Modified Project Summary/Abstract Section The prevalence of preterm birth is 14.4%, 10.0% and 9.3% among Black, Hispanic, and non-Hispanic white mothers, respectively. Hispanic and Black women are also at higher risk of maternal morbidities such as hypertension in pregnancy and gestational diabetes. Along with the compelling evidence of the impact of adverse perinatal health on the health of a mother and her infant throughout the life course comes high societal and economic costs. Yet, the etiology of adverse pregnancy outcomes is not fully explained by genetics, behavior, or access to care and other factors, including features of the neighborhood environment, likely play a role. There exist wide differences in the distribution of neighborhood characteristics, which can be classified in several domains, including the social, built, and physical environment. For example, residential segregation has led to some communities being situated in areas with lower property values and more industries and hazardous waste sites nearby. Given the proximity of these neighborhoods to key sources of air, water, and soil pollution, they experience increased exposure to environmental contaminants. Moreover, women in high-risk communities are subject to spillover stress. While there is growing evidence of the impact of neighborhood features on perinatal health, findings are equivocal, and research related to the joint impact of multiple features of the neighborhood environment is lacking. In this application, we will assess the independent effects of neighborhood features across multiple domains on both maternal morbidity (hypertension in pregnancy and gestational diabetes) and adverse pregnancy outcomes (low birth weight and preterm birth), explore whether combined exposures to multiple neighborhood features enhances these risks, and apply machine learning methods to identify the key neighborhood predictors of adverse perinatal health outcomes. To achieve our aims, we will construct a retrospective birth cohort of women who delivered infants at major obstetric hospitals in the 3rd largest county (Harris) in the U.S. (where Houston is located) that will include follow-up throughout a mother’s pregnancy to the birth of her infant. Our project leverages established partnerships among Baylor College of Medicine, UTHealth McGovern Medical School, and Texas Southern University, and draws on our collective expertise in environmental and perinatal epidemiology, women’s health, maternal-fetal medicine, criminal justice, social science, biostatistics, and bioinformatics. This work is expected to elucidate the contribution of neighborhood factors across multiple domains on several key perinatal health outcomes. Importantly, the results from this study will also enhance our understanding of the complex interplay and identification of key neighborhood-level drivers of perinatal health and lay the foundation for future studies to promote interventions.