A Pharmacogenomics study of the teratogenicity valproate based on the prospective Australian Register for Anti-epileptic Drugs in Pregnancy

Project Aims: Identify genetic markers that predict the risk of valproate-induced birth defects. It is recognised that women with epilepsy who become pregnant while taking an anti-epileptic drug (AED) have an increased risk of having a foetus or infant with a birth defect (BD). This is particularly high for valproate. Despite the increased risk associated with taking AED in pregnancy, most women with epilepsy who become pregnant, or plan to do so soon, cannot simply cease the drugs because of the risk to the health and safety of the mother and child of uncontrolled seizures. The development of methods that would allow the prediction that a specific drug would be associated with a higher risk of a birth defect in a particular woman would be of great potential benefit. There is evidence from family and twin studies that genetic factors may play a role in determining predisposing an individual to having a child with an AED associated birth defect. Clinical research utilizes a cohort of >2000 pregnant women enrolled in the Australian Pregnancy Register of Antiepileptic Drugs. This is a prospective, voluntary, telephone interview based study that enrols pregnant women with epilepsy, prior to the outcome of the pregnancy being known, and follows the outcomes of their pregnancies and relates this to genomic information. Basic research investigates the effects of antenatal exposure to valproate on brain gene expression changes in babies in an animal model of epilepsy.