CLINICAL PREDICTORS AND BIOMARKERS IN PREECLAMPSIA: …€¦ · Annual Meeting 2016 Montreal, QC...

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

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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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

BramhamK.BMJ2014

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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