Developmental outcomes at age four following maternal antiepileptic drug use

Abstract

We investigated whether prenatal antiepileptic drug (AED) exposure was associated with adverse outcomes in the Before School Check (B4SC) assessments, particularly the assessments measuring neurodevelopment. Children exposed to AEDs were identified by linking women dispensed AEDs in the Pharmaceutical Collection to births recorded on the National Minimum Dataset (NMDS). Multinomial logistic regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for outcomes of the parent-completed Parental Evaluation of Developmental Status (PEDS) questionnaire and Strengths and Difficulties Questionnaire (SDQ), after adjusting for gender, ethnicity, and socioeconomic deprivation. Between 2012 and 2016, 606 children with a mother who had been dispensed one or more AEDs during pregnancy had taken part in the B4SC. Prenatal exposure to sodium valproate (n = 161) or lamotrigine (n = 149) monotherapy was associated with an increased risk of having an abnormal SDQ — parent-completed (SDQP) score, ≥17 — indicating emotional or behavioral concerns (9.32% of children exposed to sodium valproate monotherapy had an abnormal score; aRR: 2.11; 1.23–3.63; lamotrigine 8.05%; aRR: 2.21; 1.21–4.02). Prenatal exposure to carbamazepine monotherapy (n = 201) was not associated with an increased risk of having an abnormal total SDQP score but was associated with increased risks in the individual domains of the SDQP. Prenatal exposure to AED polytherapy (n = 57) was associated with the highest risk of abnormal SDQP scores (17.54% of children exposed to polytherapy had abnormal scores; aRR: 2.75; 1.25–6.02). Prenatal exposure to sodium valproate and lamotrigine is associated with an increased risk of concerns about emotional and behavioral development being reported by parents in a neurodevelopmental screening program. Additional investigation is required into why significant differences between AEDs were not seen in this study.