None listed
Conditions
Brief summary
Neural tube defects (NTDs) are serious birth defects affecting the brain and spine. Folic acid supplementation in early pregnancy has been shown to reduce the incidence of NTDs. Currently, the World Health Organization recommends weekly iron (60 mg) and folic acid (2.8 mg) (IFA) supplementation among women and adolescents in areas where anaemia prevalence is >=20%. A weekly dose of 2.8 mg folic acid was chosen because it was seven times the daily dose known to reduce NTDs; however, evidence is lacking to confirm this is an optimal dose. We aim to conduct a three-arm randomised controlled trial to examine the effects of three different weekly doses of folic acid on red blood cell folate concentrations. We will recruit women (n=300; 18-45 y) from Kuala Lumpur, Malaysia. We will randomise women individually, to receive one of three weekly doses of folic acid (2.8, 0.4 or 0 mg) with 60 mg iron for 16 weeks (with a scheduling allowance of +2 weeks), followed by a 4-week washout period (with a scheduling allowance of +2 weeks). Fasting venous blood will be drawn at baseline, 16, and 20 weeks. We will measure plasma folate, red blood cell folate, and other markers of nutrition and inflammation, and genetic polymorphisms in folate metabolism. The primary outcome is baseline adjusted red blood cell folate at 16 weeks, analyzed with use of a generalized estimating equation (intention-to-treat). This research is expected to inform the WHO guidelines for weekly iron and folic acid supplementation, particularly on the optimal folic acid dose.
Interventions
This study is a three-arm, parallel-group, randomised controlled trial with a 16-week (with an additional scheduling allowance of +2 weeks) intervention period followed by a 4-week (with an additional scheduling allowance of +2 weeks) washout period. Interventions include: Arm 1: 60 mg of elemental iron as ferrous fumarate and 2.8 mg of folic acid once weekly. This dose will be administered orally in tablet form once weekly for 16 weeks (with an additional scheduling allowance of +2 weeks). Adherence will be assessed by counting remaining tablets at the end of the intervention period by study staff. Arm 2: 60 mg of elemental iron as ferrous fumarate and 0.4 mg of folic acid. This dose will be administered orally in tablet form once weekly for 16 weeks (with an additional scheduling allowance of +2 weeks). Adherence will be assessed by counting remaining tablets at the end of the intervention period by study staff.
Sponsors
Study design
Eligibility
Inclusion criteria
Non-pregnant (self-reported), not planning on becoming pregnant, not currently taking micronutrient supplements containing folic acid or participating in another nutritional intervention, not taking any medication known to inhibit folate status (methotrexate, anti-convulsants, or sulphasalazine), and not planning to leave the community for the timeline of the study.
Exclusion criteria
Pregnant, planning on becoming pregnant, currently taking micronutrient supplements containing folic acid or participating in another nutritional intervention, taking any medication known to inhibit folate status (methotrexate, anti-convulsants, or sulphasalazine), or planning to leave the community in durations that would interfere with the study timeline.