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Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is prenatal exposure to maternal BNT162b2 messenger RNA COVID-19 vaccine associated with adverse outcomes at birth or in early childhood?

Findings  In a population-based study including 24 288 singleton live births, the risks of preterm birth and small birth weight were similar between newborns prenatally exposed and unexposed to maternal vaccination.

Meaning  Maternal BNT162b2 vaccination in pregnancy was not associated with detrimental outcomes to the offspring.


Importance  Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization.

Objective  To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns.

Design, Setting, and Participants  Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021.

Exposure  Maternal BNT162b2 mRNA vaccination during pregnancy.

Main Outcomes and Measures  Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status.

Results  The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks’ gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72).

Conclusions and Relevance  This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

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Article Information

Accepted for Publication: January 3, 2022.

Published Online: February 10, 2022. doi:10.1001/jamapediatrics.2022.0001

Corresponding Author: Inbal Goldshtein, PhD, Maccabi Healthcare Services, 4 Yehezkel Kaufmann St, Tel Aviv, Israel 68125 (goldst_in@mac.org.il).

Author Contributions: Dr Goldshtein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Ben-Tov and Shapiro Ben David served as co–last authors and contributed equally to the manuscript.

Concept and design: Goldshtein, Steinberg, Segal, Shapiro Ben David, Ben Tov.

Acquisition, analysis, or interpretation of data: Goldshtein, Steinberg, Kuint, Chodick, Shapiro Ben David, Ben Tov.

Drafting of the manuscript: Goldshtein, Steinberg, Segal, Shapiro Ben David.

Critical revision of the manuscript for important intellectual content: Goldshtein, Kuint, Chodick, Shapiro Ben David, Ben Tov.

Statistical analysis: Goldshtein, Steinberg.

Administrative, technical, or material support: Goldshtein, Chodick, Shapiro Ben David.

Supervision: Segal, Shapiro Ben David.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Ziona Haklai from the Ministry of Health, Department of Health Information, Jerusalem, Israel, for her contribution to data collection and validation. She did not receive any additional compensation beyond usual salary for her contribution. We are grateful for the excellent comments provided by peer reviewers who improved this article.

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Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

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  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

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