Comprehensive review of Tdap vaccine during pregnancy confirms infant protection, maternal safety

A comprehensive systematic review and meta-analysis of more than 14,000 papers and 91 peer-reviewed studies has reaffirmed that receiving the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy provides essential protection for newborns while maintaining a rigorous safety profile for both mother and child. The analysis, conducted by the Vaccine Integrity Project at the University of Minnesota’s Center for Infectious Disease Research and Policy in partnership with the Evidence Foundation, represents the most current scientific evidence base, including 62 new studies published between 2020 and March 2026.^1,2

The findings arrive as pertussis rates in the United States have reached a critical threshold, exceeding prepandemic levels with more than 28,000 cases reported in 2025. Because the primary infant vaccination series of DTaP does not begin until 2 months of age, infants younger than 3 months remain at the highest risk for severe morbidity and mortality. According to the review, 41% of infants younger than 6 months who contracted pertussis in 2025 required hospitalization, compared with only 3% of children aged 1 to 6 years. Maternal immunization serves as the primary clinical intervention to bridge this "immunity gap" by facilitating the passive transfer of maternal antibodies across the placenta.

Clinical efficacy in preventing neonatal disease

The meta-analysis suggested that maternal Tdap vaccination significantly reduces the risk of laboratory-confirmed pertussis in infants. The combined estimate shows a relative risk reduction of 0.27 (95% CI; 0.17 to 0.41) compared with infants whose mothers were not vaccinated. In practical terms, during periods of high baseline risk, such as the levels seen in 2025, vaccination was estimated to prevent 146 infections per 100,000 infants.

The review also addressed the rare but severe outcome of infant mortality. One nonrandomized study included in the analysis reported a 95% vaccine efficacy against infant death from pertussis. Researchers noted that the high antibody levels found in infants at birth following maternal vaccination are sufficient to support protection until they can begin their own routine series at 8 weeks of age.

“The data show that Tdap vaccination during pregnancy is an effective way to protect infants from a serious disease at a time when they are most at risk,” said Rochelle Walensky, MD, MPH, the Vaccine Integrity Project’s medical adviser and professor of medicine at Harvard Medical School. “The safety profile remains consistently strong across a large body of research, giving prospective parents confidence that they can safely protect their newborns.”

Robust safety outcomes across pregnancy

A primary objective of the review was to assess potential associations between Tdap and adverse pregnancy or neonatal events. After analyzing 8 randomized controlled trials and 25 high-quality observational studies that adjusted for critical confounders—including maternal age, body mass index, preexisting hypertension, and smoking history—researchers found no meaningful difference in risk across a broad spectrum of outcomes.

For maternal health, the data showed no increased risk of preeclampsia, eclampsia, gestational diabetes, or chorioamnionitis. Regarding birth outcomes, the review found rates of preterm birth and low birth weight were similar between vaccinated and unvaccinated populations. Specifically, for stillbirth (fetal death at 20 weeks’ gestation or later), the pooled estimate from randomized trials showed an 18% relative risk reduction (RR: 0.82), whereas observational data from nearly 1 million pregnancies showed a 46% reduction (RR: 0.54). Researchers clarified that due to the low baseline risk of stillbirth, these figures indicate no meaningful increase in risk, providing strong reassurance for clinical practice.

The review concludes that the public health benefits of Tdap vaccination during every pregnancy far outweigh the theoretical risks. The findings support the current Centers for Disease Control and Prevention recommendation to administer the vaccine between 27 and 36 weeks’ gestation, ideally at 28 weeks to optimize antibody transport.

“As clinicians and policy makers consider vaccine recommendations, this review provides a comprehensive and up-to-date assessment of the evidence,” added Walensky. The report emphasizes that while limitations exist in measuring extremely rare outcomes, the overall consistency across 91 studies supports the continued use of Tdap in obstetric care.

References

1. New evidence review affirms Tdap vaccine protects infants during highest-risk period for whooping cough. News release. Vaccine Integrity Project. May 13, 2026. Accessed May 13, 2026. https://vaxintegrity.cidrap.umn.edu/new-evidence-review-affirms-tdap-vaccine-protects-infants-during-highest-risk-period-whooping-cough
2. Safety and effectiveness of tetanus-diphtheria-acellular pertussis (Tdap) vaccination during pregnancy: a systematic review and meta-analysis. Vaccine Integrity Project. Accessed May 13, 2026. https://vaxintegrity.cidrap.umn.edu/sites/default/files/FINAL%20REPORT%20Tdap%20Vaccine%20in%20Pregnancy%20Evidence%20Review.pdf