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

Abstract

The purpose was to examine the consequences of antiepileptic drug (AED) exposure during pregnancy on language abilities in children aged 5 and 8years of mothers with epilepsy. 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 8years, in questionnaires with validated language screening tools. AED concentrations in gestation week 17-19 and in the umbilical cord were measured. The study population included 346 AED-exposed and 388 AED-unexposed children of mothers with epilepsy, and 113674 children of mothers without epilepsy. Mothers of 117 and 121 AED-exposed children responded to the questionnaires at age 5 and 8years, respectively. For AED-exposed children, the adjusted odds ratio for language impairment was 1.6 [confidence interval (CI) 1.1-2.5, P=0.03] at age 5years and 2.0 (CI 1.4-3.0, P<0.001) at age 8years, 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 8years (adjusted odds ratio 3.8, CI 1.6-9.0, P=0.002). Higher maternal valproate concentrations correlated with language impairment at age 5years. Periconceptional folic acid supplement use protected against AED-associated language impairment. Foetal AED exposure in utero is associated with an increased risk of language impairment in children aged 5 and 8years of mothers with epilepsy. Periconceptional folic acid use had a protective effect on AED-associated language impairment.