High Dose Folic Acid Supplementation Throughout Pregnancy for Preeclampsia Prevention
Condition: Pregnancy Complications; Preeclampsia
MeSH terms: Pre-Eclampsia; Pregnancy Complications
Intervention: Folic Acid 4 mg; Placebo
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; Placebo x 4 tablets will be taken daily by oral administration.
Intervention MeSH terms: Folic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2464.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pregnancy; Folic Acid supplementation; Preeclampsia

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:

          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