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.

项目总结/摘要 大多数美国青少年没有获得足够的睡眠以保持最佳健康。睡眠健康是至关重要的 青春期，因为快速的神经发育，生长和身体成分的变化。此外，委员会认为， 不充分和低质量的睡眠会增加非稳态负荷，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之间的干扰。 有证据表明，发育暴露于无处不在的环境毒物可能会破坏 神经生物学机制调节睡眠和适应性平衡。然而，这些风险是否 青春期睡眠不佳的可改变的风险因素尚未得到严格的研究。我们的多学科 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， 早期生活暴露于环境有毒混合物是否会破坏青少年的睡眠健康， 非稳态负荷该项目侧重于邻苯二甲酸酯、全氟/多氟烷基物质（PFAS）和 金属.大多数孕妇、婴儿和儿童都通过饮食接触到这些有毒物质的混合物， 消费品该项目利用来自两个特征良好的前瞻性研究的现有和新数据， 妊娠和分娩队列、健康结果和环境措施（HOME）研究以及 母婴环境化学品研究（MIREC）。两个队列均既往入组 孕妇和随访儿童，直至7-9岁（MIREC n=300）或10-12岁（HOME n=256）， 在10-12岁（MIREC）和16-18岁（HOME）进行额外的访问。睡眠特点将是 在两个时间点使用体动记录仪检查两个队列。我们将量化环境之间的关系 妊娠期、幼儿期、学龄期和青春期毒性生物标志物与睡眠特征 (Aim 1）和非稳态负荷（目标2）在青春期。我们还将研究是否暴露于环境中， 有毒混合物与下丘脑-垂体-肾上腺（HPA）活性、儿茶酚胺和 全身性炎症，睡眠-觉醒调节和变应性平衡的生物中间体（目的3）。我们的分析 将确定环境有毒物质混合物的单独和联合影响，并检查 在关键的发展时期。确定可改变的环境因素， 睡眠健康状况差和非稳态负荷可能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。