Association between maternal folic acid supplementation in different pregnancy and infant neurobehavioral development at 6 and 18 months.

Background: It has been proven that periconceptional folic acid (FA) supplementation could prevent neural tube defects. However, FA supplementation during different stages of pregnancy and its association with the neurobehavioral development of offspring remains unclear, particularly the effects of continued FA supplementation during the second and third trimesters. This study aimed to investigate the relationship between maternal FA supplementation at various stages of pregnancy and infant neurobehavioral development.

Methods: In a prospective birth cohort study involving 3246 parent-child pairs, 2905 infants completed neurobehavioral development assessments at 6 months and 3005 infants at 18 months. Information regarding micronutrient supplementation at various stages of pregnancy was recorded. Multivariable logistic regression was used to evaluate the association between FA supplementation and infant neurobehavioral developmental delays. In addition, propensity score analysis was performed to correct the potential imbalances in the distribution of related factors between the groups.

Results: During the periconceptional period, maternal standardized FA supplementation (taking 0.4 mg FA daily before and in early pregnancy, as officially recommended) was associated with a reduced risk of possible development delays in 18-month-old infants in the communication domain (RR = 0.48, 95% CI: 0.26-0.86; P = 0.015). After the 12th gestational week, maternal continuous FA supplementation in the second and third trimesters was significantly associated with a decreased risk of possible neurobehavioral development delay in 6-month-old infants in fine motor domain (RR = 0.31, 95% CI: 0.12-0.82; P = 0.019) and the problem-solving domain (RR = 0.20, 95% CI: 0.05-0.79; P = 0.022). These associations remained significant after adjusting for confounders and propensity scores.

Conclusions: FA supplementation at different stages of pregnancy may enhance neurobehavioral development in offspring. To confirm these findings, additional investigations or trials with larger sample sizes and consistent tracking of folate status throughout pregnancy are recommended.