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Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection

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

Question  Is placental antibody transfer after COVID-19 vaccination different from that after SARS-CoV-2 infection in pregnant individuals?

Findings  In this cohort study of 585 maternal-newborn dyads, maternal and cord blood IgG antibody levels were higher after vaccination compared with after infection. An association was observed between time from infection or vaccination to delivery and transfer ratio.

Meaning  Findings of this study suggest that time from infection or vaccination to delivery was the most important factor in transfer ratio efficiency.


Importance  Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy.

Objective  To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2.

Design, Setting, and Participants  This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads.

Exposures  SARS-CoV-2 infection vs COVID-19 vaccination.

Main Outcomes and Measures  IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines.

Results  A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks’ gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks’ gestation or later by 8 weeks after vaccination.

Conclusions and Relevance  This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

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Article Information

Accepted for Publication: September 23, 2022.

Published: November 9, 2022. doi:10.1001/jamanetworkopen.2022.40993

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Flannery DD et al. JAMA Network Open.

Corresponding Author: Karen M. Puopolo, MD, PhD, Children's Hospital of Philadelphia Newborn Care at Pennsylvania Hospital, 800 Spruce St., Philadelphia, PA 19107 (karen.puopolo@pennmedicine.upenn.edu).

Author Contributions: Drs Dhudasia and Puopolo 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 Flannery and Gouma contributed equally to this work.

Concept and design: Flannery, Gouma, Dhudasia, Gerber, Hensley, Puopolo.

Acquisition, analysis, or interpretation of data: Flannery, Gouma, Dhudasia, Mukhopadhyay, Pfeifer, Woodford, Briker, Triebwasser, Gerber, Morris, Weirick, McAllister, Puopolo.

Drafting of the manuscript: Flannery, Dhudasia, Puopolo.

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

Statistical analysis: Flannery, Dhudasia, Mukhopadhyay, Morris.

Obtained funding: Hensley, Puopolo.

Administrative, technical, or material support: Flannery, Gouma, Pfeifer, Woodford, Weirick, McAllister, Puopolo.

Supervision: Mukhopadhyay, Gerber, Hensley, Puopolo.

Conflict of Interest Disclosures: Dr Flannery reported receiving grants from the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention (CDC) outside the submitted work. Dr Mukhopadhyay reported receiving a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Dr Hensley reported receiving grants from the National Institute of Allergy and Infectious Diseases outside the submitted work. Dr Puopolo reported receiving grants from the National Institutes of Health and the CDC outside the submitted work. No other disclosures were reported.

Funding/Support: This study was funded in part by a Foerderer Grant for Excellence from the Children’s Hospital of Philadelphia (Drs Puopolo and Flannery).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentation: The interim results of this study were presented at the Pediatric Academic Societies Annual Meeting; April 23, 2022; Denver, Colorado. The final results were presented at the American Academy of Pediatrics National Conference and Exhibition; October 8, 2022; Anaheim, California.

Additional Contributions: Jeffrey Lurie, the Philadelphia Eagles, and Joel Embiid, Josh Harris, and David Blitzer, the Philadelphia 76ers, provided philanthropic support to establish the serological assays used in this study. Florian Krammer, PhD, Mt. Sinai, provided the SARS-CoV-2 spike receptor-binding domain expression plasmids. Ian Wilson, DPhil, Scripps, provided plasmids to express monoclonal CR3022. These individuals received no additional compensation, outside of their usual salary, for their contributions.

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