The American College of

Obstetricians and Gynecologists

WOMEN’S HEALTH CARE PHYSICIANS

COMMITTEE OPINION
Number 638 • September 2015

Committee on Obstetric Practice

This document has been endorsed by the Society for Maternal–Fetal Medicine. This document reflects emerging clinical and scientific
advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of
treatment or procedure to be followed.

First-Trimester Risk Assessment for Early-Onset

Preeclampsia
ABSTRACT: Hypertensive disorders with adverse sequelae (including preterm birth, maternal morbidity and
mortality, and long-term risk of maternal cardiovascular disease) complicate 5–10% of pregnancies. Early identi-
fication of pregnant women at risk of developing early-onset preeclampsia would theoretically allow referral for
more intensive surveillance or application of preventive therapies to reduce the risk of severe disease. In practice,
however, the effectiveness of such triage would be hindered by the low positive predictive value for early-onset
preeclampsia reported in the literature. In spite of the modest predictive value of first-trimester preeclampsia risk
assessment and the lack of data demonstrating improved clinical outcomes, commercial tests are being marketed
for the prediction of preeclampsia in the first trimester. Taking a detailed medical history to evaluate for risk factors
is currently the best and only recommended screening approach for preeclampsia; it should remain the method
of screening for preeclampsia until studies show that aspirin or other interventions reduce the incidence of pre-
eclampsia for women at high risk based on first-trimester predictive tests.

Recommendations Introduction
In spite of the modest predictive value of first-trimester
• Taking a detailed medical history to evaluate for risk preeclampsia risk assessment and the lack of data dem-
factors is currently the best and only recommended onstrating improved clinical outcomes, commercial tests
screening approach for preeclampsia; it should are being marketed for the prediction of preeclampsia in
remain the method of screening for preeclampsia the first trimester.
until studies show that aspirin or other interventions Hypertensive disorders with adverse sequelae
reduce the incidence of preeclampsia for women at (including preterm birth, maternal morbidity and mor-
high risk based on first-trimester predictive tests. tality, and long-term risk of maternal cardiovascular dis-
• Current predictive tests for preeclampsia may harm ease) complicate 5–10% of pregnancies (1). Early-onset
more women than they benefit because of their low preeclampsia is associated with great risk for the mother
positive predictive value (PPV). These tests require a and infant. Early identification of pregnant women at
large number of women to be identified as high risk risk of developing early-onset preeclampsia would theo-
and to potentially undergo intensive surveillance in retically allow referral for more intensive surveillance or
order to detect one case of early-onset preeclampsia. application of preventive therapies to reduce the risk of
• The American College of Obstetricians and Gyne- severe disease (2).
cologists does not recommend screening to predict Clinical risk factors traditionally have been used to
preeclampsia beyond obtaining an appropriate med- identify women at high risk of developing preeclampsia
ical history. (Box 1). Several studies also have identified biophysical

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Copyright ª by The American College of Obstetricians

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Unauthorized reproduction of this article is prohibited.
 reported in the literature. For example, investigators in a
Box 1. Clinical Risk Factors cohort study of 7,797 singleton pregnancies have reported
for Preeclampsia ^ detection rates for early-onset preeclampsia as high as
93% with models incorporating clinical risk factors as
Primiparity well as ultrasonographic and biochemical markers (4).
Previous preeclamptic pregnancy However, of the 476 women who screened positive for
Chronic hypertension, chronic renal disease, or both early-onset preeclampsia, 32 developed the disease, giving
History of thrombophilia a PPV of only 7% (4). Given the relatively low prevalence
of early-onset preeclampsia, screening tests will need to
Multifetal pregnancy
have sensitivities and specificities well above what is cur-
In vitro fertilization rently achievable to produce meaningful PPVs. Moreover,
Family history of preeclampsia current predictive tests for preeclampsia may harm more
Type I diabetes mellitus or type II diabetes mellitus women than they benefit because of their low PPV. These
Obesity tests require a large number of women to be identified as
Systemic lupus erythematosus high risk and to potentially undergo intensive surveillance
in order to detect one case of early-onset preeclampsia.
Advanced maternal age (older than 40 years)
There are no randomized controlled trials of pre-
Reprinted from American College of Obstetricians and Gyne- ventive therapy for women with an elevated risk of
cologists. Hypertension in pregnancy. Washington, DC: Ameri- preeclampsia based on first-trimester biophysical screen-
can College of Obstetricians and Gynecologists; 2013. ing. Taking a detailed medical history to evaluate for
risk factors is currently the best and only recommended
screening approach for preeclampsia; it should remain the
method of screening for preeclampsia until studies show
factors that may help predict hypertensive disorders of
that aspirin or other interventions reduce the incidence
pregnancy (3–5). These studies have found associations
of preeclampsia for women at high risk based on first-
between hypertensive complications and maternal body
trimester predictive tests. Although a meta-analysis of
mass index, age, early pregnancy blood pressure, medi-
studies of low-dose aspirin showed significantly reduced
cal history, and biophysical markers such as pregnancy-
risk of severe preeclampsia, fetal growth restriction, and
associated protein A, placental growth factor, and uterine
gestational hypertension in the subgroup in which treat-
artery Doppler velocimetry. Such studies have used a
ment was initiated before 16 weeks (7), subjects in these
variety of markers and risk factors, which limits the abil-
studies were mostly identified by clinical risk factors
ity to synthesize the data available in the literature (6).
rather than biophysical tests. Prediction–intervention
Limitations of Current Predictive studies based on first-trimester biophysical risk assess-
ment are needed to determine whether women identified
Tests based on first-trimester screening might benefit from
In general, models that incorporate multiple predictive low-dose aspirin. In its 2014 recommendation for aspirin
factors demonstrate better detection rates than those to prevent preeclampsia, the U.S. Preventive Services Task
using only a single factor. Models also tend to have better Force concluded that predictive models based on bio-
predictive value (ie, proportion of patients with positive physical assessment “have not shown sufficient accuracy
test results who develop preeclampsia) for early-onset for clinical use” (8).
preeclampsia and severe preeclampsia. Overall, most
studies have reported modest PPVs. The case–control Conclusions
design, the small number of cases of early-onset pre- The American College of Obstetricians and Gynecologists
eclampsia, and the large number of predictors in available does not recommend screening to predict preeclampsia
screening models raise concerns that reported detection beyond obtaining an appropriate medical history to eval-
rates are overly optimistic. These models also have not uate for risk factors (9). Any marginal benefit of adding
been validated independently in prospective cohorts. biophysical tests, including uterine artery Doppler velo-
For a predictive test for preeclampsia to be useful, cimetry and maternal serum analytes, to screening based
it would need a high sensitivity and a high PPV, such on risk factors first must be demonstrated to justify the
that women who test positive would be at high risk of additional costs. Cost-effectiveness studies of screening
developing the disease. In addition, for a predictive test strategies should quantify the adverse effects of identifying
to be beneficial, detection before the onset of symptoms women as high risk of preeclampsia, including parental
must improve clinical outcomes. In theory, referral of anxiety, increased frequency of prenatal appointments,
women at high risk of early-onset preeclampsia to spe- and additional surveillance testing. For a first-trimester
cialists might allow for more intensive monitoring. In risk assessment for preeclampsia to be useful in clinical
practice, however, the effectiveness of such triage would practice, future screening tests will need to have sensitivi-
be hindered by the low PPV for early-onset preeclampsia ties and PPVs high enough to accurately identify women

e26 Committee Opinion First-Trimester Risk Assessment OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
who will develop preeclampsia, and interventions will graphic markers in predicting preeclampsia: a systematic
need to be available that improve clinical outcome in review. Clin Chem 2010;56:361–75. [PubMed] [Full Text]
women who test positive. ^
7. Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F,
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VOL. 126, NO. 3, SEPTEMBER 2015 Committee Opinion First-Trimester Risk Assessment e27

Copyright ª by The American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.