Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial
Wen, Shi Wu; White, Ruth Rennicks; Rybak, Natalie; Gaudet, Laura M; Robson, Stephen; Hague, William; Simms-Stewart, Donnette; Carroli, Guillermo; Smith, Graeme; Fraser, William D; Wells, George; Davidge, Sandra T; Kingdom, John; Coyle, Doug; Fergusson, Dean; Corsi, Daniel J; Champagne, Josee; Sabri, Elham; Ramsay, Tim; Mol, Ben Willem J; Oudijk, Martijn A; Walker, Mark C; FACT Collaborating Group
(2018) BMJ - Clinical research, volume 362
(Article)
Abstract
OBJECTIVE: To 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. DESIGN: Randomised, phase III, double blinded international,
... read more
multicentre clinical trial. SETTING: 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS: 2464 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. INTERVENTION: Eligible 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 MEASURE: The 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). RESULTS: Pre-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. CONCLUSION: Supplementation 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 REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: General Medicine
ISSN: 1756-1833
Publisher: BMJ Publishing Group
Note: Funding Information: Alberta, Canada 19Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada 20Departments of Medicine, School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada 21Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia 22Department of Obstetrics, University Medical Center, Utrecht, Utrecht, Netherlands 23Department of Obstetrics, Academic Medical Center, Amsterdam, Netherlands We thank the participants in FACT, site investigators, research staff at the participating sites, and staff at the Ottawa Hospital Research Institute for their support and hard work. A full list of the FACT Collaborating Group is available in the supplementary file. Contributors: MCW and SWW designed the trial, planned the analyses, and wrote the manuscript with assistance from RRW, NR, LMG, SR, WH, DSS, GC, GS, WDF, GW, STD, JK, DC, DF, DJC, JC, TR, BJM, and MAO. ES with assistance from DJC carried out the statistical analyses. All authors participated in the review and critical revisions of the final manuscript. MCW is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: This study was sponsored by the Ottawa Hospital Research Institute, and funded by the Canadian Institutes of Health Research (grants 198801 and 98030). FACT was conceived, designed, and coordinated independently of the funding source. The funder did not act as sponsor for the trial and had no role in analysis, interpretation of the data, writing of the report, or decision to submit for publication. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisations for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Publisher Copyright: © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
(Peer reviewed)