A new perspective on the association between maternal folic acid supplementation across the perinatal period and cognitive and behavioral outcomes in children at age 4: findings from the MABC birth cohort study.

Preconception folic acid intake was inversely associated with children's visual spatial cognitive function.

• Preconception FA intake was associated with lower Visual Spatial Index (VSI) scores (adjusted regression coefficient aB = -2.05, 95% CI -3.75, -0.36).
• This association was observed in the overall sample from the Ma'anshan Birth Cohort (MABC) Study.
• Pregnant women were recruited at first antenatal visit from May 2013 to September 2014.
• Cognitive development was evaluated using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition at 3.0–6.0 years old.

Maternal folic acid supplementation during the second trimester was significantly associated with increased risk of externalizing behavioral problems in children.

• Second trimester FA supplementation was associated with an increased risk of externalization problems (adjusted OR = 2.89, 95% CI 1.16, 7.19).
• Behavioral problems were assessed using the Achenbach Child Behavior Checklist for ages 1.5–5 (CBCL/1.5-5) at age 4.
• Two summary scales of the CBCL/1.5-5 were analyzed.
• Data on maternal FA supplementation were collected via questionnaires at up to four time points before and during pregnancy.

Maternal folic acid supplementation during the second trimester was associated with lower working memory cognitive function in children.

• Second trimester FA supplementation was associated with lower Working Memory Index (WMI) scores (aB = -4.81, 95% CI -8.66, -0.96).
• This association was observed in the overall study sample.
• The WMI is one of the cognitive indices from the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition.

Sex-specific analyses showed that negative associations between folic acid supplementation and cognitive outcomes were observed only in boys, not girls.

• Preconception FA supplementation was negatively associated with VSI scores in boys (aB = -3.71, 95% CI -6.23, -1.19).
• Second trimester FA supplementation was associated with lower Fluid Reasoning Index (FRI) in boys (aB = -6.64, 95% CI -12.44, -0.85).
• Second trimester FA supplementation was associated with lower WMI in boys (aB = -6.66, 95% CI -12.56, -0.77).
• No significant associations were observed in girls.

Folic acid supplementation during the second trimester was associated with increased risk of externalizing behavioral problems specifically in boys.

• Second trimester FA supplementation was significantly associated with an increased risk of externalization problems in boys (aOR = 3.39, 95% CI 1.07, 10.74).
• No significant associations between FA supplementation and externalizing problems were observed in girls.
• Behavioral problems were assessed at age 4 using the CBCL/1.5-5.

The study was based on the Ma'anshan Birth Cohort and collected FA supplementation data at multiple time points across the perinatal period.

• Pregnant women were recruited at their first antenatal visit from May 2013 to September 2014.
• Data on maternal FA supplementation before and during pregnancy were collected via questionnaires at up to four time points.
• FA supplementation was assessed for preconception, first trimester, second trimester, and third trimester periods.
• Child outcomes were assessed at age 4 for behavior and between ages 3.0–6.0 years for cognitive development.