Drug exposure before and during pregnancy and thromboembolic events: a disproportionality analysis from the FAERS database

Background: Real-world evidence on pregnancy-related thromboembolic events (PTEs) following drug exposure before or during pregnancy remains limited, with most studies based on small-scale retrospective analyses. To assess this association, we conducted a pharmacovigilance study. Methods: We analyzed reports from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. Disproportionality analysis was performed to identify drugs associated with PTEs. Multivariate logistic regression was used to explore factors associated with designated serious outcomes, including disability, life-threatening events, and death. Results: A total of 4,122 reports were included. Disproportionality analysis identified 40 drugs with positive risk signals. The three most prominent were ethinylestradiol-etonogestrel (n = 843; reporting odds ratio [ROR] = 20.12), drospirenone-ethinylestradiol (n = 351; ROR = 19.35), and rofecoxib (n = 121; ROR = 20.62). Multivariate logistic regression showed that ethinylestradiol-etonogestrel (odds ratio [OR] = 2.059; 95% confidence interval [CI]: 1.450–2.923; P < 0.001), rofecoxib (OR = 4.154; 95% CI: 2.693–6.407; P < 0.001), and dinoprostone (OR = 33.375; 95% CI: 9.987–111.534; P < 0.001) were significantly associated with serious outcomes, while drospirenone-ethinylestradiol showed a protective effect (OR = 0.401; 95% CI: 0.286–0.563; P < 0.001). Conclusions: Drawing on the FAERS database, we have provided a list of drugs with risk signals for PTEs in this exploratory study. Our findings highlight the importance of considering both before and during-pregnancy drug exposures when assessing thromboembolism risk. More well-designed studies are warranted for drugs whose association with PTEs is not fully understood.