EFFECT OF HIGH DOSE FOLIC ACID SUPPLEMENTATION THROUGHOUT PREGNANCY ON PREECLAMPSIA (FACT): A DOUBLE-BIND, RANDOMIZED CONTROLLED MULTICENTRE TRIAL

Abstract

Objectives To determine the efficacy of high dose folic acid supplementation for prevention of preeclampsia in women with at least one of these risk factors: pre-existing hypertension, pre-pregnancy diabetes (type I or II), twin pregnancy, preeclampsia in a previous pregnancy, or body mass index (BMI) > 35 (kg/m2). Methods This was a randomized, phase III, double-blinded, placebo-controlled, international multi-center trial at 70 centres in five countries (Argentina, Australia, Canada, Jamaica, UK). Eligible women were randomized to receive either daily high dose folic acid (four 1.0mg oral tablets) or placebo from 80/7 - 166/7 weeks’ gestation until delivery. Clinicians, participants, adjudicators, and all study staff were masked to study treatment allocation. The primary outcome was preeclampsia defined as diastolic blood pressure > 90mmHg on two occasions > four hours apart and proteinuria which developed in women greater than 20 weeks gestation. Results A total of 2464 pregnant women with at least one high risk factor for preeclampsia were randomized between 2011 and 2015; 2301 were included in the intention to treat analyses, with 1144 assigned to the folic acid group. Preeclampsia occurred in 169 (14.8%) women in the folic acid group and 156 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to1.34; P=0.37). No evidence of differences was found between the groups for any other adverse maternal or neonatal outcomes. Conclusions Folic acid supplementation with 4.0mg/day beyond the first trimester does not prevent preeclampsia in women at high risk for preeclampsia.