PROJECT SUMMARY/ABSTRACT Opioid misuse is a public health crisis in the United States, affecting almost 700,000 women of reproductive age in 2022. Opioid use disorder (OUD) has intergenerational impacts; infants born with prenatal opioid exposure have increased risks of neonatal opioid withdrawal syndrome (NOWS), preterm delivery, congenital abnormalities, and poor intrauterine growth. However, at a population level, our knowledge of the health and developmental trajectories of opioid-exposed children following discharge from their birth hospitalization is extraordinarily scant. Further, the vast majority of research conducted to date has been performed in predominantly non-Hispanic White populations, leaving a major knowledge gap in how health outcomes may differ on the basis of race and ethnicity as well as rurality and maternal disability. The overall goals of this project are to characterize health outcomes during the critical period of birth to five years of age in children born to people with OUD, identify disparities among populations historically and currently under-represented in research, and ascertain protective health system factors using data from the Texas Neonatal Care Research Collaborative. Given past research showing that a NOWS diagnosis may be protective against infant mortality in opioid-exposed infants, this work will first examine variation in the diagnosis of NOWS across 150 hospitals, characterize disparities in NOWS diagnosis rates, and determine the extent to which variation in NOWS diagnosis rates may be explained by clinical, social, and birth hospital factors. Second, this work will determine the cumulative incidence of neurodevelopmental and complex chronic medical conditions at five years of age in children with prenatal opioid exposure relative to children without this exposure, examining how these outcomes differ between children with and without a history of NOWS, and characterizing disparities on the basis of maternal race, ethnicity, rurality and disability. Third, this work will identify health system factors that are protective against infant mortality and neurodevelopmental and complex chronic medical conditions at 5 years of age. A research team comprised of multidisciplinary clinicians, statisticians, data scientists, and key policy and program stakeholders will conduct a population-level analysis of 1.7 million racially and ethnically diverse maternal-infant dyads insured by Medicaid using data from 2010-2023. The population will include >1.3 million women who identify as Hispanic and/or Black, >250,000 who are rural-residing, >26,000 with disabilities, and >12,000 with OUD. Investigators will develop multi-level models to account for the hierarchical data structures, adjusting for confounding variables and identifying health system factors associated with positive child health outcomes. Completion of this work will rapidly address a key knowledge gap regarding the developmental and health trajectories of children born to people with OUD, characterizing modifiable health system factors that may be leveraged to improve both maternal healthcare and child health.

PROJECT NARRATIVE Opioid misuse affects almost 700,000 women of reproductive age in the United States, and infants exposed to opioids during pregnancy are more likely to be born preterm, small for their gestational age, and to develop neonatal opioid withdrawal syndrome. Beyond infancy, outcomes in opioid exposed infants are poorly understood, especially in Hispanic and non-White populations. This research will rapidly address this knowledge gap, identifying neurodevelopmental and health outcomes in opioid-exposed children during the critical period of birth until five years of age, characterizing disparities in these outcomes on the basis of maternal race, ethnicity, rurality and disability, and identifying health system factors that may be protective, thereby informing clinical and public health interventions to support this vulnerable population.