SARS‐CoV‐2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort

Abstract

Background The COVID‐19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Questions remain about how SARS‐CoV‐2 impacts pregnant individuals and their children. Objective To expand our understanding of the effects of SARS‐CoV‐2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. Methods The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS‐CoV‐2 serologic enzyme‐linked immunosorbent assay. Additionally, RT‐PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT‐PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. Results The SARS‐CoV‐2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS‐CoV‐2 RT‐PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre‐pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. Conclusion Seropositivity for SARS‐CoV‐2 without RT‐PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes

“…Two of the IgG positive participants were also SARS-CoV-2 PCR positive (nasopharyngeal swab) at the time of the labor and delivery admission. Like in the larger Generation C cohort [19], IgG seropositive participants had higher pre-pregnancy BMI ( p =0.05) and were more often Hispanic, or non-Hispanic Black compared to IgG seronegative participants. In contrast, we did not observe differences in other maternal characteristics including age, parity, tobacco use, medical conditions, or obstetric conditions.…”

“…Other studies show that active SARS-CoV-2 infection at delivery (mainly confirmed through a PCR positive test) is associated with obstetric and neonatal complications including increased risk of preterm birth, stillbirth, miscarriage, preeclampsia, emergency cesarean section and higher neonatal morbidity [8, 10-18]. However, in other reports, including ours from New York City and a Denmark study, SARS-CoV-2 IgG seropositivity without RT-PCR positivity at delivery was not associated with adverse pregnancy outcomes [19, 20].…”

“…The Generation C study is a prospective pregnancy cohort study that aims to examine the impact of SARS-CoV-2 infection during pregnancy on obstetric and neonatal outcomes. Pregnant individuals were recruited at Mount Sinai Hospital (MSH) and Mount Sinai West (MSW) in New York City (NYC) starting April 20, 2020, and recruitment is ongoing [19]. The first COVID-19 case in NYC was officially confirmed on March 1, 2020.…”

Importance of considering infection during pregnancy: An underappreciated and preventable perinatal concern

“…To assess this, Molenaar and colleagues 4 documented seropositivity for SARS‐CoV‐2 virus during pregnancy in an ongoing, large prospective cohort study (the Generation C Study); 16% of pregnant persons in their large, US healthcare system tested positive for SARS‐CoV‐2 virus. After excluding prevalent infections detected at delivery, they found that SARS‐CoV‐2 positivity was neither associated with reductions in gestational age or Apgar scores, nor with increased risk of preterm birth, small for gestational age or NICU admission 4 . These results imply that observations of adverse foetal outcomes associated with maternal COVID‐19 could be more strongly linked with infection near the time of delivery.…”

“…In a national US-based validation study of diagnostic coding, Regan and colleagues 2 evaluated the performance of ICD-coded diagnoses and laboratory testing records In addition to concerns regarding exposure misclassification, studies that rely on viral detection at delivery will not include previously infected recovered individuals in their exposure assessments, resulting in selection bias. 1 To assess this, Molenaar and colleagues 4 documented seropositivity for SARS-CoV-2 virus during pregnancy in an ongoing, large prospective cohort study (the Generation C Study); 16% of pregnant persons in their large, US healthcare system tested positive for SARS-CoV-2 virus. After excluding prevalent infections detected at delivery, they found that SARS-CoV-2 positivity was neither associated with reductions in gestational age or Apgar scores, nor with increased risk of preterm birth, small for gestational age or NICU admission.…”