Project Summary Asthma is a chronic inflammatory lung disease that currently affects an estimated 8.4% of children in the U.S., resulting in over 600,000 emergency department visits and over 75,000 hospitalizations each year (Moorman et al., 2012). For decades the burden of asthma in the U.S. has fallen disproportionately on Black children living in low- resourced communities, for whom the prevalence, morbidity and mortality rates far exceed those for White children. Black children have 2-3 times higher rates of hospitalization and emergency department visits compared with White children, and a nearly 5-fold increase in asthma-related mortality (Volerman, et al., 2019). In some neighborhoods on the South Side of Chicago the rates of asthma among young Black children are over 40% (Gupta et al., 2008). The high rate of asthma and allergy in Black children appears to be in part influenced by prenatal stress exposure. Thus, an intervention designed to improve prenatal stress regulation in Black women may also reduce the risk of asthma in their children. The Nutrition and Pregnancy Study (NAPS) (NCT02647723) is a nearly completed double-blind, randomized controlled study (RCT) of prenatal fatty acid supplementation aiming to improve birth outcomes and infant neurodevelopment via improved prenatal stress regulation. Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been shown to protect against the development of asthma and atopy in controlled animal studies and in observational studies of humans. Results from two small RCTs of infant formula supplementation provide further support for the protective effects of dietary fatty acids against asthma (Birch et al., 2010; Foiles et al., 2016). The NAPS study provides an unprecedented opportunity to test the effects of prenatal DHA levels on childhood asthma and atopic disease, and to further examine how patterns of prenatal stress regulation impact that effect. We propose to conduct clinical assessments of asthma and other atopic outcomes in 130 children at 5-6 years of age whose mothers participated in the NAPS study, and to collect data from medical records and maternal report to test two aims. Aim 1: Test whether prenatal fatty acid levels are associated with asthma and atopic disease in early childhood. We hypothesize that higher prenatal blood levels of DHA will be associated with lower levels of asthma and atopy in the offspring as measured via laboratory assessments of asthma and allergic sensitization at ages 5-6 years, as well as medical record abstraction and maternal report. Aim 2: Test whether prenatal stress regulation impacts the association between prenatal fatty acid levels and asthma and atopic disease in early childhood. Our primary hypothesis is that cortisol and cytokine levels, heart rate variability, and perceived stress during pregnancy will partially mediate the association between prenatal DHA levels and childhood asthma and atopic disease. We will also test whether the associat...