title: The long-term neurodevelopmental effects of intrauterine antiepiletic drug exposure in children born to women with epilepsy
Creators: name: Vinten, Jacqueline.
Publisher: name: University of Liverpool Repository
Year: 2023

description: Epilepsy is the most common neurological disease with a prevalence of 5.25 per 1000 for treated epilepsy. One third of this population are women of reproductive age. Approximately 1 in 200 women that attend antenatal clinics in the United Kingdom are receiving antiepileptic medication. At present it is difficult to provide pre-conceptual advice regarding the safest antiepileptic medication to take during pregnancy. Previous research has reported a 2-3 fold increase in major malformations in children born to women with epilepsy, compared to the general population. A growing number of both retrospective and prospective studies have documented the psychomotor and cognitive functioning in children exposed to AEDs in utero, with conflicting results reported. Some studies report a high prevalence of developmental delay and cognitive dysfunction associated with AED exposure, others report a transient impairment, and some studies report no deficit. Due to the wide variation of tests that have been applied and the failure of a standardised approach it has been difficult to draw any meaningful conclusions regarding the neurodevelopmental outcomes and the degree of risk associated with intrauterine AED exposure especially for specific drug regimes. The aim of this research was to investigate the long-term differential drug effects on cognitive functioning in children born to women with epilepsy. This was the first large scale study to use an adequate sized group and to provide a neuropsychological profile for the differential drug effects in children aged between 6 months and 16 years, using standardised tests and controlling for confounding factors. This was achieved by assessing 356 children aged 6 months to 16 years born to women with epilepsy. Each child received a medical examination that documented any malformations and dysmorphic features associated with exposure to AEDs. The neurop~chological assessment included the Wechsler Intelligence Scale for Children (WISC-III ), to assess intellectual functioning, The Schedule of Growing Skills II (SGS II), to assess development, the Rivermead Behavioural Memory Test for Children (RBMT -C), to assess everyday memory functioning and in order to assess each child's behaviour each parent was interviewed using the Vineland Adaptive Behaviour Scale (VABS) and stress in the parent-child relationship was measured using the Parenting Stress Index (PSI). The results for this study indicate that intrauterine exposure to valproate monotherapy and valproate as part of polytherapy is associated with an increase risk of: malformations, dysmorphic features, developmental delay, impaired verbal intelligence, impaired memory functioning, special educational needs, behavioural problems and stress in the parent-child relationship. In light of these findings it is essential that more adequately controlled prospective studies are conducted in order to assess the teratogenic risks associated with the established and newer AEDs so that pre-conceptual counselling can be provided regarding the teratogenic risks to the unborn child.