Environment, Epigenetics, Neurodevelopment & Health of Extremely Preterm Children

项目摘要/摘要 ECHO联盟的目标是在早期确定与环境相关的暴露和机制 从生命到儿童的发展和健康结果。这项提案致力于ECHO联盟 极低胎龄新生儿(ELGAN)研究中的大量资源。自1951年启动以来 2001年，ELGAN研究的主要目标是评估围产期炎症和 极早产儿(即出生后28周前)的神经发育障碍 怀孕)。在拟议的项目中，我们将在埃尔根研究的成功基础上增加新的信息 关于：1)环境暴露，2)研究参与者在15岁和18岁时的神经发育结果 年龄，以及3)胎盘表观遗传变异，这是一种将生命早期的炎症与 神经发育障碍。 在项目的头两年(UG3阶段)，埃尔根团队的调查人员将参与 设计可在整个ECHO联盟中实施并努力协调数据的研究 在组成财团的队列中。在提案的第二年，我们将开始评估 Elgan队列的成员，当他们达到15岁时，使用标准化的神经发育 评估和脑磁共振成像(MRI)。我们亦会完成初步研究，包括 产前环境暴露、早期生命炎症与神经发育的关系 减损，使用埃尔根队列的现有数据。此外，我们还将完成表观遗传学的分析 Elgan研究参与者出生前后收集的胎盘样本中的标志物。这些 数据将用于拟议项目的最后5年(UH3阶段)。 如果达到了预定的里程碑，该项目将过渡到UH3阶段。标准化 神经发育评估和脑磁共振成像(MRI)将作为研究完成 参与者的年龄达到15岁。当参与者年满18岁时，神经发育评估将再次 才能完成。在18年的评估中，我们将获得血液，用于表观遗传激活标记的研究 先天免疫，然后我们可以联系到我们现有的关于生命早期全身炎症的数据。 该项目UH3阶段的具体目标是检查早期生命的生物标志物之间的关系 炎症(关于新生儿全身炎症的现有数据和关于胎盘表观遗传学的新数据)和 18岁时的神经发育障碍。需要解决的总体假设是 产前暴露可引发早期生命炎症，从而增加神经发育的风险。 减损。该项目的创新方面包括其纵向视角、对胎盘的考虑 表观遗传学作为一种将产前暴露与儿童结局联系起来的机制，并对广泛的范围进行评估 神经发育结果。这项研究有可能为治疗方法的发展提供信息。 以表观遗传过程为目标，预防或改善认知障碍，从而提高生活质量 在美国，每年有16000人在极早产中幸存下来。

Project Summary/Abstract The goal of the ECHO Consortium is to identify exposures and mechanisms that link the environment in early life to childhood development and health outcomes. This proposal commits to the ECHO Consortium numerous resources from the Extremely Low Gestation Age Newborn (ELGAN) Study. Since its initiation in 2001, the broad goal of the ELGAN Study is to evaluate the relationship between perinatal inflammation and neurodevelopmental impairments among individuals born extremely premature (i.e., before 28 weeks of gestation). In the proposed project we will build on the success of the ELGAN Study by adding new information about: 1) environment exposures, 2) neurodevelopmental outcomes of study participants at 15 and 18 years of age, and 3) placental epigenetic variation, a mechanism that could link inflammation early in life to neurodevelopmental impairments. In the first two years of the project (the UG3 phase) investigators from the ELGAN team will participate in the design of studies that can be implemented across the ECHO Consortium and in efforts to harmonize data across cohorts comprising the consortium. In the second year of the proposal, we will begin to evaluate members of the ELGAN cohort, as they reach 15 years of age, using standardized neurodevelopmental assessments and brain magnetic resonance imaging (MRI). We also will complete preliminary studies of relationships between prenatal environmental exposures, early life inflammation, and neurodevelopmental impairments, using extant data from the ELGAN cohort. In addition, we will complete analysis of epigenetic markers in placenta specimens collected around the time of the births of ELGAN Study participants. These data will be utilized in the last 5 years of the proposed project (the UH3 phase). If pre-specified milestones are met, the project will transition into the UH3 phase. Standardized neurodevelopmental assessments and brain magnetic resonance imaging (MRI) will be completed as study participants reach 15 years. As participants reach 18 years of age neurodevelopmental assessments will again be completed. At the assessment at 18 years we will obtain blood for study of epigenetic markers of activation of innate immunity, which we can then relate to our extant data about systemic inflammation early in life. Specific aims in the UH3 phase of the project are examine relationships between biomarkers of early life inflammation (extant data on neonatal systemic inflammation and new data on placenta epigenetics) and neurodevelopmental impairments through age 18 years. The over-arching hypothesis to be addressed is that prenatal exposures can initiate early life inflammation, thus increasing the risk of neurodevelopmental impairments. Innovative aspects of this project include its longitudinal perspective, consideration of placenta epigenetics as a mechanism linking prenatal exposures to childhood outcomes, and evaluation of a wide range of neurodevelopmental outcome. This research has the potential to inform the development of therapies targeting epigenetic processes to prevent or ameliorate cognitive disability, thereby improving the quality of life for 16,000 individuals who survive extremely premature birth each year in the United States.