The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy

Frank J E Vajda; Terence J O'Brien; Janet E Graham; Alison A Hitchcock; Cecilie M Lander; Mervyn J Eadie

doi:10.1016/j.yebeh.2021.107941

The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy

Epilepsy Behav. 2021 May:118:107941. doi: 10.1016/j.yebeh.2021.107941. Epub 2021 Apr 11.

Authors

Frank J E Vajda¹, Terence J O'Brien², Janet E Graham³, Alison A Hitchcock³, Cecilie M Lander⁴, Mervyn J Eadie⁴

Affiliations

¹ Department of Medicine and Neurosciences, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Alfred Health, and Monash University, Melbourne, Vic 3004, Australia. Electronic address: vajda@netspace.net.au.
² Department of Neuroscience, Alfred Health, and Monash University, Melbourne, Vic 3004, Australia.
³ Department of Medicine and Neurosciences, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria 3050, Australia.
⁴ Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland 4027, Australia.

PMID: 33852986
DOI: 10.1016/j.yebeh.2021.107941

Abstract

Purpose: To assess the possible contribution of factors in additional to intrauterine anti-seizure medication (ASM) exposure in the occurrence of fetal malformation in women with ASM-treated epilepsy.

Results: Logistic regression analysis showed that maternal age over 31 years, family histories of fetal malformation, and conception after assisted fertility treatment, and also dosage of valproate, carbamazepine, and topiramate, made statistically significant (P<0.05) contributions to the fetal malformation rate in 2223 pregnancies in Australian women with epilepsy. The malformation rates were lower in pregnancies where the non-ASM-associated contributory factors were not present: statistically significantly so for all ASM-exposed pregnancies, and those pregnancies exposed to the more potent teratogenic drugs.

Conclusion: It is important to consider the possible roles of identified, and also possible non-identified, non-ASM factors in relation to the occurrence of fetal malformations in the pregnancies of women with ASM-treated epilepsy.

Keywords: Age; Anti-seizure medications; Fetus; Malformation; Non-drug factors; Teratogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abnormalities, Drug-Induced* / epidemiology
Abnormalities, Drug-Induced* / etiology
Adult
Anticonvulsants / adverse effects
Australia / epidemiology
Epilepsy* / drug therapy
Female
Humans
Pregnancy
Pregnancy Complications* / drug therapy
Valproic Acid / adverse effects

Substances

Anticonvulsants
Valproic Acid