PROJECT SUMMARY/ABSTRACT The burden of America's opioid crisis has heavily fallen on children, a vulnerable population increasingly exposed to opioids in utero or childhood through parental opioid use (POU). POU exposure in utero may lead to a newborn experiencing neonatal opioid withdrawal syndrome, while POU exposure in childhood may lead to a child experiencing maltreatment and family separation due to parental drug overdose mortality, parental institutionalization, or foster care placement. Life course theory postulates that early life adversity, especially in utero and early childhood, may lead to lifelong physical and mental health, substance use, behavioral, and socioeconomic problems. This K01 Mentored Research Scientist Development Award application proposes a training and research plan that will support Dr. Angélica Meinhofer on a path towards independence, focused on elucidating the impact of exposure to POU in early life (in utero up to age 8) on mental health disorders, chronic conditions, infectious diseases, injuries, and healthcare utilization in early and middle childhood. The training plan supplements Dr. Meinhofer's prior expertise in opioid use disorders, health economics, and policy evaluation with training in (1) child health with a life course perspective, (2) behavioral health systems and services for children and families, (3) epidemiology and biostatistics methods, and (4) complex data management and linkage algorithms. Dr. Meinhofer will achieve the proposed training objectives with a combination of formal coursework, workshops, and hands-on experience, as well as the mentorship of Dr. Bruce Schackman, Dr. Yuhua Bao, Dr. Katherine Keyes, and Dr. Rachel Dunifon. Drawing from the Medicaid Analytic eXtract (MAX) linked with other datasets and combining a longitudinal, population-based study design with difference-in-differences and propensity score methods, Dr. Meinhofer will use the knowledge and skills acquired through these training activities to achieve the following aims: (1) Estimate the association between exposure to opioids in utero and physical and mental health, and healthcare utilization in early childhood; (2) Estimate the association between exposure to parental drug overdose mortality in early childhood and physical and mental health, injuries, and healthcare utilization in early and middle childhood; and (3) Estimate the association between exposure to parental opioid use disorders medication treatment in early childhood and physical and mental health, injuries, and healthcare utilization in early and middle childhood. Understanding how early life exposure to POU may affect offspring outcomes over the life course provides a strong foundation upon which clinicians and policymakers can design a more proactive, coordinated, family-centered, and overall more effective agenda. The proposed K01 Award will provide Dr. Meinhofer with the resources, training, and mentoring needed to become an R01-funded independent investigator leading a multidisciplinary research program to inform policies for improving the wellbeing of children and families affected by parental substance use.

PROJECT NARRATIVE Early life adversity, including in utero and early childhood, may lead to lifelong physical and mental health, substance use, and behavioral problems. This longitudinal, population-based cohort study aims to elucidate the early and middle childhood health and healthcare outcomes of exposure to parental opioid use in early life. Results will shed light on the intergenerational effects of America's opioid crisis and inform the development of policies and early interventions for improving the wellbeing of children affected by parental opioid use.