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.
Methods:The male Wistar rats (200-250 g) were trained for Morris water maze (MWM), passive avoidance (pA) and elevated plus maze (EPM) test and baseline trials conducted before subjecting to pentylenetetrazole (pTZ)induced kindling. SV and LEV were used in combination with SRT and ESC to evaluate effect on seizure development, cognition, and biochemical parameters. SRT (25 mg/kg), ESC (15 mg/kg), SV (150 mg/kg), and LEV (300 mg/kg) were injected daily at the same time and seizure stimuli given every alternate day 4-h,1-h, and 30 minutes, respectively, after dosing with above drugs. On day 49, retention trials performed, rats sacrificed, and blood and brains collected for malondialdehyde (MDA) and glutathione (GSH) estimation.Results: SRT 25 mg/kg per se showed no protective effect, with SRT and LEV 12.5% and ESC and SV group none of the rats were kindled. In EPM, kindling increased transfer latency and drug treatments were ineffective. In PA, kindling did not alter transfer latency but SRT alone and SRT + LEV treatment decreased it as compared with baseline (p < 0.001). On combining SRT with LEV, opposite effects in MWM and PA were observed. There was a significant decrease in level of MDA in SRT as well as ESC + SV group as compared with normal control on day 49.Conclusion: Use of antidepressants in PWE has to be done cautiously as their effect on seizure and cognitive impairment may vary.
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