Adverse Events During Pregnancy Associated with Third Generation Antiseizure Medications: A Real-World Analysis
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Background The third generation antiseizure medications (ASMs) have been widely used in clinical practice due to their safety and effectiveness. Given the scarcity of research on the risks of prenatal exposure to third generation ASMs for maternal and fetal, certain challenges persist. This study investigates the frequency and rate of pregnancy-related adverse events (PRAEs) associated with third generation ASMs in the FDA Adverse Event Reporting System (FAERS) database. Methods The adverse events (AEs) of ASMs were selected from FAERS database. The reporting odds ratio (ROR), proportional reporting ratio (PRR) and bayesian confidence propagation neural network (BCPNN) were utilized to conduct disproportionality analysis. Additionally, subgroup analyses were conducted to compare the PRAEs between the newer ASMs and reference drugs. Results In total, 48,321 AEs were identified for third-generation ASMs, of which 1,162 reports (2.5%) were PRAEs. The most common PRAEs were abortion spontaneous (33.0%), premature baby (18.3%) and premature delivery (14.4%). Disproportionality analysis revealed ten signals for zonisamide, nine signals for lacosamide, four signals for brivaracetam, three signals for perampanel or rufinamide. The three most frequently reported HLT were “abortion spontaneous”, “gestational age and weight conditions” and “labour onset and length abnormalities”. The strongest PT signals were placental infarction for zonisamide (ROR = 115.4, 95% CI: 56.9–234.0), postmature baby for brivaracetam (ROR = 83.1, 95% CI: 26.5–261.1), and stillbirth for rufinamide (ROR = 83, 95% CI: 50.5–136.4). Notably, we revealed that zonisamide was related with placental abnormalities, including placental disorder and infarction. These disproportionality signals varied across different subgroup analyses. Conclusions In comparison with second-generation ASMs, newer ASMs demonstrate a comparable safety profile in pregnant women with epilepsy (PWWE). However, caution must be exercised in clinical medication, with close attention paid to the adverse reactions indicated by the risk signals of each drug. Additional prospective cohort studies should be conducted to validate these findings.
