nicolaou 2 screening for preeclampsia - sasuogsasuog.org.za/subsiteteachings/presentations/2010...
TRANSCRIPT
Screening for PreScreening for Pre--eclampsiaeclampsia
SASUOG 2010SASUOG 2010
Ermos Nicolaou
Maternal & Fetal Medicine Unit
University of the Witwatersrand
Pre-eclampsia
“Hypertensive disease of pregnancy" remains a leading cause of direct
maternal mortality and morbidity worldwide
•Hypertension and/or proteinuria is the leading single identifiable risk factor in
pregnancy associated with stillbirth (one in five stillbirths in otherwise viable
babies) babies)
•Pre-eclampsia is strongly associated with fetal growth restriction, low birth
weight, preterm delivery, respiratory distress syndrome, and admission to
neonatal intensive care
Fiona Milne at al,
BMJ 2005;330:576 580 doi:10.1136/bmj.330.7491.576
Pre-eclampsia
•Worldwide, each year, more than four million women will develop pre-
eclampsia
•Approximately 100 000 women will have eclamptic convulsions,
•Over 90% occur in developing countries.
•2% of women with pre-eclampsia will develop eclampsia•2% of women with pre-eclampsia will develop eclampsia
RCOG: Pre-eclampsia - study group consensus statement
•By conservative estimates, these disorders are responsible for 76,000
maternal and 500,000 infant deaths each year.
Preeclampsia Foundation
Pre-eclampsia
Pre-eclampsia is a multisystemic syndrome usually recognised by
1. new onset hypertension and proteinuria appearing in the second half of
pregnancy.
2. Clinicians should be aware that pre-eclampsia may occasionally occur
with hypertension in the absence of proteinuria (and proteinuria without
hypertension)
3. but with other features such as eclampsia, renal impairment, 3. but with other features such as eclampsia, renal impairment,
thrombocytopenia, liver dysfunction or fetal compromise.
RCOG: Pre-eclampsia - study group consensus statement
EPICure Study: Outcome at 30 months
Wood N et al. N Engl J Med 2000;343:378-384
EPICure Study: Outcome at 6 years
40
50
60
70
Percentage of Survivors
Severe disability Mild to Moderate No impairment
0
10
20
30
22 wks 23 wks 24 wks 25 wks
Percentage of Survivors
Gestational Age
Marlow N, et al. NEJM 2005
Improved Survival: 80’s to 90’s :500-999
1982-1989 1990-1998
Gestational Age (wks) 25.8 25.5
Birth Weight (grams) 761 756
Antenatal Steroids (%) 0 42
Caesarian Section (%) 32 45
Assisted Ventilation (%) 81 89
Surfactant (%) 1 68
Survival at 20 months (%) 49 67
Wilson-Costello D, et al. Pediatrics 2005
Improved Survival: 80’s to 90’s
30
40
50
60
70
801982-89 1990-98
0
10
20
30
Survived 500-999
Survived Normal 500-
999
Survived Impaired 500-999
Survived Impaired 500-749
For every 100 infants born weighing 500-999, there were 18 additional
survivors- 7 normal and 11 impaired. (Pediatrics 2005)
Definition
• Abdominal circumference < 5th
centile for gestation (US)
• 80% of such fetuses are
constitutionally small, with no
increased perinatal death or
15% 5%
The Small Fetus
increased perinatal death or
morbidity
• 15% are growth restricted due
to reduced placental perfusion
and "utero-placental
insufficiency“
• 5% are growth restricted due to
low growth potential
(abnormal small)
80 %
IUGR or AGA?
When both the anomaly scan and umbilical artery waveforms are
normal, the small fetus should be classified as a “normal small fetus”.
When the anomaly scan is abnormal and the waveforms are normal,
the fetus is an “abnormal small fetus”.
When the anomaly scan is normal and Doppler waveforms are
abnormal, there is IUGR.
Catherine S Bobrow, Peter W Soothill
THE LANCET • Vol 353 • May 1, 1999
Screening for pre-eclampsia
•The underlying mechanism for PE is thought to be impaired placentation,
documented by the findings of
1. abnormal blood flow in the uterine arteries and
2. reduced maternal serum levels of placental products
Screening for Pre-eclampsia
80
90
100
Detection rate (%)
Screen +ve
5%Age (yrs) <20
20-35
>35
Maternal history LR
0.7
1.0
1.5
NHSNHSNational InstituteNational Institute
for Clinical Excellencfor Clinical Excellencee
The patient-specific risk of
developing PE can be
predicted by a combination of
factors in the
0
10
20
30
40
50
60
70
Detection rate (%)
33%
Cigarette smoking
Obstetric history
Nullipara
no PET
PET
1.6
0.5
4.0
Body Mass Index <20
20-30
>30
0.7
1.0
1.5
Ethnicity White
Black
1.0
1.5
0.6
•Maternal history
•Race
•High body mass index
•Prior or family history of PE
K..and the following measurements taken at
11-13 weeks:
•maternal blood pressure
•uterine artery pulsatility index (PI)
•maternal serum level of PAPP-A
•maternal serum level of PLGF
Screening for pre-eclampsia
•Screening by this combined approach could
identify about 90% of patients developing early-
PE at a FPR of 5%
K Nicolaides
Screening in pregnancy
FMF 2009
Vascular dysfunction in pre-eclampsia
In preeclampsia, excess placental soluble Flt-1 (VEGFR-1) binds circulating VEGF and PlGF and prevents
their interaction with endothelial cell-surface receptorsPreeclampsia: A renal perspective
S ANANTH, Kidney International
Pre-eclampsiaFetal growth restriction
Fetal death
Good
diastolic
flow
Impaired placentation
Poor
diastolic
flow
Early
diastolic
notch
Preeclampsia: A renal perspective
S ANANTH, Kidney International
The placenta is a two compartment nutrient, fluid and gas exchange organ:
The maternal compartment is assessed by uterine artery Doppler
The fetal compartment is assessed by umbilical artery Doppler
Vascular dysfunction in pre-eclampsia
A Baschat,
Doppler Ultrasound,
FMF 2010
Umbilical Arteries
Abnormal villous vascular perfusion results in abnormal waveform in the
umbilical arteries;
Depending on the degree of impaired vasculature:
30% impairment results in high pulsatility index
50% impairment results in absent end-diastolic velocity 50% impairment results in absent end-diastolic velocity
70% impairment results in reversed end-diastolic velocity
The risk for hypoxemia / acidemia is proportional to the decrease in
umbilical end-diastolic flow
A Baschat,
Doppler Ultrasound,
FMF 2010
Arterial BP (m
mHg) 105
95
Ute
rine
artery
PI 3.5
3.0
2.5
2.0
1.5
1.0
0.5 Normal PET
Screening for pre-eclampsia at 11-13+6 wks
Mate
rnal se
rum PAPP
-A (MoM
)
4.0
3.5
3.0
2.5
2.0
1.5
90%
Arterial BP (m
mHg)
95
85
75
65
55
Normal PET
Card
iac ou
tput (L/m
in)
8
7
6
5
4
3
2 Normal PET
PET
Mate
rnal se
rum
1.0
0.5
0.0
Normal
J. E. A. K. BAMFO, et al
Maternal cardiac function in fetal growth-restricted
and non-growth-restricted small-for-gestational
age pregnanciesUltrasound Obstet Gynecol 2007; 29: 51–57
K Spencer at al
First-trimester maternal serum PP-13, PAPP-A
and second-trimester uterine artery Doppler
pulsatility index as markers of pre-eclampsia
Ultrasound Obstet Gynecol 2007; 29: 128–134
Maternal history, uterine artery Doppler & serum biochemistry
70
80
90
100
De
tectio
n r
ate
(%
)
90%
80%
Screen +ve 5%
Screening for Pre-Eclampsia
0
10
20
30
40
50
60
De
tectio
n r
ate
(%
)
PET <33w
33%
0
10
20
30
40
50
60
70
80
90
0.5 1 1.5 2 2.5 3
Mean uterine artery PI
Risk (%)
Yu et al 2004 + Biochemistry
+ Uterine PI
His
tory
K Nicolaides
Editorial: Some thoughts on the true value of ultrasound
Ultrasound Obstet Gynecol 2007; 30: 671–674
PAPP-A as a predictor of IUGR
Spencer, Nicolaides et al, 2006 – outcome of 55,000 pregnancies
PAPP-A as a predictor of PET
The value of Biochemical Screening in the 1st and 2nd Trimester
K Spenser, SASUOG, 2006
PAPP-A as a predictor of poor outcome
• Our series of 1236 patients (WITS) April 2008- April 2009
• 152 patients with low PAPP-A (normal karyotype)
Nicolaou E, Naidoo P, Bister S
PAPP-A as a predictor of poor pregnancy outcome
Mat & Fetal Med Unit, University of the Witwatersrand
2.0
2.5
3.0
3.5
4.0
4.5
5.0LR
of
PIH
0.0
0.5
1.0
1.5
0.4 0.45 0.5 0.55 0.6 0.65 0.7 0.75 0.8 0.85 0.9 0.95 1
LR
of
PIH
PAPP-A MOM
Nicolaou E, Naidoo P, Bister S
PAPP-A as a predictor of poor pregnancy outcome
Mat & Fetal Med Unit, University of the Witwatersrand
40%
50%
60%
70%
80%
90%
100%
NORMAL
ICU
MB
ER
OF
PA
TIE
NT
S (
%)
0%
10%
20%
30%
ICU
NU
MB
ER
OF
PA
TIE
NT
S (
%)
PAPP-A MOM Nicolaou E, Naidoo P, Bister S
PAPP-A as a predictor of poor pregnancy outcome
Mat & Fetal Med Unit, University of the Witwatersrand
40%
50%
60%
70%
80%
90%
100%
ABRUPTIO
HYPERTENSION
UNEVENTFUL
NU
MB
ER
OF
PA
TIE
NT
S (
%)
0%
10%
20%
30%
40%
<0.45 0.46-0.65 >0.65
NU
MB
ER
OF
PA
TIE
NT
S (
%)
PAPP-A MOM Nicolaou E, Naidoo P, Bister S
PAPP-A as a predictor of poor pregnancy outcome
Mat & Fetal Med Unit, University of the Witwatersrand
Simon Glerup et al
Proteinase Inhibition by Proform of Eosinophil Major Basic Protein (pro-MBP)
Is a Multistep Process of Intra- and Intermolecular Disulfide Rearrangements*J. Biol. Chem., Vol. 280, Issue 11, 9823-9832, March 18, 2005
Screening for Pre-Eclampsia
K Spencer at al
Ultrasound Obstet Gynecol 2007; 29: 128–134
First-trimester maternal serum PP-13, PAPP-A
and second-trimester uterine artery Doppler
pulsatility index as markers of pre-eclampsia
PP13 is a protein expressed
only in the placenta. It is
involved in gluing the placenta
to the uterus, and in
remodelling the maternal
arteries to expand them
Screening for Pre-Eclampsia
R Romero at al, Am J Obstet Gynecol, 2008, 199-(2); 122e1-122e11
First Trimester Maternal Serum PP13 in the Risk Assessment for Preeclampsia
Screening for Pre-Eclampsia
Aspirin 150 mg / day
for abnormal Doppler at 23 wks
DRUG Aspirin Placebo
280 280
• Pre-eclampsia 18% 19%
• FGR <5th Centile 22% 24%
• Abruption 4% 2%
Yu et al 2003
Prevention of PET / FGR
Vitamin C 1000 mg / day &
Vitamin E 400 IU / day
DRUG Vitamins Placebo
935 942
• Pre-eclampsia 6% 5%
• Antihypertensives 4.6%* 2.8%
• FGR (<10th centile) 8.7% 9.9%
Low-risk (nulliparous) women
Yu et al 2003
High-risk women
DRUG Vitamins Placebo
1199 1205
• Pre-eclampsia 15% 16%
• Antihypertensives 7%* 3%
• FGR (BW<2.5Kg) 28%* 24%
• Baby deaths 4% 3%
Poston et al 2006
• FGR (<10 centile) 8.7% 9.9%
• Baby deaths 1.3% 1.8%
Rumbold et al 2006
Conclusion
Preeclampsia and its complications are as common today as they were
more than 30 years ago.
This is mainly because of our
•Failure to understand adequately the patho-physiology of the condition
•Failure (so-far) to develop adequate methods of screening to identify the
patients at high risk.
•Failure to develop effective strategies for their prevention, and
•Failure to develop adequate treatment strategies
Proposed screening for Preeclampsia
Universal 1st
trimester
Normal test: Review at 20weeks
Fetal anomaly scan,
Cx length, Dopplers
Increased NT, low PAPP-A
Consider karyotyping
If karyotype normal
Low dose Aspirin review at 20weeks trimester
screening
(NT, PAPP-A & free beta HCG,
UA-PI, BP)
low PAPP-A karyotyping review at 20weeks monitor BP,
Doppler
Normal NT
low PAPP-A,
UA PI
Low dose Aspirin, monitor BP,
Doppler
High BP, Hx of PET Low dose Aspirin,
monitor BP, Doppler