Prediction and prevention of

PE and IUGR
Eduard Gratacos

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Preeclampsia

IUGR

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Normal and
abnormal
placental
implantation

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 EARLY-ONSET PE AND IUGR
Relation between placental and maternal disease

HTA

PREDISPOSITION
Endothelial disease
MOTHER proteinuria

DAMAGE platelets
hemolysis
DYSFUNCTION
liver
HYPERSTIMULATION HELLP

eclampsia

IUGR
Endothelial disease
(poor implantation) Fetal hypoxia
PLACENTA
DPPNI
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 EARLY-ONSET LATE-ONSET

4-8 %
PREECLAMPSIA

1%

PREECLAMPSIA + IUGR

1%

IUGR
4-8 %

35 40
20 25 30

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 PREECLAMPSIA
Disease of the vascular endothelium which requires

baseline hyperstimulation state (gestation)

+ maternal predisposition
+/- additional insult (anomalous placentation)

Gestational
Age

MATERNAL
PREDISPOSITION
ANOMALOUS
PLACENTATION

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 %
34 10

5
PE
0

20 25 30 35 40

EARLY-ONSET PE (1%) LATE-ONSET PE (4-8%)

PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS

Degree plac. insufficiency: HIGH Degree plac. insufficiency: LOW

Maternal predisposition + Maternal predisposition +++

Prediction 1 trimester Prediction 2-3 T

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 PREECLAMPSIA: EARLY VERSUS LATE

EARLY LATE
(<34w) (>34w)

Maternal severe disease 83% 30%

Association IUGR 78% 15%

Abnormal Umbilical Artery

78% 43%
Doppler

Abnormal Uterine Artery

95% 46%
Doppler

Abnormal placental
+++ +
pathology

Sibai06, Levine06, Crispi06, Egbor06, Zhang03, Sibai03

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 Prediction of PE
11-14w

PE
INTEGRATED FIRST TRIMESTER APPROACH
maternal + UtA Doppler + biomarkers

Detection Rates (for FPR 10%)

EARLY PE LATE PE

80-90% 25-50%

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 Prediction of PE
11-14w

PE
INTEGRATED FIRST TRIMESTER APPROACH
maternal + UtA Doppler + biomarkers

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Epidemiological risk PREECLAMPSIA

Previous PE / antiphospholipid syndrome x8

BMI 35 kg/m2 / Diabetes x4

Nuliparity/ Multiples /Familiar history x3

Age 40 y., HTA, renal/autoimmune disease x2

Blood Pressure 1T (10% FP)

Early PE ~50%
Late PE ~35%

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 Prediction of PE
11-14w

PE
INTEGRATED FIRST TRIMESTER APPROACH
maternal + UtA Doppler + biomarkers

Detection Rates (for FPR 10%)

EARLY PE LATE PE

50% 25%

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Uterine Artery Doppler

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 Before pregnancy

6-12 w

16-24 w

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 Transvaginally
Feasible throughout pregnancy
Sagittal plane
Measurement at the internal cervical os level

Transabdominally
Feasible after 12 weeks
Lateral plane
Measurement at the crossover with the iliac artery

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Iliac art.

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 UtA Doppler: QuanKtaKve assessment
PulsaKlity index
4,0

3,0

2,0

1,0

0
10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42

Gmez O, Figueras F. Reference ranges for uterine artery mean pulsaKlity index at 11-41 weeks of
gestaKon. Ultrasound Obstet Gynecol. 2008 Aug;32(2):128-32

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 Prediction of PE
11-14w

PE
INTEGRATED FIRST TRIMESTER APPROACH
maternal + UtA Doppler + biomarkers

Detection Rates (for FPR 10%)

EARLY PE LATE PE

80-90% 25-50%

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 Biomarkers 1T and PE

DR (FP 10%)

Early PE Late PE

PlGF 60% -

PAPP-A 60% 45%

sEng 47% -

Inhibin A 40% 17%

PP13 38% -

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Poon 2009, Akolekar 2009, Poon 2010, Audibert 2010, Foidart 2010, Wortelboer 2010,
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 High risk of PE: management

Calcium (only if low intake=suppl. 1gr/24h)

Vitamin C + E (no reduction risk, possible secondary effects)

Aspirin (75-300 mg/d): reduction global risk 10%

if start <16w 47%
60%
if high risk

Hofmeyr G, Cochrane Database Syst Rev 2006

Askie LM, Lancet 2007
Bujold, Eur Obstet Gynecol 2010

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 Prediction of PE
11-14w

PE
INTEGRATED FIRST TRIMESTER APPROACH
maternal + UtA Doppler + biomarkers

Detection Rates (for FPR 10%)

EARLY PE LATE PE

80-90% 25-50%

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 Prediction of PE
32-34w

PE
THIRD TRIMESTER APPROACH
maternal OR UtA Doppler OR biomarkers

Detection Rates (for FPR 10%)

Lai et al. Fetal Diagn Ther 2013
(BP, UtA Doppler, sEng)
LATE PE
Chaiworapongsa et al. AJOG 2013
(PlGF, sFlt-1, sEng)
70-75 %

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 EARLY-ONSET PE
First T combined algorithms=90% DR (10% FPR)
AAS 100 mg/24 h seem to reduce risk

LATE-ONSET IUGR
Detection in 1T still very low.
Future: 3rd T strategies improving definition

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Preeclampsia

IUGR

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 N cases
UA Doppler +
(EARLY-ONSET)

UA Doppler N
(LATE-ONSET)

N cases

Savchev 2013
GA@diagnosis 20 25 30 35 40

32w @diagnosis

EARLY IUGR (1%) LATE IUGR (5-7%)

PROBLEM: MANAGEMENT PROBLEM: DIAGNOSIS

Placental disease: high (UA+, PE high) Placental disease: low (UA-, PE low)

Hypoxia ++: systemic CV adaptation Hypoxia +/-: central CV adaptation

Tolerance to hypoxia. Natural history Low tolerance: no natural history

High mortality and morbidity Low mortality but poor long outcome.

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 signs perinatal
adaptation outcome
%
3
yes poorer
IUGR
CLINICAL PROBLEMS
3
SGA

no normal 0

PROBLEM 1: DIAGNOSIS
20 detection
25<50% 30 35 40

PROBLEM 2: LATE-IUGR VS SGA

Late-IUGR = poor perinatal outcome 5-7% newborns
late-IUGR = 40% term IUFDs detection < 50%
> 40% late pregnancy IUFD
Neurological, cardiovascular and
PROBLEM 3: LONG TERM OUTCOME
metabolic impact
Fetal programming
diagnosis SGA vs. Late-IUGR

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Neonatal and Fetal GA-adjusted normal
weight in the same population

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 PROBLEM 1: IMPROVING DETECTION: THE DEFINITION OF RESTRICTION
Birthweight inverse relation with perinatal outcome AND brain-cardiac remodelling

INTEGRATED 3T SCREENING FOR LATE-PREGNANCY COMPLICATIONS

Late-PE, Late-IUGR, Stillbirth
!
Mula et al., Fetal Diagn Ther 2013
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 PROBLEM 3:
INTEGRATED THIRD TRIMESTER SCREENING
FOR THE PREDICTION OF PERINATAL AND
LONG-TERM OUTCOME
(4P fetal medicine)
IDENTIFICATION OF RISK

INDIVIDUAL
BIOMARKERS

INTERVENTION

WINDOW OF
OPPORTUNITY
BIRTH

Fetus Child

Func4onal / structural
organ remodeling Problem
evident
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KEY ISSUE TO IMPROVE OUTCOMES IS EARLY
DETECTION AND TIMELY INTERVENTION

LATE-ONSET PE
Poor prediction in 1st T.
Future: 3rd T strategies

LATE-ONSET IUGR
Detection is still very low.
Future: 3rd T strategies improving definition

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