with depleted iron stores and normal women (119875 =0005) There was no increase of maternal complications inwomen with anemia and in women with depleted iron stores
The mean gestational age at delivery was 387 plusmn 29weeks (25ndash42) and birth weight was 3320 plusmn 646 g (730ndash5250) (Table 3) Preterm delivery was observed in 76(29382) low birth weight in 81 (31382) and perinatalmortality in 05 (2382) There was a significant differenceof meconium stained amniotic fluid between women with
Journal of Pregnancy 3
Table 1 Demographic and clinical characteristics
(a)
Group 1 Group 2 Group 3 Group 4 All womenPregnant women 25382 (65) 123382 (322) 45382 (118) 189382 (495) 382
Origin of motherEurope + North America 225 (80) 37123 (301) 745 (156) 76189 (402) 122382 (319)Former Yugoslavia 1228 (480) 49123 (398) 1645 (356) 50189 (265) 127382 (332)Developing countries 1125 (440) 37123 (301) 2245 (489) 63189 (333) 133382 (348)
Data expressed as mean plusmn sd (range) or number ()
(b)
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Maternal age 0827 0068 0336 0082Gravidity 0121 0144 0913 0153Parity 0029lowast 0005lowastlowast 0797 0006lowast
Gestational age at delivery 0633 0687 0485 0919BMI 019 0383 0941 031Origin of mother 005 0038lowast 0008lowast 0001lowastlowastlowastP value lt 005 lowastlowastP value lt 0005Group 1 iron deficiency anemiaGroup 2 depleted iron storesGroup 3 anemia for other reasonsGroup 4 normal status
depleted iron stores and nonanemic women (1123 versus14189) (119875 = 0006) (Table 3) No difference of low birthweight IUGR pretermdelivery or PPROMbetween anaemicand nonanemic women was ascertained Macrosomia wasmore often in women with iron deficiency anemia and withdepleted iron stores (16 and 114)
The logistic regression analysis showed that anemia anddepleted iron stores are not significant risk factors for adversepregnancy outcome (Table 4) The upper limits of the 95confidence intervals of the odds ratios for preterm deliveryLBW IUGR and caesarean section showed that mild anemiaand depleted iron stores are not associated with those adverse
outcomes in iron supplemented women Placental abruptionabnormal placentation and puerperal infection were too rareto draw any conclusions
4 Discussion
The prevalence of anemia and depleted iron stores in thepresent study was 505 (193382) namely anemia in 183(70382) and depleted iron stores in 322 (123382) Ourresults are in accordance with other studies performed inEuropean countries [15] A higher parity was observed inwomen with iron deficiency anemia and depleted iron stores
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Hb at delivery 0001lowastlowastlowast 0005lowastlowast 0001lowastlowastlowast 0001lowastlowastlowast
Postpartum hemorrhage 0482 011 0613 0217Puerperal infection 1 055 1 1Subinvolution 0312 0386 1 0685lowastP value lt 005 lowastlowastP value lt 0005 lowastlowastlowastP value lt 0001
Depleted iron stores were higher in women from formerYugoslavia and anemia for other reasons in women fromdeveloping countries
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse outcomes in ironsupplemented women In our study macrosomia was moreoften in nondiabetic women with iron deficiency anemia(160) Early nonexcessive placental hyperplasia in womenwith mild anemia might lead to increased nutrition supportin later pregnancy if a stress situation is experienced Toour knowledge no studies exist observing the increasedprevalence of macrosomia in women with iron deficiencyanemia
There is a lot of controversial information about anemia inpregnancy and adverse outcomes Two points are importantfor assessment of this relationship the gestational age atwhich the determination of hemoglobin is performed and thedegree of anemia
Hemoglobin and hematocrit decline due to physiologicexpansion of the plasma volume throughout the 1st and 2ndtrimesters [7] Plasma volume expansion reaches its lowestpoint late in the second to early in the third trimester andthen rises again nearer to term It is thus becoming clearthat the best time to detect any risk associated with maternalanemia may be early in pregnancy This was also confirmedin the following current studies [10 16] Any estimation ofhemoglobin concentration taken after 20weeksrsquo gestationwillbe reasonably representative of the fall induced by pregnancy[17] The mean gestational age at enrolment in our study was16 weeks
The second important point is the degree of anemia inpregnancy This is the reason why there is a lot of con-troversial information about the relationship between anemiaand adverse outcomes The extensive literature review pre-sented strong evidence for an association between maternalhemoglobin and birth weight as well as between maternal
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Meconium in amniotic fluid 0428 0006lowast 1 012LBW 1 0211 0583 0192IUGR 0368 1 1 0666Macrosomia 025 0324 082 0717Preterm delivery 1 0287 038 0179PPROM 1 0491 0351 0216Still birth NoS NoS 0192 1Neonatal death 1 1 1 0495NICU admissions 1 1 1 0495Apgar score lt5 at 51015840 1 0281 0577 0368lowastP value lt 005NoS no statistics are computed because variable is a constant
Table 4 Logistic regression analysis of adverse outcomes among anemic women and women with depleted iron stores (Groups 1 2 and 3)versus nonanemic women (Group 4)
Adverse outcome Groups 1 2 and 3 Group 4 OR (95 CI) P value(119899 = 193) (119899 = 189)
hemoglobin and preterm delivery [18] Mild anemia whichwas present in our study was not associated with adverse out-comes in iron supplemented women Therefore we assumethat iron supplementation had a protective effect on adverseoutcome On the other hand severe maternal anemia par-ticularly in the first trimester is associated with adverse out-comes namely preterm birth low birth weight intrauterinegrowth restriction low Apgar score and operative deliveries[5 9 10 16 19 20] The association between the degree
of anemia and adverse outcome was investigated by manystudies in which this association was confirmed [5 9 1021] Extremely high maternal mortality (62) and perinatalmortality (60) were determined in the study by Patra et alin which severematernal anemia was determined in the thirdtrimester [20]
A meta-analysis of studies on the association betweenhemoglobin concentration and adverse outcome conductedbetween 1985 and 1998 showed that maternal anemia during
6 Journal of Pregnancy
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
Origin of motherEurope + North America 225 (80) 37123 (301) 745 (156) 76189 (402) 122382 (319)Former Yugoslavia 1228 (480) 49123 (398) 1645 (356) 50189 (265) 127382 (332)Developing countries 1125 (440) 37123 (301) 2245 (489) 63189 (333) 133382 (348)
Data expressed as mean plusmn sd (range) or number ()
(b)
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Maternal age 0827 0068 0336 0082Gravidity 0121 0144 0913 0153Parity 0029lowast 0005lowastlowast 0797 0006lowast
Gestational age at delivery 0633 0687 0485 0919BMI 019 0383 0941 031Origin of mother 005 0038lowast 0008lowast 0001lowastlowastlowastP value lt 005 lowastlowastP value lt 0005Group 1 iron deficiency anemiaGroup 2 depleted iron storesGroup 3 anemia for other reasonsGroup 4 normal status
depleted iron stores and nonanemic women (1123 versus14189) (119875 = 0006) (Table 3) No difference of low birthweight IUGR pretermdelivery or PPROMbetween anaemicand nonanemic women was ascertained Macrosomia wasmore often in women with iron deficiency anemia and withdepleted iron stores (16 and 114)
The logistic regression analysis showed that anemia anddepleted iron stores are not significant risk factors for adversepregnancy outcome (Table 4) The upper limits of the 95confidence intervals of the odds ratios for preterm deliveryLBW IUGR and caesarean section showed that mild anemiaand depleted iron stores are not associated with those adverse
outcomes in iron supplemented women Placental abruptionabnormal placentation and puerperal infection were too rareto draw any conclusions
4 Discussion
The prevalence of anemia and depleted iron stores in thepresent study was 505 (193382) namely anemia in 183(70382) and depleted iron stores in 322 (123382) Ourresults are in accordance with other studies performed inEuropean countries [15] A higher parity was observed inwomen with iron deficiency anemia and depleted iron stores
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Hb at delivery 0001lowastlowastlowast 0005lowastlowast 0001lowastlowastlowast 0001lowastlowastlowast
Postpartum hemorrhage 0482 011 0613 0217Puerperal infection 1 055 1 1Subinvolution 0312 0386 1 0685lowastP value lt 005 lowastlowastP value lt 0005 lowastlowastlowastP value lt 0001
Depleted iron stores were higher in women from formerYugoslavia and anemia for other reasons in women fromdeveloping countries
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse outcomes in ironsupplemented women In our study macrosomia was moreoften in nondiabetic women with iron deficiency anemia(160) Early nonexcessive placental hyperplasia in womenwith mild anemia might lead to increased nutrition supportin later pregnancy if a stress situation is experienced Toour knowledge no studies exist observing the increasedprevalence of macrosomia in women with iron deficiencyanemia
There is a lot of controversial information about anemia inpregnancy and adverse outcomes Two points are importantfor assessment of this relationship the gestational age atwhich the determination of hemoglobin is performed and thedegree of anemia
Hemoglobin and hematocrit decline due to physiologicexpansion of the plasma volume throughout the 1st and 2ndtrimesters [7] Plasma volume expansion reaches its lowestpoint late in the second to early in the third trimester andthen rises again nearer to term It is thus becoming clearthat the best time to detect any risk associated with maternalanemia may be early in pregnancy This was also confirmedin the following current studies [10 16] Any estimation ofhemoglobin concentration taken after 20weeksrsquo gestationwillbe reasonably representative of the fall induced by pregnancy[17] The mean gestational age at enrolment in our study was16 weeks
The second important point is the degree of anemia inpregnancy This is the reason why there is a lot of con-troversial information about the relationship between anemiaand adverse outcomes The extensive literature review pre-sented strong evidence for an association between maternalhemoglobin and birth weight as well as between maternal
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Meconium in amniotic fluid 0428 0006lowast 1 012LBW 1 0211 0583 0192IUGR 0368 1 1 0666Macrosomia 025 0324 082 0717Preterm delivery 1 0287 038 0179PPROM 1 0491 0351 0216Still birth NoS NoS 0192 1Neonatal death 1 1 1 0495NICU admissions 1 1 1 0495Apgar score lt5 at 51015840 1 0281 0577 0368lowastP value lt 005NoS no statistics are computed because variable is a constant
Table 4 Logistic regression analysis of adverse outcomes among anemic women and women with depleted iron stores (Groups 1 2 and 3)versus nonanemic women (Group 4)
Adverse outcome Groups 1 2 and 3 Group 4 OR (95 CI) P value(119899 = 193) (119899 = 189)
hemoglobin and preterm delivery [18] Mild anemia whichwas present in our study was not associated with adverse out-comes in iron supplemented women Therefore we assumethat iron supplementation had a protective effect on adverseoutcome On the other hand severe maternal anemia par-ticularly in the first trimester is associated with adverse out-comes namely preterm birth low birth weight intrauterinegrowth restriction low Apgar score and operative deliveries[5 9 10 16 19 20] The association between the degree
of anemia and adverse outcome was investigated by manystudies in which this association was confirmed [5 9 1021] Extremely high maternal mortality (62) and perinatalmortality (60) were determined in the study by Patra et alin which severematernal anemia was determined in the thirdtrimester [20]
A meta-analysis of studies on the association betweenhemoglobin concentration and adverse outcome conductedbetween 1985 and 1998 showed that maternal anemia during
6 Journal of Pregnancy
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Hb at delivery 0001lowastlowastlowast 0005lowastlowast 0001lowastlowastlowast 0001lowastlowastlowast
Postpartum hemorrhage 0482 011 0613 0217Puerperal infection 1 055 1 1Subinvolution 0312 0386 1 0685lowastP value lt 005 lowastlowastP value lt 0005 lowastlowastlowastP value lt 0001
Depleted iron stores were higher in women from formerYugoslavia and anemia for other reasons in women fromdeveloping countries
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse outcomes in ironsupplemented women In our study macrosomia was moreoften in nondiabetic women with iron deficiency anemia(160) Early nonexcessive placental hyperplasia in womenwith mild anemia might lead to increased nutrition supportin later pregnancy if a stress situation is experienced Toour knowledge no studies exist observing the increasedprevalence of macrosomia in women with iron deficiencyanemia
There is a lot of controversial information about anemia inpregnancy and adverse outcomes Two points are importantfor assessment of this relationship the gestational age atwhich the determination of hemoglobin is performed and thedegree of anemia
Hemoglobin and hematocrit decline due to physiologicexpansion of the plasma volume throughout the 1st and 2ndtrimesters [7] Plasma volume expansion reaches its lowestpoint late in the second to early in the third trimester andthen rises again nearer to term It is thus becoming clearthat the best time to detect any risk associated with maternalanemia may be early in pregnancy This was also confirmedin the following current studies [10 16] Any estimation ofhemoglobin concentration taken after 20weeksrsquo gestationwillbe reasonably representative of the fall induced by pregnancy[17] The mean gestational age at enrolment in our study was16 weeks
The second important point is the degree of anemia inpregnancy This is the reason why there is a lot of con-troversial information about the relationship between anemiaand adverse outcomes The extensive literature review pre-sented strong evidence for an association between maternalhemoglobin and birth weight as well as between maternal
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Meconium in amniotic fluid 0428 0006lowast 1 012LBW 1 0211 0583 0192IUGR 0368 1 1 0666Macrosomia 025 0324 082 0717Preterm delivery 1 0287 038 0179PPROM 1 0491 0351 0216Still birth NoS NoS 0192 1Neonatal death 1 1 1 0495NICU admissions 1 1 1 0495Apgar score lt5 at 51015840 1 0281 0577 0368lowastP value lt 005NoS no statistics are computed because variable is a constant
Table 4 Logistic regression analysis of adverse outcomes among anemic women and women with depleted iron stores (Groups 1 2 and 3)versus nonanemic women (Group 4)
Adverse outcome Groups 1 2 and 3 Group 4 OR (95 CI) P value(119899 = 193) (119899 = 189)
hemoglobin and preterm delivery [18] Mild anemia whichwas present in our study was not associated with adverse out-comes in iron supplemented women Therefore we assumethat iron supplementation had a protective effect on adverseoutcome On the other hand severe maternal anemia par-ticularly in the first trimester is associated with adverse out-comes namely preterm birth low birth weight intrauterinegrowth restriction low Apgar score and operative deliveries[5 9 10 16 19 20] The association between the degree
of anemia and adverse outcome was investigated by manystudies in which this association was confirmed [5 9 1021] Extremely high maternal mortality (62) and perinatalmortality (60) were determined in the study by Patra et alin which severematernal anemia was determined in the thirdtrimester [20]
A meta-analysis of studies on the association betweenhemoglobin concentration and adverse outcome conductedbetween 1985 and 1998 showed that maternal anemia during
6 Journal of Pregnancy
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
P value 1 versus 4 2 versus 4 3 versus 4 1 2 and 3 versus 4Meconium in amniotic fluid 0428 0006lowast 1 012LBW 1 0211 0583 0192IUGR 0368 1 1 0666Macrosomia 025 0324 082 0717Preterm delivery 1 0287 038 0179PPROM 1 0491 0351 0216Still birth NoS NoS 0192 1Neonatal death 1 1 1 0495NICU admissions 1 1 1 0495Apgar score lt5 at 51015840 1 0281 0577 0368lowastP value lt 005NoS no statistics are computed because variable is a constant
Table 4 Logistic regression analysis of adverse outcomes among anemic women and women with depleted iron stores (Groups 1 2 and 3)versus nonanemic women (Group 4)
Adverse outcome Groups 1 2 and 3 Group 4 OR (95 CI) P value(119899 = 193) (119899 = 189)
hemoglobin and preterm delivery [18] Mild anemia whichwas present in our study was not associated with adverse out-comes in iron supplemented women Therefore we assumethat iron supplementation had a protective effect on adverseoutcome On the other hand severe maternal anemia par-ticularly in the first trimester is associated with adverse out-comes namely preterm birth low birth weight intrauterinegrowth restriction low Apgar score and operative deliveries[5 9 10 16 19 20] The association between the degree
of anemia and adverse outcome was investigated by manystudies in which this association was confirmed [5 9 1021] Extremely high maternal mortality (62) and perinatalmortality (60) were determined in the study by Patra et alin which severematernal anemia was determined in the thirdtrimester [20]
A meta-analysis of studies on the association betweenhemoglobin concentration and adverse outcome conductedbetween 1985 and 1998 showed that maternal anemia during
6 Journal of Pregnancy
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
early pregnancy is associated with slightly increased pretermdelivery but not with significantly increased low birth weightor with fetal growth restriction [16] This meta-analysisdid not consider the degree of anemia nor did it use dif-ferent parameters for the definition of anemia Generallythe hematological parameters and criteria for anemia differwidely Some authors use hematocrit lt33 as criteria foranemia [22] and others use hemoglobin concentrationwith adifferent cut-off namely less than 110 gdL 105 or 100 gdL[5 6 8ndash10 17 19] We defined anemia as hemoglobinconcentration of 110 gdL or less since we previously sawhigh intraindividual variations between Hb 105 and 110 gdLand there was a large group of women with hemoglobinbetween 105 and 109 gdL (39382 102)
The limitation of our study is the absence of CRP deter-mination since ferritin is a marker of inflammation Conse-quently high serum ferritin could actually be a false positivein patients with inflammation The second disadvantage isthe lack of any comparison of our results with an untreatedgroup of anemic women However if we compare our resultswith other studies we can say that iron supplementationhad a protective effect on adverse pregnancy outcome Sincewe wished to simulate normal supplementation the womendid not have to return any residual supplementation Thuscompliance was not monitored in this study
Systematic iron prophylaxis and iron-folic acid supple-mentation during pregnancy has been debated [23ndash26] Thefirst choice in the prophylaxis of iron deficiency anemia foralmost all women is oral iron replacement because of itseffectiveness safety and low cost [24] However in practicephysicians are frequently faced with poor compliance whichcan lead to anemia The second choice is intravenous ironsupplementation with no drug-related serious adverse effects[25] The commonly cited disadvantages of intravenous ironsupplementation are high cost and the invasive nature of theprocedure
We recommend screening for hemoglobin and iron statusin early pregnancy When there is a good compliance withiron supplementation and the pregnancy is uncomplicatedthere is no need for hematological tests during further pre-natal visits even in cases of mild iron deficiency anemia anddepleted iron stores detected in early pregnancy One clear setof hematological test results early in pregnancy indicates thatthere is no increased risk of adverse maternal and perinataloutcomes due to mild iron deficiency anemia and depletediron stores in iron supplemented women further testing laterin pregnancy is therefore superfluous
5 Conclusions
Mild anemia and depleted iron stores detected early inpregnancy were not associated with adverse maternal andperinatal outcomes
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
References
[1] E DeMaeyer and M Adiels-Tegman ldquoThe prevalence ofanaemia in the worldrdquoWorld Health Statistics Quarterly vol 38no 3 pp 302ndash316 1985
[2] T O Scholl ldquoIron status during pregnancy setting the stage formother and infantrdquoThe American Journal of Clinical Nutritionvol 81 no 5 pp 1218Sndash1222S 2005
[3] A C Looker P R Dallman M D Carroll E W Gunter and CL Johnson ldquoPrevalence of iron deficiency in the United StatesrdquoThe Journal of the AmericanMedical Association vol 277 no 12pp 973ndash976 1997
[4] F E Viteri ldquoThe consequences of iron deficiency and anaemiain pregnancy onmaternal health the foetus and the infantrdquo SCNNews no 11 pp 14ndash18 1994
[5] L-M ZhouW-W Yang J-Z Hua C-Q Deng X Tao and R JStoltzfus ldquoRelation of hemoglobin measured at different timesin pregnancy to preterm birth and low birthweight in ShanghaiChinardquo American Journal of Epidemiology vol 148 no 10 pp998ndash1006 1998
[6] H Hamalainen K Hakkarainen and S Heinonen ldquoAnaemia inthe first but not in the second or third trimester is a risk factorfor low birth weightrdquo Clinical Nutrition vol 22 no 3 pp 271ndash275 2003
[7] M F McMullin R White T Lappin J Reeves and GMacKenzie ldquoHaemoglobin during pregnancy relationship toerythropoietin and haematinic statusrdquo European Journal ofHaematology vol 71 no 1 pp 44ndash50 2003
[8] FW Lone R NQureshi and F Emmanuel ldquoMaternal anaemiaand its impact on perinatal outcome in a tertiary care hospitalin Pakistanrdquo Eastern Mediterranean Health Journal vol 10 no6 pp 801ndash807 2004
[9] MMalhotra J B Sharma S Batra S SharmaN SMurthy andR Arora ldquoMaternal and perinatal outcome in varying degreesof anemiardquo International Journal of GynecologyampObstetrics vol79 no 2 pp 93ndash100 2002
[10] A Levy D FraserM KatzMMazor and E Sheiner ldquoMaternalanemia during pregnancy is an independent risk factor forlow birthweight and preterm deliveryrdquo European Journal ofObstetrics amp Gynecology and Reproductive Biology vol 122 no2 pp 182ndash186 2005
[11] V R Lops L P Hunter and L R Dixon ldquoAnemia in pregnancyrdquoAmerican Family Physician vol 51 no 5 pp 1189ndash1197 1995
[12] T O Scholl M L Hediger R L Fischer and J W ShearerldquoAnemia vs iron deficiency increased risk of pretermdelivery ina prospective studyrdquoTheAmerican Journal of Clinical Nutritionvol 55 no 5 pp 985ndash988 1992
[13] A F Fleming ldquoMaternal anemia and fetal outcome in pregnan-cies complicated by thalassemia minor and ldquostomatocytosisrdquordquoAmerican Journal of Obstetrics and Gynecology vol 116 no 3pp 309ndash319 1973
[14] Centers for Disease Control ldquoCDC criteria for anaemia in chil-dren and childbearing-aged womenrdquo Morbidity and MortalityWeekly Report vol 38 pp 400ndash404 1989
[15] S Hercberg P Preziosi and P Galan ldquoIron deficiency inEuroperdquo Public Health Nutrition vol 4 no 2 pp 537ndash545 2001
[16] X Xiong P Buekens S Alexander N Demianczuk and EWollast ldquoAnemia during pregnancy and birth outcome a meta-analysisrdquoAmerican Journal of Perinatology vol 17 no 3 pp 137ndash146 2000
[17] P Steer M A Alam J Wadsworth and A Welch ldquoRelationbetweenmaternal haemoglobin concentration and birth weight
Journal of Pregnancy 7
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010
in different ethnic groupsrdquo British Medical Journal vol 310 no6978 pp 489ndash491 1995
[18] K M Rasmussen ldquoIs there a causal relationship between irondeficiency or iron-deficiency anemia and weight at birth lengthof gestation and perinatal mortalityrdquo Journal of Nutrition vol131 no 2 pp 590Sndash601S 2001
[19] O I Fareh D E E Rizk L Thomas and B Berg ldquoObstetricimpact of anaemia in pregnant women in United Arab Emi-ratesrdquo Journal of Obstetrics amp Gynaecology vol 25 no 5 pp440ndash444 2005
[20] S Patra S Pasrija S S Trivedi and M Puri ldquoMaternal andperinatal outcome in patients with severe anemia in pregnancyrdquoInternational Journal of Gynecology and Obstetrics vol 91 no 2pp 164ndash165 2005
[21] K S Scanlon R Yip L A Schieve and M E Cogswell ldquoHighand low hemoglobin levels during pregnancy differential risksfor preterm birth and small for gestational agerdquo Obstetrics ampGynecology vol 96 no 5 pp 741ndash748 2000
[22] G T Bondevik R T Lie M Ulstein and G Kvale ldquoMaternalhematological status and risk of low birth weight and pretermdelivery in Nepalrdquo Acta Obstetricia et Gynecologica Scandinav-ica vol 80 no 5 pp 402ndash408 2001
[23] A Kumar S Jain N P Singh and T Singh ldquoOral versus highdose parenteral iron supplementation in pregnancyrdquo Interna-tional Journal of Gynecology and Obstetrics vol 89 no 1 pp7ndash13 2005
[24] N Milman ldquoIron prophylaxis in pregnancymdashgeneral or indi-vidual and in which doserdquo Annals of Hematology vol 85 no12 pp 821ndash828 2006
[25] R M Schaefer R Huch A Krafft et al ldquoThe iron lettermdashanupdate on the treatment of iron deficiency anemiardquo Praxis vol95 no 10 pp 357ndash364 2006
[26] T G Sanghvi P W J Harvey and E Wainwright ldquoMaternaliron-folic acid supplementation programs evidence of impactand implementationrdquo Food and Nutrition Bulletin vol 31 no 2pp S100ndashS107 2010