PROJECT SUMMARY The ongoing COVID-19 pandemic has led to significant changes in social, economic and health resource availability and associated escalations in substance use and mental health problems. The consequences of the pandemic for pregnant and postpartum individuals and their offspring will reveal themselves over the next several decades as these children become adolescents and young adults. The current proposal seeks to take advantage of a unique opportunity to continue and enrich an ongoing data collection effort with potential to reveal mechanisms through which the COVID-19 pandemic may impact future generations. This proposal builds on a project at Oregon Health & Science University (OHSU), which is harmonized with data collection efforts at seven geographically-representative sites from the NIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai Medical Center, University of Vermont and Northwestern University (R34 DA05029-S1). The OHSU site has exceeded enrollment targets for this initial project (N=371 versus the proposed N=100), successfully captured longitudinal trajectories of maternal stress and depressive symptoms during the early phase of the pandemic, and met targets for collection of biological samples and behavioral observations of mother-infant dyads (N=40). The OHSU site also serves as a central repository for biological samples collected at several other sites. The current proposal seeks to expand and enrich the sample at OHSU by enrolling pregnant individuals at heightened risk for substance use during the perinatal period (N=50). We additionally propose to expand biological sample collection of blood, breastmilk, hair, nails and saliva to include a larger sample of mothers and infants (N=100), and to occur at four time points (pregnancy, and infant age 1-, 6-, and 12-months). Finally, we propose to collect birth samples, umbilical cord blood and placenta, in a subsample of these participants (N=50). The continued follow up of our current sample, additional enrollment of higher-risk pregnant individuals and enhanced biological sampling will allow us to: 1) characterize trajectories of and heterogeneity in maternal perinatal psychological stress during the pandemic and identify key contributing factors differentiating subgroups; 2) advance understanding of the prevalence, longitudinal course and contributing factors to maternal perinatal substance use during the pandemic; and 3) test the hypothesis that heightened maternal-placental-fetal inflammation may serve as a common pathway for effects of maternal psychological stress and substance use on infant development. Accomplishing these aims will advance understanding of intergenerational transmission of risk during times of chronic stress and reduced resource availability, such as the COVID-19 pandemic. By enhancing capacity to examine contributors to maternal stress and substance use and mechanisms of impact on infant development, this work can also aide in identification of targets for preventive interventions to improve maternal and child health.

PROJECT NARRATIVE Increased risk of substance use and mental health problems due to the ongoing COVID-19 pandemic are particularly concerning for pregnant and postpartum individuals due to the enhanced likelihood of intergenerational transmission of negative sequelae during these sensitive periods for maternal health and infant development. This proposal would expand upon and enrich an existing, unique, longitudinal cohort of mother-infant dyads at Oregon Health & Science University by enrolling pregnant individuals at heightened risk for substance use problems, and including more in-depth measurement of mother and infant biology and behavior. The proposed project would allow for addressing critical questions regarding the impacts of the COVID-19 pandemic on future generations through advancing understanding of individual differences in maternal mental health and substance use and the mechanisms through which these factors influence infant socioemotional development.