Folic Acid Supplementation in Pregnant Women: Dose Response
Condition: Pregnancy
Study type: Interventional

Summary: 
      The proposed study is a double-blind randomized controlled trial in healthy pregnant women
      (BMI 18.5 - 29.9 kg/m2, age 18 - 40 yr) receiving prenatal care at Athens Regional Midwifery
      clinic (ARMC).

      The primary goal of the proposed study is to determine relative changes in blood folate and
      DNA methylation levels in response to 2 different supplemental doses of folic acid one of
      which will provide the Institute of Medicine's recommended folate intake for pregnant women
      and the second will provide a higher dose as routinely taken by pregnant women in
      over-the-counter prenatal supplements.

      The specific aims of the study are:

        1. to compare maternal serum and red blood cell (RBC) folate levels and % change in women
           taking either 400 or 800 mcg/day of supplemental folic acid from the first prenatal
           visit (< 10 weeks) through delivery;

        2. to compare the infant's cord blood folate levels in response to different maternal folic
           acid intakes (400 mcg/d vs 800 mcg/d);

        3. to determine relative differences in the levels of oxidized folic acid in maternal and
           infant blood in response to 400 or 800 mcg/d folic acid dose, and

        4. to determine genome wide and gene specific DNA methylation response in pregnant women
           receiving prenatal supplements containing either 400 or 800 mcg folic acid per day
    

Detailed description: 
      The study will be conducted in healthy women with a BMI within the ranges of 18.5 - 35.0
      kg/m2. There will be two treatment groups: (1) one group taking 400 mcg per day of folic acid
      as part of a prenatal supplement, beginning at study enrollment (< 10 weeks gestational age)
      and (2) a second group taking 800 mcg per day of folic acid as part of the prenatal
      supplement. Both groups will be provided identical composition of prenatal supplements other
      than folic acid content. Repeated measures of outcome variables will be determined in blood
      samples collected at various times during pregnancy and at delivery. Due to the role of
      prenatal supplementation in helping maintain optimal nutrition status throughout pregnancy,
      there will be no placebo control.

      Women will be recruited through the Athens Regional Medical Center Midwifery Practice and all
      blood draws associated with this study will be conducted during scheduled prenatal visits.
      The research protocol is consistent with the standard of care provided by the clinic and will
      not affect the prenatal services provided to the research participants. Following consent at
      the first prenatal visit, participants will be randomly assigned to receive prenatal
      supplements containing either 400 or 800 mcg of folic acid (all other ingredients at
      unmodified concentrations). The 400 mcg dose approximates the current Recommended Dietary
      Allowance (RDA) for pregnant women of 600 mcg Dietary Folate Equivalents (400 mcg folic acid
      ≈ 600 mcg DFEs; conversion factor based on higher bioavailability of folic acid is: 1 mcg
      folic acid = 1.7 mcg DFE). The higher dose of 800 mcg folic acid represents an amount
      commonly found in over-the-counter prenatal supplements. Women will be asked to take the
      supplements daily throughout the duration of gestation and to follow their standard prenatal
      diet, with the exception of avoiding highly fortified (> 100% RDA) ready-to-eat cereals and
      fortified energy/snack bars and drinks, due to their high folic acid content.

      At the first visit, the participants will be instructed in the use of a dietary recall data
      collection sheet (food diary) which they will be asked to complete during specific time
      points during the study. Each set of dietary recalls will include information for three 24-hr
      periods on non-consecutive days including one weekend day. Dietary recall information will be
      obtained at approximately weeks 16 and 32 of gestation. This will permit assessment of
      typical dietary intake of total calories and specific nutrients, including folate.

      Blood samples will be collected, in the non-fasting state, at the first, 28 week and 36 week
      prenatal visits and from the mother and cord blood at delivery for determination of primary
      outcome measures.
    

Intervention name(s): Folic acid, 400 mcg/day; Folic acid 800 mcg/day
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The supplement regime for this arm will consist of (1) a women's multivitamin/ multimineral (MVM) supplement containing 400 mcg folic acid, (2) a capsule containing 200 mg DHA and (3) a capsule formulated to contain 10 mg iron (which represents the difference in the amount of iron in the women's MVM formulation and that in prenatal MVM supplements).; The supplement regime for this arm will consist of (1) a women's multivitamin/ multimineral (MVM) supplement containing 400 mcg folic acid, (2) a capsule containing 200 mg DHA and (3) a capsule formulated to contain 10 mg iron (which represents the difference in the amount of iron in the women's MVM formulation and that in prenatal MVM supplements) and 400 mcg folic acid.
Intervention MeSH terms: Folic Acid; Vitamin B Complex
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Folate requirements; Pregnancy; Folic acid; DNA methylation; Folate biomarkers