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Peripartum Outcomes Associated With COVID-19 Vaccination During PregnancyA Systematic Review and Meta-analysis

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To identify the key insights or developments described in this article
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Key Points

Question  Is COVID-19 vaccination during pregnancy associated with increased risks of peripartum adverse outcomes?

Findings  In this systematic review and meta-analysis, COVID-19 vaccination during pregnancy was not associated with increased risks of peripartum adverse outcomes, including preterm birth, small size for gestational age, low Apgar score at 5 minutes, cesarean delivery, postpartum hemorrhage, and chorioamnionitis. Furthermore, COVID-19 vaccination during pregnancy was associated with lower risks of neonatal intensive care unit admission, intrauterine fetal death, and maternal SARS-CoV-2 infection.

Meaning  In this study, COVID-19 vaccination appeared to be safe and beneficial to pregnant individuals.


Importance  The risk and benefits of COVID-19 vaccination during pregnancy are under investigation. Pooled evidence regarding neonatal and maternal outcomes in association with COVID-19 vaccination during pregnancy is scarce.

Objective  To evaluate the association between COVID-19 vaccination during pregnancy and peripartum outcomes.

Data Sources  PubMed and EMBASE databases were searched on April 5, 2022. Language restrictions were not applied.

Study Selection  Prospective trials and observational studies comparing the individuals who received at least 1 COVID-19 vaccination during pregnancy with those who did not and reporting the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, neonatal intensive care units (NICU) admission, and intrauterine fetal death (IFD).

Data Extraction and Synthesis  Two independent investigators extracted relevant data from each study. Odds ratios (ORs) were calculated using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.

Main Outcomes and Measures  The primary outcomes were the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, NICU admission, and IFD. The secondary outcomes were maternal outcomes, including maternal SARS-CoV-2 infection, cesarean delivery, postpartum hemorrhage, and chorioamnionitis.

Results  Nine observational studies involving 81 349 vaccinated (mean age, 32-35 years) and 255 346 unvaccinated individuals during pregnancy (mean age, 29.5-33 years) were included. COVID-19 vaccination during pregnancy was associated with lower risk of NICU admission (OR, 0.88; 95% CI, 0.80-0.97) and IFD (OR, 0.73; 95% CI, 0.57-0.94), whereas there was no statistically significant association with preterm birth (OR, 0.89; 95% CI, 0.76-1.04), small for gestational age (OR, 0.99; 95% CI, 0.94-1.04), and low Apgar score (OR, 0.94; 95% CI, 0.87-1.02). COVID-19 vaccination during pregnancy was associated with a lower risk of maternal SARS-CoV-2 infection (OR, 0.46; 95% CI, 0.22-0.93), whereas it was not associated with increased risk of cesarean delivery (OR, 1.05; 95% CI, 0.93-1.20), postpartum hemorrhage (OR, 0.95; 95% CI, 0.83-1.07), and chorioamnionitis (OR, 1.06; 95% CI, 0.86-1.31).

Conclusions and Relevance  COVID-19 vaccination during pregnancy was not associated with an increase in the risk of peripartum outcomes, was associated with a decreased risk of NICU admission, IFD, and maternal SARS-CoV-2 infection. Thus, COVID-19 vaccination should be encouraged for pregnant individuals.

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Article Information

Accepted for Publication: July 19, 2022.

Published Online: October 3, 2022. doi:10.1001/jamapediatrics.2022.3456

Correction: This article was corrected on November 7, 2022, to fix an incorrect odds ratio and 95% CI in the Results section of the Abstract.

Corresponding Author: Toshiki Kuno, MD, PhD, Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 E 210th St, Bronx, New York, NY 10467-2401 (tkuno@montefiore.org; kuno-toshiki@hotmail.co.jp).

Author Contributions: Drs Watanabe and Yasuhara had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Watanabe and Yasuhara contributed equally as co–first authors.

Concept and design: Watanabe, Yasuhara, Iwagami, Kuno.

Acquisition, analysis, or interpretation of data: Watanabe, Yasuhara, Miyamoto, Yamada, Suzuki, Takagi, Kuno.

Drafting of the manuscript: Watanabe, Yasuhara, Kuno.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Watanabe, Yasuhara, Iwagami, Takagi.

Administrative, technical, or material support: Yasuhara, Suzuki, Kuno.

Supervision: Yasuhara, Yamada, Kuno.

Conflict of Interest Disclosures: None reported.

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