Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Emily Bartsch, Karyn E Medcalf, Alison L Park, Joel G Ray, High Risk of Pre-eclampsia Identification Group, Ziad T A Al-Rubaie, Lisa M Askie, Howard Berger, Jennifer Blake, Lisa Graves, John C Kingdom, Gordon C Leitch, Gerald Lebovic, Sally J Lord, Jonathon L Maguire, Muhammad M Mamdani, James Meloche, Marcelo L Urquia, Vicki Van Wagner, Emily Bartsch, Karyn E Medcalf, Alison L Park, Joel G Ray, High Risk of Pre-eclampsia Identification Group, Ziad T A Al-Rubaie, Lisa M Askie, Howard Berger, Jennifer Blake, Lisa Graves, John C Kingdom, Gordon C Leitch, Gerald Lebovic, Sally J Lord, Jonathon L Maguire, Muhammad M Mamdani, James Meloche, Marcelo L Urquia, Vicki Van Wagner

Abstract

Objective: To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of pre-eclampsia.

Design: Systematic review and meta-analysis of cohort studies.

Data sources: PubMed and Embase databases, 2000-15.

Eligibility criteria for selecting studies: Cohort studies with ≥ 1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤ 16 weeks' gestation.

Data extraction: Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.

Results: There were 25,356,688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.

Conclusions: There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4837230/bin/bare029374.f1_default.jpg
Fig 1 PRISMA flow diagram of selection and inclusion of studies in current meta-analysis of risk factor for pre-eclampsia
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4837230/bin/bare029374.f2_default.jpg
Fig 2 Risk of pre-eclampsia among women with and without individual clinical risk factors determined by 16 weeks’ gestation. IUGR=intrauterine growth restriction; SLE=systemic lupus erythematosus; ART=assisted reproductive technology; BMI=body mass index; aPL=antiphospholipid antibody syndrome; N/A=not applicable
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4837230/bin/bare029374.f3_default.jpg
Fig 3 Population attributable fraction for pre-eclampsia in relation to individual clinical risk factors determined by 16 weeks’ gestation. IUGR=intrauterine growth restriction; SLE=systemic lupus erythematosus; ART=assisted reproductive technology; BMI=body mass index; aPL=antiphospholipid antibody syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4837230/bin/bare029374.f4_default.jpg
Fig 4 Threshold number of women needed to receive aspirin prophylaxis to prevent one case of pre-eclampsia, based on individual clinical risk factors determined by 16 weeks’ gestation. Dashed line is clinically important minimum NNPT of 250 women. IUGR=intrauterine growth restriction; SLE=systemic lupus erythematosus; ART=assisted reproductive technology; BMI=body mass index; aPL=antiphospholipid antibody syndrome

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