Evidence map›Paper›PMID 30209050›Full record

Trial reportBMJ (Clinical research ed.)2018

Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.

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 and 13 more

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMJ (Clinical research ed.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 48 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 5 pooled it
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01355159 phase3completednot on this map

Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia-Folic Acid Clinical Trial (FACT)

TypeinterventionalSponsorOttawa Hospital Research InstituteRan2011 to 2016Enrolled2,464ConditionsPregnancy Complications, PreeclampsiaArmsFolic Acid 4 mg, Placebo
NCT03981029 completednot on this map

Folic Acid Clinical Trial (FACT): Biomarker Subgroup Analysis

TypeobservationalSponsorOttawa Hospital Research InstituteRan2011 to 2016Enrolled51ConditionsPre-EclampsiaArms4.0mg Folic Acid received through participation in FACT (NCT01355159), Placebo received through participation in FACT
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 5 syntheses or guidelines pooled it, 114 citations in OpenAlex.

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  19. Folic acid supplementation on congenital heart disease and its dual character.Current research in pharmacology and drug discovery · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 13 institutions in 6 countries.

Shi Wu WenOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ruth Rennicks WhiteOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Natalie RybakOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Laura M GaudetOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Stephen RobsonInstitute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
William HagueObstetric Medicine, Robinson Research Institute, University of Adelaide, South Australia, Australia.
Donnette Simms-StewartDepartment of Obstetrics and Gynaecology, Faculty of Medical Sciences, The University of the West Indies, Mona, Kingston, Jamaica.
Guillermo CarroliCentro Rosarino de Estudios Perinatales (CREP), Rosario, Santa Fé, Argentina.
Graeme SmithQueen's Perinatal Research Unit, Kingston General Hospital, Department of Obstetrics and Gynecology, Queens University, Kingston, Ontario, Canada.
William D FraserMother & Child Axis, Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
George WellsSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Sandra T DavidgeWomen and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
John KingdomMaternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Doug CoyleSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Dean FergussonClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Daniel J CorsiOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Josee ChampagneClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Elham SabriClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Tim RamsayClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ben Willem J MolObstetric Medicine, Robinson Research Institute, University of Adelaide, South Australia, Australia.
Martijn A OudijkDepartment of Obstetrics, University Medical Center, Utrecht, Utrecht, Netherlands.
Mark C WalkerOMNI Research Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada mwalker@ohri.ca.
FACT Collaborating Group
Ottawa Hospital Research InstituteUniversity of Ottawa · CAOttawa Hospital · CACentro Rosarino de Estudios Perinatales · ARKingston General Hospital · CAMonash University · AUNewcastle University · GBUniversité de Sherbrooke · CAUniversity Medical Center Utrecht · NLUniversity of Adelaide · AUUniversity of Alberta · CAUniversity of the West Indies System · JMUniversity of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

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.

Indexed as

AdultArgentinaAustraliaCanadaDiabetes, GestationalDietary SupplementsDouble-Blind MethodFemaleFolic AcidHELLP SyndromeHumansHypertensionJamaicaPre-EclampsiaPregnancyProteinuriaFolic AcidVitamin B Complex

Identifiers

PMID30209050
PMCPMC6133042
OpenAlexW2891604583

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.