ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

环境对早产儿神经发育结果的影响

基本信息

批准号：
10412194
负责人：
Barry M. Lester
金额：
$ 6.5万
依托单位：
WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-21 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10412194
关键词：
Acute Address Adrenal Cortex Hormones Affect Age Anti-Inflammatory Agents Behavioral Biological Markers Birth Blood Bronchopulmonary Dysplasia Cells Cessation of life Child Child Health Chronic Disease DNA Methylation Data Development Epigenetic Process Exposure to Extremely low gestational age newborn Future Gases Genes Genome Glucocorticoids Health Impairment Infant Inflammation Intervention Interview Knowledge Lead Length of Stay Life Link Longevity Medical Molecular Morbidity - disease rate Neonatal Neonatal Intensive Care Units Neurodevelopmental Impairment Outcome Parents Performance Pharmacology Phenotype Pregnancy Premature Birth Premature Infant Problem behavior Psyche structure Public Health Reactive Oxygen Species Respiration Disorders Risk Risk Factors Severities Site Spottings Steroids Stress Survivors System Testing Tissues United States antenatal base biological adaptation to stress cohort early childhood early life stress epidemiology study epigenetic marker experience experimental study hypothalamic-pituitary-adrenal axis improved in utero lung development maternal anxiety maternal depression neonatal corticosteroid therapy neonatal exposure neonatal morbidity neonate neurobehavior neurodevelopment prediction algorithm pregnant premature prenatal exposure prospective pulmonary function response supplemental oxygen treatment response ventilation

项目摘要

PROJECT SUMMARY Approximately 1 in 10 babies are born prematurely each year in the United States, and these neonates are at heightened risk for acute morbidities and early death. While medical advancements have dramatically improved survival for infants born prematurely, survivors, especially if born very preterm (< 30 weeks gestation) have an increased risk for long term neurodevelopmental impairments. Bronchopulmonary dysplasia (BPD), the most common neonatal morbidity among preterm infants, is a risk factor for future chronic diseases and neurodevelopmental impairments. How BPD and its treatments lead to long-term negative health outcomes requires further study. Altered programming of the HPA axis, which modulates glucocorticoid (GC) activity, has been implicated as one potential mechanism, because infants with BPD are more likely to have been exposed to corticosteroids and BPD itself may activate the stress response system. Others have developed a cross-tissue polyepigenetic predictor, an algorithm that uses DNAm levels at specific sites on the genome, to estimate a score that is associated with exogenous and endogenous GC exposure, which has been associated with maternal anxiety and depression throughout pregnancy and with later mental and behavioral issues. However, this potentially useful biomarker has not been studied within infants that were born very preterm with BPD, who are more likely to have elevated exogenous and endogenous GCs and are at increased risk of neurodevelopmental impairments. To address this gap in our knowledge we aim to 1) investigate whether BPD is associated with neonatal GC scores (as risk factor, and as a response), and 2) examine whether the neonatal GC scores are associated with performance on neurodevelopmental assessments at 24 months corrected age, in two ECHO cohorts of infants that were born very preterm (NOVI and ELGAN). These analyses will provide evidence as to whether this epigenetic biomarker is associated with BPD, and will elucidate whether the GC scores may be an early indicator of children that are at increased risk for impairments. 1

项目概要在美国，每年大约有十分之一的婴儿早产，这些新生儿处于急性发病和过早死亡的风险增加。虽然医学进步已经显着改善早产儿的存活率、幸存者，尤其是极早产儿（妊娠 < 30 周）的存活率长期神经发育障碍的风险增加。支气管肺发育不良（BPD）是最常见的早产儿常见的新生儿发病率，是未来慢性疾病的危险因素神经发育障碍。 BPD 及其治疗如何导致长期的负面健康结果需要进一步研究。调节糖皮质激素 (GC) 活性的 HPA 轴编程改变被认为是一种潜在机制，因为患有 BPD 的婴儿更有可能接触过皮质类固醇和 BPD 本身可能会激活应激反应系统。其他人已经开发出跨组织多表观遗传预测器，一种使用基因组特定位点 DNAm 水平来估计分数的算法这与外源性和内源性GC暴露有关，而GC暴露又与母体相关整个怀孕期间的焦虑和抑郁以及随后的精神和行为问题。然而，这尚未在患有 BPD 的早产婴儿中研究潜在有用的生物标志物，这些婴儿更有可能外源性和内源性 GC 升高，并且神经发育障碍的风险增加损伤。为了弥补我们知识上的这一差距，我们的目标是 1）调查 BPD 是否与新生儿 GC 评分（作为危险因素和反应），以及 2) 检查新生儿 GC 评分是否符合在两项 ECHO 中，与 24 个月校正年龄时的神经发育评估表现相关非常早产的婴儿队列（NOVI 和 ELGAN）。这些分析将提供证据该表观遗传生物标志物是否与 BPD 相关，并将阐明 GC 评分是否可能是儿童受损风险增加的早期指标。 1