• Shi Wu Wen, Ruth Rennicks White, Natalie Rybak, Laura M Gaudet, Stephen Robson, William Hague, Donnette Simms-Stewart, Guillermo Carroli, Graeme Smith, William D Fraser, George Wells, Sandra T Davidge, John Kingdom, Doug Coyle, Dean Fergusson, Daniel J Corsi, Josee Champagne, Elham Sabri, Tim Ramsay, MolBen Willem JBWJObstetric Medicine, Robinson Research Institute, University of Adelaide, South Australia, Australia.Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia., Martijn A Oudijk, Mark C Walker, and FACT Collaborating Group.
• OMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
• BMJ. 2018 Sep 12; 362: k3478.

ObjectiveTo determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35.DesignRandomised, phase III, double blinded international, multicentre clinical trial.Setting70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK).Participants2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses.InterventionEligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation.Main Outcome MeasureThe primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets).ResultsPre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes.ConclusionSupplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition.Trial RegistrationCurrent Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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