screening for preeclampsia · pre-eclampsia , multivariable risk algorithm: maternal factors,...

Mila Cervar-Zivkovic

2014

Screening for Preeclampsia

• early diagnosis of fetal anomalies

• early diagnosis of pregnancy-associated

diseases


2014

1st Trimester-Screening

Multivariable risk algorithm for 1st

trimester screening

• IUGR

• early onset preeclampsia

• late onset preeclampsia

• preterm delivery

• fetal anomalies


2014

Multivariable risk algorithm for

1st trimester, cutoffs

• IUGR 1:150

• early onset

preeclampsia 1:200

• fetal chromosomal

anomalies 1:300


2014

• IUGR 55%

• early onset

preeclampsia 95 %

• fetal chromosomal

anomalies 95 %

Cutoffs Detection rate

Maternal data included in multivariable

risk algorithm for 1st trimester screening

• chronic hypertension

• history of preeclampsia, IUGR, preterm

delivery

• associated diseases (diabetes, immunological,

renal, thrombophilia)


2014

Biophysical measurements included in

multivariable risk algorithm for 1st trimester

• blood pressure

• Doppler measurements of uterine arteries

• cervical length

• fetal 1st trimester sonography


2014

1st Trimester Prediction of early onset pre-eclampsia, multivariable risk algorithm:

maternal factors, biophysical and biochemical markers (PAPP-A, PlGF)

2nd Trimester

Prediction for adverse

pregnancy outcome:

sFlt-1/PlGF, prediction

time 4-5 weeks before

onset of disease



2014

Biochemical parameters included in

multivariable risk algorithm for 1st trimester


2014

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0 2 4 6 8

PAPP-A (MoM)

0

0,2

0,4

0,6

0,8

1

1,2

0 1 2 3

PLGF (MoM)

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0,4

0,45

0 5 10 15

ß-hCG (MoM)

?• < 34. SSW• severeearly onset

• > 34. SSW• mildlate onset

Ätiologie

anchoring villus

cell column

basal plate

spiral artery

decidua

syncytio-trophoblast

proliferative trophoblast

ETAETB

ETB

invasivetrophoblast

ET-1 im 1. Trimestar

JCEM, Aug. 2011ET-1 in early third trimester

placenta

0

2

4

6

8

10

12

Controls FGR PE PE + FGR

fold

ch

ang

e

-6-5-4-3-2-10123

fold

cha

nge

ET-1 in late third trimesterplacenta

Life Sci, 2011

HealthyPräeklampsie

IUGR

De

zid

ua

My

om

etr

ium

I Trimester Termin I Trimester Termin

Nelson DM, Walsh SW

AJOG 1987

TXA2 PGI2

Aspirin (100 mg)

N %

Screened for preeclampsia 231

Pathologic uterine artery doppler (>2,35) 40 20

Positive medical history for preeclampsia 40 20

High risk for early-onset preeclampsia 21 10

High risk for late-onset preeclampsia 73 36

Women post partum 161

Onset of preeclampsia 2 1

1st trimester screening


2014

Effect of Aspirin Use After positive First Trimester

Screening on the Onset of Preeclampsia

I. Lakovschek, B. Csapo, V. Kolovetsiou-Kreiner, K. Mayer-

Pickel, C. Stern, D. Ulrich, U. Lang, M. Cervar-Zivkovic

1st Trimester Screening

Placenta associated adverse pregnancy

outcome

Biomarkers

• PlGF

• sFLT-1


2014

Healthy Endothelium Dysfunction

PlGF & sFlt-1

PlGF PlGF

PlGF PlGFCell

membrane

Cell

membrane


2014

0

50

100

150

200

250

300

350

400

450

500

12 40weeks

PE and P.

abruption

P. abruption

IUGR, HELLPIUGRPE ITP

sFlt

/PlG

F

Normal

pregnancies

sFlt/PlGF

2nd trimester screening


2014

1st trimesterscreening

positive

2nd trimesterscreening

intensive follow up

negativepregnancy

managementas usually


2014


Recommendations for prevention of preeclampsia

� ASS 75 mg/day

� diagnostic of associated

maternal diseases

� low fat, high fiber, no salt

restriction, vitamins, 1-2 g

calcium

� avoiding of stress, moderate

physical activity

� 2nd trimester screening for

preeclampsia and associated

maternal diseases

� thrombophilia: LWMH

� previous preeclampsia:

psychological treatment

� interdisciplinary for

associated diseases

� all patients: high quality

obstetric treatment


2014

• Thrombophilia & Fetal Demise: 68

• Thrombophilia & Fetal Growth Restriction: 62

• Thrombophilia & Preeclampsia: 128

• Thrombophilia & Abruptio Placentae: 35

• Thrombophilia & Fetal Loss: 75

• Thrombophilia & Habitual Abortion: 82

• Thrombophilia Screening in Pregnancy: 358

• Thrombophilia and Pregnancy: 696

• Thrombophilia and Pregnancy Complications: 594

• Thrombophilia and Placental Complications: 176

Thrombophilia: publications in Pub Med - last 5

years


2014

• Preeclampsia & APC-R, PS, PC, AT III,

Prothrombin

• Fetal death & Prothrombin

• Habitual abortions & Prothrombin, PAI, Factor V

• Placental abruption & elevated Factor VIII

activity, APC-R

Coagulation and Pregnancy Complications


2014

Diagnosis, prophylaxis and treatment of pregnant women

with Activated Protein C Resistance- How can we optimize

the management of these patients?

Third Generation APC Resistance Testing Supersedes

Genetic Factor V Leiden Mutation Testing

F. Prüller, E.-C. Weiss, R. B . Raggam, M. Cervar-Zivkovic

W. Renner, J. Wagner

NEJM 371:7,2014


2014

• myostatin,

• irisin,

• follistatin,

• cytokeratin 19

• ...

Potential New Biomarkers


2014

Platelet proteomics - Biomarkers of platelet function

• Established workflow for proteome

analysis of patient-specific platelet

samples

• High-resolution LC-MS/MS

• Cost-effective semiquantitative analysis

using dimethyl labeling

• Enrichment of platelet membrane

proteins, when feasible

• Enrichment and network analysis of over-

and underexpressed proteins

• Western blot analysis of platelet receptor

levels.

• Correlation with platelet function testing

Figure: Network analysis of overexpressed proteins

Schlagenhauf A, Schweintzger S, Birner-Gruenberger R et al., Platelets 2010

Schlagenhauf A, Kozma N, Leschnik B et al., Transfusion 2012

Biobank

Bioinformatics and biostatistics (also for public health)

Genetic, genomics

MetabolomicsAdditional advanced analytic methods

In silico modeling

Imaging

Biomarker Research

Medical University of Graz

Clinical research


2014


2014

Biobank

Ob GynEndocrinology

ZMF

Cardiology

Hepatology

Center of

Clinical Research

Bayer Schering

Pharma AG

BG Stats

Consulting

BIOCRATES

Lifesciences AG

Biomarker Design

Forschungs GmbH

BioVendor

Laboratorni

medicina a.s.

IASON GmbH

IDS GmbH

JSW Lifesciences

GmbH

LBI Traumatologie

Lab. f. Molekular-

biol. Analytik

M&R

Automation

GmbHNoxygen Science

GmbH

Protagen AG

Proteopharm GmbH

Siemens Healthcare

Diagnostics GmbH

SustSol GmbH

TU Graz

Joanneum

Research

Biomarker Research, MUG


2014

Thank you for your attention!

screening for preeclampsia · pre-eclampsia , multivariable risk algorithm: maternal factors,...

Documents