Abstracts

RATIONALE: A systematic review summarisng the existing evidence for the potential adverse effects of antiepileptic drugs (AEDs) on the development of children born to mothers with epilepsy
METHODS: A systematic search of Medline (from 1966) and Embase (from 1988) to December 2001 was conducted to identify case control and prospective controlled cohort studies of the developmental outcome in children born to mothers with epilepsy. An adapted version of the Newcastle-Ottowa scale for non-randomised studies was used for qualitative assessment. Data was extracted from each study for developmental outcomes in children exposed to AEDs per se, monotherapy (MT) and polytherapy (PT) regimes compared to non-exposed children in the general population.
RESULTS: 24 prospective cohort controlled studies were identified. After qualitative assessment 2 studies were excluded, and only 14 were found to be independent studies, with the remainder reporting further follow-up of a related cohort. The population studied, age of follow-up, drug exposure in utero and assessment of the children varied widely amongst the studies making a quantative summary of the data difficult. Whilst the majority of studies examined children between the ages of 8 months and 3.5 years, 8 studies looked at children in the preschool or school age. Most studies reported the effects of AED exposure per se or MT and PT regimes in general without reference to specific regimes. 4 of 7 studies showed a poorer developmental outcome in children exposed to PT in utero in both early and later years compared to MT regimes. 8 studies had data on children exposed to MT in the younger age group, and 5 in the older age group. The numbers exposed were small with most exposures being to phenytoin (PHT) or carbamazepine (CBZ). Only one study included a significant number of children exposed to valproate (VPA). The results of the studies were conflicting. Among 8 studies of PHT exposure, 1 study showed an adverse effect for PHT in early development and 3 an advesre effect in later life. Of the 5 studies of CBZ exposure in utero, 2 studies suggested an adverse effect on development in the first years of life, while 3 studies including older children failed to show a difference. In the one study of VPA exposure in utero, there was a poorer outcome in the first 3 years of life. Few studies icluded data on how common these adverse effects were.
CONCLUSIONS: On the basis of current studies conclusive evidence regarding the relative risks of specific AEDs are fraught with limitations. There is a need to ground advice to women of reproductive age on high quality evidence.This has vital implications for the design and reporting of studies of the longer term risks of AED exposure in utero.
[Supported by: University Department of Neurological Science, University of Liverpool]