Developmental Impact of NICU Exposures (DINE)

项目摘要。在美国，每年有超过300，000名早产儿进入新生儿监护室。 重症监护病房（NICU），他们暴露在化学密集的医院环境中。很多生命- 在NICU暴露中的挽救和支持性呼吸、营养、血液学和药物治疗 早产儿在类似妊娠晚期的生命阶段接触潜在有害的化学物质。 对足月婴儿和动物模型的研究表明，妊娠晚期子宫内接触邻苯二甲酸酯 - 用于使塑料柔软的无处不在的化学物质-与适应不良的神经发育有关， 肺、生殖和生长表型。铅（Pb）和锰（Mn）--一种必需的微量金属 在新生儿重症监护室营养中给予--过量可能具有神经毒性，导致认知和运动缺陷。 在NICU环境中常见的非化学品暴露，包括心理压力，也是 与神经发育异常有关在敏感期内的多次环境暴露 早产儿在NICU的发育期可能会增加其不良反应的风险。 健康和行为的影响。无论是NICU的邻苯二甲酸酯，锰， 铅或压力暴露，也没有同时和随后的暴露对早产儿健康的影响，风险， 恢复力或疾病轨迹之前已经探索过。 我们的研究利用了四个现有的基础设施，生物储存库和广泛的临床数据库 早产儿队列，以探索早期生活暴露于邻苯二甲酸盐，金属和压力的科学前提， 对神经发育、肺功能、生长和肥胖以及青春期发育有不利影响， 童年.作为ECHO儿科队列计划的一部分，我们将追求以下三个具体目标： 目标1.在一个大的、地理上多样化的环境中确定基于NICU的邻苯二甲酸酯暴露的具体来源 早产儿人口。目标1（UG 3）将使用现有的NICU数据集和生物储存库来确定 邻苯二甲酸酯暴露的具体途径和来源。目标2.测量NICU邻苯二甲酸酯的影响 3-10岁儿童的多系统健康结果。目标2（UG 3/UH 3）审查了 NICU邻苯二甲酸酯暴露的尿生物标志物和儿童期肺功能、认知、运动 以及行为表现、生长和青春期发育。目标3。确定的影响和 幼儿期邻苯二甲酸盐、锰、铅和压力暴露之间的相互作用 早产儿和足月儿的神经发育结果。目标3（UH 3）使用牙齿，头发和唾液 暴露的生物标志物，以研究早产儿和足月儿的神经行为发育。 我们独特的队列提供了一个窗口，直接测量暴露在“晚期”阶段的快速 在敏感人群中发展。这项研究将有助于减少NICU的暴露，并提供 与胎儿和幼儿发育有关的信息。

Project Summary. Each year in the United States, over 300,000 preterm infants are admitted to neonatal intensive care units (NICUs) where they are exposed to a chemical-intensive hospital environment. Many life- saving and supportive respiratory, nutritional, hematologic and pharmaceutical therapies in the NICU expose preterm infants to potentially harmful chemicals during a life stage analogous to the third trimester of gestation. Studies in term-born infants and animal models demonstrate that third trimester in utero exposure to phthalates –ubiquitous chemicals used to make plastics flexible - is associated with maladaptive neurodevelopmental, pulmonary, reproductive, and growth phenotypes. Lead (Pb) and manganese (Mn) -- an essential trace metal administered in NICU nutrition -- can be neurotoxic in excess resulting in both cognitive and motor deficits. Non-chemical exposures including psychological stress, common in the NICU environment, are also associated with abnormal neurodevelopment. Multiple environmental exposures during the sensitive developmental period when preterm infants are in the NICU may contribute to their increased risk of adverse health and behavioral outcomes later in life. Neither the individual contribution of NICU-based phthalate, Mn, Pb or stress exposure, nor the impact of concurrent and subsequent exposures on preterm infant health, risk, resilience, or disease trajectories have been explored previously. Our research capitalizes on the infrastructure, biorepositories, and extensive clinical databases of four existing preterm cohorts to explore the scientific premise that early life exposure to phthalates, metals, and stress adversely impacts neurodevelopment, lung function, growth and adiposity, and pubertal development in childhood. As part of the ECHO Pediatric Cohorts program, we will pursue the following three specific aims: Aim 1. Identify specific sources of NICU-based phthalate exposure in a large, geographically diverse population of preterm infants. Aim 1 (UG3) will use existing NICU datasets and biorepositories to determine specific routes and sources of phthalate exposure. Aim 2. Measure the impact of NICU-based phthalate exposure on multisystem health outcomes at ages 3-10. Aim 2 (UG3/UH3) examines associations among urine biomarkers of NICU phthalate exposure and childhood measures of pulmonary function, cognitive, motor, and behavioral performance, growth and pubertal development. Aim 3. Determine the impact of and interactions among early childhood phthalate, manganese, lead and stress exposures on neurodevelopmental outcomes in preterm and term children. Aim 3 (UH3) uses tooth, hair and saliva biomarkers of exposures to investigate neurobehavioral development in children born preterm and at term. Our unique cohort offers a window for direct measurement of exposures in the “third trimester” phase of rapid development in a sensitive population. This study will facilitate exposure abatement in the NICU and provide information relevant to fetal and early childhood development.