Skip to main content

01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Medicine 1/2017

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

BMC Medicine > Ausgabe 1/2017
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12916-017-0827-3) contains supplementary material, which is available to authorized users.



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.


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.


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.


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.
Additional file 1: Table S1. Definition of the inclusion criteria for women recruited in the PREP study. Table S2. Crude univariable and multivariable analyses of candidate predictors and adverse fetal outcomes in women with early onset pre-eclampsia. Table S3. Definitions of the individual components of the composite outcomes evaluated in the PREP study*. Table S4. Changes since original application. Table S5. Rates of individual complications in women with early onset pre-eclampsia in the PREP study. Table S6. Characteristics of predictors available in the PREP study and external validation cohorts (PIERS and PETRA). (DOCX 43 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

BMC Medicine 1/2017 Zur Ausgabe

Neu im Fachgebiet Allgemeinmedizin

Meistgelesene Bücher aus dem Fachgebiet

2018 | Buch

Repetitorium Geriatrie

Geriatrische Grundversorgung - Zusatz-Weiterbildung Geriatrie - Schwerpunktbezeichnung Geriatrie

Das vorliegende Werk orientiert sich an den Fort-bzw. Weiterbildungsinhalten der Zusatz-Weiterbildung „Geriatrie“ , der Schwerpunktbezeichnung „Geriatrie“ sowie der strukturierten curricularen Fortbildung „Geriatrische Grundversorgung“ und wendet …

Dr. Rainer Neubart

2012 | Buch

Häufige Hautkrankheiten in der Allgemeinmedizin

Klinik Diagnose Therapie

Patienten mit Hautkrankheiten machen einen großen Anteil der Patienten in der Allgemeinarztpraxis aus. Prägnante Texte und zahlreiche Abbildungen zu Klinik, Pathogenese, Diagnose und Therapie helfen, die häufigsten dermatologischen Probleme zu lösen.

Prof. Dr. med. Dietrich Abeck

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Allgemeinmedizin und bleiben Sie gut informiert – ganz bequem per eMail.