Enduring language deficits in children of women with epilepsy and the potential role of intrauterine exposure to antiepileptic drugs

Abstract

Objective: Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9-13 years in comparison with their peers, and its relationship with intrauterine AED exposure. Methods: We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records. Results: The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% confidence interval [CI] = −8.8 to −0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = −13.8 to −0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (−14.7, 95% CI = −23.1 to −6.4, P = .001) as compared to carbamazepine. Significance: Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

Neurodevelopment Following Exposure to Antiseizure Medications in Utero: A Review

“…Despite a relatively small group size (n=22), the effect difference was relatively large at 8 IQ points in comparison to control children and was replicated when phenobarbital use in polytherapy (n=69) was considered [ 48 ]. Further, recent work from this group has documented enduring language difficulties in children exposed to monotherapy and polytherapy phenobarbital [ 71 ].…”

What Should We Do When the Kids Grow Up? Studying the Long-Term Cognitive Effects of In-Utero Anti-Seizure Medication Exposure

“…In the article that is the focus of this commentary, the authors report on the language scores of 191 children born to mothers with epilepsy (CWE) when the children were between the ages of 9 and 13. 6 The control group in this study was a group of 144 children randomly selected from 2 schools in the regional school district. This study complements a similar study from KREP that focused on IQ scores of their cohort in the same age group.…”

Valproate usage in pregnancy: An audit from the Kerala Registry of Epilepsy and Pregnancy

“…[1][2][3][4][5][6] Furthermore, children exposed in utero to VPA have lower intelligence when examined at 1 year, 7 3 years, 8 6 years, 9 and as late as 12 years of age. 10,11 They are also at increased risk of autism spectrum disorders. 12 On the basis of the present data, the structural and functional teratogenicity of VPA is considered to be high.…”

“…About 9% of children exposed to VPA in utero have been reported to develop MCMs, including neural tube defects, cardiac malformations, cleft palate and lip, and hypospadias 1–6 . Furthermore, children exposed in utero to VPA have lower intelligence when examined at 1 year, 7 3 years, 8 6 years, 9 and as late as 12 years of age 10,11 . They are also at increased risk of autism spectrum disorders 12 .…”