Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality

Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunat ely its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore childre n with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.