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岁的早产儿的生命轨迹中的同性载荷和表观遗传机制婴儿最激烈的逆境经历是早产。每年，十分之一（450,000英寸美国，全球1500万）婴儿过早出生。美国早产的社会成本是估计为每年260亿美元。婴儿的早期诞生标志着长期轨迹的开始影响家庭，医疗保健，教育，社会系统以及幸存者本身。但是，研究与年轻人相比，成年后的早产婴儿很少占早产儿的20％。我们确实知道他们向成年的过渡是具有挑战性的，并且经常受到阻碍认知，身心健康，运动和独立困难。在此应用程序中，我们回应医学研究所建议长期成年的长期结局研究过早的成年婴儿。现在，我们提出了30-33岁时的第10波，对于215的特征良好的早产样本代表各种新生儿发病率，出生体重和所有SES地层的婴儿。我们保留了 17至23岁之间的样本中有96％，自出生以来为85％。在前瞻性，纵向设计中，具体目的是：（1）确定医疗风险，社会经济的生命力和累积影响风险和保护成人身体和心理健康，适应性功能，执行官的风险和保护功能，工作和社会能力到30岁；（2）确定跨早产组的同层负载和社会经济水平，及其对身体和心理健康，适应性功能的影响，执行功能，工作和社会能力，截至30岁；在探索目的（3）中，检查和比较全性的DNA甲基化和年龄加速度的估计值（Horvath的表观遗传钟）术语和早产群体30岁。早产组的DNA甲基化和“时钟”的可变性，以及将检查性别，以及与肥胖的30年心血管指标的关联。我们将探索与表观遗传钟之间的医疗风险，SES和保护之间的纵向关联。这项目代表罗德岛大学，罗德岛纪念医院之间的合作和加利福尼亚大学尔湾分校。跨学科研究团队由护理专家组成，医学，发育小儿，压力和心理内分泌学，营养，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分类结果的二进制概率模型的逻辑回归）。线性混合模型（LMM）和广义线性混合模型（GLMM），在时间中包含时间的固定和随机效应随着时间的流逝，模型检查结果变量的轨迹差异。适当的协变量如果适用，将在基线和所有数据点进行评估。鉴于科学的状态，提议项目具有新颖的生命观点，可以解释新生儿时期的压力发育环境（风险，保护），分子和表观遗传机制以及个人弹性时间。同级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监管系统的生理影响。我们将探索全依性性的DNA甲基化作为一种同层负荷过程的基础机制。同级负荷和DNA甲基化都在应力上构建范式在健康起源理论的理论上。在这个项目中，我们建议从生命的角度综合，以确定早产和环境压力如何效应早产成人健康。据我们所知，这将是美国唯一对30-33岁过早婴儿的研究。因此，基于研究的证据有限，尽管数百万早产幸存者。

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。