ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

项目总结 在美国，每年大约十分之一的婴儿早产，这些新生儿在 急性疾病和过早死亡的风险增加。虽然医学的进步已经显著地改善了 存活对于早产儿，幸存者，特别是如果早产儿(妊娠30周)有一个 增加长期神经发育障碍的风险。支气管肺发育不良(BPD)，最多的 早产儿中常见的新生儿发病率是未来慢性疾病和 神经发育障碍。BPD及其治疗如何导致长期的负面健康后果 需要进一步研究。调节糖皮质激素(GC)活动的HPA轴的编程改变，有 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本身可能会激活应激反应系统。其他人已经形成了一种交叉组织 多表观遗传预测，一种使用基因组上特定位置的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，这与母体 怀孕期间的焦虑和抑郁，以及后来的精神和行为问题。不过，这个 潜在有用的生物标记物还没有在早产的BPD婴儿中进行研究，这些婴儿 外源性和内源性GC升高的可能性更大，神经发育风险更高 减损。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(作为危险因素和反应)，以及2)检查新生儿GC评分是否 与24个月校正年龄的神经发育评估的表现相关，在两个ECHO中 早产儿的队列(Novi和Elgan)。这些分析将提供证据，证明 这个表观遗传生物标记物是否与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

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