ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

项目摘要 在美国，每年大约有十分之一的婴儿早产，这些新生儿在 急性发病率和早逝的风险增加。虽然医学的进步已经大大改善了 早产儿的存活率，幸存者，特别是早产儿（妊娠< 30周）， 增加长期神经发育障碍的风险。支气管肺发育不良（BPD）， 早产儿中常见的新生儿发病率是未来慢性疾病的风险因素， 神经发育障碍BPD及其治疗如何导致长期负面健康结果 需要进一步研究。调节糖皮质激素（GC）活性的HPA轴编程改变， 被认为是一种潜在的机制，因为患有BPD的婴儿更有可能接触到 皮质类固醇和BPD本身可能激活应激反应系统。其他人则发展出一种跨组织的 多表观遗传预测器，一种使用基因组上特定位点的DNAm水平来估计得分的算法 这与外源性和内源性GC暴露有关，这与母体 焦虑和抑郁在整个怀孕和后来的精神和行为问题。但这 尚未在患有BPD的极早产婴儿中研究潜在有用的生物标志物， 更有可能具有升高的外源性和内源性GC，并且神经发育风险增加 损伤为了解决我们知识中的这一差距，我们的目标是：1）调查BPD是否与 新生儿GC评分（作为风险因素和响应），以及2）检查新生儿GC评分是否 与24个月矫正年龄时的神经发育评估表现相关，在两个ECHO中， 极早产婴儿队列（诺维和ELGAN）。这些分析将提供证据， 这种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BPD的一个重要因素。 这是儿童面临更大损伤风险的早期指标。 1

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