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Am J Clin Nutr. 2012 Jun;95(6):1413-21. doi: 10.3945/ajcn.111.030791. Epub 2012 May 9.

Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study.

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  • 1Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.



Maternal prenatal folate status has been linked to neurodevelopmental disorders, but the association with child emotional and behavioral problems is unclear.


We assessed the association of maternal folate status during pregnancy with child emotional and behavioral problems. Also, we examined whether any association between folate status and child problems is a consequence of maternal folic acid supplement use or variation in maternal MTHFR genotype.


Within a population-based cohort, we measured maternal plasma folate concentrations in early pregnancy and assessed folic acid supplement use by questionnaire. Mothers of European descent were genotyped for the MTHFR 677 C→T polymorphism. Child emotional and behavioral problems were assessed with the Child Behavior Checklist at 3 y in 3209 children.


Children of mothers with prenatal folate deficiency were at higher risk of emotional problems (OR: 1.57; 95% CI: 1.03, 2.38) but not behavioral problems (OR: 1.00; 95% CI: 0.64, 1.56) after adjustment for confounders. A higher risk of emotional problems was also found in children whose mothers started using folic acid supplements late or did not use supplements at all (OR: 1.45; 95% CI: 1.14, 1.84) than in children whose mothers started periconceptionally. However, low plasma folate concentrations only partly explained this association (OR: 1.38; 95% CI: 1.08, 1.78). Although related to plasma folate concentrations, maternal MTHFR genotype did not explain the association of folate status with offspring emotional problems.


Low maternal folate status during early pregnancy is associated with a higher risk of emotional problems in the offspring.

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