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

摘要 每年，估计有1500万婴儿早产（<37周胎龄[GA]） 在全球这些早产儿暴露于反复的压力和往往是痛苦的程序， 治疗作为新生儿重症监护病房（NICU）内常规救生护理的一部分。这些 压力暴露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，可能是不可逆的，包括，钝化 或夸大的压力反应，增加负面行为模式和大脑改变的风险 微观结构了解调节基因持续变化的表观遗传修饰 表达可能会导致干预，这将改善这些婴儿的结果， 有机会享受更好的生活。该申请旨在严格检查：1）基因组- 纵向广泛甲基化; 2）基因表达纵向变化; 3）绝对端粒 长度，一种创新的压力生物标志物，据我们所知，还没有被连续研究 将在从出生到24个月的多个时间点测量NICU后出院情况- 在后续临床访问期间校正的年龄; 4）甲基化，基因表达， 端粒长度和神经发育结果。这种创新的测量组合 有潜力产生必要的知识，可能证明是至关重要的，以改善 神经发育的结果。

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.