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Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy

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Question  What were the maternal and neonatal SARS-CoV-2 immunoglobulin G antibody levels at birth after messenger RNA (mRNA) COVID-19 vaccination during the second trimester of pregnancy?

Findings  In this cohort study of 130 pregnant women who received the BNT162b2 mRNA vaccine during their second trimester, antibody titers were positive for all women during delivery, and neonatal titers were higher than maternal titers, representing 100% placental antibody transfer.

Meaning  The findings suggest that administration of the mRNA COVID-19 vaccine during the second trimester is associated with a maternal humoral response that is sustained during labor and transfers antibodies to the neonate, supporting early vaccination of pregnant women.

Abstract

Importance  BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in the third trimester was found to be associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn.

Objective  To evaluate maternal and neonatal SARS-CoV-2 immunoglobulin G (IgG) antibody levels at birth after mRNA COVID-19 vaccination during the second trimester of pregnancy.

Design, Setting, and Participants  This prospective cohort study, conducted at a single medical center in Haifa, Israel, from May to July 2021, included women with a singleton pregnancy over 24 weeks of gestation at least 7 days after receipt of their second COVID-19 vaccine dose who were not known to be previously infected with COVID-19.

Exposures  BNT162b2 (Pfizer/BioNTech) vaccination.

Main Outcomes and Measures  The primary outcomes were SARS-CoV-2 IgG antibody titers measured in the parturient at admission and in the umbilical cord blood within 30 minutes after delivery. Secondary outcomes were the correlation between antibody titers, feto-maternal characteristics, maternal adverse effects after vaccination, and time interval from vaccination to delivery.

Results  Antibody levels were measured for 129 women (mean [SD] age, 31.9 [4.9] years) and 114 neonates, with 100% of the tests having positive results. The mean (SD) gestational age at administration of the second vaccine dose was 24.9 (3.3) weeks. Neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1-17 643.5] AU/mL vs 1185.2 [146.6-32 415.1] AU/mL). A positive correlation was demonstrated between maternal and neonatal antibodies (r = 0.92; 95% CI, 0.89-0.94). Multivariable analysis revealed that for each week that passed since receipt of the second vaccine dose, maternal and neonatal antibody levels changed by −10.9% (95% CI, −17.2% to −4.2%; P = .002) and −11.7% (95% CI, −19.0 to −3.8%; P = .005), respectively. For each 1-year increase in the mother’s age, maternal and neonatal antibody levels changed by −3.1% (95% CI, −5.3% to −0.9%; P = .007) and −2.7% (95% CI, −5.2% to −0.1%; P = .04), respectively.

Conclusions and Relevance  In this cohort study, receipt of the BNT162b2 mRNA COVID-19 vaccine during the second trimester of pregnancy was associated with maternal and neonatal humoral responses, as reflected in maternal and neonatal SARS-CoV-2 IgG antibody levels measured after delivery. These findings support COVID-19 vaccination of pregnant individuals during the second trimester to achieve maternal protection and newborn safety during the pandemic.

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Article Information

Accepted for Publication: November 5, 2021.

Published Online: December 21, 2021. doi:10.1001/jamapediatrics.2021.5683

Corresponding Author: Nir Kugelman, MD, Department of Obstetrics and Gynecology, Carmel Medical Center, 7 Michal St, Haifa 3436212, Israel (nirkug@gmail.com).

Author Contributions: Drs Bardicef and Kedar contributed equally. Drs Kugelman and Kedar had full access to all the data in the study and take full responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kugelman, Nahshon, Lavie, Bardicef, Kedar.

Acquisition, analysis, or interpretation of data: Kugelman, Nahshon, Shaked-Mishan, Cohen, Lahav Sher, Gruber, Marom, Zolotarevsky, Lavie, Damti, Zilberlicht, Kedar.

Drafting of the manuscript: Kugelman, Nahshon, Shaked-Mishan, Marom, Zolotarevsky, Lavie, Damti, Bardicef, Kedar.

Critical revision of the manuscript for important intellectual content: Kugelman, Nahshon, Cohen, Lahav Sher, Gruber, Lavie, Zilberlicht.

Statistical analysis: Kugelman, Nahshon.

Obtained funding: Kugelman.

Administrative, technical, or material support: Kugelman, Shaked-Mishan, Cohen, Lahav Sher, Gruber, Zolotarevsky, Lavie, Damti, Zilberlicht, Bardicef, Kedar.

Supervision: Lavie, Bardicef, Kedar.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Ms Nili Stein, MPH (Department of Community Medicine and Epidemiology, the Lady Davis Carmel Medical Center), helped with the calculations and analysis of the statistical section of the study and was not compensated for this work.

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