Pregnancy-related adverse events and congenital disorders associated with aspirin: A real-world pharmacovigilance analysis of the FDA adverse event reporting system

This study aimed to investigate the reporting association between aspirin use and pregnancy-related adverse events (AEs), and to explore potential disproportionality signals for congenital disorders. A disproportionality analysis was performed using the Food and Drug Administration Adverse Event Reporting System data from Q1 2004 to Q3 2024. Four statistical approaches were applied: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean (EBGM). In addition, 2 sensitivity analyses were performed to verify the robustness of the results by excluding certain confounders. The analysis identified 1647 reports documenting aspirin-associated AEs related to pregnancy and congenital disorders. Eighty-nine high-level term signals were detected, including 19 significant disproportionality signals, with the strongest signals in each category being “fetal growth complications” (n = 139, ROR = 9.89, PRR = 9.88, EBGM = 9.67, information component = 3.27) and “vascular anomalies congenital NEC” (n = 282, ROR = 39.68, PRR = 39.6, EBGM = 36.10, information component = 5.17). At the preferred term level, 269 signals were identified, with 47 significant disproportionality signals. The strongest signals in their respective categories were peripartum hemorrhage (n = 3, ROR = 41.11) and cyclopia (n = 5, ROR = 662.32). Sensitivity analyses, including adjustments for healthcare professional reports and the exclusion of patients with hypertension or gestational hypertension, confirmed the robustness of these signals. In conclusion, this large-scale pharmacovigilance study identified significant disproportionality signals for several pregnancy-related AEs and congenital disorders reported with aspirin use. While these findings provide preliminary signals for further investigation, they cannot establish causality. Clinical decisions should continue to be guided by established guidelines and evidence from randomized controlled trials.