Thangaratinam, S and Allotey, J and Marlin, N and Dodds, J and Cheong-See, F and von Dadelszen, P and Ganzevoort, W and Akkermans, J and Kerry, S and Mol, BW and Moons, KGM and Riley, RD and Khan, KS (2017) Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models. BMC Medicine, 15 (1). 68 -?. ISSN 1741-7015

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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.

Item Type: Article
Additional Information: PREP Collaborative Network. This is the final published version of the article (version of record). It first appeared online via BioMed Central at http://dx.doi.org/10.1186/s12916-017-0827-3 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Early-onset, Pre-eclampsia, Prognostic models, Maternal, Complications
Subjects: R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 20 Apr 2017 15:13
Last Modified: 20 Apr 2017 15:18
URI: http://eprints.keele.ac.uk/id/eprint/3289

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