Phthalate Exposure and Mechanisms of Action in the Neonatal Intensive Care Unit

新生儿重症监护病房中邻苯二甲酸盐的暴露及其作用机制

基本信息

批准号：
10736301
负责人：
Annemarie Stroustrup
金额：
$ 199.91万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736301
关键词：
Address Admission activity Age Angiogenic Factor Animal Model Animals Architecture Biological Markers Birth Birth Weight Blood Transfusion Bone Marrow Bronchopulmonary Dysplasia Caring Cells Chemicals Child Chronology Clinical Controlled Environment Coupled Data Development Disease Dose Drug Kinetics Endocrine disruption Environment Equipment Erythrocytes Exposure to Face Family Future Genetic Predisposition to Disease Gestational Age Growth Histopathology Hospitalization Hospitals Hyperoxia Infant Infant Care Inflammatory Inhalation Inhalation Exposure Inpatients Intravenous Intravenous Bolus Life Link Lung Lung diseases Measures Medical Metabolism Modeling Natural experiment Nebulizer Neonatal Intensive Care Units Newborn Infant Organic Chemicals Outcome Patients Perinatal Plasticizers Plastics Population Population Heterogeneity Premature Infant Rattus Research Risk Rodent Model Role Sentinel Source Sprague-Dawley Rats System Testing Third Pregnancy Trimester Toxic effect Transfusion Translating Tube United States Weight Gain Work adverse outcome blood product clinical investigation endotracheal epidemiologic data epidemiology study exposure route improved improved outcome in utero insight neonate neurobehavioral neurodevelopment personal care products phthalates premature pulmonary function pup respiratory urinary

项目摘要

PROJECT SUMMARY Each year in the United States, over 300,000 newborns are admitted to a neonatal intensive care unit (NICU), where they are exposed to a chemical-intensive hospital environment. The majority of NICU inpatients are admitted for management of prematurity. In the NICU, infants face treatments that convey high-dose exposure to phthalates, a family of ubiquitous endocrine-disrupting organic chemical plasticizers, during a life stage equivalent to the third trimester of in utero development. We know that elevated exposure to phthalates during the same in utero developmental window can result in suboptimal neurobehavioral, growth, and pulmonary outcomes among term-born children. Past research shows that preterm infants are also at significant risk of adverse multisystem outcomes potentially impacted by early life phthalate exposure. Our group has spent the past decade investigating the contribution of in-hospital phthalate exposure to adverse outcomes among preterm infants. Through robust epidemiological studies, we have demonstrated that NICU-based phthalate exposure alters the trajectory of neurodevelopment and weight gain during the preterm period. Emerging data indicates that phthalate exposure may contribute to the development of chronic lung disease of prematurity. Yet many fundamental questions remain about the pharmacokinetics of phthalate metabolism in preterm infants, specific care practices that confer phthalate exposure, and the mechanism of action of major phthalate species in preterm infant disease. We propose to address these questions through the following Specific Aims: Aim 1. Determine the pharmacokinetic profile of common phthalate diesters and their monoester metabolites in neonates of varying postmenstrual and chronological ages using the “natural experiment” of blood transfusion as a sentinel intravenous exposure. Aim 2. Test five commonly used respiratory circuits to determine the relative phthalate exposure conveyed by each. Aim 3: Use a rodent model to examine the effects of inhalational phthalate exposure on the pathobiology of chronic lung disease of prematurity. The proposed study will provide actionable data that can rapidly translate into improvements in NICU practice and facilitate future clinical investigation.