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Canadian Society of Internal Medicine Annual Meeting 2016
Montreal, QC
CLINICAL PREDICTORS AND BIOMARKERS IN PREECLAMPSIA: WHAT
SHOULD WE TELL OUR PATIENTS?
Dr Evelyne Rey, Obstetric Medicine Division, CHU Sainte-Justine, University of Montreal
Montreal
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Canadian Society of Internal Medicine Annual Meeting 2016
Montreal, QC
Someofthedrugs,devices,ortreatmentmodalitiesmentionedinthispresentationare:aspirin
No Conflict Disclosures
E. Rey. CLINICAL PREDICTORS AND BIOMARKERS IN PREECLAMPSIA. 2016-10-29 2
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Canadian Society of Internal Medicine Annual Meeting 2016
Montreal, QC
The following presentation represents the views of the speakerat the time of the presentation. This information is meant for educational purposes, and should not replace other sources
of information or your medical judgment.
E. Rey. CLINICAL PREDICTORS AND BIOMARKERS IN PREECLAMPSIA. 2016-10-293
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OBJECTIVES
• Identifyspecificelementsfrompastmedicalhistory,physicalexaminationandobstetrichistorythatcanhelppredictpreeclampsia
• Selectpatientsthatcanbenefitfromimagingtechniquestohelppredictpreeclampsia
• Recognizetheclinicalutilityofexistingorpromisingbiomarkersforpredictionofpreeclampsia(PE)
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PLAN
• Physiology
• Predictors– Clinicalriskfactors
– Biomarkers
– Doppler
– Cell-freefetalDNA
– Podocyturia,Microalbuminuria
• Cases
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
ModifiedfromRedmanCW2005
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CSIM2016 Adapted from Redman 20057
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
Stage3
ModifiedfromRedmanCW2005
Sub-clinicalinflammation,genetics,behavioralfactors
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
Stage3
Placentalmarkers
ModifiedfromRedmanCW2005
Sub-clinicalinflammation,genetics,Behavioralfactors
• ↓PP13• ↓PAPP-A• ↓ADAM12• ↓Metastin
• ↓β-hCG
• ↑Activin-A
• ↑Inhibin-A
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
Stage3
Vascularmarkers
ModifiedfromRedmanCW2005
AngiogenicF.
↓VEGF↓PlGF
AntiAngiogenicF.↑sFlt-1 ↑sEndoglin
↑sFlt-1/PlGF
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
Stage3
Imaging
ModifiedfromRedmanCW2005
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PartialmaternaltoleranceofallogenictrophoblastStage1
Stage2
Stage3
ModifiedfromRedmanCW2005
PredictionProphylaxisPreventoccurrencePreventseverity
EarlydiagnosisPrognosisClosematernalandfetalfollow-up
Severityprediction,Transfer,Delivery
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CLINICALRISKFACTORS
• Familyhistory
• Personalmedicalhistory
• Demographiccharacteristics
• Pregnancy-relatedfactors
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MageeLASOGC2008
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BartschE.BMJ2016
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CLINICALRISKFACTORS
PredictorModelsMetaanalysisAL-RubaieZTAetalBJOG2016
ParityPreviousPEEthnicitycHTConceptionmethodMeanBP
EPESensitivity70%Specificity70%
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Poonetal.
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BLOODPRESSURE
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UADOPPLERVELOCIMETRY1stT• Sensitivity48%,specificity92%• Notalone• NotdoneroutinelyinCanada
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When?AnytimeifIUGR19-20w• Ifabnormalbiomarkers:usefulness?• IfriskofIUGR
LausmanA.JOGC2013
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BIOMARKERS
• Availability
• Aneuploidyscreening
– 1TPAPP-A
– 2T-hCG
–alphaFP–Estriol–Inhibin-A
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BIOMARKERS
1stT/earlysecondtrimester
– PAPP-A– Inhibin-A–PlGF
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Nicolaides2008
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EPE• Parity• PreviousPE• Ethnicity• cHT• Conception• MeanBP
LPE• +• FamilyHPE• Age• BMI
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OlivieraNetal.UltrasoundObstetGynecol2014
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EFFICACYOFTHEMODELS?
• NoRCT
• ASPRE
• CohortscomparisonParksetal2015
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ParkFetal.UltrasundObstetGynecol2015;46:419
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Cell-freeFETALDNA• Increaseswithmarkersofplacentasize• Markerfortrophoblasticcelldeath• YuH2013:Increasesat11-14winEPE:sensitivity90%specificity85%
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NEXTMARKER?
LevineRJAJOG2004
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Medicaldictionnonary2011
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MollerCCetal.JAmSocNephrol2009
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Craicietal.Hypertension2013:1289-96
Lateentryinthestudy
PODOCYTURIA
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MICROALBUMINURIA< 20wks
– Lowrisk:no
– cHtorpreviousPreeclampsia
• higherlevel• Laura-Gonzalez2003:20mg/l
–Sensitivity79%etspecificity63%
–PPV46%NPV88%
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CotéAMCurrentHypertensionreviews2010
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MICROALBUMINURIAINDB
• StrongriskfactorforPE• JensenDMDiabCare2010:846womenT1DB
–NoMicroA:12%PEvs
–MicroA:40%PE
–MicroA:ORa4,nulliparityORa3
•CastiglioniMTPregnancyHyper2014– cHTOR17(3-91),MicroAOR3.8(1.2-11.6),1TGHcOR2.8(1.1-7)
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Case1
• Kimberly,29y,G1P0,
• Essentialchronichypertension
• Blackrace
• BMI36
• 154/104at12w
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Riskofpreeclampsia?.5-10%.10-20%.20-30%.>30%
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BartschE.BMJ2016
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Abnormalif< 0.4MoM
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Case2
• Sandra,37y,G1,
• Type2DBx10y.Notsmoking
• Whiterace
• BMI44
• BP114/76at15w
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Riskofpreeclampsia?
.5-10%
.10-20%
.20-30%
.>30%
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OTHERINFORMATION?
GH
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Sandra=7.9%
Microalbuminuria
Sandra=none
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MICROALBUMINURIAINDB
• StrongriskfactorforPE• JensenDMDiabCare2010:846womenT1DB
–NoMicroA:12%PEvs
–MicroA:40%PE
–MicroA:ORa4,nulliparityORa3
• CastiglioniMTPregnancyHyper2014
– cHTOR17(3-91),MicroAOR3.8(1.2-11.6),1TGHcOR2.8(1.1-7)
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Abnormalif< 0.4MoM
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Case3
• Mandy,35y,G2P1
• PreviousEPE25w+IUGR.CS27w.
• Blackrace,BMI25
• BP130/80
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Riskofpreeclampsia?
.10-20%
.20-30%
.30-40%
.>40%
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OTHERINFORMATION?
• Placenta• Recurrence• Vascularmalperfusionlesionsassociatedwithrecurrence
WeinerE.PrenatalDiagnosis2015
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Abnormalif< 0.4MoM
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Preeclampsiarisk?
Dany Suzy
Age 22 29
BMI 30.2 24.8
Race White Black
BP12sem 120/50 120/80
PAPP-A 0.34 1.72
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HypothyroïdismNonsmokingG1NoFHofPrE
ClinicalF. 4.8% 6.9%
+MAPANDPAPP-A
2.1% 7.3%
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CONCLUSIONS
• HIGHRISKdefinedbyCLINICALFACTORS:REMAINMAJORTOOL
• Impactofbiomarkersonthisgroupofwomen?
• Biomarkersinmoderateriskwomenmoreuseful?
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HAVEALOOK!GEMOQ.CA
JOINUSATtheNASOM/GEMOQmeeting
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WithoutpreviousEPE
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BartschE.BMJ2016