Developmental Impact of NICU Exposures (DINE)

NICU 暴露 (DINE) 对发育的影响

• 批准号: 9355748
• 负责人: Judy Lynn Aschner
• 金额: $ 446.71万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355748
• 关键词: Abate; Age; Animal Model; Behavioral; Biological Markers; Blood; Caring; Chemicals; Child; Childhood; Clinical; Cognitive; Cognitive deficits; Cohort Studies; Data; Data Set; Databases; Development; Disease; Environment; Environmental Exposure; Environmental Health; Environmental Pollution; Equipment; Equipment and Supplies; Erythropoietin; Evaluation; Exposure to; Funding Opportunities; General Population; Geography; Growth; Hair; Health; Hospital Units; Hospitals; Individual; Infant; Infant Care; Infant Health; Lead; Life; Lung; Manganese; Measurement; Measures; Medical; Metals; Methodology; Methods; Motor; Multicenter Studies; Neonatal Intensive Care Units; Neurodevelopmental Impairment; Nutritional; Obesity; Outcome; Participant; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Plasticizers; Plastics; Population; Population Heterogeneity; Pregnancy; Premature Infant; Psychological Stress; Research; Research Infrastructure; Respiratory physiology; Risk; Route; Saliva; Savings; Severity of illness; Site; Source; Stress; Techniques; Testing; Third Pregnancy Trimester; Time; Tooth structure; Trace metal; United States; Urine; Variant; base; behavioral outcome; biobank; clinically relevant; cohort; deciduous tooth; early childhood; early life exposure; ethnic diversity; experience; fetal; flexibility; infant animal; motor deficit; neurobehavior; neurobehavioral; neurodevelopment; neuroprotection; neurotoxic; nutrition; phthalates; premature; prenatal exposure; programs; pulmonary function; reproductive; resilience; respiratory; response; surfactant; urinary

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.

项目摘要。在美国，每年有超过 300,000 名早产儿被送进新生儿科 重症监护病房 (NICU) 暴露在化学品密集的医院环境中。许多生命—— 新生儿重症监护病房 (NICU) 中的保存和支持性呼吸、营养、血液和药物治疗 早产儿在类似于妊娠晚期的生命阶段接触潜在有害的化学物质。 对足月出生的婴儿和动物模型的研究表明，妊娠晚期在子宫内接触邻苯二甲酸盐 – 用于使塑料变得柔韧的普遍化学物质 – 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)——一种重要的微量金属 在新生儿重症监护室（NICU）营养中施用的营养——过量可能会产生神经毒性，导致认知和运动缺陷。 NICU 环境中常见的非化学物质暴露（包括心理压力）也 与神经发育异常有关。敏感期间多次环境暴露 早产儿在新生儿重症监护病房（NICU）的发育期可能会增加其不良反应的风险 晚年的健康和行为结果。 NICU 中的邻苯二甲酸盐、锰、 铅或压力暴露，以及同时和随后的暴露对早产儿健康、风险、 恢复力或疾病轨迹之前已被探索过。 我们的研究利用了四个现有的基础设施、生物样本库和广泛的临床数据库 早产儿队列探索生命早期接触邻苯二甲酸盐、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，我们将追求以下三个具体目标： 目标 1. 确定位于不同地理区域的新生儿重症监护病房 (NICU) 邻苯二甲酸盐暴露的具体来源 早产儿人口。目标 1 (UG3) 将使用现有的 NICU 数据集和生物样本库来确定 邻苯二甲酸盐接触的具体途径和来源。目标 2. 衡量 NICU 中邻苯二甲酸盐的影响 3-10 岁时接触多系统健康结果。目标 2 (UG3/UH3) 检查之间的关联 NICU 邻苯二甲酸盐暴露的尿液生物标志物和儿童肺功能、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 (UH3) 使用牙齿、头发和唾液 暴露的生物标志物，用于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，可以直接测量快速妊娠的“妊娠晚期”阶段的暴露情况 敏感人群的发展。这项研究将促进新生儿重症监护病房 (NICU) 中的暴露减少，并提供 与胎儿和幼儿发育相关的信息。