Phase 3
N=2,464
High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention
Pregnancy Complications · Preeclampsia
Bottom Line
View on ClinicalTrials.gov: NCT01355159 ↗Enrolled (actual)
2,464
Serious AEs
17.1%
Results posted
Jul 2020
Primary outcome: Primary: Preeclampsia — 169; 156 Participants — p=0.37
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Folic Acid 4 mg (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Ottawa Hospital Research Institute
- Primary completion
- Jul 2016
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 Neonatal Death |
151; 144 | 0.79 |
| SECONDARY Periventricular Leukomalacia |
4; 2 | 0.42 |
| SECONDARY Neonatal Intensive Care Unit (NICU) Admission |
299; 267 | — |
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.
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). 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.