Allostatic Load & Epigenetic Mechanisms in Lifecourse Trajectories of Premature Infants at Age 30

静态负荷

• 批准号: 9888435
• 负责人: Mary C Sullivan
• 金额: $ 62.35万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-06 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888435
• 关键词: 37 weeks gestation; Acceleration; Adult; Affect; Age; Age-Years; Biological; Biometry; Birth; Birth Weight; California; Cardiovascular system; Categories; Chemicals; Childhood; Chronic; Chronic stress; Cognitive; Collaborations; Coupled; CpG dinucleotide; DNA Methylation; Data; Databases; Development; Discipline of Nursing; Disease; Economic Burden; Education; Environment; Environmental Risk Factor; Epigenetic Process; Exposure to; Family health status; Gender; Goals; Health; Healthcare; Heterogeneity; Hospitals; Independent Living; Individual; Infant; Inflammatory; Institute of Medicine (U.S.); Interdisciplinary Study; Intervention; Learning; Linear Regressions; Logistic Regressions; Longevity; Measures; Mediating; Medical; Medicine; Memory; Mental Health; Metabolic; Modeling; Molecular; Motor; Neonatal; Neonatal Intensive Care Units; Neurosecretory Systems; Obesity; Occupational; Outcome; Outcome Study; Participant; Pediatrics; Perinatal; Physiological; Pregnancy; Premature Birth; Premature Infant; Procedures; Process; Psychoneuroendocrinology; Public Health; Recommendation; Reporting; Research; Rhode Island; Risk; Sampling; Science; Signal Transduction; Signaling Molecule; Social Functioning; Stress; Survivors; System; Time; United States; Universities; Work; allostatic load; biological adaptation to stress; cohort; comparison group; cost; emerging adult; evidence base; executive function; experience; follow-up; hypothalamic-pituitary-adrenal axis; immune function; indexing; innovation; longitudinal design; maternal separation; methyl group; neonatal morbidity; neonatal period; novel; nutrition; peer; physical conditioning; postnatal; predictive modeling; premature; prospective; protective effect; protective factors; psychobiology; resilience; social; social skills; societal costs; socioeconomics; stressor; theories; young adult

Allostatic Load & Epigenetic Mechanisms in Lifecourse Trajectories of Premature Infants at Age 30 Among the most intense experiences of adversity for infants is premature birth. Annually, 1 in 10 (450,000 in the US, 15 million worldwide) infants are born prematurely. The societal cost of preterm birth in the US is estimated to be $26 billion/year. An infant's early birth marks the beginning of a long trajectory that broadly impacts families, health care, education, social systems, and the survivors themselves. Yet, studies of premature infants at adulthood are few compared to those at younger ages and most focus on the smallest 20% of premature infants. We do know that their transition to adulthood is challenging, and often hampered by cognitive, physical and mental health, motor and independence difficulties. In this application, we respond to an Institute of Medicine recommendation for long-term outcome studies into young adulthood for premature infants. We now propose the 10th wave at 30-33 years of age for a well-characterized preterm sample of 215 infants representing a wide range of neonatal morbidity, birth weight, and all SES strata. We have retained 96% of the sample between ages 17 and 23 years, and 85% since birth. In a prospective, longitudinal design, the specific aims are to: (1) Determine the lifecourse and cumulative impact of medical risk, socioeconomic risk, and protection on adult outcomes of physical and psychological health, adaptive function, executive function, work, and social competence to age 30y; (2) Determine the allostatic load across prematurity groups and socioeconomic levels, and its impact on outcomes of physical and psychological health, adaptive function, executive function, work, and social competence to age 30y; and in exploratory aim (3), examine and compare epigenomewide DNA methylation and estimates of age acceleration (Horvath's epigenetic clock) across full- term and preterm groups at age 30y. Variability of DNA methylation and the `clock' across preterm groups and gender will be examined as well as the association with 30y cardiovascular indicators of obesity. We will explore longitudinal associations between medical risk, SES, and protection with the epigenetic clock. The project represents collaboration between the University of Rhode Island, Memorial Hospital of Rhode Island, and the University of California Irvine. The interdisciplinary research team is comprised of experts in nursing, medicine, developmental pediatrics, stress and psychoneuroendocrinology, nutrition, epigenetics and biostatistics. The analysis approach includes adjusted models (e.g. linear regression model for continuous, logistic regression for binary, generalized odds model for categorical outcomes). Linear mixed models (LMM) and generalized linear mixed models (GLMM) with both fixed and random effects of time included in the models to examine the differences in trajectories of the outcome variables over time. Appropriate covariates will be assessed at baseline and all data points if applicable. Given the state of the science, the proposed project takes a novel lifecourse perspective that accounts for the stress of the neonatal period, the cumulative developmental context (risk, protection), molecular and epigenetic mechanisms, and individual resilience over time. The allostatic load index adds a cumulative measure of biological risk since it captures cumulative physiological effects across major regulatory systems. We will explore epigenomewide DNA methylation as a mechanism underlying allostatic load processes. Both allostatic load and DNA methylation build on a stress paradigm theorized at Developmental Origins Theory of Health and Disease. In this project we propose a synthesis in a lifecourse perspective to determine how prematurity and environmental stress effect preterm-to- adult health. To our knowledge, this would be the only U.S. study of premature infants to age 30-33y. Thus, there is limited research-based evidence to inform the timing and content for interventions despite millions of preterm survivors.

30 岁早产儿生命历程轨迹的稳态负荷和表观遗传机制 对于婴儿来说，最强烈的逆境经历之一就是早产。每年，十分之一（450,000 美国、全球有 1500 万）婴儿早产。美国早产的社会成本是 估计为 260 亿美元/年。婴儿的早产标志着一个漫长轨迹的开始，广泛地 影响家庭、医疗保健、教育、社会系统和幸存者本身。然而，研究 与年轻时相比，成年后的早产儿很少，而且大多数集中在最小的婴儿身上 20%的早产儿。我们确实知道他们向成年的过渡是充满挑战的，并且常常受到以下因素的阻碍 认知、身心健康、运动和独立困难。在此应用程序中，我们响应 医学研究所建议对早产儿的成年早期进行长期结果研究 婴儿。我们现在建议在 30-33 岁进行第 10 波，以收集 215 名特征明确的早产儿样本 代表各种新生儿发病率、出生体重和所有 SES 阶层的婴儿。我们保留了 96% 的样本年龄在 17 岁至 23 岁之间，85% 的样本自出生以来。在前瞻性的纵向设计中， 具体目标是： (1) 确定生命周期和医疗风险、社会经济风险的累积影响 对成人身心健康、适应功能、执行力等结果的风险和保护 30 岁之前的功能、工作和社交能力； (2) 确定早产儿组的别静负荷 和社会经济水平，及其对身心健康、适应功能、 30 岁之前的执行功能、工作和社交能力；在探索性目标（3）中，检查和比较 全表观基因组 DNA 甲基化和年龄加速估计（Horvath 的表观遗传时钟） 30 岁的足月儿组和早产儿组。 DNA甲基化和早产儿组“时钟”的变异性 将检查性别以及与 30 岁肥胖心血管指标的关联。我们将 探索医疗风险、SES 和表观遗传时钟保护之间的纵向关联。这 该项目代表了罗德岛大学、罗德岛纪念医院、 和加州大学欧文分校。跨学科研究团队由护理专家、 医学、发育儿科、压力和心理神经内分泌学、营养学、表观遗传学和 生物统计学。分析方法包括调整模型（例如连续的线性回归模型， 二元逻辑回归，分类结果的广义赔率模型）。线性混合模型 (LMM) 以及广义线性混合模型 (GLMM)，其中包含时间的固定效应和随机效应 模型来检查结果变量随时间变化的轨迹差异。适当的协变量 将在基线和所有数据点（如果适用）进行评估。鉴于科学状况，建议 该项目采用了一种新颖的生命历程视角，考虑了新生儿期的压力、累积的压力 发展背景（风险、保护）、分子和表观遗传机制以及个人的适应力 时间。非稳态负荷指数增加了生物风险的累积衡量标准，因为它捕获了累积的风险 主要监管系统的生理效应。我们将探索表观基因组 DNA 甲基化作为 动态负载过程的基础机制。稳态负荷和 DNA 甲基化都建立在压力的基础上 健康与疾病发展起源理论的范式理论化。在这个项目中我们提出了一个 从生命历程的角度进行综合，以确定早产和环境压力如何影响早产儿 成人健康。据我们所知，这将是美国唯一一项针对 30-33 岁早产儿的研究。因此， 尽管有数以百万计的研究表明干预措施的时间和内容，但基于研究的证据仍然有限 早产幸存者。