Environment, Epigenetics, Neurodevelopment & Health of Extremely Preterm Children

项目概要/摘要 ECHO联盟的目标是确定早期环境中的暴露和机制， 生命对儿童发展和健康结果的影响。该提案承诺ECHO财团 极低妊娠年龄新生儿（ELGAN）研究。自1994年启动以来， 2001年，ELGAN研究的广泛目标是评估围产期炎症与 极早产个体中的神经发育损伤（即，在28周之前， 妊娠）。在拟议的项目中，我们将在ELGAN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 3）胎盘表观遗传变异，这是一种可能将生命早期的炎症与 神经发育障碍 在项目的前两年（UG 3阶段），来自ELGAN团队的研究人员将参加 设计可在整个ECHO联盟实施的研究，并努力协调数据 在组成联合体的各个队列中。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， 产前环境暴露、早期炎症和神经发育之间的关系 使用ELGAN队列的现有数据。此外，我们还将完成表观遗传分析， 在ELGAN研究参与者出生时收集的胎盘样本中的标记物。这些 数据将在拟议项目（UH 3阶段）的最后5年使用。 如果达到预先规定的里程碑，项目将过渡到UH 3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 参与者达到15岁。当参与者达到18岁时， 完成。在18岁时进行评估时，我们将采集血液用于表观遗传标记物的活化研究 我们可以将其与现存的关于生命早期全身性炎症的数据联系起来。 项目UH 3阶段的具体目标是检查早期生命生物标志物之间的关系。 炎症（新生儿全身性炎症的现有数据和胎盘表观遗传学的新数据）， 18岁时的神经发育障碍。需要解决的首要假设是 产前暴露可引发早期炎症，从而增加神经发育风险。 损伤该项目的创新之处包括纵向视角，胎盘的考虑， 表观遗传学作为一种机制，连接产前暴露儿童的结果，并评估了广泛的 神经发育的结果。这项研究有可能为治疗方法的发展提供信息 靶向表观遗传过程，以预防或改善认知障碍，从而改善生活质量 在美国，每年有16,000名早产儿存活下来。

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.