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）：该提案的目的是扩展我们正在进行的研究的范围，以测试有关母体 - 植物 - 易于 - 易于应激生物学在宫内寿命中对人类新生儿和婴儿端粒生物学系统的影响的特定假设。阐明宫内环境对随后的健康和疾病风险结果（胎儿/发育节目）影响的生物学机制是一个积极关注和强烈调查的领域。我们推进了端粒生物学的假设可能代表了一种重要而新颖的机制，即观察到的属于宫内宫内宫内的影响对随后感兴趣的健康和疾病风险表型的影响。我们建议专注于两种与端粒生物学相关的关键结果 - 出生时和12个月时的白细胞端粒长度，以及出生时有丝分裂原刺激的白细胞端粒酶表达，以及主要生物途径在人类妊娠中的影响 - 与压力相关的孕产妇（mpf）的延伸（MPF）的影响，并具有不同发育中的胎儿的一组次优条件。我们将对从出生（T1）和产后早期生长阶段到12个月大的代表性，基于人群的n = 120个新生儿（T2）进行前瞻性，纵向的随访研究（T2）。我们提案的一个独特优势是我们的“父”项目（RO1 HD-060628，RO1 HD-065825）的可用性，这些新生儿和婴儿在本研究中所需的措施中所需的措施，在始终内和产后生活的过程中都广泛地表征了一群新生儿和婴儿。另一个值得注意的功能包括我们的跨学科调查人员团队，具有合作记录和广泛的出版专业知识，领域的专业知识（Pathik Wadhwa，Sonja Entringer），Telomere Biology（Elizabeth Blackburn，Elizabeth Blackburn，Elissa Epel，Elissa Epel，Jue Lin），Immunology（Edward Nelson）和NEONATICS/NEONATICS/NEONATIST（EDER），校友（evor）。我们将解决以下具体目的：1）检验以下假设：暴露于宫内生物学压力升高的情况下可以预测a）新生儿白细胞端粒长度（LTL）和b）LTL从出生到12个月大的LTL变化。 2）检验以下假设：暴露于宫内生物胁迫升高会预测新生白细胞端粒酶活性。 3）在确定了宫内应激生物学的哪些度量（以及妊娠中的特定时间点）预测新生儿和婴儿LTL和远程合酶活动后，我们将使用正在进行的“父母”项目中收集的可用综合数据来解决其决定因素的探索性问题。这项研究的重要性和影响来自于更好地理解基本过程（机制）的重要性，这些过程（机制）改变了随后的健康和疾病风险结果的风险或脆弱性。这项研究将收集新的数据（新生儿和婴儿端粒生物学的序列测量），并解决为转化研究奠定阶段的假设。我们认为这项拟议的研究代表了父母项目的科学范围的适当扩展。