Folic Acid Supplements in Pregnancy and Severe Language Delay in Children

Abstract

It is well established from randomized controlled trials and other studies that periconceptional folic acid supplements reduce the risk of neural tube defects (NTDs). It has been suggested that prenatal administration of folic acid supplements may have beneficial effects on aspects of neurodevelopment after birth. No follow-up trials have investigated whether prenatal exposure to folic acid affects child neurodevelopment. This prospective observational study used data from the Norwegian Mother and Child Cohort Study to investigate whether maternal use of folic acid supplements was associated with a reduced risk of severe language delay in children at age 3 years. The cohort comprised pregnant women from Norway recruited between 1999 and 2008 who received folic acid supplements and/or other supplements from 4 weeks before to 8 weeks after conception. The questionnaire was sent to the participants at 17 weeks of gestation and periodically up to age 3 years. All children included in the study were born before 2008. Multiple logistic regression analysis was used to compare the effect of exposure and no exposure to folic acid on severe language delay and to adjust for potential confounders. The primary study outcome measure was children's language competency at age 3 years assessed by maternal report on a 6-point ordinal language grammar scale; ratings ranged from no word production to complete sentences. Children rated as having severe language delay used minimal expressive language (only 1 word or unintelligible utterances). Severe language delay was evaluated in 4 categories based on exposure or no exposure to folic acid during the specified interval: (1) reference group (no folic acid or other supplements); (2) supplements and no folic acid; (3) only folic acid; and (4) folic acid plus supplements. Of the 38,954 children in the cohort, 204 (0.5%) had severe language delay. Compared with no use of dietary supplements, the adjusted odds ratio were 1.04 (95% confidence interval [CI], 0.62–1.74) for the other supplements and no folic acid group; 0.55 (95% CI, 0.35–0.86) for the folic acid only group; and 0.55 (95% CI, 0.39–0.78) for the folic acid plus other supplements group. These findings suggest that maternal use of supplements containing folic acid within the period from 4 weeks before to 8 weeks after conception is associated with a reduced risk of severe language delay in children at age 3 years in a cohort of Norwegian women.