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

静态负荷

• 批准号: 10335154
• 负责人: Amy L D'Agata
• 金额: $ 52.25万
• 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/10335154
• 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岁早产儿生命轨迹的非稳态负荷与表观遗传机制 对婴儿来说，最强烈的逆境经历之一是早产。每年，十分之一（45万人） 美国，全球1500万）婴儿早产。美国早产的社会成本是 预计为260亿美元/年。婴儿的早产标志着一个漫长的轨迹的开始， 影响到家庭、医疗保健、教育、社会制度和幸存者本身。然而，研究 与年轻时的早产儿相比，成年时的早产儿很少，大多数早产儿都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具有挑战性的，而且往往受到以下因素的阻碍： 认知、身心健康、运动和独立困难。在本申请中，我们回应 医学研究所建议对早产儿进行长期的成年期研究， 婴儿。我们现在建议在30-33岁的第10波为215例特征良好的早产样本 代表新生儿发病率、出生体重和所有社会经济地位分层的婴儿。我们保留 96%的样本年龄在17岁至23岁之间，85%的样本出生后就有了。在前瞻性纵向设计中， 具体目标是：（1）确定医疗风险的生命过程和累积影响，社会经济 风险，并保护成年人的身心健康，适应功能，执行 功能、工作和社会能力到30岁;（2）确定早产儿组的非稳态负荷 和社会经济水平，及其对身心健康、适应功能、 在探索性目标（3）中，检查并比较 表观基因组DNA甲基化和估计年龄加速（霍瓦特的表观遗传时钟）在整个 30岁时足月和早产儿组。DNA甲基化和“时钟”在早产儿组中的变异性， 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和保护与表观遗传时钟之间的纵向关联。的 该项目代表了罗得岛大学，罗得岛纪念医院， 和加州尔湾大学。跨学科研究团队由护理专家组成， 医学，发育儿科学，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后的模型（例如，用于连续， 二元逻辑回归，分类结果的广义优势模型）。线性混合模型 和广义线性混合模型（GLMM）的固定和随机效应的时间包括在 模型，以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（如适用）进行评估。考虑到科学的现状， 项目采取了一种新的生命过程的角度来看，占新生儿期的压力，累积 发展背景（风险，保护），分子和表观遗传机制，以及个人的弹性超过 时间非稳态负荷指数增加了生物风险的累积测量，因为它捕获了累积的 对主要调节系统的生理影响。我们将探索表观基因组DNA甲基化作为一种 非稳态负荷过程的机制。非稳态负荷和DNA甲基化都是建立在应激基础上的 健康与疾病的发展起源理论（Developmental Origins Theory of Health and Disease）在这个项目中，我们提出了一个 从生命过程的角度进行综合，以确定早产和环境压力如何影响早产- 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，在本发明中， 尽管有数百万人，但只有有限的基于研究的证据来告知干预的时间和内容。 早产儿幸存者