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UltrasoundUltrasound markers markers of of prepre--eclampsiaeclampsia

G.MacéG.Macé, , E.CynoberE.Cynober, , B.CarbonneB.Carbonne

Hôpital SaintHôpital Saint--Antoine, ParisAntoine, Paris

PlacentalPlacental diseasedisease

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Abnormal trophoblastic invasionAbnormal trophoblastic invasion

EndothelialEndothelial activationactivation

AbnormalAbnormal trophoblastictrophoblasticinvasioninvasion

PlacentalPlacental ischemiaischemia

Vasoconstriction / microVasoconstriction / micro--thrombosesthromboses

majorationmajoration of ischemiaschemia

MaternalMaternal endothelialendothelial activation activation

IUGRIUGR abruptionabruption

PrePre--eclampsiaeclampsia HELLPHELLPsyndromesyndrome

stillbirthstillbirth

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UltrasoundUltrasound markersmarkers

•• UterineUterine DopplersDopplers

•• FetalFetal growthgrowth

•• FetalFetal DopplersDopplers•• FetalFetal DopplersDopplers

PI= S-D/m RI= S-D/S

S

D

/

S

D

or DI=D/S

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Insufficient colonization normal colonization

A A, C, D and B

B/A: Diastolic IndexA-B/A: Resistance Index

C DB

A-B/A: Resistance IndexA-B/m : Pulsatility Index

B

« The Notch »

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Notch 1 Notch 3

Notch 2 Notch 4

Severity

PlacentalPlacental sideside

2 2 arteriesarteries

IndexIndex

N+IndexN+Index

antiplacentalantiplacental sideside

1 1 arteryarteryNotchingNotching

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Technical aspects of measurement

Transabdominal Pseudo-crossing

TransvaginalUterine crossing

Transversal view

Para sagittal right UA Para sagittal left UA

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Slight changes: pathologic threshold

33% 46%

Factors altering the measurement

P th b• Pressure on the probe• Maternal hemodynamic fluctuations• Level of signal on the artery• Uterine contractions

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Abdominal pressure

D/S = 32% D/S = 48%

Factors influencing the notching

• Maternal heart rate• Maternal heart rate• Decreased speed: spread intervals

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AmplitudeChange probe axis: parallel to the artery

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Differential diagnosis

arcuate artery

Diagnosis of notching

• Adequate artery at the adequate level• Adequate artery at the adequate level• Significant if permanent• Increased RI frequently associated• Evolution during pregnancy

= Clinical impact= Clinical impact

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reference curves for PIfirst trimester, and until term

1,00

1,25

1,50

1,75

2,00

2,25

2,50

2,75

3,00

Chagnaud et al 2008 Gomes et al 2008

,50

,75

1,00

75 77 79 81 83 85 87 89 91 93 95 97 99

Evolution of notching

Gomes et al, 2008

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Choice of indices (Cnossen CMAJ 2008)Meta-analysis, 74 studies, n= 79547

Maternal risk factors for preeclampsia

African (LR+= 1.45)BMI ≥ 35 (LR+= 2.18)h i HTA (LR+ 12 52)chronic HTA (LR+= 12.52)

Personal history PE (LR+= 3.19)Nullipara (LR+= 1.23)Parity ≥ 2 (LR+= 1.72)

Papagiorghiou 2005

Define standard high risk population

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Maternal risk factors for preeclampsia

African (LR+= 1.45)BMI ≥ 35 (LR+= 2.18)h i HTA (LR+ 12 52)chronic HTA (LR+= 12.52)

Personal history PE (LR+= 3.19)Nullipara (LR+= 1.23)Parity ≥ 2 (LR+= 1.72)

Prediction of PE (FP fixed 25%)Prediction of PE (FP fixed 25%)

Maternal Characteristics = 45.3%Uterine artery Doppler = 63.1%Combination of both = 67.5%

Papagiorghiou 2005

T2 Doppler Screening

00 55 1010

PI + 1N+

2N+

RI + 1N+

00 55 1010

LR low risk second trimester (Cnossen 2008)

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Low risk T2 Doppler n=1580 (Papageorghiou 2005)

Prevalence 3-5%: For FP rate 5%, 50% PE identified

Identifies 30% Identifies 30% severesevere PE, PE, betterbetter afterafter 13 SA 13 SA

Early screening, low risk

Harrington et alHarrington et al

CnossenCnossen et alet al

Melchiorre et alMelchiorre et al

Martin et alMartin et al

LikelihoodLikelihood Ratio for Ratio for PrePre--eclampsiaeclampsia

00 55 1010

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Optimization of uterine artery Doppler, maternal history and evolution during pregnancy

Early and late PE, ROC curves. (Plasencia, UOG 2008)

PredictivePredictive value of value of NotchingNotching

in a in a highhigh--riskrisk population population (Bats 2002)(Bats 2002)

11st st trim.trim. 22dd trim.trim. 33dd trim.trim.

92 %92 % 91 %91 % 81 %81 %

50 %50 % 50 %50 % 40 %40 %

% % notchnotch

PPVPPV

NPVNPV

38 %38 % 19 %19 % 18 %18 %

75 %75 % 90 %90 % 85 %85 %

75 %75 % 50 %50 % 33 %33 %Sens.Sens.

SpecSpec..

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TreatmentTreatment: : AspirinAspirin ??RecurrenceRecurrence of of prepre--eclampsiaeclampsia Duley et al. BMJ 2001Duley et al. BMJ 2001

Prospective Randomised trials

Low-risk: Doppler at 20-24 SA, aspirin if pathologicControl group: No DopplerOutcome measure: prevalence of pre-eclampsia

cohortcohort

45604560

LR totalLR total

3.23.2Subtil et alSubtil et al

BJOG 2003BJOG 2003

InterventionIntervention

1.141.14

[0.7[0.7--1.4]1.4]

33173317 2.12.1GoffinetGoffinet et alet al

BJOG 2001BJOG 2001

1.021.02

[0.8[0.8--1.5]1.5]

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AspirinAspirin in a in a highhigh riskrisk population population duringduring first first trimestertrimester

VainioVainio et al 2002et al 2002

Selection on Bilateral notching at 12 weeksRandomised Control Study45 aspirin / 45 placebo30 controls without notching

AS (43) Placebo (43)AS (43) Placebo (43) RRRRHTA of pregnancy HTA of pregnancy 11,611,6 37,237,2 0,31(0,130,31(0,13--0,78)0,78)PEPE 4,74,7 23,323,3 0,20(0,050,20(0,05--0,86)0,86)IUGRIUGR 2,32,3 7 7 0,33(0,040,33(0,04--3,08)3,08)

• Bilateral notching T1 as screening test? – prevalence 55% (Martin et al)– Not randomised

• Clinical impact– Aspirin in identified groups leads to a decreasing of

mild proteinuric HTA– Lack of power considering severe PE

Clinical benefit to prove regarding difficult ultrasound practice to generalised

Comments on Vainio et al 2002

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low dose Aspirin in high risk population before 20 WG

Coomarasamy RCOG 2002

Strategy for PE prediction

Previous obstetrical history Second trimester UDPrevious obstetrical history Chronic HTA

Early Uterine artery doppler in low risk?

Second trimester UD

LR > 5, PPV > 50%NPV similar to low risk

Cnossen, 2008

Optimal surveillance but no treatment exists after 22WG

early UD in high risk / Biomarkers / algorythms ?

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Conclusion

• Uterin doppler is a « physiological » marker• Uterin doppler is a « physiological » marker• Effective tool if skilled operator• Time screening dilemna• No clinical benefit on RCT• Associated maternal factors optimization

Others predictive markers?