PROJECT SUMMARY / ABSTRACT A majority of U.S. adolescents are not getting sufficient sleep for optimal health. Sleep health is critical during adolescence because of rapid neurodevelopment, growth, and body composition changes. Moreover, inadequate and poor-quality sleep can increase allostatic load, or cumulative physiological ‘wear and tear’, from disruptions across multiple regulatory systems that coordinate immune, cardiovascular, and metabolic function. Evidence indicates that developmental exposures to ubiquitous environmental toxicants may disrupt neurobiological mechanisms that regulate sleep and allostasis. However, whether these exposures are modifiable risk factors for poor sleep during adolescence has not been rigorously examined. Our multidisciplinary project brings together experts in pediatric environmental health, sleep, and cardiometabolic health to identify whether early life exposure to environmental toxicant mixtures disrupts adolescent sleep health and increases allostatic load. This project focuses on mixtures of phthalates, per-/polyfluoroalkyl substances (PFAS), and metals. Most pregnant people, infants, and children are exposed to mixtures of these toxicants through diet and consumer goods. The project leverages existing and new data from two well-characterized prospective pregnancy and birth cohorts, the Health Outcomes and Measures of the Environment (HOME) Study and the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. Both cohorts previously enrolled pregnant women and followed children until ages 7-9 (MIREC n=300) or 10-12 (HOME n=256) years with additional visits underway at ages 10-12 (MIREC) and 16-18 (HOME) years. Sleep characteristics will be examined at two timepoints in both cohorts using actigraphy. We will quantify relations between environmental toxicant biomarkers during gestation, early childhood, school age, and adolescence with sleep characteristics (Aim 1) and allostatic load (Aim 2) during adolescence. We will also examine whether exposure to environmental toxicant mixtures is associated with hypothalamus-pituitary-adrenal (HPA) activity, catecholamines, and systemic inflammation, biological intermediates of sleep-wake regulation and allostasis (Aim 3). Our analyses will identify individual and joint effects of environmental toxicant mixtures and examine periods of heightened susceptibility during critical developmental periods. Identifying modifiable environmental factors that contribute to poor sleep health and allostatic load may inform novel interventions to reduce the risk of cardiovascular disease, the leading cause of morbidity and mortality in adulthood worldwide.

PROJECT NARRATIVE Exposure to environmental toxicants during early life development may negatively impact sleep health during adolescence. This project will examine whether mixtures of phthalates, per-/polyfluoroalkyl substances (PFAS), and metals during gestation, infancy, childhood, and adolescent development are related to poorer sleep and higher allostatic load, cumulative ‘wear and tear’ from physiological disruptions. Understanding whether environmental toxicants that are commonly found in consumer products and residential environments impact sleep characteristics may lay the foundation for novel interventions to improve health.