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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models

Authors: Shakila Thangaratinam, John Allotey, Nadine Marlin, Julie Dodds, Fiona Cheong-See, Peter von Dadelszen, Wessel Ganzevoort, Joost Akkermans, Sally Kerry, Ben W. Mol, Karl G. M. Moons, Richard D. Riley, Khalid S. Khan, for the PREP Collaborative Network

Published in: BMC Medicine | Issue 1/2017

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Abstract

Background

Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required.

Method

Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes.

Results

A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81–0.87; PREP-S) and 0.82 (0.80–0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets.

Conclusions

PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care.

Trial registration

ISRCTN40384046, retrospectively registered.
Appendix
Available only for authorised users
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Metadata
Title
Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models
Authors
Shakila Thangaratinam
John Allotey
Nadine Marlin
Julie Dodds
Fiona Cheong-See
Peter von Dadelszen
Wessel Ganzevoort
Joost Akkermans
Sally Kerry
Ben W. Mol
Karl G. M. Moons
Richard D. Riley
Khalid S. Khan
for the PREP Collaborative Network
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0827-3

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