Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

Abstract

Importance: Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies.

Objective: To assess the association between maternal and neonatal SARS-CoV-2-specific antibody concentrations.

Design, setting, and participants: This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads.

Exposures: SARS-CoV-2.

Main outcomes and measures: IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data.

Results: The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery.

Conclusions and relevance: In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

Figure 1.. Study Flow Diagram

SARS-CoV-2 indicates severe acute respiratory syndrome coronavirus 2. ^aIncludes 29 sets of twins; only the first twin is included in all analyses. ^bIncludes 21 sets of twins.

Figure 2.. Correlation Between Maternal and Neonatal Cord Sera Severe Acute Respiratory Syndrome Coronavirus 2–Specific Antibody Concentrations

A, Correlation between IgG concentrations in sera from seropositive women and matched cord blood from seropositive (n = 72; filled circles) and seronegative (n = 11; open circles) infants. IgG concentrations in cord blood positively correlate with maternal IgG concentrations (r = 0.886; P < .001). B, IgM concentrations in sera from seropositive women with seropositive (n = 72; filled circles) and seronegative (n = 11; open circle) infants. Horizontal lines represent geometric mean titers and error bars indicate the 95% CI (P = .57 using an unpaired t test on log₂-transformed IgM concentrations). In panels A and B, the horizontal dashed line indicates 0.48 arbitrary units/mL, which was the cutoff used to distinguish positive vs negative samples. Samples that were below this cutoff were assigned an antibody concentration of 0.24 arbitrary units/mL. C, Association of duration in days from nasopharyngeal polymerase chain reaction (NP-PCR) test to delivery with transplacental antibody transfer. Transfer ratio of IgG antibodies from mother to infant (n = 26 matched mother-infant dyads) is positively correlated with days from NP-PCR test to delivery (r = 0.620; P < .001).