Possible Association of Folic Acid Supplementation During Pregnancy With Reduction of Preterm Birth: A Population-Based Study

Abstract

The administration of folic acid (FA) or multivitamin (MV) supplements during preconception to prevent neural tube defects is well established. Most pregnant women in Hungary use high doses of FA early in pregnancy, but it is unclear whether continuing these supplements after the first trimester reduces the rate of preterm delivery and low birth weight. The results of 2 meta-analyses on supplementation were inconclusive as to the benefits of continuation and recommended further investigation. Some practitioners have suggested that increased birth weight resulting from supplementation may increase the risk of complications. To address this issue, this study compared the effects of administering vitamin supplements in the second and the third trimester on length of gestation and fetal growth. Birth outcomes were determined using a population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The participants included 3 groups of women who ingested daily supplements containing (1) FA alone (n = 6293), (2) FA plus MV (n = 311), or (3) MV without FA (n = 169). The controls were a reference group comprising 7319 pregnant women who did not take the supplements. There was special emphasis on the third trimester, during which the most intensive fetal growth occurs. Compared to the reference sample, the mean gestational age at delivery in the FA alone group was 0.3 week longer (39.5 vs. 39.2) and the mean birth weight 37 g higher (3253 vs. 3216 g). The continuation of FA was associated with a significant reduction (7.6%) in the rate of preterm births compared with the reference sample (11.8%), but there was no similar reduction in the rate of low birth weight newborns. In the third trimester, the use of FA was associated with a 0.6 week prolongation of gestation (FA alone: 39.8 vs. reference sample: 39.2 weeks) and a lower rate of preterm birth (4.8%). These findings show that high dose FA supplementation during pregnancy, especially during the third trimester, are associated with a decreased risk of preterm birth.