A 28-year-old woman with a history of migraine, bipolar disorder, and epilepsy is considering starting valproate. The prescriber must counsel her primarily about which teratogenic risk?
- A Neural tube defects (spina bifida) due to inhibition of folate metabolism and histone deacetylase ✓
- B Fetal hypoglycemia due to stimulation of fetal β cells
- C Cardiac septal defects due to blockade of Na+ channels in the developing myocardium
- D Ebstein anomaly of the tricuspid valve
Correct answer: A. Neural tube defects (spina bifida) due to inhibition of folate metabolism and histone deacetylase
Explanation
Valproate carries the highest teratogenic risk among antiepileptics: neural tube defects (spina bifida, approximately 1–2% risk vs. background 0.03%) occur because valproate inhibits histone deacetylase, disrupts folic acid metabolism, and impairs neural tube closure in early embryogenesis (weeks 3–4). It also causes cognitive teratogenicity (reduced IQ). Lithium is associated with Ebstein anomaly. Cardiac septal defects are linked to phenytoin. Fetal hypoglycemia is a concern with insulin secretagogues.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.