UAB Outcomes of Babies with Opioid Exposure (OBOE study) - Project Summary Limited data are available on the effects of prenatal opioid exposure on the brain and neurodevelopment. The Outcomes of Babies with Opioid Exposure (OBOE) study, an ongoing NICHD-funded longitudinal study enrolling infants with and without prenatal opioid exposure at birth and following them to 2 years of age, is collecting comprehensive exposure data including infant umbilical cords, advanced neuroimaging data to evaluate brain development, and standardized and thorough information on the home environment, maternal mental health, and parenting. The OBOE consortium has completed our goal enrollment of 200 opioid-exposed infants and 100 unexposed infants with complete data at 0-1 months of age. In response to RFA-HD-24-014, we now propose to complete follow-up to age 2, to fulfill our main study objectives. The UAB site has contributed to the OBOE study by enrolling 52 opioid-exposed and 26 control infants, completing 92 MRIs so far, and contributing to the publication of multiple abstracts and three manuscripts using OBOE data. The Specific Aims for this renewal grant are to: Specific Aim 1: To determine the impact of prenatal opioid exposure on brain structure and connectivity over the first two years of life. We have made progress toward this aim and have submitted 2 abstracts showing that prenatal opioid exposure is associated with increased white matter injury, reductions in global, regional, and tissue-specific brain volumes, and altered functional connectivity. Specific Aim 2: To define medical, developmental, and behavioral trajectories over the first 2 years of life in infants exposed to opioids. As we recently completed enrollment, this aim is ongoing. We have analyzed umbilical cord data showing that infants with prenatal opioid exposure are often exposed to other psychotropic drugs, and are analyzing the effects of polysubstance exposure on newborn behavior. Specific Aim 3: To determine how the home environment, maternal mental health, and parenting modify trajectories of brain connectivity and neurodevelopment over the first two years of life. This aim is also ongoing. We have published our data from maternal questionnaires showing that mothers with opioid use during pregnancy experience more stigma in the healthcare environment, and that mothers in our cohort with more depression and anxiety symptoms have poor quality attachment with their infants. Our progress so far in OBOE, with completion of enrollment and success at following this difficult population, demonstrates ability to complete this study. Our centers have an excellent track record of enrollment of high-risk infants in clinical studies with successful participant retention and follow-up to 2 years of age, with trained certified examiners for neurodevelopment and established infrastructure for unsedated neonatal and infant cranial MRI. We therefore anticipate successful completion of follow-up of the enrolled infants.