title: Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study.
abstract: BACKGROUND
  Maternal prenatal folate status has been linked to neurodevelopmental disorders, but the association with child emotional and behavioral problems is unclear.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Low maternal folate status during early pregnancy is associated with a higher risk of emotional problems in the offspring.
authors.affiliation: Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: Steenweg-de Graaff
authors.forename: Sabine J
authors.initials: SJ
authors.lastname: Roza
authors.forename: Eric Ap
authors.initials: EA
authors.lastname: Steegers
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.forename: Vincent Wv
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000209:etiology*; D002653:Child Behavior Disorders; D002675:Child, Preschool; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000627:therapeutic use; D005494:Folic Acid Deficiency / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications; D011295:Prenatal Care; D039401:Prenatal Nutritional Physiological Phenomena; D012307:Risk Factors; D055815:Young Adult
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)