The Role of COVID-19 Vaccination in Improving Maternal and Perinatal Outcomes: A Comprehensive Review

Highlights

• COVID-19 vaccination during pregnancy substantially reduces maternal hospitalization, critical care admission, and preterm birth risks across both Delta and Omicron variant periods.
• Vaccination prior to or during pregnancy confers protective benefits without increasing adverse neonatal or maternal outcomes.
• Observational data and meta-analyses consistently support vaccine safety and effectiveness in preventing severe COVID-19 complications during pregnancy.
• Newborn protection improves with maternal vaccination, especially with booster doses administered close to delivery.

Background

The COVID-19 pandemic posed significant challenges for pregnant individuals due to increased susceptibility to severe disease and adverse pregnancy outcomes such as preterm birth and neonatal complications. Initial hesitancy surrounding vaccination in pregnancy stemmed from limited data on safety and effectiveness. Understanding the impact of SARS-CoV-2 vaccination in pregnant populations is crucial to inform guidance and improve maternal and neonatal outcomes globally. The advent of SARS-CoV-2 variants including Delta and Omicron, alongside evolving vaccination recommendations, highlight the need for comprehensive evidence synthesis.

Key Content

Population-level Evidence from the CANCOVID-Preg Surveillance

A pivotal population-level surveillance study utilizing the Canadian CANCOVID-Preg database (McClymont et al., 2025) analyzed 19,899 pregnancies with SARS-CoV-2 infection between April 2021 and December 2022. Of these, 72% were vaccinated prior to COVID-19 diagnosis (80% vaccinated before pregnancy, 20% during pregnancy). Cases spanned the Delta (n=6120) and Omicron (n=13,799) variant periods. Vaccination was associated with a marked reduction in COVID-19-associated hospitalization risk during Delta (RR 0.38; ARD 8.7%) and Omicron (RR 0.38; ARD 3.8%), critical care admissions (Delta RR 0.10; Omicron RR 0.10), and preterm birth (Delta RR 0.80; Omicron RR 0.64). Adjusted analyses controlling for comorbidities confirmed these protective effects. Unvaccinated individuals showed substantially higher hospitalization rates with adjusted relative risks of 3.82 (Delta) and 2.43 (Omicron).

Clinical Outcomes Among Pregnant Hospitalized COVID-19 Patients

The Michigan Medicine COVID-19 Cohort study (Hull et al., 2025) documented that pregnant patients hospitalized for COVID-19 had greater need for respiratory support and higher preterm birth rates compared to non-hospitalized counterparts. Notably, mechanical ventilation was more frequent in unvaccinated patients. High cesarean delivery and neonatal intensive care unit (NICU) admission rates highlighted severe maternal and neonatal morbidity linked to COVID-19 hospitalization. Vaccination was associated with attenuation of these severe outcomes.

Meta-Analyses and Systematic Reviews on Vaccination Safety and Effectiveness

Multiple meta-analyses encompassing hundreds of thousands of pregnant individuals affirm the robust safety profile of COVID-19 vaccines during pregnancy. For example, Chen et al. (2023) analyzed 30 studies involving 862,272 individuals, demonstrating significant reductions in SARS-CoV-2 infection risk (60%), COVID-19 hospitalization (53%), intensive care admission (82%), as well as preterm births and stillbirths without increased risks of miscarriage, congenital anomalies, or other adverse outcomes. Other systematic reviews corroborate these findings, highlighting lowered preterm birth, NICU admissions, and favorable Apgar scores associated with vaccination.

Neonatal Outcomes and Protective Effects of Maternal Vaccination

INTERCOVID-2022, a large multinational prospective cohort study, revealed that neonates born to booster-vaccinated mothers during the Omicron period had significantly reduced rates of neonatal SARS-CoV-2 infection, preterm birth, respiratory distress syndrome, and NICU stay duration. Vaccine effectiveness waned with time, emphasizing the benefit of boosters administered within 14 weeks of delivery to maximize neonatal protection.

Immunologic Insights and Transplacental Antibody Transfer

Studies assessing breast milk antibody titers demonstrate that vaccinated and naturally infected mothers exhibit higher and more sustained anti-Spike immunoglobulins (IgA, IgG) providing passive immunity to infants. Additionally, gestational timing impacts mucosal antibody responses and viral control, with evidence suggesting booster vaccination may bolster mucosal immunity in pregnancy.

Comparisons Across Variant Periods

Retrospective observational data indicate that the Omicron variant generally associates with milder clinical manifestations compared to Delta among pregnant patients, including lower pregnancy loss, preterm birth, and NICU admissions. However, risks of severe maternal outcomes remain elevated compared with non-infected populations, and vaccination maintains protective benefits across variant periods.

Expert Commentary

Accumulating high-quality data convincingly demonstrate that COVID-19 vaccination during pregnancy is both safe and efficacious. The CANCOVID-Preg findings elucidate crucial risk reduction for severe maternal illness and preterm birth conferred by vaccination, irrespective of SARS-CoV-2 variant period. These data address significant gaps and inform clinical guidelines advocating vaccination as standard prenatal care.

There remains the challenge of vaccine uptake due to hesitancy driven by safety concerns, underscoring the need for continual public health messaging and patient education. The observed waning vaccine effectiveness on neonatal protection mandates consideration of optimal timing of booster doses during pregnancy. With evolving variants and vaccine formulations, ongoing surveillance and randomized controlled trials are essential to refine recommendations.

Mechanistically, enhanced humoral immunity from mRNA vaccines and robust transplacental antibody transfer are key in mediating protection against SARS-CoV-2 infection and severity in mothers and neonates. The role of cellular immunity and mucosal antibody responses requires further elucidation.

Conclusion

COVID-19 vaccination before or during pregnancy significantly lowers the risk of severe maternal COVID-19, hospitalization, critical care admission, and adverse perinatal outcomes including preterm birth. Meta-analyses reinforce the excellent safety profile of vaccines in pregnant populations without increased risk of miscarriage, congenital anomalies, or other adverse maternal/neonatal outcomes. Booster vaccination optimizes neonatal protection, particularly near term.

Clinical practice should prioritize vaccination counseling and accessibility for pregnant individuals to mitigate COVID-19-associated maternal and perinatal morbidity and mortality. Future research should focus on long-term outcomes, variant-specific vaccine effectiveness, and strategies addressing vaccination hesitancy.

References

• McClymont E, Blitz S, Forward L, et al.; CANCOVID-Preg Team. The Role of Vaccination in Maternal and Perinatal Outcomes Associated With COVID-19 in Pregnancy. JAMA. 2025 Dec 15:e2521001. doi:10.1001/jama.2025.21001. PMID: 41396589; PMCID: PMC12706698.
• Chen J, Deng Y, He R, et al. Effects of COVID-19 vaccination during pregnancy on SARS-CoV-2 infection and maternal and neonatal outcomes: A systematic review and meta-analysis. Rev Med Virol. 2023 May;33(3):e2434. doi:10.1002/rmv.2434. PMID: 36896895.
• Castaño D, Simões E, Suárez A, et al. Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study. Am J Obstet Gynecol. 2024 Oct;231(4):460.e1-460.e17. doi:10.1016/j.ajog.2024.02.008. PMID: 38367758.
• Hull J, Redeker C, et al. Pregnant hospitalized COVID-19 patients: disease, delivery, maternal and fetal outcomes. BMC Pregnancy Childbirth. 2025 Oct 14;25(1):1089. doi:10.1186/s12884-025-07907-3. PMID: 41087963.
• Chen LH, Dixon S, et al. BNT162b2 mRNA COVID-19 vaccine effectiveness in pregnancy: Emulating trial NCT04754594 using observational data from Norwegian health registries. Vaccine. 2025 Dec 5;68:127908. doi:10.1016/j.vaccine.2025.127908. PMID: 41202612.
• Blitz S, Shalom H, et al. COVID-19 in pregnancy: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss. Hum Reprod Update. 2024 Mar 1;30(2):133-152. doi:10.1093/humupd/dmad030. PMID: 38016805.