Folic acid supplements during pregnancy and child psychomotor development after the first year of life

JAMA Pediatr. 2014 Nov;168(11):e142611. doi: 10.1001/jamapediatrics.2014.2611. Epub 2014 Nov 3.


Importance: Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear.

Objective: To examine the association between the use of high dosages of FA supplements during pregnancy and child neuropsychological development after the first year of life.

Design, setting, and patients: The multicenter prospective mother-child cohort Infancia y Medio Ambiente (INMA) Project recruited pregnant women from 4 areas of Spain (Asturias, Sabadell, Gipuzkoa, and Valencia) between November 2003 and January 2008. Pregnant women completed an interviewer-administered questionnaire on the usual dietary folate intake and FA supplements at 10 to 13 weeks and 28 to 32 weeks of gestation. The main analyses were based on a sample of 2213 children with complete information on neuropsychological development and FA supplement intake during pregnancy. Multiple linear and logistic regression analyses were used to explore the effects of FA supplements on child neuropsychological development.

Main outcomes and measures: Neuropsychological development was assessed using the Bayley Scales of Infant Development. We calculated mental scale and psychomotor scale scores. One SD below the mean established a delay in neurodevelopment (score <85).

Results: A high proportion of women (57.3%) did not reach the recommended dosages of FA supplements (400 μg/d), but 25.2% women took more than 1000 μg/d of FA supplements (3.5% consuming >5000 μg/d). In multivariate analysis, we observed that children whose mothers used FA supplement dosages higher than 5000 μg/d during pregnancy had a statistically significantly lower mean psychomotor scale score (difference, -4.35 points; 95% CI, -8.34 to -0.36) than children whose mothers used a recommended dosage of FA supplements (400-1000 μg/d). An increased risk of delayed psychomotor development (psychomotor scale score <85) was also evident among children whose mothers took FA supplement dosages higher than 5000 μg/d, although the association was not statistically significant (odds ratio = 1.59; 95% CI, 0.82-3.08).

Conclusions and relevance: To our knowledge, this is the first time a detrimental effect of high dosages of FA supplements during pregnancy on psychomotor development after the first year of life has been shown. Further research from longitudinal studies is warranted to confirm these results.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child Development / physiology*
  • Dietary Supplements* / adverse effects
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / adverse effects
  • Humans
  • Infant
  • Male
  • Pregnancy*
  • Prospective Studies
  • Psychomotor Performance / physiology*
  • Regression Analysis
  • Surveys and Questionnaires


  • Folic Acid