Respiratory Diseases Roundup

COVID-19 in Pregnancy: Vaccination and Child Outcomes

Edited by:
Kate Young

Key highlights

  • Among pregnant people with SARS-CoV-2 infection, prior vaccination was associated with lower risks of hospitalization, critical care admission, and preterm birth during Delta and Omicron periods.1
  • In a French national cohort, first-trimester mRNA COVID-19 vaccination was not associated with increased risk of major congenital malformations overall or by organ system.2
  • In a Canadian prospective cohort survey, vaccine risk concerns and attitudes were associated with acceptance; prenatal care providers and partners were among the most influential sources.3
  • In a health system cohort, maternal SARS-CoV-2 infection during pregnancy was associated with higher odds of neurodevelopmental diagnoses by age 3 years, with larger effects after third-trimester exposure and among male offspring.4

Vaccination linked to better outcomes with maternal COVID-191

In a population-level surveillance study using the CANCOVID-Preg database, investigators examined maternal and perinatal outcomes among pregnant individuals with SARS-CoV-2 infection in 9 Canadian provinces/territories from April 5, 2021, through December 31, 2022, with follow-up into 2023 for pregnancy and infant outcomes. Among 19,899 eligible cases, 72% were vaccinated before diagnosis (80% before pregnancy and 20% during pregnancy). The primary outcomes were COVID-19–associated hospitalization, critical care unit admission, and preterm birth.

Across both variant periods, vaccination before infection was associated with lower risks of severe maternal outcomes and preterm birth. During the Delta period, vaccination was associated with reduced risk of hospitalization (relative risk [RR], 0.38) and critical care unit admission (RR, 0.10), and a lower risk of preterm birth (RR, 0.80). During Omicron, similar reductions were observed for hospitalization (RR, 0.38) and critical care admission (RR, 0.10), with a larger relative reduction in preterm birth (RR, 0.64). In multivariable analyses accounting for comorbid conditions, vaccination remained associated with lower hospitalization risk; compared with vaccinated cases, unvaccinated cases had higher adjusted risks of hospitalization in both Omicron and Delta periods.

Early pregnancy mRNA vaccination not tied to malformations2

A nationwide, population-based French cohort study evaluated whether first-trimester exposure to mRNA COVID-19 vaccines was associated with major congenital malformations (MCMs) during the teratogenic window. The analysis used the Mother-Child EPI-MERES Register, including all eligible live-born infants from pregnancies starting April 1, 2021, through January 31, 2022, with follow-up available through December 2024. Exposure was defined as receipt of at least 1 mRNA vaccine dose during the first trimester.

Among 527,564 eligible infants, 130,338 (24.7%) were exposed in the first trimester. MCMs were identified per European Surveillance of Congenital Anomalies guidelines, and confounding was addressed using propensity score–based standardized mortality ratio weighting with weighted odds ratios estimated via logistic regression. The prevalence of MCMs was 176.6 per 10,000 among exposed infants (2,302 infants) and 179.4 per 10,000 among nonexposed infants (7,128 infants). No increased risk was observed overall (weighted OR, 0.98; 95% CI, 0.93-1.04), by organ system (weighted OR range, 0.84 to 1.20), or for any of 75 individual MCMs assessed; sensitivity and stratified analyses were consistent with the primary findings.

Canadian survey: attitudes and influences on vaccine uptake3

Investigators reported findings from COVERED (Canadian COVID-19 Vaccine Registry for Pregnant Individuals), a national prospective cohort that collected self-reported data via online surveys across Canada. The analysis focused on attitudes and acceptance factors among pregnant respondents completing a vaccine attitudes module between July 2021 and December 2023, with most responses submitted in July through December 2021. After exclusions (including vaccination before pregnancy), 1,093 respondents were included: 890 (81.4%) had received a COVID-19 vaccination by survey completion, 69 (6.3%) reported being somewhat/very likely to be vaccinated, and 134 (12.3%) were categorized as not accepting (neutral to very unlikely).

In univariable analyses, higher perceived vaccine risk on the WHO Vaccine Hesitancy Scale was associated with lower acceptance (odds ratio [OR], 0.78; 95% CI, 0.71-0.86), while more favorable attitudes toward COVID-19 vaccines (theory of planned behavior framework) were associated with higher acceptance (OR, 1.11; 95% CI, 1.08-1.14). Measures of social norms also differed: respondents reporting that important others supported vaccination were more likely to accept vaccination, and indirect social norms (including influence of prenatal care providers and partners) were reported as influential in acceptance. Most participants cited clinicians as common and reliable sources of health care information, including family physicians and prenatal care providers.

In utero SARS-CoV-2 exposure and child neurodevelopment at 3 years4

A retrospective cohort study in the Mass General Brigham health system evaluated whether maternal SARS-CoV-2 infection during pregnancy was associated with neurodevelopmental diagnoses in offspring by 36 months. The cohort included 18,124 live births from March 1, 2020, to May 31, 2021. Exposure was defined by a positive SARS-CoV-2 polymerase chain reaction result during pregnancy. Neurodevelopmental outcomes were identified using ICD-10 diagnostic codes through age 3 years; models adjusted for maternal age, race and ethnicity, insurance type, hospital type, and preterm birth.

Among 861 offspring from exposed pregnancies (4.8%), 140 (16.3%) received a neurodevelopmental diagnosis by 36 months compared with 1,680 of 17,263 unexposed offspring (9.7%). The unadjusted odds ratio was 1.80 (95% CI, 1.49-2.17), and the adjusted odds ratio was 1.29 (95% CI, 1.05-1.57). In sensitivity analyses, larger associations were reported for third-trimester exposure overall (adjusted odds ratio, 1.36; 95% CI, 1.07-1.72) and among male offspring (adjusted odds ratio, 1.43; 95% CI, 1.05-1.91).

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. 2026;335(2):154-162. doi:10.1001/jama.2025.21001.
  2. Bernard C, Duchemin T, Marty L, et al. First-trimester mrna covid-19 vaccination and risk of major congenital anomalies. JAMA Netw Open. 2025;8(10):e2538039. Published 2025 Oct 1. doi:10.1001/jamanetworkopen.2025.38039.
  3. Bondy S, McClymont E, Av-Gay G, et al. Acceptance and attitudes towards COVID-19 vaccination during pregnancy in Canada. Hum Vaccin Immunother. 2025;21(1):2458353. doi:10.1080/21645515.2025.2458353.
  4. Shook LL, Castro V, Ibanez-Pintor L, Perlis RH, Edlow AG. Neurodevelopmental outcomes of 3-year-old children exposed to maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in utero. Obstet Gynecol. 2026;147(1):11-20. doi:10.1097/AOG.0000000000006112.