- Valproic acid is known to have the highest teratogenic risk among antiepileptic drugs (AEDs), particularly for causing neural tube defects (NTDs) such as spina bifida when used during pregnancy.
- This is due to its strong interference with folate metabolism, which is crucial for neural tube closure in early embryonic development.

Here are the key points to consider:
- Valproic acid significantly increases the risk of congenital malformations, with neural tube defects being the most prominent and well-documented.
- Other AEDs such as carbamazepine and phenytoin also carry teratogenic risks but generally at a lower incidence compared to valproic acid.
- Lamotrigine has a better safety profile and is associated with a comparatively lower risk of congenital anomalies.
- The critical period for risk of NTDs is during the first trimester of pregnancy, especially between weeks 3 to 4 of gestation when the neural tube is closing.
- Women of childbearing age on valproic acid should be counseled about the risks and the importance of folic acid supplementation and consideration of alternative AEDs if possible.

Therefore, when managing epilepsy during pregnancy, valproic acid is usually avoided due to its high teratogenic potential, especially for inducing neural tube defects.

Reference: Epilepsy: A Comprehensive Textbook, 2nd Edition, Volume 1, Chapter 32 - Antiepileptic Drugs and Pregnancy, Page 1124-1127