[Skip to Content]
[Skip to Content Landing]

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.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

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.

References
1.
Zambrano  LD , Ellington  S , Strid  P ,  et al; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team.  Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647. doi:10.15585/mmwr.mm6944e3 PubMedGoogle ScholarCrossref
2.
Villar  J , Ariff  S , Gunier  RB ,  et al.  Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID Multinational cohort study.   JAMA Pediatr. 2021;175(8):817-826. doi:10.1001/jamapediatrics.2021.1050 PubMedGoogle ScholarCrossref
3.
Gurol-Urganci  I , Jardine  JE , Carroll  F ,  et al.  Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study.   Am J Obstet Gynecol. 2021;225(5):522.e1-522.e11. doi:10.1016/j.ajog.2021.05.016 PubMedGoogle ScholarCrossref
4.
Abu-Raya  B .  Vaccination of pregnant women against COVID-19.   Neoreviews. 2021;22(9):e570-e573. doi:10.1542/neo.22-9-e570 PubMedGoogle ScholarCrossref
5.
Bhuiyan  MU , Stiboy  E , Hassan  MZ ,  et al.  Epidemiology of COVID-19 infection in young children under five years: a systematic review and meta-analysis.   Vaccine. 2021;39(4):667-677. doi:10.1016/j.vaccine.2020.11.078 PubMedGoogle ScholarCrossref
6.
Rashidian  T , Sharifi  N , Fathnezhad-Kazemi  A , Mirzamrajani  F , Nourollahi  S , Ghaysouri  A .  Death of a neonate with suspected coronavirus disease 2019 born to a mother with Coronavirus Disease 2019 in Iran: a case report.   J Med Case Rep. 2020;14(1):186. doi:10.1186/s13256-020-02519-1 PubMedGoogle ScholarCrossref
7.
Hinojosa-Velasco  A , de Oca  PVB , García-Sosa  LE ,  et al.  A case report of newborn infant with severe COVID-19 in Mexico: detection of SARS-CoV-2 in human breast milk and stool.   Int J Infect Dis. 2020;100:21-24. doi:10.1016/j.ijid.2020.08.055 PubMedGoogle ScholarCrossref
8.
Saha  S , Pal  P , Mukherjee  D .  Neonatal MIS-C: managing the cytokine storm.   Pediatrics. 2021;148(5):e2020042093. doi:10.1542/peds.2020-042093 PubMedGoogle ScholarCrossref
9.
Centers for Disease Control and Prevention. CDC statement on pregnancy health advisory. Accessed November 23, 2021. https://www.cdc.gov/media/releases/2021/s0929-pregnancy-health-advisory.html
10.
Mithal  LB , Otero  S , Shanes  ED , Goldstein  JA , Miller  ES .  Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy.   Am J Obstet Gynecol. 2021;225(2):192-194. doi:10.1016/j.ajog.2021.03.035 PubMedGoogle ScholarCrossref
11.
Flannery  DD , Puopolo  KM .  Perinatal COVID-19: guideline development, implementation, and challenges.   Curr Opin Pediatr. 2021;33(2):188-194. doi:10.1097/MOP.0000000000000997 PubMedGoogle ScholarCrossref
12.
Bookstein Peretz  S , Regev  N , Novick  L ,  et al.  Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine.   Ultrasound Obstet Gynecol. 2021;58(3):450-456. doi:10.1002/uog.23729 PubMedGoogle ScholarCrossref
13.
Collier  AY , McMahan  K , Yu  J ,  et al.  Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women.   JAMA. 2021;325(23):2370-2380. doi:10.1001/jama.2021.7563 PubMedGoogle ScholarCrossref
14.
Beharier  O , Plitman Mayo  R , Raz  T ,  et al.  Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine.   J Clin Invest. 2021;131(13):150319. doi:10.1172/JCI150319 PubMedGoogle ScholarCrossref
15.
Cassaniti  I , Percivalle  E , Zelini  P ,  et al.  Both SARS-CoV-2 infection and vaccination in pregnancy elicited neutralizing antibodies in pregnant women and newborns.   Clin Microbiol Infect. 2021;27(11):1708-1709. doi:10.1016/j.cmi.2021.08.004 PubMedGoogle ScholarCrossref
16.
Gloeckner  S , Hornung  F , Heimann  Y ,  et al.  Newborns’ passive humoral SARS-CoV-2 immunity following heterologous vaccination of the mother during pregnancy.   Am J Obstet Gynecol. 2022;226(2):261-262. doi:10.1016/j.ajog.2021.10.006 PubMedGoogle ScholarCrossref
17.
Gill  L , Jones  CW .  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies in neonatal cord blood after vaccination in pregnancy.   Obstet Gynecol. 2021;137(5):894-896. doi:10.1097/AOG.0000000000004367 PubMedGoogle ScholarCrossref
18.
Prabhu  M , Murphy  EA , Sukhu  AC ,  et al.  Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates.   bioRxiv. Preprint posted online April 6, 2021. doi:10.1101/2021.04.05.438524 Google Scholar
19.
Flannery  DD , Gouma  S , Dhudasia  MB ,  et al.  SARS-CoV-2 seroprevalence among parturient women in Philadelphia.   Sci Immunol. 2020;5(49):eabd5709. doi:10.1126/sciimmunol.abd5709 PubMedGoogle ScholarCrossref
20.
National Institutes of Health. COVID-19 Treatment Guidelines. Clinical spectrum of SARS-CoV-2 infection. Accessed April 12, 2022. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/
21.
Flannery  DD , Gouma  S , Dhudasia  MB ,  et al.  Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios.   JAMA Pediatr. 2021;175(6):594-600. doi:10.1001/jamapediatrics.2021.0038 PubMedGoogle ScholarCrossref
22.
Gray  KJ , Bordt  EA , Atyeo  C ,  et al.  Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.   Am J Obstet Gynecol. 2021;225(3):303.e1-303.e17. doi:10.1016/j.ajog.2021.03.023 PubMedGoogle ScholarCrossref
23.
Nir  O , Schwartz  A , Toussia-Cohen  S ,  et al.  Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.   Am J Obstet Gynecol MFM. 2022;4(1):100492. doi:10.1016/j.ajogmf.2021.100492 PubMedGoogle ScholarCrossref
24.
Kashani-Ligumsky  L , Lopian  M , Cohen  R ,  et al.  Titers of SARS CoV-2 antibodies in cord blood of neonates whose mothers contracted SARS CoV-2 (COVID-19) during pregnancy and in those whose mothers were vaccinated with mRNA to SARS CoV-2 during pregnancy.   J Perinatol. 2021;41(11):2621-2624. doi:10.1038/s41372-021-01216-1 PubMedGoogle ScholarCrossref
25.
Dickerman  BA , Gerlovin  H , Madenci  AL ,  et al.  Comparative effectiveness of BNT162b2 and mRNA-1273 vaccines in U.S. veterans.   N Engl J Med. 2022;386(2):105-115. doi:10.1056/NEJMoa2115463 PubMedGoogle ScholarCrossref
26.
Halasa  NB , Olson  SM , Staat  MA ,  et al; Overcoming COVID-19 Investigators; Overcoming COVID-19 Network.  Effectiveness of maternal vaccination with mRNA COVID-19 vaccine during pregnancy against COVID-19-associated hospitalization in infants aged <6 months—17 states, July 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(7):264-270. doi:10.15585/mmwr.mm7107e3 PubMedGoogle ScholarCrossref
27.
Fouda  GG , Martinez  DR , Swamy  GK , Permar  SR .  The impact of IgG transplacental transfer on early life immunity.   Immunohorizons. 2018;2(1):14-25. doi:10.4049/immunohorizons.1700057 PubMedGoogle ScholarCrossref
28.
Douxfils  J , Gillot  C , De Gottal  É ,  et al.  Efficient maternal to neonate transfer of neutralizing antibodies after SARS-CoV-2 vaccination with BNT162b2: a case-report and discussion of the literature.   Vaccines (Basel). 2021;9(8):907. doi:10.3390/vaccines9080907 PubMedGoogle ScholarCrossref
29.
Kassis  NE , Abdallah  W , Chakra  RA , Arab  W , Sassine  S , Atallah  D .  COVID-19 mRNA vaccine in pregnancy and newborn passive immunization: a case report.   Future Sci OA. 2021;8(1):FSO761. doi:10.2144/fsoa-2021-0043PubMedGoogle ScholarCrossref
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close