Marqueurs biologiques de l`éclampsie

Centre de gestion
des risques
obstétricaux
Prévention des
RIsques
MAternels et
Fœtaux par une
Action de
Conseil et
Information
Eclairée
MARQUEURS PRECOCES DE LA PRE-ECLAMPSIE:
Centre de gestion
des risques
obstétricaux
De nouveaux chantiers !
Anomalies foetales
•Accouchement prématuré
•Pathologies vasculaires placentaires
Centre de gestion
des risques
obstétricaux
Dépistage & gestion de risques
Centre de gestion
des risques
obstétricaux
Proteinuria
Centre de gestion
des risques
obstétricaux
Centre de gestion
des risques
obstétricaux
Centre de gestion
des risques
obstétricaux
Morbidité et Mortalité
MATERNAL ILLNESS:
Hypertensive disorders of pregnancy complicate
10% of all pregnancies or the lives of 358,784
women @ a cost of ~$8,374 per case or
$3,004,457,216
3 Billion per year
MATERNAL DEATH
18% of U.S. maternal deaths -several hundred
women
Incalculable
Source of data extrapolated from statistics at
http://www.ahrq.gov/data/hcup/hcupnet.htm
http://www.cdc.gov/nchs/
Centre de gestion
des risques
obstétricaux
Morbidité et Mortalité
INFANT ILLNESS
81,708 premature births (~15%) @ a cost of ~$50,
303 per case or ~ 4 Billion per year
INFANT DEATH 1252 infant deaths
ONGOING ISSUES:
- 6,000 cases of Respiratory Distress Syndrome at a
cost of $67, 622 per case or $405 Million
- ~75,000 of the cerebral palsy cases currently living
in the US.
- 15% of blindness, epilepsy, deafness, lung
conditions, learning disabilities, due to prematurity.
Centre de gestion
des risques
obstétricaux
Centre de gestion
des risques
obstétricaux
Screening for preeclampsia ?
Medical history
and disease
Genetics
hCG, PAPP-A
PP-13, ADAM12…
Abnormal vascular bed
Preeclampsia Impaired placentation
MAP
Oxidative stress Endothelial dysfunction
VEGF, PlGF,
sFlt-1, Endoglin…
Do
pp
le
r
Centre de gestion
des risques
obstétricaux
Risk factors for Pre-eclampsia
Centre de gestion
des risques
obstétricaux
L’accumulation de FDR
augmente le risque de PE
August et al. Am J Obstet Gynecol 2004
Centre de gestion
des risques
obstétricaux
Dépistage PE T1
Pression artérielle à 11-14 SA
cMean arterial pressure (MoM)
1.3
1.2
1.1
1.0
0.9
0.8
0.7
MAP = Diastolic BP + (Systolic BP – Diastolic BP) / 3
9,149 pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%
Normal
Early
PE
Late
PE
Centre de gestion
des risques
obstétricaux
Dépistage PE T1
Detection & FP 5%
100
ATCD
90
Maternal age (yr)
BMI
80
(Kg/m2)
70
Racial origin
3.0
White
Black
No previous PE
Previous PE
Maternal history of
PE
History of
hypertension
Ovulation drugs
Mean arterial pressure (MoM)
Parous
2.5
Uterine artery PI MoM
Indian or
Pakistani
1.3
2.0
1.5
1.0
0.5
60
1.2
50
1.1
40
1.0
30
20
0.9
10
0.8
0.0
Normal Early
PE
Late
PE
0.7
0
Normal Early
PE
Late
PE
Early-PE
Late-PE
Centre de gestion
des risques
obstétricaux
Marqueurs sériques
Am J Obstet Gynecol 1939
Smith G, Smith O.
« Anterior pituitary like hormone in late
pregnancy toxemia: summary of results
since 1932 »
• Increased hCG in women with preeclampsia
• Release from damaged placenta?
Centre de gestion
des risques
obstétricaux
Marqueurs sériques....
• PP 13 is lower in women with pre-eclampsia requiring early
delivery, compared to the level of PP-13 in normotensive
pregnancies
Romero et al AJOG 2008
• Inhibin-A elevated at 7-13 wks in women who subsequently
developed PE
(OR=4.9 [1.8;13.2])
Salomon et al. AJOG 2003
• ADAM 12 moderately lower in pre-eclamptic pregnancies
compared to normal pregnancies
Laigard et al. Obstet Gynecol 2005
• Endoglin, sflt-1, MMP-9, TNF.....!
Centre de gestion
des risques
obstétricaux
Marqueurs sériques
7
Likelihood of A dverse Outcom e
6
MoM
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
5
4
Cumulative %
0.02%
0.03%
0.08%
0.27%
0.75%
1.59%
2.95%
4.72%
7.11%
3
2
1
0
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
PAPP-A MoM
Spencer, Nicolaides et al, 2006 – outcome of 55,000 pregnancies
1.3
Centre de gestion
des risques
obstétricaux
Marqueurs sériques
PAPP-A as a predictor of PET
Spencer et al.
18
Likelihood Ratio PET
16
14
12
10
8
6
4
2
0
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0.55
0.6
0.65
PAPP-A MoM Cut Off
0.7
0.75
0.8
0.85
0.9
0.95
1
Centre de gestion
des risques
obstétricaux
Dépistage PE T1
Placental growth factor, PAPP-A, PP13 à
11-14 SA
3.0
PlGF (MoM)
3.0
PAPP-A (MoM)
3.0
2.5
2.5
2.5
2.0
2.0
2.0
1.5
1.5
1.5
1.0
1.0
1.0
0.5
0.5
0.5
0.0
0.0
0.0
Normal Early Late
PE
PE
Normal Early Late
PE
PE
PP13 (MoM)
Normal Early Late
PE
PE
Centre de gestion
des risques
obstétricaux
Dépistage RCIU
ATCD maternels et PAPP-A à 11-13 SA
80
80
White
%
Black
%
70
70
Nulliparous
B2
Parous
90
A Non-smoker
B Smoker
BMI > 25
BMI < 25
1 Age > 30
2 Age < 30
80
B1
60
60
B2
B1
B2
50
50
B1
B2
40
40
B1
30
20
10
B1
A1
B2
A2
A1
B2
100
B1
70
60
50
44%
A2
B1
B2
30
B1
A1
B2
A2
A1
A2
A1
A2
A1
A2
20
40
A1
A2
A1
A2
30%
30
20
10
10
0
0
0
0
Detection rate
for FPR 10%
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
PAPP-A MoM
0
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
PAPP-A MoM
FGR
No PE
FGR
+ PE
Centre de gestion
des risques
obstétricaux
Doppler utérin au premier trimestre
100
PET <34w
80
78
Detection rate (%)
Total
PET
60
40
38
20
Prospective screening
N=3,315; PET 82
(2.5%)
Plasencia et al 2007
0
0
10 20
40
60
False +ve rate (%)
80
100
Centre de gestion
des risques
obstétricaux
Dépistage PE T1
Doppler artères utérines 11-14 SA
80
3.0
Highest PI
Mean PI
Lowest PI
DR (%) at FPR of 10%
Uterine artery PI MoM
2.5
2.0
1.5
1.0
0.5
60
40
20
0.0
Normal Early
PE
Late
PE
9,149 pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%
0
Early-PE
Late-PE
Centre de gestion
des risques
obstétricaux
Early screening for PE
Detection rate for FPR 5%
100
90
PLGF
PAPP-A
80
2.5
2.0
1.5
1.0
3.0
1.3
60
2.5
1.2
50
PlGF MoM
Uterine artery PI MoM
3.0
cMean arterial pressure (MoM)
70
1.1
1.0
0.9
0.5
Early
PE
1.5
30
1.0
20
10
0.0
0.7
Normal
40
0.5
0.8
0.0
2.0
Normal
Early
PE
0
Normal
Early
PE
Early-PE
Late-PE
Centre de gestion
des risques
obstétricaux
Centre de gestion
des risques
obstétricaux
« Combined screening »
Down syndrome screening
70% detection
for 5%FPR
70% detection
for 5%FPR
Ultrasound
Biochemistry
90% detection
for 5% FPR
Centre de gestion
des risques
obstétricaux
« Combined screening »
Preeclampsia screening ?
X% detection
for Y% FPR ?
Centre de gestion
des risques
obstétricaux
En pratique…
Centre de gestion
des risques
obstétricaux
En pratique…
Centre de gestion
des risques
obstétricaux
Prevention of preeclampsia?
…Antioxidants
Calcium…
Aspirin…