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.
