Characterizing the early childhood neurodevelopmental impact of infants exposed to maternal SARS-CoV-2 infection during pregnancy

Project Abstract Pregnant people are uniquely susceptible to SARS-CoV-2 infection, with risks of severe maternal COVID-19 illness and obstetric complications. However, far less is known about the long-term impact of pregnancy- associated SARS-CoV-2 infection on developing infants. Given the global burden, it is estimated that millions of pregnant people have had SARS-CoV-2 infection. Prior work by our Studying Novel Infectious Pathogens in Pregnancy (SNIPP) research team has identified distinct types of SARS-CoV-2-associated injury to the placenta, such as maternal vascular malperfusion and COVID placentitis. Further, we have identified unique inflammatory cytokine alterations in patients with specific types of placental lesions following SARS-CoV-2 during pregnancy. Maternal infection and inflammation can have a complex impact on early brain development and neurodevelopmental health outcomes. However, there have been very limited studies with differing conclusions addressing neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 in pregnancy. The existing literature to date utilizes methods limited by assessment of infants too early (≤12 months) and with diagnosis codes rather than direct evaluation of the child. With continued viral evolution and a generation of infants affected by the COVID-19 pandemic, it remains critical to learn if and how SARS-CoV-2 infection in pregnancy impacts childhood neurodevelopment health and risk of future dysfunction. Our central hypothesis is that pregnancy-associated SARS-CoV-2 infection and associated placental injury increases risk of adverse early childhood neurodevelopmental outcomes. We will investigate this hypothesis by utilizing our longitudinal SNIPP cohort of mother-infant pairs affected by SARS-CoV-2 infection during pregnancy (n~4000) with archived placental histopathology. We aim to characterize early childhood neurodevelopmental outcomes of infants following maternal SARS-CoV-2 during pregnancy by Aim 1(a): performing developmental assessments on infants born to the SARS-CoV-2-infected cohort along with pandemic timeframe uninfected controls; and Aim 1(b): exploring associations between neurodevelopmental abnormalities and placental injury with or without SARS-CoV-2 infection. In collaboration with Institute for Innovations in Developmental Sciences faculty, assessments will be performed using validated online parent surveys and remote video visits, focusing on both broad neurodevelopment and key domains for adaptive functioning: self-regulation and communication. A major impact of this work would be the identification of high-risk children who need close developmental monitoring. Strengths of our proposal include our large SNIPP cohort with paired biospecimens, sampling across the pandemic timeframe, and our transdisciplinary approach harnessing expertise in perinatal infection, placental pathology, and cutting-edge, pragmatic neurodevelopmental paradigms. This project uniquely poises us to address an important gap in knowledge that can impact near-term neurodevelopmental care and, through future research, lead to innovative risk stratification, mechanistic insight, and novel therapeutics to reduce harm.