Folic Acid Supplementation in Pregnant Women: Dose Response

NCT02124642 | Completed

• 1 other identifier: FASUPPPREG-2014
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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. 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

Conditions

Pregnancy

Keywords

Folate requirements; Pregnancy; Folic acid; DNA methylation; Folate biomarkers

Outcome Measures

Primary Outcomes (4)

• Serum folate

  Change in serum folate concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Cord blood serum folate at delivery will also be determined by the microbiological assay. Differences in serum folate response to the two levels of folic acid supplementation will be compared.

  Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery

• Red blood cell (RBC) folate

  Change in red blood cell (RBC) folate concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by microbiological assay using Lactobacillus rhamnosus. Cord blood RBC folate at delivery will also be determined by the microbiological assay. Differences in RBC folate response to the two levels of folic acid supplementation will be compared.

  Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery

• Serum folic acid

  Change in serum folic acid concentrations in response to supplementation during pregnancy with one of two levels of folic acid will be determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cord blood serum folic acid at delivery will also be determined by LC-MS/MS. Differences in serum folic acid in response to the two levels of folic acid supplementation will be compared.

  Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery

• Gene-specific DNA methylation

  Change in DNA methylation in response to folic acid supplementation during pregnancy will be determined in DNA isolated from whole blood. Illumina Infinium HumanMethylatio450 bead chip microarrays will be used to assess changes in multiple methylation sites of specific genes within regulatory pathways for folate metabolism and/or development. Differences in DNA methylation in response to the two levels of folic acid supplementation will be compared. We anticipate analyzing DNA methylation response at multiple time points and in all participants. Due to the expense associated with the analysis, however, we may be able to perform the analysis only at baseline and delivery and in only a subset of the participants if we are unable to secure additional funding.

  Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery

Secondary Outcomes (5)

• Cell-type-specific DNA methylation

  Baseline (Initial Prenatal Visit), 28 and 36 weeks gestation, delivery

• Infant birth weight

  Delivery

• Infant length

  Delivery

• Infant head circumference

  Delivery

• Apgar score

  Delivery

Study Arms (2)

Folic acid, 400 mcg/day

ACTIVE COMPARATOR

A daily 400 microgram (mcg) dose of folic acid will be taken orally, along with the recommended intake for pregnancy of other vitamins, minerals and docosahexaenoic acid (DHA), beginning at enrollment until delivery. 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).

Dietary Supplement: Folic acid, 400 mcg/day

Folic acid, 800 mcg/day

EXPERIMENTAL

A daily 800 microgram (mcg) dose of folic acid will be taken orally, along with the recommended intake for pregnancy of other vitamins, minerals and docosahexaenoic acid (DHA), beginning at enrollment until delivery. The 800 microgram dose, which is considerably higher than the current RDA, represents an amount commonly found in over-the-counter prenatal vitamin formulations.

Dietary Supplement: Folic acid 800 mcg/day

Interventions

Folic acid, 400 mcg/day DIETARY_SUPPLEMENT

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).

Folic acid, 400 mcg/day

Folic acid 800 mcg/day DIETARY_SUPPLEMENT

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.

Folic acid, 800 mcg/day

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy women with singleton pregnancy
• \< 10 weeks gestation at enrollment
• body mass index 18.5 - 35.0 kg/m2
• willingness to comply with study protocol ( i.e. take assigned daily prenatal vitamin; complete diet recall and study questionnaire)
• not consuming super-fortified ready-to-eat cereal products (with \> 100% RDA for folate per serving)

You may not qualify if:

• BMI \< 18.5 or \> 35.0 kg/m2
• use of prescription drugs
• anemia
• chronic disease (diabetes, hypertension, epilepsy, cancer, kidney disease, cardiovascular disease)
• acute illness (e.g. pneumonia, urinary tract infection, mononucleosis)
• use of antibiotics in past 2 weeks
• follows vegan dietary regime
• current smoker
• typical alcohol consumption of 2 or more drinks per day
• having undergone in vitro fertilization treatment
• carrying more than one fetus
• pregnancy-associated complications (i.e gestational diabetes, pre-eclampsia)

Sponsors & Collaborators

• University of Georgia: lead
• University of Florida: collaborator
• Emory University: collaborator
• Cornell University: collaborator

Study Sites (1)

Athens Regional Medical Center Midwifery Practice

Athens, Georgia, 30606, United States

Location

MeSH Terms

Interventions

Folic Acid

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lynn B Bailey, PhD

  University of Georgia

  PRINCIPAL INVESTIGATOR

• Dorothy B Hausman, PhD

  University of Georgia

  STUDY DIRECTOR

• Hea Jin Park, PhD

  University of Georgia

  STUDY DIRECTOR

• Gail P A Kauwell, PhD, RDN

  University of Florida

  STUDY DIRECTOR

• Marie A Caudill, PhD, RD

  Cornell University

  STUDY DIRECTOR

• Alicia K Smith, PhD

  Emory Univeristy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Head and Professor

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: April 28, 2014
• Study Start: May 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2017
• Last Updated: March 5, 2018

Record last verified: 2018-03

Locations

US (1)