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

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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.