ENVIRONMENTAL INFLUENCES ON NEURODEVELOPMENTAL OUTCOME IN INFANTS BORN VERY PRETERM

摘要 超过三分之一的绝经后30周出生的婴儿患有长期的神经发育 赤字。自闭症谱系障碍(ASD)的患病率在这些人中大约高出5倍 婴儿比一般人群中的婴儿多。这种环境影响儿童健康结果的目的 (ECHO)应用旨在利用我们正在进行的NIH(1R01HD072267-01A)纵向多站点前景 约600名出生30周的PMA婴儿从出生到2岁的研究，题为“新生儿神经行为” 以及极早产儿的结局。我们的长期目标是辨别这些婴儿中哪些最有可能 成为发育障碍的人，一种个性化的医学方法，可以导致干预 防止或减轻以后的赤字。我们在Echo的总体目标是跟踪这些儿童直到7岁和 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了解所涉及的机制。我们计划确定 产前、围产期和产后环境暴露(例如，身体、人口、产妇 心理、医疗、化学)、DNA甲基化和出院时的婴儿神经行为)将 与儿童注意力、认知、情绪、社交、语言、行为和运动发育的测量有关 在5岁、6岁和7岁时被诊断为ASD。我们预计遗传变异会改变环境的影响 暴露在这些儿童的结局上，并计划开发一种算法来确定哪些婴儿将是 5-7岁时有发育障碍。我们还计划确定DNA甲基化的轨迹和 神经发育测量(注意力、认知、情绪、社交、语言、行为和运动 发育)在4-7岁之间，确定神经发育轨迹如何“跟踪”DNA的轨迹 甲基化，并确定这些轨迹是如何被环境暴露和基因 变种。我们的队列对于ECHO的整个合成队列工作具有实质性的重要性，以解决如何预先， 围产期和产后环境暴露以多种多层次的方式影响儿童的发展。 提供的观点将有助于ECHO开发一个独特的模型，以更好地理解 发展，并使用轨迹分析来调查敏感期和拐点。

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.