07/03/11
Ultrasound markers
of pre
pre--eclampsia
G.Macé,, E.Cynober
G.Macé
E.Cynober,, B.Carbonne
Hôpital SaintSaint-Antoine, Paris
Placental disease
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Abnormal trophoblastic invasion
Abnormal trophoblastic
invasion
Placental ischemia
Endothelial activation
Vasoconstriction / micro
micro--thromboses
majoration of ischemia
schemia
Maternal endothelial activation
IUGR
Pre--eclampsia
Pre
HELLP
syndrome
abruption
stillbirth
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Ultrasound markers
• Uterine Dopplers
• Fetal growth
• Fetal Dopplers
RI= S-D/S
or DI=D/S
PI= S-D/m
/
S
S
D
D
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Insufficient colonization
A
normal colonization
A, C, D and B
B/A:
Diastolic Index
A-B/A: Resistance Index
A-B/m : Pulsatility Index
C
D
B
« The Notch »
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Notch 3
Notch 1
Notch 4
Notch 2
Severity
N+Index
Placental side
2 arteries
Index
antiplacental side
1 artery
Notching
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Technical aspects of measurement
Transvaginal
Uterine crossing
Transabdominal
Pseudo-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
•
•
•
•
Pressure on th
P
the probe
b
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
• Decreased speed: spread intervals
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Amplitude
Change probe axis: parallel to the artery
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Differential diagnosis
arcuate artery
Diagnosis of notching
•
•
•
•
Adequate artery at the adequate level
Significant if permanent
Increased RI frequently associated
Evolution during pregnancy
= Clinical impact
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reference curves for PI
first trimester, and until term
3,00
2,75
2,50
2,25
2,00
1,75
1,50
1,25
1,00
,75
,50
75 77 79 81 83 85 87 89 91 93 95 97 99
Chagnaud et al 2008
Gomes et al 2008
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
BMI ≥ 35
chronic
h i HTA
Personal history PE
Nullipara
Parity ≥ 2
(LR+= 1.45)
(LR+= 2.18)
(LR+ 12.52)
(LR+=
12 52)
(LR+= 3.19)
(LR+= 1.23)
(LR+= 1.72)
Define standard high risk population
Papagiorghiou 2005
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Maternal risk factors for preeclampsia
African
BMI ≥ 35
chronic
h i HTA
Personal history PE
Nullipara
Parity ≥ 2
(LR+= 1.45)
(LR+= 2.18)
(LR+ 12.52)
(LR+=
12 52)
(LR+= 3.19)
(LR+= 1.23)
(LR+= 1.72)
Prediction of PE (FP fixed 25%)
Maternal Characteristics =
Uterine artery Doppler =
Combination of both =
45.3%
63.1%
67.5%
Papagiorghiou 2005
T2 Doppler Screening
RI + 1N+
2N+
PI + 1N+
0
5
10
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
Early screening, low risk
Identifies 30% severe PE, better after 13 SA
Harrington et al
Cnossen et al
Melchiorre et al
Martin et al
0
5
10
Likelihood Ratio for Pre
Pre--eclampsia
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Optimization of uterine artery Doppler, maternal
history and evolution during pregnancy
Early and late PE, ROC curves. (Plasencia, UOG 2008)
Predictive value of Notching
in a high
high--risk population
(Bats 2002)
1st trim.
2d trim.
3d trim.
% notch
38 %
19 %
18 %
PPV
50 %
50 %
40 %
NPV
92 %
91 %
81 %
Sens.
75 %
50 %
33 %
Spec..
Spec
75 %
90 %
85 %
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Treatment:: Aspirin ?
Treatment
Recurrence of prepre-eclampsia
Duley et al. BMJ 2001
Prospective Randomised trials
Low-risk: Doppler at 20-24 SA, aspirin if pathologic
Control group: No Doppler
Outcome measure: prevalence of pre-eclampsia
cohort
LR total
4560
3.2
3317
2.1
Subtil et al
BJOG 2003
Goffinet et al
BJOG 2001
Intervention
1.14
[0.7--1.4]
[0.7
1.02
[0.8--1.5]
[0.8
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Aspirin in a high risk population during first trimester
Vainio et al 2002
Selection on Bilateral notching at 12 weeks
Randomised Control Study
45 aspirin / 45 placebo
30 controls without notching
AS (43)
HTA of pregnancy
11,6
PE
4,7
IUGR
2,3
Placebo (43)
37,2
23,3
7
RR
0,31(0,130,31(0,13-0,78)
0,20(0,050,20(0,05-0,86)
0,33(0,040,33(0,04-3,08)
• 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
Æ 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
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
Æearly UD in high risk / Biomarkers / algorythms ?
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Conclusion
•
•
•
•
•
Uterin doppler is a « physiological » marker
Effective tool if skilled operator
Time screening dilemna
No clinical benefit on RCT
Associated maternal factors optimization
Æ Others predictive markers?
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