ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

摘要 超过三分之一的月经后 30 周以下出生的婴儿患有长期神经发育障碍 赤字。在这些地区，自闭症谱系障碍 (ASD) 的患病率大约高出 5 倍 婴儿的比例高于一般人群。本《环境对儿童健康结果的影响》的目的 (ECHO) 应用程序是利用我们正在进行的 NIH (1R01HD072267-01A) 纵向多站点前瞻性 对大约 600 名出生 <30 周的婴儿进行的研究，从出生到 2 岁，题为“新生儿神经行为 以及极早产儿的结果。”我们的长期目标是辨别这些婴儿中哪些最有可能 发育障碍，个性化医疗方法可能导致干预措施 预防或减轻以后的赤字。我们 ECHO 的总体目标是跟踪这些儿童直至 7 岁 确定导致这些儿童发育结果的潜在机制。为了做到这一点， 这些孩子需要在现场进行研究。我们的假设是环境暴露、行为、遗传 需要变异和表观遗传因素来理解所涉及的机制。我们计划确定 产前、围产期和产后环境暴露（例如身体、人口、孕产妇）如何 心理、医学、化学）、DNA 甲基化和 NICU 出院时的婴儿神经行为）将 与儿童注意力、认知、情感、社交、语言、行为和运动发展的测量相关 5、6、7 岁和 ASD 诊断。我们期望遗传变异能够改变环境的影响 暴露这些儿童的结局，并计划开发一种算法来识别哪些婴儿将被 5-7岁发育障碍。我们还计划确定 DNA 甲基化的轨迹 神经发育测量（注意力、认知、情感、社交、语言、行为和运动 发育）4-7岁，确定神经发育轨迹如何“追踪”DNA的轨迹 甲基化并确定这些轨迹如何被环境暴露和遗传改变 变化。我们的队列对于 ECHO 的整个合成队列工作具有重要意义，以解决如何预、 围产期和产后环境暴露以多种多层次的方式影响儿童发育。 ECHO 提供的观点将帮助 ECHO 开发独特的模型，以更好地理解 发展，并使用轨迹分析来研究敏感期和拐点。

ABSTRACT Upwards of one-third of infants born <30 weeks postmenstrual age suffer long term neurodevelopmental deficits. The prevalence rate of Autism Spectrum Disorders (ASDs) is approximately 5 times higher in these infants than in the general population. The purpose of this Environmental Influences on Child Health Outcomes (ECHO) application is to leverage our ongoing NIH (1R01HD072267-01A) longitudinal multisite prospective study of approximately 600 infants born <30 weeks PMA from birth to age 2 entitled “Neonatal Neurobehavior and Outcomes in Very Preterm Infants.” Our long-term goal is to discern which of these infants are most likely to become developmentally impaired, a personalized medicine approach that could lead to interventions that prevent or mitigate later deficits. Our overall objective in ECHO is to follow these children through age 7 and determine potential mechanisms that lead to developmental outcome in these children. In order to do this, these children need to be studied in situ. Our hypothesis is that environmental exposures, behavioral, genetic variation and epigenetic factors are required to understand the mechanisms involved. We plan to determine how prenatal, perinatal and postnatal environmental exposures (e.g., physical, demographic, maternal psychological, medical, chemical), DNA methylation, and infant neurobehavior at NICU discharge) will be related to child measures of attention, cognition, emotion, social, language, behavioral and motor development at ages 5, 6, and 7 and ASD diagnosis. We expect genetic variation to modify the effects of environmental exposures on these child outcomes and plan to develop an algorithm to identify which individual infants will be developmentally impaired at ages 5-7. We also plan to determine the trajectories of DNA methylation and neurodevelopmental measures (attention, cognition, emotion, social, language, behavioral and motor development) over ages 4-7, determine how neurodevelopmental trajectories “track” the trajectory of DNA methylation and determine how these trajectories are modified by environmental exposures and genetic variation. Our cohort is of substantive import for the entire synthetic cohort effort of ECHO to address how pre-, peri-, and postnatal environmental exposures impact childhood development in a multitude of multi-level ways. The perspective proffered ECHO will help ECHO develop a unique model to better understand mechanisms of development, and use trajectory analysis to investigate sensitive periods and inflection points.