Brain development during the early years goes through rapid change with vulnerable periods where a variety of environmental exposures can have a large and enduring impact in early neurodevelopment and long-term health outcomes. Experiences will permanently modify brain structure and function through epigenetic changes that contribute to individual differences, in addition to reciprocal interactions among brain plasticity and autonomic neuroendocrine, metabolic, and immune functions. Few studies have addressed how early brain development and trajectories are impacted by early experiences and potential biological interactions within a diverse population inclusive of rural and minority populations. The central goal of the HEAL Initiative: HEALthy Brain and Child Development study is to prospectively examine brain and behavioral development from birth through childhood with emphasis on the impact of in utero substance exposure on outcome. At the University of Alabama at Birmingham (UAB) and the University of Alabama (UA) we will enroll pregnant women during their second trimester and follow their infants with a comprehensive multimodal data longitudinal study. Strengths to UAB include the Comprehensive Addiction in Pregnancy Program (CAPP) that provides prenatal care and support to pregnant women with history of substance use. UAB OB supports several prenatal clinics within Jefferson and Blount County Departments of Health, neighborhood health centers, and the Complications clinic. UAB is actively enrolling participants for the HEAL Outcomes of Babies with Opioid exposure and the ACT NOW Weaning study. UAB is a site for the NICHD Maternal Fetal Medicine Network and the NICHD Neonatal Research Network for >25 years, with long-standing, well-established and highly productive collaborations with other centers. UA operates at the University Medical Center in Tuscaloosa that serves the majority of the Medicaid recipients in the region as well as rural clinics in surrounding counties, including those in the Alabama Black Belt. The UA team has expertise in neuroimaging, EEG, rural health, maternal health and child development. Therefore, there is demonstrated adequacy of clinical, research, administrative and facilities to accomplish this project. We clearly express our intent to participate in a cooperative manner with the other research sites, the HDCC, HCAC, the NIH Program Scientist and the NIH Program Official in all aspects of research in a manner consistent with the terms of the award. Specific Aims: 1. Determine typical neurodevelopmental trajectories and typical range of variability of brain development from birth through childhood in a diverse population. 2. Determine how early life exposure to opioids, other substances, and other adverse environmental circumstances affect these trajectories. 3. Determine how genetic influences interact with environmental factors to influence neurodevelopment. Design: 300 mother/child dyads (100 with and 200 without history of drug exposure) with complete longitudinal brain, behavioral and biological assessment in conjunction with other research sites within the HEAL Initiative.

Project Narrative Our center (University of Alabama at Birmingham and University of Alabama) will join other centers from the consortium in enrolling pregnant women and their infants in a comprehensive prospective, longitudinal and multimodal data collection. We will examine variability in outcomes and the effect of substance exposure in utero as well as other experiences in development and the interaction with genetic, biological and endocrine system. Our center, has extensive experience in participating in similar multicenter studies and, will be able to enroll dyads of mothers and their infants.