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Updated: Dec 22, 2025
03:19
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
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Valproate and folate: Congenital and developmental risks.
Edward H Reynolds1, Ralph Green2
1Department of Clinical Neurosciences, King's College, London, UK.
Epilepsy & Behavior : E&B
|May 7, 2020
Summary
Sodium valproate (VPA) use in pregnancy poses risks due to interference with folate metabolism. Standard folic acid doses may be insufficient; higher doses and vitamin B12 are recommended for at-risk pregnancies.
Area of Science:
- Pharmacology
- Developmental Biology
- Nutritional Science
Background:
- Sodium valproate (VPA) is associated with significant congenital and developmental risks.
- European guidelines recommend avoiding VPA in pregnancy when alternatives exist.
- Periconceptual folic acid is known to reduce neural tube defects (NTDs).
Purpose of the Study:
- To review evidence linking VPA to folate metabolism disruption.
- To assess VPA's contribution to congenital/developmental issues via folate pathways.
- To evaluate the adequacy of standard folic acid supplementation against VPA risks.
Main Methods:
- Literature review of VPA's effects on one-carbon metabolism.
- Analysis of VPA's interaction with folate receptors in brain and placenta.
- Examination of genetic polymorphisms in one-carbon metabolism and VPA risk.
Main Results:
- VPA interferes with one-carbon metabolism, including methylfolate transport.
- VPA's impact on folate metabolism contributes to observed congenital and developmental problems.
- Genetic variations in folate metabolism increase vulnerability to VPA-induced risks.
Conclusions:
- Standard 400µg folic acid may not fully protect against VPA-induced risks.
- Higher periconceptual folic acid doses (up to 5mg) are proposed for at-risk women.
- Supplementary vitamin B12 may be beneficial due to common deficiencies and additive risks.
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