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

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

Abstract

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

Objectives: 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.

Design: 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.

Results: 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affective Symptoms / etiology*
  • Child Behavior Disorders
  • Child, Preschool
  • Cohort Studies
  • Dietary Supplements*
  • Female
  • Folic Acid / blood*
  • Folic Acid / therapeutic use
  • Folic Acid Deficiency / blood
  • Folic Acid Deficiency / complications*
  • Folic Acid Deficiency / drug therapy
  • Genotype
  • Humans
  • Infant, Newborn
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Nutritional Status*
  • Polymorphism, Genetic
  • Pregnancy
  • Pregnancy Complications*
  • Prenatal Care
  • Prenatal Nutritional Physiological Phenomena*
  • Risk Factors
  • Young Adult

Substances

  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)