EMA Assessment of Biobehavioral Processes in Human Pregnancy

人类妊娠生物行为过程的 EMA 评估

基本信息

批准号：
8514381
负责人：
Sonja Entringer
金额：
$ 31.79万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514381
关键词：
Address Age-Months Aging Area Biological Biological Markers Biology Birth Birth length Cells Child Classification Clinical Collaborations Complex Data Development Discipline of obstetrics Disease Disease susceptibility Dose Endocrine Environment Epidemiology Exercise Expeditions Exposure to Fetal Growth Fetus First Pregnancy Trimester Fishes Functional disorder Funding Future Generations Goals Growth Health Human Hydrocortisone Immune Immunology Individual Infant Infection Inflammatory Interleukin-6 Intervention Investigation Isoprostanes Knowledge Length Leukocytes Life Malnutrition Maternal Behavior Measures Mediating Mitogens Molecular Neonatology Newborn Infant Outcome Overnutrition Oxidative Stress Pathway interactions Perinatal Exposure Peripheral Blood Mononuclear Cell Phase Phenotype Physiological Play Predisposition Pregnancy Process Protocols documentation Public Health Publishing Research Research Personnel Risk Role Second Pregnancy Trimester Staging Stress Systems Biology T-Lymphocyte Telomerase Testing Third Pregnancy Trimester Time Translational Research Trees Umbilical Cord Blood Validation Wing adverse outcome age related biobehavior burden of illness cohort cost effective disorder risk fetal fetal programming follow-up in utero infant nutrition interest maternal stress novel offspring parent project population based postnatal prenatal prenatal stress prevent programs prospective response telomere

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to extend the scope of our on-going studies to test specific hypotheses regarding the effects of maternal-placental-fetal stress biology during intrauterine life on the human newborn and infant telomere biology system. The elucidation of biological mechanisms underlying the effects of the intrauterine environment on subsequent health and disease risk outcomes (fetal/developmental programming) is an area of active interest and intense investigation. We advance the hypothesis that telomere biology may represent an important and novel mechanism underlying the observed effects of disparate suboptimal intrauterine exposures on subsequent health and disease risk phenotypes of interest. We propose to focus on two key telomere biology-related outcomes - leukocyte telomere length at birth and at 12 months age, and mitogen-stimulated leukocyte telomerase expression at birth, and on the effects of a major biological pathway in human gestation - stress-related maternal-placental-fetal (MPF) endocrine, immune/inflammatory and oxidative state - that may mediate the effects of a diverse set of suboptimal conditions on the developing fetus. We will conduct a prospective, longitudinal, follow-up study in a representative, population-based cohort of N=120 newborns from birth (T1) and over the early postnatal growth phase until 12 months age (T2). A unique strength of our proposal is the availability in our "parent" projects (RO1 HD-060628, RO1 HD-065825) of a cohort of newborns and infants who are extensively characterized over the course of intrauterine and postnatal life with the measures required in the present study. Another notable feature includes our trans-disciplinary team of investigators with a collaboration record and extensive, published expertise in maternal-placental-fetal stress biology (Pathik Wadhwa, Sonja Entringer), telomere biology (Elizabeth Blackburn, Elissa Epel, Jue Lin), immunology (Edward Nelson), and obstetrics/neonatology (Deborah Wing, Hyagriv Simhan). We will address the following Specific Aims: 1) To test the hypothesis that exposure to elevated intrauterine biological stress predicts a) newborn leukocyte telomere length (LTL) and b) change in LTL from birth till 12 months age. 2) To test the hypothesis that exposure to elevated intrauterine biological stress predicts newborn leukocyte telomerase activity. 3) After identifying which measures of intrauterine stress biology (and at which specific time points in gestation) predict newborn and infant LTL and telomerase activity, we will address exploratory questions of their determinants using the available comprehensive data collected in the on-going "parent" projects. The significance and impact of this study derives from the importance of achieving at a better understanding of underlying processes (mechanisms) that alter risk or vulnerability for subsequent health and disease risk outcomes. This study will collect novel data (serial measures of newborn and infant telomere biology) and address hypotheses that set the stage for translational research. We submit that this proposed study represents an appropriate expansion of the scientific scope of the parent project.

描述（由申请人提供）：本提案的目标是扩大我们正在进行的研究范围，以测试有关宫内生活期间母体-胎盘-胎儿应激生物学对人类新生儿和婴儿端粒生物学系统影响的具体假设。阐明宫内环境对后续健康和疾病风险结果（胎儿/发育规划）影响的生物学机制是人们积极关注和深入研究的领域。我们提出这样的假设：端粒生物学可能代表了一种重要而新颖的机制，是观察到不同的次优子宫内暴露对随后感兴趣的健康和疾病风险表型的影响的基础。我们建议重点关注两个关键的端粒生物学相关结果——出生时和 12 个月大时的白细胞端粒长度，以及出生时促细胞分裂原刺激的白细胞端粒酶表达，以及人类妊娠期主要生物学途径——压力相关的影响母体-胎盘-胎儿 (MPF) 内分泌、免疫/炎症和氧化状态 - 可能介导多种次优条件对发育中胎儿的影响。我们将对 N=120 名新生儿从出生 (T1) 到产后早期生长阶段直至 12 月龄 (T2) 的代表性、基于人群的队列进行前瞻性、纵向、随访研究。我们提案的独特优势在于我们的“父母”项目（RO1 HD-060628、RO1 HD-065825）中提供了一组新生儿和婴儿，这些新生儿和婴儿在宫内和产后生活过程中具有广泛的特征，并采取了以下措施所需的措施：目前的研究。另一个值得注意的特点包括我们的跨学科研究团队，他们在母体-胎盘-胎儿应激生物学（Pathik Wadhwa、Sonja Entringer）、端粒生物学（Elizabeth Blackburn、Elissa Epel、Jue Lin）、免疫学方面拥有合作记录和广泛的已发表的专业知识（爱德华·纳尔逊）和产科/新生儿科（Deborah Wing、Hyagriv Simhan）。我们将实现以下具体目标：1) 检验以下假设：暴露于升高的宫内生物应激可预测 a) 新生儿白细胞端粒长度 (LTL) 和 b) 从出生到 12 个月龄期间 LTL 的变化。 2) 检验宫内生物应激升高可预测新生儿白细胞端粒酶活性的假设。 3) 在确定哪些宫内应激生物学指标（以及妊娠的哪个特定时间点）可预测新生儿和婴儿 LTL 和端粒酶活性后，我们将利用正在进行的“母婴研究”中收集的可用综合数据来解决其决定因素的探索性问题。 ”项目。这项研究的意义和影响源于更好地理解改变后续健康和疾病风险结果的风险或脆弱性的潜在过程（机制）的重要性。这项研究将收集新数据（新生儿和婴儿端粒生物学的系列测量）并提出为转化研究奠定基础的假设。我们认为，这项拟议的研究代表了母项目科学范围的适当扩展。