Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohortBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1875 (Published 07 April 2011) Cite this as: BMJ 2011;342:d1875
- Robyn A North, professor of maternal and fetal medicine1,
- Lesley M E McCowan, professor of obstetrics and gynaecology2,
- Gustaaf A Dekker, professor of obstetrics and gynaecology3,
- Lucilla Poston, professor of maternal and fetal health1,
- Eliza H Y Chan, research fellow2,
- Alistair W Stewart, senior research fellow4,
- Michael A Black, senior lecturer5,
- Rennae S Taylor, project manager2,
- James J Walker, professor of obstetrics and gynaecology6,
- Philip N Baker, professor of obstetrics and gynaecology7, visiting professor of obstetrics and gynaecology8,
- Louise C Kenny, professor of obstetrics9
- 1Division of Women’s Health, King’s College London, London, United Kingdom
- 2Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- 3Department of Obstetrics and Gynaecology, Lyell McEwin Hospital, University of Adelaide, Adelaide, Australia
- 4Department of Epidemiology and Biostatistics, Faculty of Medical and Health Sciences, School of Population Health, University of Auckland, Auckland
- 5Department of Biochemistry, University of Otago, Dunedin, New Zealand
- 6Leeds Institute of Molecular Medicine, University of Leeds, Leeds
- 7Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
- 8Department of Obstetrics and Gynaecology, University of Manchester, Manchester
- 9Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Republic of Ireland
- Correspondence to: R A North
- Accepted 14 February 2011
Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.
Design Prospective multicentre cohort.
Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland.
Participants 3572 “healthy” nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%).
Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks’ gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37+0 weeks’ gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia.
Results Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks’ gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively.
Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added.
Trial registration ACTRN12607000551493.
We thank the pregnant women who participated in the SCOPE study, Claire Roberts for her contributions in establishing the SCOPE study in Adelaide, Denise Healy for coordinating the Australian SCOPE study, Annette Briley for coordinating the UK MAPS (SCOPE) study, Nicolai Murphy for coordinating the Cork SCOPE study, the SCOPE research midwives, and Steven Wu for his assistance with data imputation.
Contributors: RAN was responsible for conception and design, analysis and interpretation of data, and drafting the article and revising it critically for important intellectual content. LMEMcC, GAD, LP, JJW, and PNB were responsible for conception and design and interpretation of data, and critical revision of paper for important intellectual content. EHYC, AWS, and MAB were responsible for statistical analyses and interpretation of data, and revising the article critically for important statistical content. RST was responsible for study design, coordination of clinical study, and revising the article critically for important intellectual content. LCK was responsible for conception and design, interpretation of data, drafting the article, and critical revision of paper for important intellectual content. All authors had full access to all of the data (including statistical reports and tables) in the study, can take responsibility for the integrity of the data and the accuracy of the data analysis, and approved the final version to be published. RAN is guarantor.
Funding: This study was funded by New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council (04/198); Evelyn Bond Fund, Auckland District Health Board Charitable Trust; Premier’s Science and Research Fund, South Australian Government; Guy’s and St Thomas’ Charity, Tommy’s the baby Charity; Biotechnology and Biological Sciences Research Council (GT084), UK National Health Services (NEAT grant FSD025), University of Manchester Proof of Concept Funding, NIHR; Health Research Board, Ireland (CSA/2007/2). The study sponsors had no role in study design, data analysis or writing this report. MAB received consultancy fees from the SCOPE Study, University of Auckland, which were funded by the New Zealand Health Research Council and the New Enterprise Research Fund, Foundation for Research Science and Technology.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; RAN and PNB have had consultancy relationships with Pronota in the previous three years; RAN has a consultancy relationship with Alere; LCK and PNB declare a US Provisional Patent Application in the name of University College Cork, Ireland (Louise Kenny and Philip Baker) “Detection of risk of pre-eclampsia” Application No USSN 61/288,465; RAN and MAB declares the following patent, which to date has not been licensed to a company: Blumenstein M, North RA, McMaster MT, Black MA, Kasabov NK, Cooper GJS. Biomarkers for prediction of pre-eclampsia and/or cardiovascular disease, PCT number WO/2009/108073. LP has a consultancy relationship with Tate and Lyle Research Advisory Group and is chairing a working party with ILSI Europe; both are outside the area of the submitted work.
Ethical approval: This study was approved by local ethics committees (New Zealand AKX/02/00/364, Australia REC 1712/5/2008, London and Manchester 06/MRE01/98, and Cork ECM5 (10) 05/02/08), and all women provided written informed consent.
Data sharing: No additional data available.
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