Verbal abilities in children of mothers with epilepsy

Abstract

ObjectiveTo examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy.MethodsChildren of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.ResultsA total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9–7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0–10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2–2.6, p = 0.01) and 1.7 (95% CI 0.9–3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester.ConclusionFolic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.

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

“…Nevertheless, a correlation was found between maternal valproate concentrations during pregnancy and language impairment. This is consistent with our previous study of children aged 18 months in the MoBa [12] and with previous reports on dose-dependent valproate-mediated language impairment [4,5,8].…”

“…The protective effect of periconceptional folic acid supplementation on AEDassociated language impairment was highly evident in our study. This protection, previously reported for age 1.5 and 3 years [12] remained equally evident at age 5 and 8 years. This strongly suggests a role of folate in the mechanism of AED-associated language impairment.…”

“…Covariates from the MoBa questionnaires and MBRN based on clinical relevance were included (Table , Appendix S1: Methods S1 and Fig. S1).…”

“…Few studies have examined the influence of AED concentrations during pregnancy on language abilities in older children. It has been shown previously that language impairment and risk of autistic traits at age 1.5 and 3 years depend on maternal plasma AED concentrations and folate status [10][11][12].…”

“…Similarly, children at age 8 years with a result above cut-off for the Language 20 semantic subscale in Q8Y were classified with language impairment. Criteria for language impairment at age 1.5 and 3 years have been described elsewhere [12]. Children who fill criteria for language impairment by any of the screening instruments are recommended for referral for clinical assessment and diagnosis [18][19][20] Covariates Covariates from the MoBa questionnaires and MBRN based on clinical relevance were included [12,21] ( Table 1, Appendix S1: Methods S1 and Fig.…”