Folic Acid Supplementation May Protect Against Language Delay in AED-Exposed Children

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The odds of language delay were lower at 18 months and 36 months in children exposed to AEDs in utero whose mothers took folic acid.
The odds of language delay were lower at 18 months and 36 months in children exposed to AEDs in utero whose mothers took folic acid.

Pregnant women who take supplementation with folic acid prior to conception and during early pregnancy are less likely to have children with language delays, particularly if these children were exposed to antiepileptic drugs (AEDs) in utero, according to a study published in Neurology.

The Norwegian Mother and Child Cohort study included women with epilepsy whose children had in utero AED exposure (n=335) and women without epilepsy and their unexposed children (n=104,222). Parents completed questionnaires designed to obtain information on their medical history, AED use, and folic acid supplementation during pregnancy. Additionally, researchers assessed mothers' blood samples at gestational weeks 17 to 19 and following birth for maternal plasma folate and maternal plasma and umbilical cord AED concentrations, respectively. The investigators also assessed language development at 18 months and 36 months using the Ages and Stages Questionnaire.

AED-exposed children of mothers with no maternal periconceptional folic acid supplementation were significantly more likely to exhibit language delays at 18 months (odds ratio [OR] 3.9; 95% CI, 1.9-7.8; P <.001) and 36 months (OR 4.7; 95% CI, 2.0-10.6; P <.001) compared with children of mothers who did not have epilepsy. The odds of language delay were lower at 18 months (OR 1.7; 95% CI, 1.2-2.6; P =.01) and 36 months (OR 1.7; 95% CI, 0.9-3.2; P =.13) in children exposed to AEDs in utero whose mothers took folic acid. The preventive effect of folic acid supplementation on language delay in children exposed to AEDs was significant if folic acid was taken approximately 4 weeks prior to conception and to the end of the first trimester.

The unequal number of patients in each arm and the lack of data on familial language development risk represented 2 limitations of the study.

Study findings emphasize the routine prescription and “daily folic acid intake in all women on AEDs who are likely to become pregnant to decrease the risk of AED-mediated language delay.”

Reference

Husebye ESN, Gilhus NE, Riedel B, Spigset O, Daltveit AL, Bjørk MH. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018;91:e811-e821.

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