Development and validation of Prediction models for Risks of complications in Early-onset Pre-eclampsia (PREP): a prospective cohort study.

BACKGROUND: The prognosis of early-onset pre-eclampsia (before 34 weeks' gestation) is variable. Accurate prediction of complications is required to plan appropriate management in high-risk women. OBJECTIVE: To develop and validate prediction models for outcomes in early-onset pre-eclampsia. DESIGN: Prospective cohort for model development, with validation in two external data sets. SETTING: Model development: 53 obstetric units in the UK. Model transportability: PIERS (Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia TRial Amsterdam) studies. PARTICIPANTS: Pregnant women with early-onset pre-eclampsia. SAMPLE SIZE: Nine hundred and forty-six women in the model development data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability (external validation) data sets. PREDICTORS: The predictors were identified from systematic reviews of tests to predict complications in pre-eclampsia and were prioritised by Delphi survey. MAIN OUTCOME MEASURES: The primary outcome was the composite of adverse maternal outcomes established using Delphi surveys. The secondary outcome was the composite of fetal and neonatal complications. ANALYSIS: We developed two prediction models: a logistic regression model (PREP-L) to assess the overall risk of any maternal outcome until postnatal discharge and a survival analysis model (PREP-S) to obtain individual risk estimates at daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) and external validation (of the reduced models in the transportability data), we computed the ability of the models to discriminate between those with and without poor outcomes (c-statistic), and the agreement between predicted and observed risk (calibration slope). RESULTS: The PREP-L model included maternal age, gestational age at diagnosis, medical history, systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum urea concentration, oxygen saturation, baseline treatment with antihypertensive drugs and administration of magnesium sulphate. The PREP-S model additionally included exaggerated tendon reflexes and serum alanine aminotransaminase and creatinine concentration. Both models showed good discrimination for maternal complications, with anoptimism-adjusted c-statistic of 0.82 [95% confidence interval (CI) 0.80 to 0.84] for PREP-L and 0.75 (95% CI 0.73 to 0.78) for the PREP-S model in the internal validation. External validation of the reduced PREP-L model showed good performance with a c-statistic of 0.81 (95% CI 0.77 to 0.85) in PIERS and 0.75 (95% CI 0.64 to 0.86) in PETRA cohorts for maternal complications, and calibrated well with slopes of 0.93 (95% CI 0.72 to 1.10) and 0.90 (95% CI 0.48 to 1.32), respectively. In the PIERS data set, the reduced PREP-S model had a c-statistic of 0.71 (95% CI 0.67 to 0.75) and a calibration slope of 0.67 (95% CI 0.56 to 0.79). Low gestational age at diagnosis, high urine protein-to-creatinine ratio, increased serum urea concentration, treatment with antihypertensive drugs, magnesium sulphate, abnormal uterine artery Doppler scan findings and estimated fetal weight below the 10th centile were associated with fetal complications. CONCLUSIONS: The PREP-L model provided individualised risk estimates in early-onset pre-eclampsia to plan management of high- or low-risk individuals. The PREP-S model has the potential to be used as a triage tool for risk assessment. The impacts of the model use on outcomes need further evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40384046. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Development and validation of prediction models for risk of adverse outcomes in women with early-onset pre-eclampsia: protocol of the prospective cohort PREP study.

BACKGROUND: Early-onset pre-eclampsia with raised blood pressure and protein in the urine before 34 weeks' gestation is one of the leading causes of maternal deaths in the UK. The benefits to the child from prolonging the pregnancy need to be balanced against the risk of maternal deterioration. Accurate prediction models of risks are needed to plan management. METHODS: We aim to undertake a multicentre prospective cohort study (Prediction of Risks in Early onset Pre-eclampsia (PREP)) to develop clinical prediction models in women with early-onset pre-eclampsia, for risk of adverse maternal outcomes by 48 h and by discharge. We will externally validate the models in two independent cohorts with 634 and 216 women. In the secondary analyses, we will assess risk of adverse fetal and neonatal outcomes at birth and by discharge. DISCUSSION: The PREP study will quantify the risk of maternal complications at various time points and provide individualised estimates of overall risk in women with early-onset pre-eclampsia to plan the management. TRIAL REGISTRATION: ISRCTN registry, ISRCTN40384046.