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

静态负荷

基本信息

批准号：
10569056
负责人：
Amy L D'Agata
金额：
$ 43.53万
依托单位：
UNIVERSITY OF RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-06 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10569056
关键词：
37 weeks gestation Acceleration Adult Affect Age Age Years Biological Biological Process Biometry Birth Birth Weight California Cardiovascular system 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 Gender Goals Health Healthcare Heterogeneity Hospitals Independent Living Individual Infant Inflammatory Institute of Medicine (U.S.)Interdisciplinary Study Intervention Learning Life Cycle Stages Linear Regressions Logistic Regressions Longevity Measures Mediating Medical Medical Economics 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

项目摘要

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岁早产儿生命轨迹中的恒定负荷和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(450,000英寸美国，全球有1500万)婴儿早产。在美国，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影响家庭、卫生保健、教育、社会制度和幸存者本身。然而，对生物多样性的研究与年轻的婴儿相比，成年期的早产儿很少，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具有挑战性的，而且经常受到认知、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对早产儿青壮年长期结局研究的建议婴儿。我们现在建议在30-33岁的第10波，对215个特征良好的早产样本婴儿代表了广泛的新生儿发病率、出生体重和所有SES阶层。我们保留了 96%的样本年龄在17岁到23岁之间，85%的人出生后。在前瞻性的纵向设计中，具体目标是：(1)确定医疗风险、社会经济风险的生命过程和累积影响对成年人身心健康、适应功能、执行力的风险和保护 30岁前的功能、工作和社交能力；(2)确定早产儿组之间的平衡负荷和社会经济水平，及其对身心健康、适应功能、 30岁以下的执行职能、工作和社会能力；在探索性目标(3)中，检查和比较表观全基因组DNA甲基化和年龄加速(Horvath表观遗传学时钟)的估计 30岁时的足月组和早产组。早产儿和早产儿之间DNA甲基化和时钟的变异性将研究性别以及与肥胖的30年心血管指标之间的关系。我们会探索医疗风险、SES和保护与表观遗传学时钟之间的纵向联系。这个该项目代表罗德岛大学、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组成，医学、发育儿科学、压力和精神神经内分泌学、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，连续的线性回归模型，二元Logistic回归，分类结果的广义优势模型)。线性混合模型(LMM) 和广义线性混合模型(GLMM)，其中包含固定和随机的时间效应检验结果变量随时间变化的轨迹差异的模型。适当的协变量将在基线和所有数据点(如果适用)进行评估。鉴于目前的科学状况，拟议的项目采用了一种新的生命过程视角，解释了新生儿期的压力，累积发育背景(风险、保护)、分子和表观遗传机制以及个体的复原力时间到了。恒定负荷指数增加了生物风险的累积度量，因为它捕获了累积主要调控系统的生理效应。我们将探索表观全基因组DNA甲基化作为不平衡负荷过程的潜在机制。变态负荷和DNA甲基化都建立在应激的基础上健康与疾病的发展起源理论的范式理论。在这个项目中，我们提出了一个从生命周期的角度进行综合，以确定早产和环境压力如何影响早产至早产成人健康。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，尽管数以百万计的研究表明干预的时机和内容，但基于研究的证据有限早产幸存者。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

DOI：
10.1097/nnr.0000000000000612
发表时间：
2022-11-01
期刊：
NURSING RESEARCH
影响因子：
2.5
作者：
Sullivan, Mary C.;D'Agata, Amy L.;Stanley, Zachary;Brewer, Pamela;Kelly, Michelle M.
通讯作者：
Kelly, Michelle M.

A new patient population for adult clinicians: Preterm born adults.

成人临床医生的新患者群体：早产成人。