• N Adab, U Kini, J Vinten, J Ayres, G Baker, J Clayton-Smith, H Coyle, A Fryer, J Gorry, J Gregg, G Mawer, P Nicolaides, L Pickering, L Tunnicliffe, and D W Chadwick.
• Department of Neurological Science, The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK. n.adab@virgin.net
• J. Neurol. Neurosurg. Psychiatr. 2004 Nov 1; 75 (11): 1575-83.

ObjectivesTo determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero.DesignRetrospective study of children born to mothers with epilepsy.SettingRegional epilepsy clinics in Liverpool and Manchester, UK.ParticipantsChildren aged between 6 months and 16 years born to mothers with epilepsy.Main Outcome MeasuresStructured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features.ResultsA total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate.ConclusionsThis study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

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