Predicting Neurodevelopmental Outcomes in Premature Infants with Multi-omic Measures (PRENOP)

摘要 据估计，每年有1500万婴儿早产(胎龄37周[GA]) 全球范围内。这些早产儿暴露在反复的压力下，往往是痛苦的程序或 治疗是新生儿重症监护病房(NICU)常规救生护理的一部分。这些 应激暴露会导致甲基化模式和基因表达的改变 与婴儿的许多负面后遗症有关，可能是不可逆转的，包括钝化 或过度的应激反应，增加消极行为模式的风险和大脑的改变 微观结构。理解调控基因持续变化的表观遗传修饰 表达可能会导致干预措施，从而改善这些婴儿的结局，给他们 享受更好生活的机会。拟议的申请旨在严格检查：1)基因组- 纵向广泛的甲基化；2)纵向基因表达的变化；3)绝对端粒 长度，一个创新的压力生物标记物，据我们所知，还没有被连续研究 NICU后的出院将在从出生到24个月的多个时间点进行测量- 4)甲基化、基因表达、 端粒长度和神经发育结果。这一创新的测量组合 有可能产生重要的知识，这些知识可能被证明是改进 这一弱势群体的神经发育结果。

Abstract Each year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and often painful procedures or treatments as part of routine life-saving care within the neonatal intensive care unit (NICU). These stressful exposures result in altered methylation patterns and gene expression that have been associated with numerous negative sequelae for the infant and may be irreversible, including, blunted or exaggerated stress reactivity, increased risk for negative behavior patterns and alterations in brain microstructure. Understanding the epigenetic modifications that regulate persistent changes in gene expression may lead to interventions that would improve outcomes for these infants giving them the opportunity to enjoy a better life. The proposed application aims to rigorously examine: 1) genome- wide methylation longitudinally; 2) changes in gene expression longitudinally; 3) absolute telomere length, an innovative stress biomarker which has not, to our knowledge, been investigated serially post-NICU discharge will be measured at multiple time points from birth through 24-months- corrected-age during follow-up clinic visits; 4) associations between methylation, gene expression, telomere length and neurodevelopmental outcomes. This innovative combination of measurements has the potential to generate essential knowledge that may prove critical to improving neurodevelopmental outcomes for this vulnerable population.