Pre- and postnatal chemical mixture exposure, adolescent sleep health, and allostatic load

产前和产后化学混合物暴露、青少年睡眠健康和稳态负荷

• 批准号: 10639218
• 负责人: Clara G Sears
• 金额: $ 56.24万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639218
• 关键词: Adolescence; Adolescent; Adolescent Development; Adrenal Glands; Adult; Age; Biological; Biological Markers; Biometry; Birth; Body Composition; Cardiovascular system; Catecholamines; Characteristics; Chemicals; Child; Childhood; Cortisone; Data; Development; Diet; Disease; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epidemiology; Exposure to; Foundations; Glycoproteins; Goals; Growth; Hair; Health; Homeostasis; Hydrocortisone; Hypertension; Hypothalamic structure; Immune; Individual; Infant; Inflammation; Intervention; Joints; Knowledge; Life; Link; Longitudinal Studies; Longitudinal cohort; Measures; Metabolic; Metals; Middle School Student; Morbidity - disease rate; Neurobiology; Neurosecretory Systems; Obesity; Outcome; Outcome Measure; Pathway interactions; Persons; Physiological; Pituitary Gland; Pituitary-Adrenal System; Poly-fluoroalkyl substances; Predisposition; Pregnancy; Pregnant Women; Process; Prospective cohort; Questionnaires; Regulation; Research; Risk; Risk Factors; Risk Reduction; School-Age Population; Serum; Shapes; Sleep; System; Testing; Toxic Environmental Substances; Toxicant exposure; Visit; actigraphy; adequate sleep; allostasis; allostatic load; blood pressure elevation; cardiometabolism; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; cohort; consumer product; critical developmental period; design; early childhood; early life exposure; environmental chemical; high school; improved; improvement on sleep; indexing; infancy; modifiable risk; mortality; multidisciplinary; neurobiological mechanism; neurodevelopment; neurotoxic; novel; phthalates; pollutant; poor sleep; postnatal; pregnant; prenatal; prospective; public health intervention; sleep health; sleep quality; systemic inflammatory response; toxic metal; toxicant; urinary

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.

项目概要/摘要 大多数美国青少年都没有获得充足的睡眠，因此睡眠健康对于保持最佳健康至关重要。 青春期是因为神经发育、生长和身体成分快速变化。 睡眠不足和质量差会增加稳态负荷，或累积的生理“磨损”， 协调免疫、心血管和代谢功能的多个调节系统受到破坏。 有证据表明，发育过程中接触普遍存在的环境毒物可能会破坏 然而，这些暴露是否是调节睡眠和动态平衡的神经生物学机制。 我们的多学科研究尚未对青春期睡眠不良的可改变危险因素进行严格研究。 该项目汇集了儿科环境健康、睡眠和心脏代谢健康方面的专家，以确定 生命早期接触环境有毒混合物是否会扰乱青少年的睡眠健康并增加睡眠质量 该项目重点关注邻苯二甲酸盐、全氟烷基物质/多氟烷基物质 (PFAS) 和的混合物。 大多数孕妇、婴儿和儿童通过饮食和接触接触这些有毒物质的混合物。 该项目利用了来自两个特征明确的预期的现有数据和新数据。 怀孕和出生队列、健康结果和环境措施（HOME）研究以及 环境化学物质母婴研究 (MIREC) 研究先前已入组。 孕妇和随访儿童直至 7-9 岁 (MIREC n=300) 或 10-12 (HOME n=256) 岁 10-12 岁（MIREC）和 16-18 岁（家庭）睡眠特征正在进行中。 使用体动记录仪在两个时间点对两个队列进行检查，我们将量化环境之间的关系。 妊娠期、幼儿期、学龄期和青春期的有毒生物标志物与睡眠特征 （目标 1）和青春期期间的稳态负荷（目标 2）我们还将检查是否暴露于环境。 有毒混合物与下丘脑-垂体-肾上腺 (HPA) 活性、儿茶酚胺和 全身炎症、睡眠-觉醒调节和动态平衡的生物中间体（目标 3）。 将识别环境有毒混合物的个体和联合影响并检查花期 确定关键发育时期的易感性。 睡眠健康状况不佳和稳态负荷可能会为降低心血管疾病风险的新干预措施提供信息 疾病，是全世界成年人发病和死亡的主要原因。