Publication date: Jun 10, 2025

Although multiple post-licensure studies demonstrated that coronavirus disease-2019 (COVID-19) vaccines are safe for use during pregnancy, none of them have identified a signal of disproportionate reporting. To assess the disproportionality in reported adverse events among pregnant persons receiving COVID-19 vaccination compared with influenza vaccines in spontaneous reporting databases. Individual case safety reports (ICSRs) with COVID-19 vaccines (Pfizer, AstraZeneca, Moderna and Johnson & Johnson) and influenza vaccines were retrieved from spontaneous reporting databases in the Vaccine Adverse Event Report System (VAERS) and the EudraVigilance (EV) system between 1 December 2020 and 31 October 2023. Both datasets were combined through a common data model. Pregnancy-associated ICSRs were identified using adaptations to the European Medicines Agency (EMA) algorithm based on age groups and key medical conditions. We compared the disproportionate reporting of High-Level Terms (HLT) after COVID-19 vaccines of interest (e. g. mRNA vaccine) with another COVID-19 viral vector-based/protein subunit and influenza vaccines during pregnancy. The proportional reporting ratio (PRR) with 95% confidence intervals (CIs) was calculated using a combined dataset. PRR met the predefined criteria (PRR ≥ 2, lower 95% CI ≥ 2 and N ≥ 3), confirming a potential signal of disproportionate reporting (SDR). A total of 22,383 pregnancy-related ICSRs were included. Five associations met the PRR threshold: inborn errors of steroid synthesis 35. 1 (95% CI 7. 8-158. 3); non-site-specific embolism and thrombosis 15. 9 (95% CI 3. 1-82. 2); general signs and symptoms not elsewhere classified (NEC) 11. 17 (95% CI 3. 3-38. 1); peripheral nervous system disorders congenital NEC 4. 2 (95% CI 2. 3-7. 7); and vascular anomalies congenital NEC 3. 7 (95% CI 2. 4-5. 6), all associated with viral vector-based/protein subunit. Despite this analysis, several statistical disproportionalities were identified during pregnancy; the case-by-case analysis shows that embolism and thrombosis require prioritized investigation through proper causal inference studies.

Semantics

Original Article