The prospective Norwegian Mother and Child Cohort Study of pregnant women between 1999 and 2008 was used by researchers at the Norwegian Institute of Public Health, Oslo to examine the association between mothers’ use of prenatal folic acid supplements and risk of severe language delay in the children at age 3 years. Language development assessment was based on follow-up questionnaires returned by 61% of mothers in 2010. Children with only 1-word or unintelligible utterances were rated as having severe language delay. Children who could only produce 2- to 3-word phrases were rated as having moderate language delay, an outcome that is less readily interpreted than severe delay. Children producing fairly complete sentences were rated as having no language delay. Among a total of 38,954 children, 204 (0.5%) had severe language delay. Of the reference group (24%) who took no dietary supplements, 81 (0.9%) had severe language delay. (In Norway, foods are not fortified with folic acid).

Relative risks of severe language delay by estimating odds ratios for 3 patterns of exposure to folic acid were (1) 0.9% [OR 1.04] in children of mothers taking other supplements but no folic acid; (2) 0.4% [0.55] for those taking folic acid only; and (3) 0.4% [0.55] for those taking folic acid and other supplements. The adjusted ORs and risk of moderate language delay for the three groups were 1.04, 0.82, and 0.79, respectively. Maternal use of folic acid supplements in early pregnancy, 4 weeks before to 8 weeks post-conception, was associated with a reduced risk of severe language delay in children at age 3 years. Maternal reports and Vineland test scores for receptive and expressive communication skills in a subsample of 425 children were highly correlative. A higher proportion of children with severe language delay had not yet attained expected motor skills at 18 months and 3 years, but use of folic acid supplements was not correlated with attainment of gross motor skills. [1]

COMMENT. Periconceptional folic acid supplements are known to reduce risk of neural tube defects [2], but the present study is considered the first to demonstrate effects on language development. The average child usually says his first word by 1 year, and delay beyond 18 months may indicate a severe physical, mental or hearing handicap. Failure to put 2 or 3 words together in short phrases by 2 years and sentences by age 3 years is a significant delay in language development. Adequate hearing is the first requisite for normal language development. If the hearing is normal, the differential diagnosis includes congenital dysphasia, mental retardation, and infantile autism. The brain MRI, fMRI [3] or pathological studies [4] may uncover subtle cerebral anomalies. An EEG may be indicated to rule out an acquired epileptic aphasia (Landau-Kleffner syndrome) that develops at 2 to 5 years of age.[5] The cause of severe language delay associated with periconceptional folic acid deficiency is unclear. Prenatal effects on brain development [6], and epigenetic dysregulation of gene expression are proposed possible mechanisms. [7]