Project Summary/Abstract Over a year into the global pandemic, COVID-19 poses serious threats to physical health and emotional well-being. Pregnant women are at risk for serious morbidity due to COVID-19 and may be particularly vulnerable to psychological distress, compounded by continued social isolation, financial insecurity, and uncertainty about their own health, as well as that of their unborn child. To date, 73,617 pregnant women in the U.S. have tested positive for COVID-19. Understanding how prenatal exposure to COVID-19 and associated stress impact the developing fetus is of critical relevance to public health. Prenatal exposure to maternal infection and related stress has been strongly associated with disrupted child neurodevelopment. Although risk for vertical transmission of COVID-19 is low (Golden & Simmons, 2020), maternal immune activation is a potential mechanism by which prenatal exposure to infection can impact neurodevelopment. Epidemiological studies have revealed that maternal infections during pregnancy are linked to higher incidence of autism, schizophrenia, and central nervous system disorders (e.g., cerebral palsy) among offspring (Solek et al., 2018; Knuesel et al., 2014; Bauman & Van de Water, 2020). Animal models suggest that maternal immune activation can alter fetal brain development, increasing neurodevelopmental risk (Bergdolt & Dunaevsky, 2019). Effects of maternal stressors are observed at multiple levels, including disrupted brain maturation, epigenetic alterations, and poor developmental outcomes among offspring (Bick & Nelson, 2016; Nelson, 2020; Lupien et al., 2019; McEwen, 2012, 2017; Vanderberg et al., 2017; Wu et al., 2020). Cumulative effects of prenatal infection and stress may exacerbate neuropsychiatric risk: for example, mothers who experienced an infection and elevated stress during pregnancy are more likely to have adolescent offspring with depression (Murphy et al., 2017). To inform effective interventions, it is critical to examine whether–– and how–– maternal COVID-19 exposure and related stress affect infant neurodevelopment. At Boston Children's Hospital (BCH), we are ideally positioned to build on current funding (R34 DA050289) and an approved IRB protocol (IRB-P00035929) to perform neurodevelopmental follow-up of infants born to COVID-19-positive women, enrolled in the Massachusetts General Hospital (MGH) COVID-19 Pregnancy Biorepository (PI: Edlow). In the next 6 months, we will enroll 60 mother-infant dyads from this large cohort to participate in two visits at the PI's BCH lab (ages 9 and 12 months). At each visit, we will conduct study procedures assessing maternal stress, neurophysiology (EEG, eyetracking), and developmental outcomes. A subset of participants will complete an MRI at 9 months.