The Fetal Medicine Foundation Prof Fabricio Costa MD, PhD, FRANZCOG, COGU, Diploma in Fetal Medicine (FMF-London, UK) Department of Gynecology and Obstetrics University of São Paulo at Ribeirão Preto Brazil State of the art of first trimester pre-eclampsia screening DISCLAIMER Copying, distribution and any kind of use require the written consent of the author. Downloads and copies of the presentation are only permitted for private, non-commercial use.
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The Fetal Medicine
Foundation
Prof Fabricio Costa MD, PhD, FRANZCOG, COGU,
Diploma in Fetal Medicine (FMF-London, UK)
Department of Gynecology and Obstetrics
University of São Paulo at Ribeirão Preto
Brazil
State of the art of first trimester
pre-eclampsia screening
DISCLAIMER
Copying, distribution and any kind of use require the written consent of the author.
Downloads and copies of the presentation are only permitted for private, non-commercial use.
The Fetal Medicine
Foundation
Why am I here?
The Fetal Medicine
Foundation
The Fetal Medicine
Foundation
- Identifying women at high risk in the first trimester allows preventive
actions such as low-dose aspirin intake starting before 16 weeks
- However, the number of women attending their first antenatal visit after
14 weeks is often more than 50% and can be as high as 88.5% in
developing countries
- Screening for PE in the second trimester could still be of benefit, since
close monitoring looking for early signs of PE allows timely treatment
and delivery
MUFW & SUFW
Who we are
Mid-2013
6 sites 10 sites
40,000 1st trim PE screenings
Largest dedicated O&G ultrasound practice in Australasia
~ 80,000 scans per year; 10,000 NIPT; 10,000 PE screenings
The Fetal Medicine
Foundation
We have a problem….
The Fetal Medicine
Foundation
2 - 8% of the pregnancies
6.6 million cases per year worldwide
US - 18% of maternal deaths
1 maternal death caused by PE every 12 minutes
15% of premature deliveries
Future cardiovascular risk
Pre-eclampsia
Background
Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33: 130-137.
Wu P et al. Circ Cardiovasc Qual Outcomes 2017; 10.
The Fetal Medicine
Foundation
The Fetal Medicine
Foundation
The Fetal Medicine
Foundation
Mortality
Morbidity
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Foundation
How are we addressing
this problem?
The Fetal Medicine
Foundation
Ministry of Health Report. 1929
Memorandum on antenatal clinics: their
conduct and scope. His Majesty’s Stationery
Office, London; 1930.
The Fetal Medicine
FoundationJAMA April 25, 2017 Volume 317, Number 16
The Fetal Medicine
Foundation Obstetricians in action…
The Fetal Medicine
FoundationClinical Chemistry 58:5 837–845 (2012)
The Fetal Medicine
Foundation
The Fetal Medicine
Foundation
Screening strategies
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Foundation
High risk factors
Hypertensive disease in a previous pregnancy
Chronic renal disease
Chronic hypertension
Diabetes mellitus
Autoimmune disease such as SLE or APS
Moderate risk factors
First pregnancy
Age > 40 years
Body mass index > 35 kg/m2
Inter-pregnancy interval > 10 years
Family history of preeclampsia
NICE guidelines 2010
High-risk in need of aspirin
Preeclampsia in >2 previous pregnancies
Preeclampsia <34w in previous pregnancy
Task Force on Hypertension in Pregnancy
ACOG 2013
Risk factors
Preeclampsia in a previous pregnancy
Chronic renal disease
Chronic hypertension
Diabetes mellitus
SLE or thrombophilia
First pregnancy
Age > 40 years
Body mass index > 30 kg/m2
Conception by in vitro fertilization
Family history of preeclampsia
Prediction of pre-eclampsia
Guidelines
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Foundation
Tan MY et al. Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining
maternal factors and biomarkers: results of SPREE. Ultrasound Obstet Gynecol 2018, DOI 10.1002/uog.19039.
23%
High-risk x prevention – Nice, UK
0
10
20
30
40
50
60
80
90
100
70
Dete
cti
on
ra
te (
%)
<37w >37w Total
FP 10.2%
41%
26%30%
Prediction of pre-eclampsia
SPREE study, n=16,747
The Fetal Medicine
Foundation
10 %
High-risk x prevention
Prediction of pre-eclampsia
History-based screening
Ortved D, Hawkins TL, Johnson JA, et al. The cost-effectiveness of first trimester
screening and early preventative use of aspirin in women at high risk of early
But is it really the placenta ? Or is it all about the heart ?
- Poor placentation
- Damage to endothelium and cardiovascular
system are secondary
- Aspirin is anti-inflammatory
- Bad heart
- Failure to reach fetal and placental demands
- Parallel with GDM, resolves with delivery
- Aspirin for prevention of cardiovascular disease
+
Preterm PE Term PE
37 weeks
The Fetal Medicine
Foundation
The Fetal Medicine
Foundation
Determine prior risk:• Maternal characteristics• Medical / obstetric history
Estimate posterior risk
• Measure biomarkers• Express as MoMs• Modify prior risk
Prediction of pre-eclampsia
New approach
The Fetal Medicine
Foundation
Effect on time to delivery with PE (w)
-8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4
Chronic Hypertension
Race Black
South Asian
SLE / APS
Family history of PE
Diabetes mellitus
Conception by IVF
Age 35 y
40 y
45 y
Weight 50 kg
70 kg
90 kg
110 kg
Wright D et al. Competing risks model in screening for preeclampsia by
maternal characteristics and medical history. Am J Obstet Gynecol 2015
Low risk
24 28 32 36 40 44 48 52 56 60 64 68 72 76 80
Gestational age at delivery with preeclampsia (w)
High risk
1%
30%
2-3%
24 28 32 36 40 44 48 52 56 60 64 68 72 76 80
Average risk
Prediction of pre-eclampsia
Maternal characteristics, n=120,492
The Fetal Medicine
Foundation
Gestational age (w)
24 28 32 36 40 44
0.05
0.1
0.2
0.30.40.5
1.0
1.52.0
3.44.45.0
Gestational age (w)
24 28 32 36 40 44
0.05
0.10.1
0.2
0.3
0.40.5
1.0
1.5
2.0
3.0
4.0
Gestational age (w)
24 28 32 36 40 44
0.7
0.8
0.9
1
1.1
1.2
1.3
1.4
1.5
1.6
0.3
0.4
0.5
0.6
0.8
1.0
1.5
2.0
2.5
3.03.54.0
Gestational age (w)
24 28 32 36 40 44
PLGF (MoM)PAPP-A (MoM)MAP (MoM)UTPI (MoM)
O’ Gorman N et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation. Am J Obstet Gynecol 2016
FPR 10%
Prediction of pre-eclampsia
Biomarkers, n=33,840
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• Age: every 10 years above 30 y• Weight: every 10 kg above 70 kg
• Racial origin Afro-CaribbeanSouth Asian
• Obstetric history First pregnancy
• Family history of preeclampsia
• Autoimmune : SLE / APS
• Chronic hypertension• Diabetes mellitus
Previous preeclampsia
• Conception by IVF
Maternal risk factors
Wright D et al. Competing risks model in screening for preeclampsia by maternal characteristics and medical
history. Am J Obstet Gynecol 2016;
O’Gorman N et al. Competing risks model in screening for preeclampsia by maternal factors and biomarkers
at 11-13 weeks’ gestation. Am J Obstet Gynecol 2016; 214: 103
0
10
20
30
40
50
60
80
90
100
70
PE <32w
De
tec
tio
n
rate
(%
)
FPR 10%
PE <37w PE >37w
History, MAP, UT PI, PLGF
75%
89%
47%
Prediction of pre-eclampsia
FMF algorithm – Bayes theorem
The Fetal Medicine
Foundation
High risk factors
Hypertensive disease in a previous pregnancy
Chronic renal disease
Chronic hypertension
Diabetes mellitus
Autoimmune disease such as SLE or APS
Moderate risk factors
First pregnancy
Age > 40 years
Body mass index > 35 kg/m2
Inter-pregnancy interval > 10 years
Family history of preeclampsia
NICE guidelines 2010
0
10
20
30
40
50
60
80
90
100
70
PE <37w
De
tec
tio
n ra
te (
%)
FMF: FPR 10.0%
NICE: FPR 10.3%
ACOG: FPR 0.2%
PE >37w
39%34%
75%
45%
ACOG 2013: High-risk in need of aspirin
Preeclampsia in >2 previous pregnancies
Preeclampsia <34w in previous pregnancy
5%2%
Prediction of preeclampsia
ASPRE screening validation
O'Gorman N et al. Multicenter screening for pre-eclampsia by maternal factors and biomarkers at
11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.
Ultrasound Obstet Gynecol 2017.
O'Gorman N et al. Accuracy of competing-risks model in screening for pre-eclampsia by maternal
factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol 2017.
Prediction of pre-eclampsia
ASPRE screening study, n=8,775
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PE 239 (2.7%)
8,775 underwent screening
No PE 8,536 (97.3%)
Virgen de la Arrixaca, Murcia, Spain
San Cecilio Hospital, Granada, Spain
Hospiten Sur, Tenerife, Spain
Chu Brugmann Brussels, Belgium
Attikon University Hospital, Greece
Ospedale Maggiore Policlinico, Italy
Rabin Medical Center, Israel
King’s College Hospital, UK
Medway Maritime Hospital, UK
Lewisham University Hospital, UK
North Middlesex Hospital, UK
Southend University Hospital, UK
Homerton University Hospital, UK
Statistical analysis: D Wright, A Wright PE <34 wD
ete
cti
on
rate
(%
)20
30
40
50
60
70
80
90
100
PE <37 w PE >37 w
Prediction of pre-eclampsia
ASPRE screening validation
The Fetal Medicine
Foundation History repeats itself...
PE screeningPatient
acceptability
Efficacy
Safety
Cost
The skepticism The fear of the unknown
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Foundation
External validation
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Prof Jon Hyett
Sample 3066
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First trimester screening for early and late preeclampsia based on
maternal characteristics, biophysical parameters and
Universal Aspirin 100% – 99.2% - 496 No screening 202
800 PE < 37 weeks
Prevalence 0.8%
100,000 pregnancies
Prevention of pre-eclampsia
Clinical implementation
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Foundation
Future perspectives
The Fetal Medicine
Foundation
Screening of pre-eclampsia
Our research
Chasing novel biomarkers to predict PE
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The Fetal Medicine
Foundation
BJOG. 2018 Jun;125(7):848-855
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Fetal fraction as a marker of placentation ? – potential marker
Prevention of pre-eclampsia
New markers
Rolnik DL, da Silva Costa F, Lee TJ, et al. Association between fetal fraction on cell-free DNA testing and first trimester markers for pre-eclampsia. Ultrasound Obstet Gynecol. 2018
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The cardiovascular toll of pre-eclampsia:
determining impacts on the maternal, fetal and placental vasculature
• Markers of endothelial dysfunction: sFlt-1, sFlt-1 e15a, PlGF, ICAM-1 and VCAM-1