Developmental Impact of NICU Exposures (DINE)

项目摘要。在美国，每年有超过30万名早产儿被接纳为新生儿 重症监护病房(NICU)，在那里他们暴露在化学密集型医院环境中。很多生命- NICU抢救和支持呼吸、营养、血液学和药物治疗暴露 早产儿在类似于妊娠晚期的生命阶段对潜在有害化学物质的反应。 对足月出生的婴儿和动物模型的研究表明，妊娠晚期在宫内暴露于邻苯二甲酸盐 -用于使塑料变得灵活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。铅和锰--一种必需的痕量金属 在NICU营养中给予--过量的神经毒性会导致认知和运动障碍。 非化学暴露，包括心理压力，在NICU环境中很常见，也是 与神经发育异常有关。在敏感时期多次暴露在环境中 早产儿在NICU的发育期可能会增加他们患不良反应的风险 晚年的健康和行为结果。无论是以NICU为基础的邻苯二甲酸盐， 铅或压力暴露，以及同时和随后暴露对早产儿健康、风险、 恢复力，或疾病轨迹，以前已经被探索过。 我们的研究利用了基础设施、生物信息库和现有的四个临床数据库 早产儿队列，探索早期生命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产生不利影响 童年。作为ECHO儿科队列计划的一部分，我们将实现以下三个具体目标： 目标1.在不同地域的大范围内确定基于NICU的邻苯二甲酸盐暴露的具体来源 早产儿的数量。AIM 1(UG3)将使用现有的NICU数据集和生物信息库来确定 接触邻苯二甲酸盐的具体途径和来源。目的2.测量以NICU为基础的邻苯二甲酸酯的影响 暴露于3-10岁的多系统健康后果。目标2(UG3/UH3)审查了 NICU邻苯二甲酸盐暴露的尿液生物标志物与儿童肺功能、认知、运动、 以及行为表现、生长发育和青春期发育。目标3.确定和 儿童早期邻苯二甲酸盐、锰、铅和应激暴露之间的相互作用 早产儿和足月儿的神经发育结局。目标3(UH3)使用牙齿、头发和唾液 用于研究早产儿和足月儿神经行为发育的暴露生物标志物。 我们独特的队列提供了一个窗口，用于直接测量快速反应的“晚期”阶段的暴露情况。 在敏感人群中的发展。这项研究将有助于减少NICU中的暴露，并提供 与胎儿和儿童早期发育有关的信息。

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.