Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero - The Norwegian Mother and Child Cohort Study.

BACKGROUND: To examine the consequences of antiepileptic drug (AED) exposure during pregnancy on language abilities in children of mothers with epilepsy aged 5 and 8 years.

METHODS: The study population included children of mothers with and without epilepsy enrolled in the Norwegian Mother and Child Cohort study 1999-2008. Mothers prospectively provided information on epilepsy diagnosis, AED use during pregnancy, and the child's language abilities at age 5 and 8 years, in questionnaires with validated language screening tools. We measured AED concentrations in gestation week 17-19 and the umbilical cord.

RESULTS: The study population included 346 AED-exposed and 388 AED-unexposed children of mothers with epilepsy, and 113,674 children of mothers without epilepsy. Mothers of 117 and 121 AED-exposed children responded to the questionnaires at age 5 and 8 years, respectively. For AED-exposed children, the adjusted odds ratio (aOR) for language impairment was 1.6 (CI 1.1-2.5, p=0.03) at age 5 years and 2.0 (CI 1.4-3.0, p<0.001) at age 8 years, compared to children of mothers without epilepsy. Children exposed to carbamazepine monotherapy had a significantly increased risk of language impairment compared to control children at age 8 years (aOR 3.8, CI 1.6-9.0, p=0.002). Higher maternal valproate concentrations correlated with language impairment at age 5 years. Periconceptional folic acid supplement use protected against AED-associated language impairment.

CONCLUSION: Fetal AED exposure in utero is associated with an increased risk of language impairment in children of mothers with epilepsy aged 5 and 8 years. Periconceptional folic acid use had a protective effect on AED-associated language impairment.