Development of an Artificial Placenta for Support of Premature Infants

开发用于支持早产儿的人工胎盘

• 批准号: 8696049
• 负责人: George Boris Mychaliska
• 金额: $ 55.51万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8696049
• 关键词: Address; Age; Air; Anticoagulation; Blood Circulation; Brain; Breathing; Cardiovascular system; Caring; Cerebrum; Clinical Trials; Coagulation Process; Data; Development; Embolism; Environment; Environmental air flow; Event; Fetus; Gases; Gestational Age; Goals; Grant; Growth and Development function; Hemorrhage; Heparin; Human; Infant; Infection; Intrauterine Devices; Laboratories; Life; Lung; Maintenance; Mechanical ventilation; Mechanics; Metabolic; Modeling; Morbidity - disease rate; Neonatal; Newborn Infant; Perfusion; Phase; Physiological; Physiology; Placenta; Positioning Attribute; Pregnancy; Premature Birth; Premature Infant; Recovery; Research Project Grants; Research Proposals; Sheep; Simulate; Staging; Surface; System; Technology; United States; United States National Institutes of Health; Weaning; clinical application; conventional therapy; design; disability; effective therapy; fetal; gastrointestinal function; hemodynamics; improved; in utero; lung development; mortality; nutrition; premature; prevent; public health priorities; public health relevance; research study; simulation; surfactant; white matter injury

DESCRIPTION (provided by applicant): Treatment of prematurity remains an unsolved problem and a top public health priority. There are nearly 500,000 premature births each year and more infants die of preterm-related problems than from any other single cause. Although many of these babies recover with conventional management, the mortality and morbidity of extremely low gestational age newborns (ELGANs, defined as <28 weeks estimated gestational age) is extremely high, with less than 50% surviving without disability. Many of these complications are caused, in part, by our attempts to ventilate the immature lungs and reverse fetal circulation. Although incremental progress has been made in treating premature infants with surfactant and less invasive ventilation strategies, effective treatment options remain an unsolved problem. A major paradigm shift in the post-natal treatment of prematurity would be to simulate the intrauterine environment with a specially designed extracorporeal gas exchange system which maintains fetal circulation and allows growth and development without air breathing; we call this technology the Artificial Placenta (AP). Our long term goal is the clinical application of the AP to improve survival and reduce morbidity in ELGANs. We have developed fetal lamb models which correspond to various stages of prematurity in humans. We initially developed the AP in fetal lambs of 130 day gestation (corresponding to 29 weeks human gestation; saccular stage of lung development) with recovery to air breathing. More recent preliminary data demonstrate the feasibility of providing complete extracorporeal support for one week in a 110 day sheep model (equivalent to a 22 week gestation human fetus; canalicular stage of lung development) with hemodynamic stability, excellent gas exchange, normally developing alveolarization, stable cerebral perfusion and maintenance of fetal circulation, all without mechanical ventilation. The goal of this research proposal is to evaluate and refine this system of intrauterine simulation to support fetal lambs from extreme prematurity, at the canalicular stage of lung development, to viable extra-uterine neonatal physiology. To accomplish this goal, the specific aims of this proposal are: 1. to evaluate fetal circulation, hemodynamics, and lung development under variable conditions of airway management and controlled fetal/newborn circulation in the 118 day lamb model. 2. To evaluate brain and systemic bleeding and embolism during AP without heparin and assess cerebral perfusion, function, development, and white matter injury. 3. To maintain the simulated intrauterine environment using the artificial placenta until lung development and circulation can support air breathing, including addressing potential problems with long-term support (infection, nutrition, gastrointestinal function, and metabolic issues).

描述（由申请人提供）：早产的治疗仍然是一个未解决的问题，并且是最高公共卫生的优先事项。每年有将近500,000个早产，而婴儿与早产相关的问题的死亡比其他任何原因。尽管这些婴儿中有许多通过常规管理恢复，但胎龄新生儿的死亡率和发病率（Elgans，定义为估计为胎龄<28周）非常高，没有残疾而存活不到50％。这些并发症中的许多并发症部分是由于我们试图通风未成熟肺并反向胎儿循环引起的。尽管在治疗表面活性剂和侵入性通风较低的早产婴儿方面取得了进步，但有效的治疗选择仍然是一个未解决的问题。产后治疗早产治疗的主要范式转变是通过专门设计的体外气体交换系统模拟宫内环境，该系统可以维持胎儿循环，并允许而无需空气呼吸而生长和发育；我们将此技术称为人造胎盘（AP）。我们的长期目标是临床 AP的应用以提高生存率并降低Elgans的发病率。我们已经开发了胎儿羔羊模型，这些模型与人类早产的各个阶段相对应。最初，我们在130天妊娠的胎儿羔羊中开发了AP（对应于29周人类妊娠；肺发育的糖果阶段），并恢复到空气呼吸。最新的初步数据表明，在110天的绵羊模型（相当于22周的妊娠妊娠胎儿；肺发育的管道阶段），提供血液动力学稳定性，出色的气体交换，通常会发展肺泡，稳定的脑灌注和维持胎儿循环的可行性。这项研究建议的目的是评估和完善该宫内模拟系统，以支持肺部发育的管道阶段，从极端早产的胎儿羔羊，以便可行的外部新生儿生理学。为了实现这一目标，该提案的具体目的是：1。在118天的羔羊模型中，在气道管理和受控胎儿/新生儿循环的可变条件下评估胎儿循环，血液动力学和肺发育。 2。在没有肝素的情况下评估AP期间的大脑和全身性出血和栓塞，并评估脑灌注，功能，发育和白质损伤。 3。使用人造胎盘座维持模拟的宫内环境，直到肺发育和循环可以支持空气呼吸，包括解决长期支持（感染，营养，胃肠道功能和代谢问题）的潜在问题。