Efficacy of 4.0 mg versus 0.4 mg Folic Acid Supplementation on the Reproductive Outcomes: A Randomized Controlled Trial.

Bortolus, Renata; Filippini, Francesca; Cipriani, Sonia; Trevisanuto, Daniele; Cavallin, Francesco; Zanconato, Giovanni; Somigliana, Edgardo; Cesari, Elena; Mastroiacovo, Pierpaolo; Parazzini, Fabio

Folic acid (FA) supplementation prevents neural tube defects (NTDs), but the effects on other reproductive outcomes are unclear. While common recommendation is 0.4 mg/day in addition to regular nutrition, the most appropriate dose of FA is still under debate. We investigated the effects of a higher dose of periconception FA on reducing adverse reproductive outcomes. In this multicenter double-blind randomized controlled trial (RCT), 1060 women (aged 18–44 years and planning a pregnancy) were randomly assigned to receive 4.0 mg or 0.4 mg of FA daily. The primary outcome was the occurrence of congenital malformations (CMs). A composite outcome including one or more adverse pregnancy outcomes was also evaluated. A total of 431 women had a natural conception within 1 year. The primary outcome occurred in 8/227 (3.5%) women receiving 4.0 mg FA and 9/204 (4.4%) women receiving 0.4 mg FA (RR 0.80; 95%CI 0.31 to 2.03). The composite outcome occurred in 43/227 (18.9%) women receiving 4.0 mg FA and 75/204 (36.8%) women receiving 0.4 mg FA (RR 0.51; 95%CI 0.40 to 0.68). FA 4.0 mg supplementation was not associated with different occurrence of CMs, compared to FA 0.4 mg supplementation. However, FA 4.0 mg supplementation was associated with lower occurrence of other adverse pregnancy outcomes.

NEURAL tube defect prevention; DRUG efficacy; CONFIDENCE intervals; DIETARY supplements; PREGNANCY outcomes; RANDOMIZED controlled trials; DESCRIPTIVE statistics; FOLIC acid; STATISTICAL sampling; DOSE-response relationship in biochemistry; REPRODUCTIVE health; WOMEN'S health

Nutrients, 2021, Vol 13, Issue 12, p4422

2072-6643

Academic Journal

10.3390/nu13124422