# Risk signal assessment of Tdap vaccine use alone by pregnant women: An updated pharmacoepidemiological study

## TL;DR

This study examines the safety of the Tdap vaccine in pregnant women using 20 years of U.S. data, identifying potential risks like stillbirth and preterm delivery that need further research.

## Contribution

The study identifies novel safety signals such as fetal hypokinesia and chorioamnionitis in Tdap vaccine use during pregnancy using updated VAERS data analysis.

## Key findings

- Strong safety signals for stillbirth, preterm delivery, and fetal death were detected with high ROR values.
- Novel signals like fetal hypokinesia and urinary tract infection emerged as unlabeled risks.
- Pregnancy-specific adverse events accounted for 22.3% of significant outcomes, with most cases having documented obstetric risk factors.

## Abstract

Despite global recommendations for maternal tetanus-diphtheria-acellular pertussis (Tdap) vaccination to protect neonates, safety concerns persist regarding pregnancy-specific adverse events (AEs). We conducted a 20-year analysis of U.S. Vaccine Adverse Event Reporting System (VAERS) data (2005–2024) to characterize Tdap-associated AEs during pregnancy, with emphasis on understudied outcomes like chorioamnionitis.

We analyzed 870 pregnancy-related reports (128 serious) from 20,358 Tdap submissions using disproportionality analysis (Reporting Odds Ratio, ROR). Cases were identified via MedDRA-coded terms and free-text mining. Outcomes were stratified by System Organ Class (SOC), trimester, and AE seriousness. Novel signals were evaluated against product labeling and prior studies.

71.9% of AEs occurred within 30 days post-vaccination. No AEs of maternal death were found. Strong safety signals stillbirth (ROR 285.77, IC 8.01), preterm delivery (ROR 196.8, IC 7.51), and fetal death (ROR 140.83, IC 7.06) were found via disproportionality from a passive surveillance system, which required further validation in active surveillance studies. Pregnancy-specific AEs represented 22.3% of significant PTs, including 6 chorioamnionitis cases with most cases having documented obstetric risk factors. Novel signals fetal hypokinesia and urinary tract infection emerged as unlabeled risks.

This analysis affirms Tdap’s favorable safety profile while detecting statistically significant signals that merit additional research. The low absolute risk supports continued maternal immunization, but warrants enhanced monitoring in high-risk pregnancies. The findings highlight the importance of ongoing post-marketing surveillance for evaluating vaccine safety in pregnant populations and contribute to evidence-based decision-making in clinical practice and public health policy.