Development of maternal and neonatal composite outcomes for trials evaluating management of late-onset pre-eclampsia

Pre-eclampsia is associated with significant maternal and neonatal complications, and delivery is often expedited to minimise complications. For randomised trials evaluating interventions in women with late-onset (>34 weeks) mild to moderate pre-eclampsia, no single outcome has been identified to be the most clinically important. Existing composite outcomes with more than one clinically relevant endpoint to evaluate interventions in pre-eclampsia provide limited justification for selection of the components. Our objective was to develop robust, valid composite maternal and neonatal outcome measures for clinical trials evaluating interventions in women with late-onset mild and moderate pre-eclampsia. Study design: A two-generational Delphi method was used to identify these clinically important maternal and neonatal outcomes. Composite outcomes were developed based on biological plausibility, independence from each other, frequency of occurrence and level of importance. Results: The final maternal composite outcome included maternal death, eclampsia, stroke or reversible ischaemic neurological deficit, pulmonary oedema, major obstetric haemorrhage, need for positive inotropic support, haemolysis, elevated liver enzymes and low platelets syndrome and placental abruption; and the neonatal composite outcome included neonatal death, respiratory distress syndrome needing ventilator support and neurological outcomes as cystic periventricular leukomalacia and grade III/IV intraventricular haemorrhage. Conclusion: The composite outcomes developed will enable clinical trials to provide robust estimates on the effectiveness of the interventions in women with mild to moderate late onset pre-eclampsia to inform clinical practice. Caution is needed in the interpretation of composite outcomes due to variation in the importance of individual components.