PROJECT SUMMARY/ABSTRACT Opioid use during pregnancy is widespread and associated with adverse outcomes for the pregnant individual and the developing child, including reduced fetal growth, premature birth, lower birth weight, congenital defects, increased neonatal healthcare, and heightened risk for later behavioral (e.g., anxiety, inattention), cognitive (e.g., memory deficits, delayed language acquisition), and metabolic problems. Despite opioid use being linked to adverse maternal, fetal, and child outcomes, the mechanisms through which these arise and the potential consequences of prenatal opioid exposure for child health and development (e.g., brain and behavior) remain largely unexplored. This lack of etiologic knowledge has contributed to stagnant treatment, prevention, and mitigation efforts leaving individuals and families susceptible to reverberating adverse outcomes. The HEALthy Brain and Child Development (HBCD) Study is a 25-site longitudinal prospective study of early child development in the US that will assess a broad spectrum of biological (e.g., neuroimaging, genetics, epigenetics), behavioral (e.g., cognition and emotional regulation), experiential (e.g., trauma), social (e.g., racism), and health (e.g., psychopathology) factors among ~7,500 nationally-representative pregnant women and their children from pregnancy to mid-childhood. A major goal of the HBCD Study is to increase understanding of the potential consequences of prenatal substance exposures. It will be enriched for maternal substance use during pregnancy (i.e., ~25% of the sample will be using opioids, cannabis, alcohol, and/or tobacco during pregnancy) and offers a unique opportunity to inform our understanding of how the adverse consequences associated with opioid use during pregnancy arise. Although HBCD will be the largest long-term study of early brain and child development outcomes in the US, the core protocol does not include the collection of delivery biospecimens. This Administrative Supplement in response to the NIDA/ORWH Administrative Supplement Notice of Special Interest: HEAL Initiative: Biospecimen Collection in Pregnancy (NOT-DA-23-005) proposes to leverage the HBCD Study by expanding the biospecimen collection of the Core HBCD Protocol to include delivery specimens (placenta, cord tissue, cord blood). Delivery samples will be collected from a sample of HBCD Study participants across up to 14 HBCD sites (encompassing over 2,000 participants) who have submitted applications in response to this NOSI. This will provide an unprecedented resource generating opportunity for the larger scientific community to comprehensively evaluate pathophysiological mechanisms that mediate the connection between opioid and polysubstance use during pregnancy and adverse neonatal, infant, and/or maternal health outcomes and, in turn, inform innovative preventive strategies.