Dual Maternal Immunization During Pregnancy (Tetanus, Diphtheria, and Acellular Pertussis and Influenza): Maternal–Fetal Clinical Effectiveness, Timing Effects, and Safety – A Systematic Review and Meta-analysis

Abstract Maternal vaccination during pregnancy is a key strategy to prevent severe influenza and pertussis in mothers and young infants. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-2020 systematic review and meta-analysis of dual maternal immunization with inactivated/recombinant influenza vaccines and tetanus, diphtheria, and acellular pertussis (Tdap). Searches of PubMed, Scopus, Web of Science, and guideline repositories (American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, Royal College of Obstetricians and Gynaecologists, World Health Organization, Perhimpunan Obstetri dan Ginekologi Indonesia) through September 2025 had no language restrictions. Eligible designs included randomized trials, cohort, case–control, test-negative studies, and meta-analyses assessing maternal or fetal/neonatal outcomes. Two reviewers independently screened, extracted, and assessed risk of bias (ROB-2, ROBINS-I, AMSTAR-2); certainty was rated with Grading of Recommendations, Assessment, Development and Evaluations. From 2,220 records, 46 studies met inclusion; 25 were core studies for detailed appraisal. Maternal influenza vaccination in any trimester reduced laboratory-confirmed infection and hospitalization, and lowered infant influenza within the first 6 months of life. Tdap administered at 27–36 weeks’ gestation reduced pertussis in infants <6 months, with earlier vaccination within that window enhancing transplacental antibody transfer. Across large datasets, there was no increase in adverse obstetric outcomes or major congenital anomalies; co-administration was tolerated. Some studies noted mild blunting of infant responses to routine vaccinations after maternal Tdap, but this did not translate into worse clinical outcomes. Limitations include the absence of formal protocol registration (e.g., PROSPERO), heterogeneity of study designs that may affect synthesis, and limited long-term follow-up beyond infancy. The evidence supports dual maternal immunization as safe, effective, and time-sensitive. Public health implementation should emphasize equitable access, timing optimization, and integration within antenatal care to strengthen global maternal–infant protection.