Pregnancy, antiseizure medications and unexplained intrauterine foetal death

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

doi:10.1016/j.yebeh.2024.109724

Pregnancy, antiseizure medications and unexplained intrauterine foetal death

Epilepsy Behav. 2024 Apr:153:109724. doi: 10.1016/j.yebeh.2024.109724. Epub 2024 Mar 4.

Authors

Frank J E Vajda¹, Terence J O'Brien², Janet E Graham³, Alison E Hitchcock⁴, Piero Perucca⁵, Cecilie M Lander⁶, Mervyn J Eadie⁷

Affiliations

¹ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia. Electronic address: [email protected].
² Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia. Electronic address: [email protected].
³ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: [email protected].
⁴ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: [email protected].
⁵ Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC 3084, Australia; Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Heidelberg, VIC 3084, Australia. Electronic address: [email protected].
⁶ Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD 4027, Australia. Electronic address: [email protected].
⁷ Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD 4027, Australia. Electronic address: [email protected].

PMID: 38442517
DOI: 10.1016/j.yebeh.2024.109724

Abstract

Objective: To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR).

Results: IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR. Factors associated with IUFD occurrence included older maternal age, enrolment in the APR at an earlier stage of pregnancy, history of pregnancies which did not result in livebirths, parental history of foetal malformations, and maternal use of carbamazepine, lamotrigine or ethosuximide. Individual ASM dosages were not associated with IUFD occurrence. Relative to no exposure, the risk of IUFD increased with the increasing number of ASMs used in combination (2 ASMs: relative risk, RR = 5.45 [95 % CI: 0.73-41.80]; 3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), >3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), but this finding was attenuated after adjusting for other factors implicated in IUFD occurrence. Several ASM pairs were associated with an increased risk of IUFD relative to no exposure, but these associations were lost after accounting for confounders.

Conclusions: Although it is possible that prenatal ASM exposure may increase the risk of IUFD, other non-pharmacological factors are more relevant to the occurrence to IUFD in pregnant WWE.

Keywords: Antiseizure medications; Carbamazepine, lamotrigine; Intrauterine foetal death; Stillbirth.

MeSH terms

Anticonvulsants / therapeutic use
Australia / epidemiology
Epilepsy* / chemically induced
Epilepsy* / drug therapy
Female
Fetal Death* / etiology
Humans
Pregnancy
Prospective Studies
Stillbirth / epidemiology

Substances

Anticonvulsants