search
Back to results

High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention (FACT)

Primary Purpose

Pregnancy Complications, Preeclampsia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Folic Acid 4 mg
Placebo
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pregnancy Complications focused on measuring Pregnancy, Folic Acid supplementation, Preeclampsia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Capability of subject to comprehend and comply with study requirements
  2. ≥ 18 years of age at time of consent
  3. Subject is taking ≤1.1 mg of folic acid daily at the time of randomization
  4. Live fetus (documented positive fetal heart prior to randomization)
  5. Gestational age between 8+0 and 16+6 weeks of pregnancy (Gestational age (GA) of subjects will be calculated based on the first day of the last menstrual period (LMP) or ultrasound performed before 12+6. If early ultrasound and LMP dates differ by ≤ 7 days, base GA estimate on LMP date; if > 7 days, use early < 12+6 ultrasound)
  6. Subject plans to give birth in a participating hospital site

  7. Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):

    • Pre-existing hypertension (documented evidence of diastolic blood pressure ≥ 90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
    • Pre-pregnancy diabetes (documented evidence of Type I or type II DM)
    • Twin pregnancy
    • Documented evidence of history of PE in a previous pregnancy
    • BMI > 35 kg/m2 within 3 months prior to this pregnancy and up to randomization of this pregnancy (documented evidence of height and weight to calculate BMI is required)

Exclusion Criteria:

  1. Known history or presence of any clinically significant disease or condition which would be a contraindication to folic acid supplementation of up to 5 mg daily for the duration of pregnancy
  2. Known major fetal anomaly or fetal demise

  3. History of medical complications, including:

    • renal disease with altered renal function,
    • epilepsy,
    • cancer, or
    • use of folic acid antagonists such as valproic acid
  4. Individual who is currently enrolled or has participated in another clinical trial or who received an investigational drug within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre)

  5. Known presence of:

    • Alcohol abuse (≥ 2 drinks per day) or alcohol dependence
    • Illicit drug/substance use and/or dependence
  6. Known hypersensitivity to folic acid
  7. Multiple Pregnancy (triplets or more)
  8. Participation in this study in a previous pregnancy

Sites / Locations

  • Hospital Escuela Eva Perón
  • Hospital Provincial
  • Hospital Roque Saenz Penia
  • Maternidad Martin
  • Sanatorio de la Mujer
  • Cemic
  • Hospital Cullen
  • Hosptial Iturraspe
  • Nepean
  • Townsville
  • Ipswich
  • Adelaide
  • Royal Women's Hospital
  • Sunshine
  • Calgary Foothills Medical Center
  • Edmonton Lois Hole Hospital for Women
  • Vancouver BC Women's Hospital and Health Center
  • St-Paul's Hospital
  • Fredericton Dr. Everett Chalmers Regional Hospital
  • Moncton Hospital
  • Saint John Regional Hospital
  • Winnipeg St. Boniface General Hospital
  • Winnipeg University of Manitoba
  • St-John's Women's Health Centre
  • Hamilton McMaster University
  • Kingston
  • London
  • Ottawa Hospital
  • Civic Hospital
  • Sault Ste- Marie Sault Area Hospital
  • Sunnybrook Health Sciences
  • Quebec City (CHUL) Centre Hospitalier Universitaire
  • Saint-Luc CHUM - Montreal
  • McGill University Royal Victoria Hospital
  • Sainte-Justine
  • St-Mary's Hospital
  • Regina Qu'Appelle Health Region
  • University of West Indies
  • Jubilee
  • Spanishtown
  • Hinchingbrooke
  • Warrington and Halton Hospitals NHS Foundation Trust
  • Darlington Memorial Hospital
  • University Hospital of North Durham
  • Cumberland Infirmary
  • West Cumberland Hospital
  • Fairfield
  • Rochdale
  • Lincolnshire
  • Ormskirk
  • Northwick Park Hospital
  • West Middlesex University Hospital
  • 49 Marine Avenue & CCGs
  • Wansbeck General Hospital
  • St George's Hospital
  • Gateshead Queen Elizabeth Hospital
  • South Tyneside District Hospital
  • The Royal Wolverhampton NHS Trust, New Cross Hospital
  • Blackburn
  • Burnley
  • North Manchester
  • Guy's & St Thomas' Hospital
  • South Tees Hospital
  • Newcastle upon Tyne Hospitals
  • North Tyneside General Hospital
  • Norfolk & Norwich
  • Nottingham City Hospital
  • Nottingham Queens Medical Centre
  • Oldham
  • North Tees Hospital
  • Sunderland Royal Hospital
  • Hillingdon Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Folic Acid 4 mg

Placebo

Arm Description

Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid

Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo

Outcomes

Primary Outcome Measures

Preeclampsia
PE is defined as diastolic blood pressure ≥90 mmHg on two occasions ≥4 hours apart and proteinuria developed in women greater than 20+0 weeks of gestation. Proteinuria is defined as: urinary protein ≥300mg in 24 hour urine collection OR in the absence of 24 hour collection, ≥2+ dipstick proteinuria, OR random protein-creatinine ratio ≥30mg protein/mmol. OR HELLP (Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome defined as: Haemolysis (characteristic peripheral blood smear), Serum LDH ≥ 600U/L, Serum AST ≥ 70U/L, and Platelet count <100 x109/L OR Superimposed pre-eclampsia, defined as history of pre-existing hypertension (diagnosed pre-pregnancy or before 20+0 weeks' gestation) with new proteinuria.

Secondary Outcome Measures

Maternal Death
According to the World Health Organization, "A maternal death is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.
Spontaneous Abortion
Spontaneous abortion or miscarriage defined as death of a fetus <500g or <20 weeks of gestation
Placenta Abruption
Placental abruption (abruptio placentae) is the premature detachment of a normally positioned placenta from the wall of the uterus.
Premature Rupture of Membranes
Rupture of the membranes (rupture of the amniotic sac) before the onset of labor.
Preterm Birth
Birth that occur earlier than 37+0 weeks of gestational age.
HELLP (Hemolysis, Elevated Liver Enzyme Levels & Low Platelet Count)
Haemolysis (characteristic peripheral blood smear), Serum LDH >=600U/L, Serum AST >=70U/L, Platelet count <100 x109/L
Severe Preeclampsia
Severe PE: Defined as PE with convulsion or HELLP or delivery <34 weeks.
Antenatal Inpatient Length of Stay
Length of inpatient stay before admission for delivery in days
Stillbirth
Fetal death defined as death of fetus of at least 500 grams birth weight or, if birth weight is unavailable, a gestational age of at least 20+0 weeks of gestation.
Intrauterine Growth Restriction (<3rd Percentile)
Intrauterine growth restriction is defined as a birth weight less than the 3rd percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.
Intrauterine Growth Restriction (<10th Percentile)
Intrauterine growth restriction is defined as a birth weight less than the 10th percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.
Neonatal Death
Neonatal death defined as death of a baby that occurred during first 28 days of life.
Perinatal Mortality
The perinatal mortality is defined as the number of deaths (fetal deaths and neonatal deaths) of babies ≥ 500 grams birth weight or, if birth weight is unavailable, a gestational age ≥ 20+0 weeks, up to 28 completed days after birth.
Retinopathy of Prematurity
Retinopathy of prematurity a retinopathy typically occurring in premature infants treated with high concentrations of oxygen, characterized by vascular dilatation, proliferation, tortuosity, edema, retinal detachment, and fibrous tissue behind the lens confirmed by retinal examination according to an International Committee for the Classification of Retinopathy of Prematurity.
Early Onset Sepsis
Within first 48hr of life, confirmed by positive blood or cerebrospinal fluid cultures
Necrotising Enterocolitis
Necrotizing enterocolitis (NEC) according to modified Bell's criteria stage 2 or higher (grossly bloody stool, plus absent bowel sounds with or without abdominal tenderness and radiographic findings such as intestinal dilation, ileus, pneumatosis intestinalis), excluding isolated spontaneous intestinal perforations.
Intraventricular Hemorrhage (IVH)
IVH Grade 1(Blood in germinal matrix) IVH Grade 2 (Blood in germinal matrix and extending into the ventricles) IVH Grade 3 (Ventricular enlargement) IVH Grade 4 (Intraparenchymal lesion)
Ventilation
Ventilatory support after initial resuscitation, with/without intubation.
Need for Oxygen at 28 Days
Composite Severe Adverse Fetal/Neonatal Outcome
Composite outcome included any of retinopathy of prematurity, periventricular leukomacia, early onset sepsis, necrotizing enterocolitis, intraventricular haemorrhage, ventilation. Need for O2at 28 days, NICU admission
Length of Stay in 'High Level' Neonatal Care Unit
Neonatal Death
Neonatal death defined as death of the infant occurred before 28 days of life
Periventricular Leukomalacia
One of the two outcomes used to measure neonatal morbidity.
Neonatal Intensive Care Unit (NICU) Admission
This outcome measured whether or not the infant was admitted into the NICU.

Full Information

First Posted
May 11, 2011
Last Updated
June 22, 2020
Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR)
search

1. Study Identification

Unique Protocol Identification Number
NCT01355159
Brief Title
High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention
Acronym
FACT
Official Title
Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia-Folic Acid Clinical Trial (FACT)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To determine the efficacy of high dose folic acid supplementation for prevention of preeclampsia in women with at least one risk factor: pre-existing hypertension, pre-pregnancy diabetes (type 1 or 2), twin pregnancy, preeclampsia in a previous pregnancy, or body mass index ≥35. It was hypothesized that high dose (4.0 mg per day) supplementation starting in early pregnancy and continued throughout the entire pregnancy will lower the incidence of preeclampsia in pregnant women at high risk of developing preeclampsia.
Detailed Description
Preeclampsia is a complication of pregnancy which affects at least 5% of all pregnancies worldwide and has serious health consequences to these women and their babies. Preeclampsia is hypertension (high blood pressure) in pregnancy with proteinuria. Proteinuria is when protein is found in the urine, and it is a sign that the kidneys are not functioning properly. The only effective treatment for preeclampsia is delivery of the baby. Because delivery may be required before the anticipated date of delivery; preeclampsia is also one of the leading causes of preterm delivery and accounts for 25% of very low birth weight infants. Recent research has also shown that women who have had preeclampsia during pregnancy are more likely to be at risk for future cardiovascular events later in life. Recently some studies have shown that supplementation with multivitamins containing folic acid is associated with a reduced risk of developing preeclampsia. These findings also suggested that for the prevention of preeclampsia, a high dose of folic acid (much higher than the amount of folate received from food intake or what is usually taken during pregnancy) may be needed. A randomized controlled trial was conducted in 70 obstetrical centres in 5 countries (Argentina, Australia, Canada, Jamaica, and the UK) to evaluate the effect of high dose folic acid started in early pregnancy on the risk of developing preeclampsia in high-risk women. A sample size of 2464 allowed for 80% power and a 10% loss to follow-up/study withdrawal. Participants received either placebo or four 1.0 mg oral tablets of folic acid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pregnancy Complications, Preeclampsia
Keywords
Pregnancy, Folic Acid supplementation, Preeclampsia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2464 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Folic Acid 4 mg
Arm Type
Experimental
Arm Description
Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo
Intervention Type
Drug
Intervention Name(s)
Folic Acid 4 mg
Other Intervention Name(s)
Folate
Intervention Description
Folic Acid 1.0 mg or placebo x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo x 4 tablets will be taken daily by oral administration.
Primary Outcome Measure Information:
Title
Preeclampsia
Description
PE is defined as diastolic blood pressure ≥90 mmHg on two occasions ≥4 hours apart and proteinuria developed in women greater than 20+0 weeks of gestation. Proteinuria is defined as: urinary protein ≥300mg in 24 hour urine collection OR in the absence of 24 hour collection, ≥2+ dipstick proteinuria, OR random protein-creatinine ratio ≥30mg protein/mmol. OR HELLP (Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome defined as: Haemolysis (characteristic peripheral blood smear), Serum LDH ≥ 600U/L, Serum AST ≥ 70U/L, and Platelet count <100 x109/L OR Superimposed pre-eclampsia, defined as history of pre-existing hypertension (diagnosed pre-pregnancy or before 20+0 weeks' gestation) with new proteinuria.
Time Frame
Participants will be followed from 20+0 weeks of gestational age until 42 days postpartum (after delivery)
Secondary Outcome Measure Information:
Title
Maternal Death
Description
According to the World Health Organization, "A maternal death is defined as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.
Time Frame
Time Frame: Participants will be followed from 20+0 weeks of gestation until 42 days postpartum (after delivery)
Title
Spontaneous Abortion
Description
Spontaneous abortion or miscarriage defined as death of a fetus <500g or <20 weeks of gestation
Time Frame
Participants will be followed from randomization until 20+0 weeks of gestation
Title
Placenta Abruption
Description
Placental abruption (abruptio placentae) is the premature detachment of a normally positioned placenta from the wall of the uterus.
Time Frame
Participants will be followed from 20+0 weeks of gestation until delivery
Title
Premature Rupture of Membranes
Description
Rupture of the membranes (rupture of the amniotic sac) before the onset of labor.
Time Frame
Participants will be followed from randomization (8-16 weeks' completed gestation) until the onset of labor
Title
Preterm Birth
Description
Birth that occur earlier than 37+0 weeks of gestational age.
Time Frame
Participants will be followed from 20+0 weeks to 36+6 weeks of gestation
Title
HELLP (Hemolysis, Elevated Liver Enzyme Levels & Low Platelet Count)
Description
Haemolysis (characteristic peripheral blood smear), Serum LDH >=600U/L, Serum AST >=70U/L, Platelet count <100 x109/L
Time Frame
Participants will be followed from 20+0 weeks of gestation until delivery
Title
Severe Preeclampsia
Description
Severe PE: Defined as PE with convulsion or HELLP or delivery <34 weeks.
Time Frame
Participants will be followed from 20+0 weeks of gestation until delivery.
Title
Antenatal Inpatient Length of Stay
Description
Length of inpatient stay before admission for delivery in days
Time Frame
Participants will be followed from date of randomization (8-16 weeks' completed gestation) until admission for delivery
Title
Stillbirth
Description
Fetal death defined as death of fetus of at least 500 grams birth weight or, if birth weight is unavailable, a gestational age of at least 20+0 weeks of gestation.
Time Frame
Participants will be followed from 20+0 weeks of gestation up to delivery.
Title
Intrauterine Growth Restriction (<3rd Percentile)
Description
Intrauterine growth restriction is defined as a birth weight less than the 3rd percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.
Time Frame
Participants will be followed from 20+0 weeks of gestation until delivery
Title
Intrauterine Growth Restriction (<10th Percentile)
Description
Intrauterine growth restriction is defined as a birth weight less than the 10th percentile of the population, adjusted for sex and gestational age, based on the current population-based Canadian reference standard.
Time Frame
Participants will be followed from 20+0 weeks of gestation until delivery
Title
Neonatal Death
Description
Neonatal death defined as death of a baby that occurred during first 28 days of life.
Time Frame
Participants will be followed from birth until 28 days of life
Title
Perinatal Mortality
Description
The perinatal mortality is defined as the number of deaths (fetal deaths and neonatal deaths) of babies ≥ 500 grams birth weight or, if birth weight is unavailable, a gestational age ≥ 20+0 weeks, up to 28 completed days after birth.
Time Frame
Participants will be followed from 20+0 weeks of gestation until 28 days of life.
Title
Retinopathy of Prematurity
Description
Retinopathy of prematurity a retinopathy typically occurring in premature infants treated with high concentrations of oxygen, characterized by vascular dilatation, proliferation, tortuosity, edema, retinal detachment, and fibrous tissue behind the lens confirmed by retinal examination according to an International Committee for the Classification of Retinopathy of Prematurity.
Time Frame
Infants born to the participant will be followed for the duration of hospital stay, or up to 6 weeks
Title
Early Onset Sepsis
Description
Within first 48hr of life, confirmed by positive blood or cerebrospinal fluid cultures
Time Frame
Infants born to the participants will be followed first 48 hours of life.
Title
Necrotising Enterocolitis
Description
Necrotizing enterocolitis (NEC) according to modified Bell's criteria stage 2 or higher (grossly bloody stool, plus absent bowel sounds with or without abdominal tenderness and radiographic findings such as intestinal dilation, ileus, pneumatosis intestinalis), excluding isolated spontaneous intestinal perforations.
Time Frame
Infants borm to the participants will be followed for the duration of hospital stay, or up to 6 weeks.
Title
Intraventricular Hemorrhage (IVH)
Description
IVH Grade 1(Blood in germinal matrix) IVH Grade 2 (Blood in germinal matrix and extending into the ventricles) IVH Grade 3 (Ventricular enlargement) IVH Grade 4 (Intraparenchymal lesion)
Time Frame
Time Frame: Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks
Title
Ventilation
Description
Ventilatory support after initial resuscitation, with/without intubation.
Time Frame
Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks.
Title
Need for Oxygen at 28 Days
Time Frame
Infants to the participants will be followed for 28 days after birth.
Title
Composite Severe Adverse Fetal/Neonatal Outcome
Description
Composite outcome included any of retinopathy of prematurity, periventricular leukomacia, early onset sepsis, necrotizing enterocolitis, intraventricular haemorrhage, ventilation. Need for O2at 28 days, NICU admission
Time Frame
Outcomes included in the composite outcome were measured for each of their respective time frames, up to 6-weeks after birth
Title
Length of Stay in 'High Level' Neonatal Care Unit
Time Frame
Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.
Title
Neonatal Death
Description
Neonatal death defined as death of the infant occurred before 28 days of life
Time Frame
Infants to the participants will be followed for 28 days after birth.
Title
Periventricular Leukomalacia
Description
One of the two outcomes used to measure neonatal morbidity.
Time Frame
Infants to the participants were followed for 28 days after birth.
Title
Neonatal Intensive Care Unit (NICU) Admission
Description
This outcome measured whether or not the infant was admitted into the NICU.
Time Frame
Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Capability of subject to comprehend and comply with study requirements ≥ 18 years of age at time of consent Subject is taking ≤1.1 mg of folic acid daily at the time of randomization Live fetus (documented positive fetal heart prior to randomization) Gestational age between 8+0 and 16+6 weeks of pregnancy (Gestational age (GA) of subjects will be calculated based on the first day of the last menstrual period (LMP) or ultrasound performed before 12+6. If early ultrasound and LMP dates differ by ≤ 7 days, base GA estimate on LMP date; if > 7 days, use early < 12+6 ultrasound) Subject plans to give birth in a participating hospital site Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE): Pre-existing hypertension (documented evidence of diastolic blood pressure ≥ 90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization) Pre-pregnancy diabetes (documented evidence of Type I or type II DM) Twin pregnancy Documented evidence of history of PE in a previous pregnancy BMI > 35 kg/m2 within 3 months prior to this pregnancy and up to randomization of this pregnancy (documented evidence of height and weight to calculate BMI is required) Exclusion Criteria: Known history or presence of any clinically significant disease or condition which would be a contraindication to folic acid supplementation of up to 5 mg daily for the duration of pregnancy Known major fetal anomaly or fetal demise History of medical complications, including: renal disease with altered renal function, epilepsy, cancer, or use of folic acid antagonists such as valproic acid Individual who is currently enrolled or has participated in another clinical trial or who received an investigational drug within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre) Known presence of: Alcohol abuse (≥ 2 drinks per day) or alcohol dependence Illicit drug/substance use and/or dependence Known hypersensitivity to folic acid Multiple Pregnancy (triplets or more) Participation in this study in a previous pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shi Wu Wen, PhD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark C Walker, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Escuela Eva Perón
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
S2000DKR
Country
Argentina
Facility Name
Hospital Provincial
City
Rosario
State/Province
Santa Fe
Country
Argentina
Facility Name
Hospital Roque Saenz Penia
City
Rosario
State/Province
Santa Fe
Country
Argentina
Facility Name
Maternidad Martin
City
Rosario
State/Province
Santa Fe
Country
Argentina
Facility Name
Sanatorio de la Mujer
City
Rosario
State/Province
Santa Fe
Country
Argentina
Facility Name
Cemic
City
Buenos Aires
Country
Argentina
Facility Name
Hospital Cullen
City
Santa Fe
Country
Argentina
Facility Name
Hosptial Iturraspe
City
Santa Fe
Country
Argentina
Facility Name
Nepean
City
Penrith
State/Province
New South Wales
ZIP/Postal Code
2750
Country
Australia
Facility Name
Townsville
City
Douglas
State/Province
Queensland
ZIP/Postal Code
4814
Country
Australia
Facility Name
Ipswich
City
Ipswich
State/Province
Queensland
ZIP/Postal Code
4305
Country
Australia
Facility Name
Adelaide
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Royal Women's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Sunshine
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Calgary Foothills Medical Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N2T9
Country
Canada
Facility Name
Edmonton Lois Hole Hospital for Women
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5H 3V9
Country
Canada
Facility Name
Vancouver BC Women's Hospital and Health Center
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4H4
Country
Canada
Facility Name
St-Paul's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
Fredericton Dr. Everett Chalmers Regional Hospital
City
Fredericton
State/Province
New Brunswick
ZIP/Postal Code
E3B 5N5
Country
Canada
Facility Name
Moncton Hospital
City
Moncton
State/Province
New Brunswick
ZIP/Postal Code
E1C 6Z8
Country
Canada
Facility Name
Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 4L2
Country
Canada
Facility Name
Winnipeg St. Boniface General Hospital
City
Winnipeg
State/Province
New Brunswick
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Winnipeg University of Manitoba
City
Winnipeg
State/Province
New Brunswick
ZIP/Postal Code
R3E 3P4
Country
Canada
Facility Name
St-John's Women's Health Centre
City
St John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Hamilton McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Kingston
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
London
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Civic Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
Sault Ste- Marie Sault Area Hospital
City
Sault Ste. Marie
State/Province
Ontario
ZIP/Postal Code
P6B 0A8
Country
Canada
Facility Name
Sunnybrook Health Sciences
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Quebec City (CHUL) Centre Hospitalier Universitaire
City
Montreal
State/Province
Quebec
ZIP/Postal Code
G1V 4G2
Country
Canada
Facility Name
Saint-Luc CHUM - Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
Facility Name
McGill University Royal Victoria Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Sainte-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
St-Mary's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1M5
Country
Canada
Facility Name
Regina Qu'Appelle Health Region
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4P 0W5
Country
Canada
Facility Name
University of West Indies
City
Kingston 7
Country
Jamaica
Facility Name
Jubilee
City
Kingston
Country
Jamaica
Facility Name
Spanishtown
City
Kingston
Country
Jamaica
Facility Name
Hinchingbrooke
City
Huntingdon
State/Province
Cambridgeshire
ZIP/Postal Code
PE29 6NT
Country
United Kingdom
Facility Name
Warrington and Halton Hospitals NHS Foundation Trust
City
Warrington
State/Province
Cheshire
ZIP/Postal Code
WA51QC
Country
United Kingdom
Facility Name
Darlington Memorial Hospital
City
Darlington
State/Province
County Durham
ZIP/Postal Code
DL3 6HX
Country
United Kingdom
Facility Name
University Hospital of North Durham
City
Durham
State/Province
County Durham
ZIP/Postal Code
DH1 5TW
Country
United Kingdom
Facility Name
Cumberland Infirmary
City
Carlisle
State/Province
Cumbria
ZIP/Postal Code
CA27HY
Country
United Kingdom
Facility Name
West Cumberland Hospital
City
Whitehaven
State/Province
Cumbria
ZIP/Postal Code
CA288JG
Country
United Kingdom
Facility Name
Fairfield
City
Bury
State/Province
Lancashire
ZIP/Postal Code
BL9 7TD
Country
United Kingdom
Facility Name
Rochdale
City
Rochdale
State/Province
Lancashire
ZIP/Postal Code
OL12 0NB
Country
United Kingdom
Facility Name
Lincolnshire
City
Lincoln
State/Province
Lincolnshire
ZIP/Postal Code
LN2 4AX
Country
United Kingdom
Facility Name
Ormskirk
City
Southport
State/Province
Merseyside
ZIP/Postal Code
PR8 6PN
Country
United Kingdom
Facility Name
Northwick Park Hospital
City
Harrow
State/Province
Middlesex
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
West Middlesex University Hospital
City
Isleworth
State/Province
Middlesex
ZIP/Postal Code
TW7 6AF
Country
United Kingdom
Facility Name
49 Marine Avenue & CCGs
City
Whitley Bay
State/Province
Newcastle Upon Tyne
ZIP/Postal Code
NE13 9BA
Country
United Kingdom
Facility Name
Wansbeck General Hospital
City
Ashington
State/Province
Northumberland
ZIP/Postal Code
NE63 9JJ
Country
United Kingdom
Facility Name
St George's Hospital
City
London
State/Province
Tooting
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Gateshead Queen Elizabeth Hospital
City
Gateshead
State/Province
Tyne And Wear
ZIP/Postal Code
NE9 6SX
Country
United Kingdom
Facility Name
South Tyneside District Hospital
City
South Shields
State/Province
Tyne And Wear
ZIP/Postal Code
NE34 0PL
Country
United Kingdom
Facility Name
The Royal Wolverhampton NHS Trust, New Cross Hospital
City
Wolverhampton
State/Province
West Midlands
ZIP/Postal Code
WV100QP
Country
United Kingdom
Facility Name
Blackburn
City
Blackburn
ZIP/Postal Code
BB2 3HH
Country
United Kingdom
Facility Name
Burnley
City
Burnley
ZIP/Postal Code
BB10 2PQ
Country
United Kingdom
Facility Name
North Manchester
City
Crumpsall
ZIP/Postal Code
M8 5RB
Country
United Kingdom
Facility Name
Guy's & St Thomas' Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
South Tees Hospital
City
Middlesbrough
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Facility Name
Newcastle upon Tyne Hospitals
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
North Tyneside General Hospital
City
North Shields
ZIP/Postal Code
NE29 8NH
Country
United Kingdom
Facility Name
Norfolk & Norwich
City
Norwich
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Nottingham Queens Medical Centre
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
Facility Name
Oldham
City
Oldham
ZIP/Postal Code
OL1 2JH
Country
United Kingdom
Facility Name
North Tees Hospital
City
Stockton
ZIP/Postal Code
TS19 9AH
Country
United Kingdom
Facility Name
Sunderland Royal Hospital
City
Sunderland
ZIP/Postal Code
SR4 7TP
Country
United Kingdom
Facility Name
Hillingdon Hospital
City
Uxbridge
ZIP/Postal Code
UB8 3NN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33851221
Citation
Rose EG, Murphy MSQ, Erwin E, Muldoon KA, Harvey ALJ, Rennicks White R, MacFarlane AJ, Wen SW, Walker MC. Gestational Folate and Folic Acid Intake among Women in Canada at Higher Risk of Pre-Eclampsia. J Nutr. 2021 Jul 1;151(7):1976-1982. doi: 10.1093/jn/nxab063.
Results Reference
derived
PubMed Identifier
32067533
Citation
Corsi DJ, Gaudet LM, El-Chaar D, White RR, Rybak N, Harvey A, Muldoon K, Wen SW, Walker M. Effect of high-dose folic acid supplementation on the prevention of preeclampsia in twin pregnancy. J Matern Fetal Neonatal Med. 2022 Feb;35(3):503-508. doi: 10.1080/14767058.2020.1725882. Epub 2020 Feb 18.
Results Reference
derived
PubMed Identifier
30209050
Citation
Wen SW, White RR, Rybak N, Gaudet LM, Robson S, Hague W, Simms-Stewart D, Carroli G, Smith G, Fraser WD, Wells G, Davidge ST, Kingdom J, Coyle D, Fergusson D, Corsi DJ, Champagne J, Sabri E, Ramsay T, Mol BWJ, Oudijk MA, Walker MC; FACT Collaborating Group. Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial. BMJ. 2018 Sep 12;362:k3478. doi: 10.1136/bmj.k3478.
Results Reference
derived
PubMed Identifier
24349782
Citation
Wen SW, Champagne J, Rennicks White R, Coyle D, Fraser W, Smith G, Fergusson D, Walker MC. Effect of folic acid supplementation in pregnancy on preeclampsia: the folic acid clinical trial study. J Pregnancy. 2013;2013:294312. doi: 10.1155/2013/294312. Epub 2013 Nov 18.
Results Reference
derived

Learn more about this trial

High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention

We'll reach out to this number within 24 hrs