Maternal Continuing Folic Acid Supplementation after the First Trimester of Pregnancy Increased the Risk of Large-for-Gestational-Age Birth: A Population-Based Birth Cohort Study

Supplementation with folic acid (FA) was proven to prevent neural tube defects (NTDs) and was recommended worldwide before and during early pregnancy. However, much less is known regarding the role of FA after the 12th gestational week (GW). This study aimed to investigate the related effects of continued FA supplementation after the first trimester of pregnancy on fetal growth. The study subjects came from the Ma'anshan-Anhui Birth Cohort Study (MABC) that recruited 3474 pregnant women from the city of Ma'anshan in Anhui Province in China during the period of May 2013 to September 2014. The information on use of vitamin and mineral supplements was recorded in different periods (the first/second/third trimester of pregnancy). Small-for-gestational-age (SGA) births were live-born infants that were <10th percentile of birth weight, and large-for-gestational-age (LGA) births were live-born infants that were ≥90th percentile of birth weight according to nomograms based on gender and gestational age from the latest standards. We used multivariable logistic regression to evaluate the effects of FA supplement consumption in the second/third trimester of pregnancy on the risk of LGA and SGA. In addition, propensity score analysis was also performed to examine the effects. In this prospective birth cohort study conducted in Chinese women who had taken FA in the first trimester of pregnancy, we found that continued FA supplementation with 400 micrograms/day in the second and third trimesters of pregnancy significantly increased the risk of LGA (RR = 1.98 (1.29, 3.04)). This relation was strong or monotonic after adjusting for maternal age, newborn's gender, maternal pre-pregnancy BMI, maternal education level, smoking, alcohol consumption and calcium supplementation. We did not observe that continuing FA supplementation after the first trimester of pregnancy remarkably decreased the risk of SGA. The propensity score analysis showed similar results. To confirm these findings, additional investigations or trials with a large sample and the tracking of folate status throughout pregnancy are recommended.