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

项目摘要在美国，每年大约有十分之一的婴儿过早出生，这些新生儿在急性病毒和早期死亡的风险增加。尽管医疗进步已大大改善过早出生的婴儿的生存，幸存者，特别是如果出生的早产（妊娠30周）有一个长期神经发育障碍的风险增加。支气管肺发育不良（BPD），最多早产儿中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及其治疗方法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轴的编程改变已被认为是一种潜在的机制，因为BPD的婴儿更有可能被暴露对皮质类固醇和BPD本身可能会激活应力反应系统。其他人开发了跨组织多层观测指标，一种使用基因组特定位点的DNAM水平的算法，以估计评分这与外源和内源性GC暴露有关，这与母亲有关整个怀孕期间的焦虑和沮丧以及以后的心理和行为问题。但是，这个潜在有用的生物标志物尚未在BPD中出生的婴儿中研究更可能具有升高的外源性和内源性GC，并且有神经发育风险增加障碍。为了解决我们的知识差距，我们的目的是1）调查BPD是否与新生儿GC分数（作为危险因素和作为反应），以及2）检查新生儿GC分数是否为与在24个月校正年龄的24个月的神经发育评估方面的表现相关，在两个ECHO中出生于早产的婴儿（Novi和Elgan）。这些分析将提供有关的证据该表观遗传生物标志物是否与BPD相关，并且会阐明GC得分是否可能是早期指标的儿童有损害风险增加。 1