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.

项目摘要/摘要 大多数美国青少年没有得到足够的睡眠来实现最佳健康。睡眠健康是至关重要的 青春期由于神经发育、生长和身体成分的快速变化。此外， 睡眠不足或睡眠质量不佳会增加人体的不平衡负荷，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的中断。 有证据表明，发育过程中暴露于无处不在的环境毒物可能会破坏 调节睡眠和异能的神经生物学机制。然而，无论这些暴露是不是 青春期睡眠不良的可改变的危险因素还没有得到严格的检查。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，以确定 早年接触环境毒物混合物是否会破坏青少年的睡眠健康并增加 不平衡负载。该项目的重点是邻苯二甲酸盐、全氟/多氟烷基物质(PFAS)和 金属。大多数孕妇、婴儿和儿童通过饮食和饮食接触到这些毒物的混合物 消费品。该项目利用了来自两个特征良好的潜在客户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(家庭)研究和 环境化学品母婴研究(MIREC)研究。这两个队列都是之前注册的 孕妇和跟踪儿童，直到7-9岁(MIREC n=300)或10-12岁(家庭n=256) 10-12岁(MIREC)和16-18岁(家庭)的额外探视正在进行中。睡眠特征将是 在两个队列中的两个时间点使用动作记录仪进行检查。我们将量化环境与环境之间的关系 具有睡眠特征的妊娠期、幼儿、学龄期和青春期有毒生物标志物 (目标1)和平衡负荷(目标2)在青春期。我们还将研究是否暴露在环境中 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-觉醒调节和异体平衡的生物中间体(目标3)。我们的分析 将确定环境毒物混合物的单独和联合影响，并检查高峰期 在关键发育期的易感性。确定对环境有影响的可更改环境因素 睡眠健康不良和变态负荷可能会提供新的干预措施来降低心血管疾病的风险 疾病是全世界成年人发病和死亡的主要原因。