COVID-19 Vaccination Linked to Lower Risk of Severe Outcomes in Pregnancy Across Delta and Omicron Periods

Pregnant individuals who received COVID-19 vaccination before infection experienced significantly lower rates of hospitalization, critical care admission, and preterm birth compared with unvaccinated individuals during both Delta and Omicron variant periods, according to a large Canadian surveillance study published online December 15, 2025, in JAMA.¹

The national population-level study analyzed 19 899 SARS-CoV-2-infected pregnancies from April 2021 through December 2022 across nine Canadian provinces and one territory. Among these cases, 72% were vaccinated and 28% were unvaccinated prior to COVID-19 diagnosis.¹

Substantial Risk Reductions Observed

Vaccination demonstrated consistent protective effects across both variant periods. During the Delta period, vaccinated individuals had a relative risk (RR) of hospitalization of 0.38 (95% CI, 0.30-0.48) compared with unvaccinated individuals—a difference of 8.7 percentage points. The Omicron period showed similar protection, with a RR of 0.38 (95% CI, 0.27-0.53) and an absolute risk difference of 3.8 percentage points.¹

Critical care unit admissions followed the same pattern, with vaccinated individuals experiencing a RR of 0.10 during both Delta (95% CI, 0.04-0.26) and Omicron (95% CI, 0.03-0.29) periods. The absolute risk reduction was 2.4 percentage points during Delta and 0.85 percentage points during Omicron.¹

Preterm birth rates were also lower among vaccinated individuals, with a RR of 0.80 (95% CI, 0.66-0.98) during Delta and 0.64 (95% CI, 0.52-0.77) during Omicron.¹

Multivariable Analysis Confirms Findings

After controlling for comorbid conditions including body mass index, gestational age at diagnosis, and other clinical factors, vaccination remained significantly associated with lower hospitalization risk. During the Omicron period, unvaccinated individuals had an adjusted RR of hospitalization of 2.43 (95% CI, 1.72-3.43) compared with vaccinated individuals. During Delta, the adjusted RR was 3.82 (95% CI, 2.38-6.14).¹

Other independent risk factors for hospitalization included BMI of 30 or greater (RR, 1.46; 95% CI, 1.17-1.83) and gestational age of 28 weeks or more at diagnosis (RR, 6.66; 95% CI, 4.29-10.34) compared with diagnosis at 13 weeks 6 days or less.¹

Study Methodology

The CANCOVID-Preg surveillance program collected data on laboratory-confirmed SARS-CoV-2 infections during pregnancy through public health agencies and provincial databases. Cases were assigned to variant periods based on the dominant circulating variant: Delta (April 5, 2021, to December 20, 2021) and Omicron (December 21, 2021, to December 31, 2022).¹

Among vaccinated cases, 80% received vaccination before pregnancy and 20% during pregnancy. The median time between vaccination and COVID-19 diagnosis was 18 weeks (IQR, 11-25).¹

Most infections occurred among individuals aged 30 to 35 years (46.3%) and those of White race (55.9%). Comorbidities were relatively uncommon, with preexisting asthma present in 6.2%, hypertension in 2.2%, and diabetes in 2.3% of cases.¹

Perinatal Outcomes

Overall, 7.9% of pregnancies resulted in preterm birth. Cesarean delivery rates were similar between vaccinated and unvaccinated groups (approximately 33%). Stillbirth occurred in 0.42% of pregnancies, with no significant difference between vaccination groups. Neonatal intensive care unit admission rates were 11.7% for infants of vaccinated individuals and 13.5% for infants of unvaccinated individuals (P = .005).¹

Among vaccinated individuals, those who received vaccination during pregnancy had lower preterm birth rates compared with those vaccinated before pregnancy (5.93% vs 7.53%; P = .05).¹

Study Limitations

The authors noted several limitations, including potential underascertainment of mild cases during the Omicron period due to decreased formal tracking, missing data on preexisting conditions from Ontario, and the observational study design. Variant assignment was based on epidemiologic data rather than individual-level laboratory confirmation.¹

Clinical Implications

"Vaccination against SARS-CoV-2 prior to and during pregnancy, before COVID-19 diagnosis, was associated with a lower risk of severe maternal disease and preterm birth regardless of variant time period," the authors concluded.¹

The findings support current recommendations for COVID-19 vaccination during pregnancy and provide data relevant to ongoing vaccination guidance as well as preparedness for future respiratory pathogen outbreaks.¹

“Pregnancy is a unique period of vulnerability but also of opportunity for prevention,” Elisabeth McClymont, PhD, lead author, assistant professor, department of obstetrics and genecology, University of British Columbia, said in a press release. “This study reinforces how vaccination can make a real difference for maternal and newborn health.”²

References:

1. McClymont E, Blitz S, Forward L, et al. The role of vaccination in maternal and perinatal outcomes associated with COVID-19 in pregnancy. JAMA. 2025. doi:10.1001/jama.2025.21001
2. COVID-19 vaccination significantly reduces risk to pregnant women and baby. University of British Columbia. December 15, 2025. Accessed December 23, 2025. https://www.eurekalert.org/news-releases/1109419