Intervention: FOLIC ACID
Trial phase: Phase 3
ATC code: B03AD01 | B03AD02 | B03AD03 | B03AD04 | B03AD05 | B03AE01 | B03AE02 | B03BB01 | B03BB51 | V04CX02
SMILES: Nc1nc(=O)c2nc(CNc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cnc2[nH]1
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1227
Group 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

Folic Acid 4 mg: 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
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