Phase 3
Completed N=2,464
High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention
Source: ClinicalTrials.gov NCT01355159 ↗Enrolled (actual)
2,464
Serious AEs
17.1%
Results posted
Jul 2020
Primary outcomePrimary: Preeclampsia — 169; 156 Participants — p=0.37
◆ Published Evidence
Highly cited
118citations · ~15 / year
Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.
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.
Linked Publications (5)
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Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.
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Effect of folic acid supplementation in pregnancy on preeclampsia: the folic acid clinical trial study.
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Effect of high-dose folic acid supplementation on the prevention of preeclampsia in twin pregnancy.
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Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation.
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Gestational Folate and Folic Acid Intake among Women in Canada at Higher Risk of Pre-Eclampsia.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Preeclampsia |
169; 156 | 0.37 |
| SECONDARY Maternal Death |
0; 0 | — |
| SECONDARY Spontaneous Abortion |
27; 21 | 0.37 |
| SECONDARY Placenta Abruption |
12; 19 | 0.21 |
| SECONDARY Premature Rupture of Membranes |
215; 224 | 0.71 |
| SECONDARY Preterm Birth |
297; 304 | 0.87 |
| SECONDARY HELLP (Hemolysis, Elevated Liver Enzyme Levels & Low Platelet Count) |
6; 5 | 0.75 |
| SECONDARY Severe Preeclampsia |
24; 16 | 0.19 |
| SECONDARY Antenatal Inpatient Length of Stay |
5.6; 5.2 | 0.61 |
| SECONDARY Stillbirth |
15; 26 | 0.14 |
| SECONDARY Intrauterine Growth Restriction (<3rd Percentile) |
20; 25 | 0.37 |
| SECONDARY Intrauterine Growth Restriction (<10th Percentile) |
151; 144 | 0.82 |
| SECONDARY Neonatal Death |
151; 144 | 0.79 |
| SECONDARY Perinatal Mortality |
23; 37 | 0.07 |
| SECONDARY Retinopathy of Prematurity |
21; 13 | 0.65 |
| SECONDARY Early Onset Sepsis |
3; 9 | 0.10 |
| SECONDARY Necrotising Enterocolitis |
8; 3 | 0.33 |
| SECONDARY Intraventricular Hemorrhage (IVH) |
18; 19 | 0.94 |
| SECONDARY Ventilation |
49; 30 | 0.06 |
| SECONDARY Need for Oxygen at 28 Days |
9; 3 | 0.21 |
| SECONDARY Composite Severe Adverse Fetal/Neonatal Outcome |
63; 51 | 0.38 |
| SECONDARY Length of Stay in 'High Level' Neonatal Care Unit |
16; 17 | 046 |
| SECONDARY Periventricular Leukomalacia |
4; 2 | 0.42 |
| SECONDARY Neonatal Intensive Care Unit (NICU) Admission |
299; 267 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT01355159) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.