The SARS-CoV-2 novel coronavirus (COVID-19) pandemic has led to over 6.25 million confirmed cases and ~375,000 deaths worldwide, yet very little is currently known about the prevalence of COVID-19 infection during pregnancy nor the impact of the pandemic on pregnant women and their unborn children. The goal of this competing revision application is to establish a new pregnancy cohort to investigate the impact of the COVID-19 pandemic on child neurodevelopment. Maternal inflammation during pregnancy can result from immune dysregulation due to infections or stress. The COVID-19 pandemic may therefore result in increased maternal inflammation during pregnancy. Several lines of evidence suggest that inflammation can have deleterious effects on fetal neurodevelopment. Our overarching hypothesis is that maternal COVID- 19 infection and/or pandemic-related stress during pregnancy will increase risk of neurodevelopmental disorders (NDD) in children via in utero exposure to heightened maternal inflammation during pregnancy. Neonatal blood reflects the maternal gestational immune profile, and IgG antibodies and pro- inflammatory cytokines measured in newborn bloodspots reflect past/present maternal infection. Thus, we further hypothesize that neonatal levels of immune markers (antibodies, cytokines, chemokines) will reflect maternal COVID-19 exposures during pregnancy and correlate with NDD risk. We propose a longitudinal pregnancy cohort study of women who were members of KPNC and pregnant during the COVID- 19 pandemic in 2020. Utilizing prospectively collected information recorded in the electronic health records of the large and diverse cohort of ~40,000 pregnant women and their children receiving care at Kaiser Permanente Northern California (KPNC), patient reported data from ~20,000 women who complete the KPNC COVID-19 pregnancy survey, and newborn bloodspots from babies born to COVID-19 positive women (N~550), we will investigate the impact of the COVID-19 pandemic on child neurodevelopment. We will compare NDD diagnosed in the first 24 months of life between children born to women 1) with and without COVID-19 infection during pregnancy, and 2) by varying levels of maternal stress during pregnancy. We will also examine levels of neonatal immune markers (antibodies, cytokines, chemokines) in relation to maternal COVID-19 infection status and NDD in the child. This large scale and comprehensive study provides a unique opportunity to examine, in real-time, the impact of the coronavirus pandemic on child neurodevelopment in the first years of life, and establishes a novel framework to continue exploring the relationships between maternal and neonatal immune dysregulation and a range of neurodevelopmental disorders as they emerge over time. Findings will contribute to the development of prenatal and newborn screening for adverse neurodevelopment, ultimately enabling earlier intervention and primary prevention.
Neurodevelopmental disorders have become increasingly common, yet their causes remain largely unknown. This large scale and comprehensive study provides a unique opportunity to examine, in real-time, the impact of the coronavirus pandemic on child neurodevelopment in the first years of life, and establishes a novel framework to continue exploring the relationships between maternal and neonatal immune dysregulation and a range of neurodevelopmental disorders as they emerge over time. Findings will contribute to the development of prenatal and newborn screening for adverse neurodevelopment, ultimately enabling earlier intervention and primary prevention.
