Investigation of spontaneous abortion and stillbirth adverse events in epilepsy patients treated with levetiracetam: A pharmacovigilance study

Qi Wang; Hao Sun; Jie Huang; Yanjie Chen; Jiameng Ni; Zaixiang Tang; Jingfang Liu

doi:10.1016/j.yebeh.2024.110077

Investigation of spontaneous abortion and stillbirth adverse events in epilepsy patients treated with levetiracetam: A pharmacovigilance study

Epilepsy Behav. 2024 Oct 11:160:110077. doi: 10.1016/j.yebeh.2024.110077. Online ahead of print.

Authors

Qi Wang¹, Hao Sun², Jie Huang², Yanjie Chen², Jiameng Ni², Zaixiang Tang³, Jingfang Liu⁴

Affiliations

¹ Department of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China; Department of Biostatistics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China.
² Department of Biostatistics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China.
³ Department of Biostatistics, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China. Electronic address: tangzx@suda.edu.cn.
⁴ Department of Gynecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China. Electronic address: liujingfang0929@163.com.

PMID: 39395296
DOI: 10.1016/j.yebeh.2024.110077

Abstract

Background: The prescription of levetiracetam during pregnancy has become more common due to its lower teratogenic risk profile. However, due to a lack of data about its association with stillbirth and spontaneous abortion, worries remain.

Objective: To investigate information on any possible association of spontaneous abortion and stillbirth adverse events with levetiracetam in women with epilepsy.

Methods: This retrospective pharmacovigilance study used disproportionality analysis to detect signals of adverse reaction of interest reported with Levetiracetam in FAERS, the FDA Adverse Event Reporting System. The ratio of reporting odds (ROR) and information component (IC) indices were used to undertake disproportionality analyses, and change point analyses were carried out to identify variations in the frequency of reporting of relevant adverse events. Sensitivity analyses included subgroup analyses by indication, treatment regimen, and reporting region.

Results: Overall, 2870 cases of spontaneous abortion and stillbirth with commonly used antiseizure medications were analyzed. A total of 65.5 % of these cases had epilepsy as the indication. In the entire dataset, we observed disproportionality signals of spontaneous abortion for 6 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, topiramate, valproic acid) and disproportionality signals of stillbirth for 4 ASMs (levetiracetam, carbamazepine, lamotrigine, oxcarbazepine). In the epileptic population, disproportionality signals for stillbirth (ROR_0.25 = 4.60; IC_0.25 = 1.30) and spontaneous abortion (ROR_0.25 = 3.98; IC_0.25 = 1.20) in levetiracetam was identified. These disproportionality signals have been consistently robust over the past years, according to a temporal assessment of them. Sensitivity studies proved how reliable the findings were.

Conclusion: Using validated pharmacovigilance methods, we found significant disproportional signals for spontaneous abortion and stillbirth associated with levetiracetam. Of these, the signals for spontaneous abortion were observed after 2011 and for stillbirth after 2014, which may be related to the rise in levetiracetam prescriptions during pregnancy in recent years. The association of spontaneous abortion and stillbirth adverse events with levetiracetam and potential biases confounding this association merit further investigation.

Keywords: Epilepsy; FAERS; Levetiracetam; Spontaneous abortion; Stillbirth.