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.
Highlights
A total of 335 antiepileptic drug (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
Folic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure
Folic acid supplementation and language delay Without periconceptional folic acid supplementation, 34% of the AED-exposed children had global language delay at 18 months compared to 11% in the control group without maternal epilepsy (p < 0.001)
Summary
Children 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. Study population The study population consisted of women and children included in the Norwegian Mother and Child Cohort Study (MoBa). MoBa is a prospective, ongoing population-based pregnancy cohort study conducted by the Norwegian Institute of Public Health and is linked to the compulsory Medical Birth Registry of Norway (MBRN).. Norwegianspeaking women were invited to participate from 1999 to 2008. Information on background, medical history, medication use, vitamin and folic acid intake, and child development, including language function, was obtained by parent-completed questionnaires.
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