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:
- 金额:$ 199.91万
- 依托单位:
- 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:
- 关键词:AddressAdmission activityAgeAngiogenic FactorAnimal ModelAnimalsArchitectureBiological MarkersBirthBirth WeightBlood TransfusionBone MarrowBronchopulmonary DysplasiaCaringCellsChemicalsChildChronologyClinicalControlled EnvironmentCoupledDataDevelopmentDiseaseDoseDrug KineticsEndocrine disruptionEnvironmentEquipmentErythrocytesExposure toFaceFamilyFutureGenetic Predisposition to DiseaseGestational AgeGrowthHistopathologyHospitalizationHospitalsHyperoxiaInfantInfant CareInflammatoryInhalationInhalation ExposureInpatientsIntravenousIntravenous BolusLifeLinkLungLung diseasesMeasuresMedicalMetabolismModelingNatural experimentNebulizerNeonatal Intensive Care UnitsNewborn InfantOrganic ChemicalsOutcomePatientsPerinatalPlasticizersPlasticsPopulationPopulation HeterogeneityPremature InfantRattusResearchRiskRodent ModelRoleSentinelSourceSprague-Dawley RatsSystemTestingThird Pregnancy TrimesterToxic effectTransfusionTranslatingTubeUnited StatesWeight GainWorkadverse outcomeblood productclinical investigationendotrachealepidemiologic dataepidemiology studyexposure routeimprovedimproved outcomein uteroinsightneonateneurobehavioralneurodevelopmentpersonal care productsphthalatesprematurepulmonary functionpuprespiratoryurinary
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.
项目摘要
在美国,每年有超过300,000名新生儿入住新生儿重症监护室(NICU),
在那里他们暴露在化学密集的医院环境中。大多数NICU住院患者
因早产而入院治疗在新生儿重症监护室,婴儿面临着高剂量暴露的治疗,
邻苯二甲酸酯,一种普遍存在的内分泌干扰有机化学增塑剂,
相当于子宫内发育的第三个三个月。我们知道,
子宫内发育窗口期同样可导致次优神经行为、生长和肺
足月儿的结局。过去的研究表明,早产儿也有很大的风险,
早期邻苯二甲酸酯暴露可能会影响不良的多系统结局。我们的团队已经花了
在过去十年中,研究了医院内邻苯二甲酸酯暴露对不良结局的影响,
早产儿通过强有力的流行病学研究,我们已经证明,基于NICU的邻苯二甲酸酯
暴露会改变早产期间神经发育和体重增加的轨迹。新出现的数据
表明邻苯二甲酸酯暴露可能导致早产儿慢性肺病的发展。
然而,关于早产儿邻苯二甲酸酯代谢的药代动力学,
婴儿,导致邻苯二甲酸酯暴露的特定护理实践,以及主要邻苯二甲酸酯的作用机制
早产儿疾病的种类。我们建议通过以下具体目标解决这些问题:
目标1。确定常见邻苯二甲酸二酯及其
不同经后和实际年龄的新生儿单酯代谢物
输血作为一种哨点静脉暴露的“自然实验”。
目标2.测试五个常用的呼吸回路,以确定相对邻苯二甲酸酯
每个人的曝光度。
目的3:使用啮齿动物模型检查吸入性邻苯二甲酸酯暴露对
早产儿慢性肺病的病理生物学
拟议的研究将提供可操作的数据,可以迅速转化为改善新生儿重症监护室的做法
并促进未来的临床研究。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Annemarie Stroustrup其他文献
Annemarie Stroustrup的其他文献
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{{ truncateString('Annemarie Stroustrup', 18)}}的其他基金
Chemical Exposures and Infant Outcomes in the Neonatal Intensive Care Unit
新生儿重症监护病房的化学品暴露和婴儿结局
- 批准号:
9271969 - 财政年份:2013
- 资助金额:
$ 199.91万 - 项目类别:
Chemical Exposures and Infant Outcomes in the Neonatal Intensive Care Unit
新生儿重症监护病房的化学品暴露和婴儿结局
- 批准号:
8851591 - 财政年份:2013
- 资助金额:
$ 199.91万 - 项目类别:
Chemical Exposures and Infant Outcomes in the Neonatal Intensive Care Unit
新生儿重症监护病房的化学品暴露和婴儿结局
- 批准号:
8425778 - 财政年份:2013
- 资助金额:
$ 199.91万 - 项目类别:
Chemical Exposures and Infant Outcomes in the Neonatal Intensive Care Unit
新生儿重症监护病房的化学品暴露和婴儿结局
- 批准号:
8729580 - 财政年份:2013
- 资助金额:
$ 199.91万 - 项目类别:
Chemical Exposures and Infant Outcomes in the Neonatal Intensive Care Unit
新生儿重症监护病房的化学品暴露和婴儿结局
- 批准号:
9061685 - 财政年份:2013
- 资助金额:
$ 199.91万 - 项目类别: