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Purpose <p>The associations between maternal folic acid (FA) supplementation across the perinatal period and childhood cognitive development and behavioral problems remain unclear. This study aimed to evaluate the relationship between maternal FA supplementation throughout the perinatal period and offspring’s cognitive function and behavioral problems at age 4.</p> Methods <p>Based on the Ma’anshan Birth Cohort Study, 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. At 4&#xa0;years of age, children’s behavioral problems were assessed using the Achenbach Child Behavior Checklist for ages 1.5–5 (CBCL/1.5-5), with two summary scales analyzed. Cognitive development was evaluated using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition at 3.0–6.0&#xa0;years old.</p> Results <p>Preconception FA intake was inversely associated with children’s cognitive function [visual spatial index (VSI), adjusted regression coefficient (a<i>B</i>) = − 2.05, 95% confidence interval (CI)  − 3.75, − 0.36]. Maternal FA supplementation during the second trimester was significantly associated with an increased risk of externalization problems [adjusted odds ratio (a<i>OR)</i> = 2.89, 95% CI 1.16, 7.19] and lower cognitive function [working memory index (WMI), a<i>B</i> = − 4.81, 95% CI − 8.66, − 0.96]. Furthermore, sex-specific associations were only observed among boys: preconception FA supplementation was negatively associated with cognitive indice (VSI, a<i>B</i> = − 3.71, 95% CI − 6.23, − 1.19); FA supplementation in the second trimester was significantly associated with an increased risk of externalization problems in boys (a<i>OR</i> = 3.39, 95% CI 1.07, 10.74) and lower cognitive function [fluid reasoning index (FRI), a<i>B</i> = − 6.64, 95% CI − 12.44, − 0.85; WMI, a<i>B</i> = − 6.66, 95% CI − 12.56, − 0.77]. No significant associations were observed in girls.</p> Conclusion <p>Among 4-year-old children, particularly boys, maternal FA supplementation during the second trimester was associated with a higher risk of externalizing behavioral problems, while supplementation in both preconception and second trimester were linked to poorer cognitive development. Well-designed, larger-scale studies are needed to validate these findings.</p>

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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

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Wenjing Qiang,
  • Tuyan Fan,
  • Jingjing Liu,
  • Shuangqin Yan,
  • Guopeng Gao,
  • Xiayan Yu,
  • Hui Gao,
  • Fangbiao Tao,
  • Beibei Zhu

摘要

Purpose

The associations between maternal folic acid (FA) supplementation across the perinatal period and childhood cognitive development and behavioral problems remain unclear. This study aimed to evaluate the relationship between maternal FA supplementation throughout the perinatal period and offspring’s cognitive function and behavioral problems at age 4.

Methods

Based on the Ma’anshan Birth Cohort Study, 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. At 4 years of age, children’s behavioral problems were assessed using the Achenbach Child Behavior Checklist for ages 1.5–5 (CBCL/1.5-5), with two summary scales analyzed. 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.

Results

Preconception FA intake was inversely associated with children’s cognitive function [visual spatial index (VSI), adjusted regression coefficient (aB) = − 2.05, 95% confidence interval (CI)  − 3.75, − 0.36]. Maternal FA supplementation during the second trimester was significantly associated with an increased risk of externalization problems [adjusted odds ratio (aOR) = 2.89, 95% CI 1.16, 7.19] and lower cognitive function [working memory index (WMI), aB = − 4.81, 95% CI − 8.66, − 0.96]. Furthermore, sex-specific associations were only observed among boys: preconception FA supplementation was negatively associated with cognitive indice (VSI, aB = − 3.71, 95% CI − 6.23, − 1.19); FA supplementation in the second trimester was significantly associated with an increased risk of externalization problems in boys (aOR = 3.39, 95% CI 1.07, 10.74) and lower cognitive function [fluid reasoning index (FRI), aB = − 6.64, 95% CI − 12.44, − 0.85; WMI, aB = − 6.66, 95% CI − 12.56, − 0.77]. No significant associations were observed in girls.

Conclusion

Among 4-year-old children, particularly boys, maternal FA supplementation during the second trimester was associated with a higher risk of externalizing behavioral problems, while supplementation in both preconception and second trimester were linked to poorer cognitive development. Well-designed, larger-scale studies are needed to validate these findings.