Folic acid dose, valproate, and fetal malformations

•The ‘appropriate’ folic acid dose for pregnant women with epilepsy is debated.•No relationship noted between folate dose and protection against birth defects.•High-dose folic acid may not reduce risk of AED-induced anatomical teratogenesis.•Future studies may determine if high-dose folate may reduc...

Full description

Saved in:
Bibliographic Details
Published in:Epilepsy & behavior 2021-01, Vol.114 (Pt A), p.107569, Article 107569
Main Authors: Vajda, Frank J.E., O'Brien, Terence J., Graham, Janet E., Hitchcock, Alison A., Perucca, Piero, Lander, Cecilie M., Eadie, Mervyn J.
Format: Article
Language:English
Subjects:
Abnormalities, Drug-Induced - epidemiology
Abnormalities, Drug-Induced - etiology
AED dosage
Anticonvulsants - adverse effects
Australia
Female
Fetal malformation
Folic Acid
Humans
Pregnancy
Pregnancy Complications - drug therapy
Spina bifida
Valproate
Valproic Acid - adverse effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•The ‘appropriate’ folic acid dose for pregnant women with epilepsy is debated.•No relationship noted between folate dose and protection against birth defects.•High-dose folic acid may not reduce risk of AED-induced anatomical teratogenesis.•Future studies may determine if high-dose folate may reduce behavioural teratogenesis. 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. 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. 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). 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.
ISSN:1525-5050
1525-5069
DOI:10.1016/j.yebeh.2020.107569