Valproate Teratogenicity — RACP Adult Medicine MCQ

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EasyClinical PharmacologyValproate TeratogenicityRACP Adult Medicine

A 30-year-old woman with epilepsy on sodium valproate becomes pregnant. She is at 6 weeks gestation. Which congenital abnormality is most specifically associated with in-utero valproate exposure?

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Correct answer: D — Neural tube defects

Valproate has the highest teratogenic risk of all antiepileptic drugs (major congenital malformation rate ~10% at standard doses, higher at >1000 mg/day). Neural tube defects (especially spina bifida) are the most characteristic. Valproate also causes a foetal valproate syndrome (facial dysmorphism, developmental delay) and is associated with reduced IQ. It should be avoided in women of childbearing potential. If unavoidable, high-dose folate (5 mg/day) is recommended pre-conception, though evidence of efficacy for valproate-associated NTDs is limited.

Reference: eTG – 2025 – Neurology; AMH – 2025 – Antiepileptics in Pregnancy; TGA – 2024 – Valproate Safety Update