Protocol for a prospective cohort study on pre-eclampsia risk prediction in Ghana, Kenya and South Africa

Background Low dose aspirin is recommended for the prevention of pre-eclampsia in high-risk women. As part of the formative work for the "Preventing pre-eclampsia: Evaluating AspiRin Low-dose regimens following risk Screening" (PEARLS) trial, we aim to validate and implement a pre-eclampsia risk-screening algorithm, based on a restricted-variable version of the Fetal Medicine Foundation (FMF) algorithm. In the trial phase, we will compare different daily aspirin doses (75 mg vs. 150 mg) for pre-eclampsia prevention and postpartum bleeding in high-risk women. This study protocol outlines the validation cohort for a restricted variable FMF algorithm in participating facilities in Ghana, Kenya, and South Africa. Methods This multi-country, prognostic accuracy study using a prospective cohort will recruit 16,007 pregnant women at 51 health facilities across Kenya, Ghana and South Africa. The eligible population are pregnant women presenting for an antenatal visit from 11 weeks and 0 days to < 20 weeks’ gestation. Eligible women will be screened using a ‘restricted variable’ approach with the FMF algorithm (i.e. history and mean arterial pressure only), to identify women at high risk of preterm pre-eclampsia. This is performed via an adapted version of the Tommy’s Clinical Decision Tool. The primary objective is to estimate a preterm pre-eclampsia risk threshold that equates to a screen-positive rate of 10%. Secondary outcomes include estimation of the prognostic accuracy and predictive performance of the tool. Discussion The study will provide critical evidence on the prognostic accuracy and predictive performance of a pre-eclampsia risk screening algorithm in sub-Saharan African settings. This study will inform the design of the PEARLS trial, as well as provide vital evidence for implementation of systematic risk screening for pre-eclampsia in African women.