Dose dependence of fetal malformations associated with valproate

Vajda, Frank J., O'Brien, Terence J., Graham, Janet E., Lander, Cecilie M. and Eadie, Mervyn J. (2013) Dose dependence of fetal malformations associated with valproate. Neurology, 81 11: 999-1003. doi:10.1212/WNL.0b013e3182a43e81

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Author Vajda, Frank J.
O'Brien, Terence J.
Graham, Janet E.
Lander, Cecilie M.
Eadie, Mervyn J.
Title Dose dependence of fetal malformations associated with valproate
Journal name Neurology   Check publisher's open access policy
ISSN 0028-3878
Publication date 2013-09-10
Year available 2013
Sub-type Article (original research)
DOI 10.1212/WNL.0b013e3182a43e81
Open Access Status
Volume 81
Issue 11
Start page 999
End page 1003
Total pages 5
Place of publication Philadelphia, United States
Publisher Lippincott Williams & Wilkins
Collection year 2014
Language eng
Formatted abstract
Objective: To study the relationships between maternal valproate dose in pregnancy and the pattern of various fetal malformations.

Methods: Analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy collected from 1999 to 2012. The specific type of fetal malformation in offspring exposed to valproate in utero was correlated with the dose of valproate taken by the mother in the first trimester.

Results: Compared with other malformations, the mean dose of valproate taken during the first trimester was higher in mothers whose offspring had spina bifida (2,000 ± 707 vs 1,257 ± 918 mg/d) and hypospadias (2,417 ± 1,320 vs 1,235 ± 715 mg/d) (both p < 0.05). The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period. This was paralleled by a statistically significant decrease in the rate of occurrence of spina bifida and hypospadias, but not other malformations.

Conclusions: Human fetal malformations associated with valproate exposure during pregnancy do not all seem to bear the same quantitative relationship to drug dose, and reduction in valproate dose in earlier pregnancy is likely to offer greater dividends in protecting against spina bifida and hypospadias than against other types of fetal malformations.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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