The distribution of dyads in each group in the heat map (Figure 3) is shown in eFigure 3 in the Supplement. Open in a separate window Figure 3. 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; diagnosis codes were validated and used RGFP966 to RGFP966 identify hypertensive disorders and diabetes, as previously described.19 Preterm delivery was defined as less than 37 weeks gestation, and term delivery was defined as 37 weeks gestation or later. During the study period, pregnant persons were routinely screened for SARS-CoV-2 using nasopharyngeal PCR testing when admitted to the hospital for RGFP966 childbirth; Tg testing could also be performed before the pregnancy or earlier during pregnancy and outside of the health system. Persons with medical record report of SARS-CoV-2 symptoms and confirmatory positive result from nasopharyngeal PCR testing were considered to have a symptomatic infection. Symptomatic illness was defined according to definitions provided by the National Institutes of Health.20 Persons with antibodies to SARS-CoV-2 but without a record of symptomatic illness or COVID-19 vaccination were considered to have asymptomatic infection whether or not they had a positive nasopharyngeal PCR test result. Serum Collection and Testing Pregnant persons routinely have blood drawn for rapid plasma reagin testing when admitted to the hospital for childbirth, and cord blood is routinely collected for newborn blood type and direct antiglobulin testing. Collection of residual serum samples from these specimens was performed as previously described.19,21 Serum samples were fully deidentified before antibody level measurements; when results were available, persons who were seropositive were reidentified for manual medical record review by one of us (K.M.P.). The IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured using enzyme-linked immunosorbent assay; this quantitative assay has been previously described.19 Serum samples with IgG and/or IgM concentrations of more than 0.48 arbitrary U/mL were considered to be seropositive; concentrations below this cutoff were considered to be seronegative and were assigned a value of 0.24 arbitrary U/mL for statistical analysis. Statistical Analysis The demographic, clinical, and antibody characteristics of pregnant persons and newborns were compared according to the following 3 exposures: (1) asymptomatic infection, (2) symptomatic infection, RGFP966 and (3) COVID-19.

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