PROMOTING RESILIENCE IN CHILDREN: PROTOCOL DEVELOPMENT FOR A BIRTH COHORT STUDY TO ASSESS FACTORS IMPACTING NEURODEVELOPMENT ABSTRACT The first ten years of life are accompanied by rapid changes to the developing brain and cognitive abilities. A multitude of complex interacting factors including genetics, early-life exposure to substances, family and social interactions, and home and community environments can affect the trajectories of brain and cognitive development. Adequate investigations of these effects and interactions have been limited by several factors, including challenges associated with the recruitment and retention of pregnant women with prenatal substance use; the legal, ethical and regulatory issues associated with studies of substance-using pregnant women and children; and the difficulties of performing neuroimaging in infants and young children without sedation. These three linked and synergistic projects aim to address these challenges by developing effective research protocols to lay a foundation for a successful future large-scale, national HEALthy Brain and Cognitive Development (HBCD) birth cohort study, which will follow the developmental trajectories for a decade. Project 1 will develop protocols for recruitment and retention of a diverse sample of pregnant and postpartum women with oversampling of mothers with prenatal opioid use. Project 2 will identify ethical, legal and regulatory challenges for investigations in this vulnerable population, and subsequently define effective solutions to enable recruitment and study of these participants. Project 3 will develop and evaluate protocols for acquiring high-quality, quantitative neuroimaging measures with magnetic resonance imaging and functional near infrared spectroscopy, as well as assess effective strategies for measuring cognitive performance in young children, including those exposed to opioids. These linked projects are essential to address the major challenges with the planned HBCD study and will leverage a highly collaborative, multidisciplinary team; leading-edge neuroimaging techniques; and outstanding institutional resources.

PUBLIC HEALTH RELEVANCE How does the healthy brain develop and how does early life exposure to substance use and other environmental factors alter the developmental trajectories of brain and behavior? Although vital, this area of research has been limited by ethical, legal and regulatory complexities, particularly in relation to prenatal substance use, a study of which is also challenged by stigma and fears of legal consequences. In order to guide our understanding of how to best promote health, well-being and resilience in children, we will develop protocols for recruitment, engagement and evaluation of brain and cognitive development over the first ten years of life and investigate the impacts of substance and other environmental exposures.