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Updated: Nov 27, 2025

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Folic acid dose, valproate, and fetal malformations
Frank J E Vajda1, Terence J O'Brien2, Janet E Graham3
1Departments of Medicine and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.
Objective:
To determine whether there is a relationship between folic acid dose and the degree of protection against valproate-associated and other antiepileptic drug (AED)-associated fetal structural malformations in women with AED-treated epilepsy.
Methods:
Statistical analysis of data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy involving 2104 folic acid-treated pregnancies in women with epilepsy.
Results:
Multiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (P = 0.640) or during early pregnancy only (P = 0.801), and in reducing spina bifida occurrence rates (P = 0.409).
Conclusions:
In the present state of knowledge, it would seem misguided to hope that a folic acid dose of 5 mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations. Future studies are required to determine whether high-dose periconceptional folate use may decrease the risk of other valproate-associated adverse fetal outcomes, including impaired post-natal neurobehavioral development.
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