NEONATAL ENCEPHALOPATHY TREATED BY MODERATE HYPOTHERMIA

中度低温治疗新生儿脑病

• 批准号: 6394031
• 负责人: DOROTHEA DENISE JENKINS
• 金额: $ 24.54万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394031
• 关键词: behavior test; blood chemistry; bradycardia; cerebral ischemia /hypoxia; clinical research; clinical trials; health services research tag; hearing tests; heart rate; human subject; human therapy evaluation; hypoxia neonatorum; induced hypothermia; neonatal intensive care; neuroprotectants; neuropsychological tests; newborn human (0-6 weeks); outcomes research; psychometrics; psychomotor function

Perinatal hypoxia-ischemia (HI) remains a serious problem in the care of newborns. Interruption in the supply of oxygenated blood to the brain may result in neuronal injury, encephalopathy and possibly death. Neonatal encephalopathy (NE) occurs in 3-9 of every 1000 term infants. Hypothermia decreases or inhibits many of the cellular events that lead to neuronal damage after reperfusion, and offers the advantage of an early and relatively uncomplicated intervention in a potentially devastating disease process. The safety and efficacy of short-term systemic hypothermia during HI has been established in adult and neonatal populations undergoing cardiac and neurosurgical procedures. The safety and efficacy of longer-term systemic hypothermia (1-5 days) has been substantiated in adult head trauma patients and in 17 newborns with junctional tachyarrhythmias, but not in this population of HI newborns. Before a full-scale clinical trial of this intervention is designed and conducted, we need to validate the uniformity of the intervention protocol and define outcome measures. In this pilot study we will enroll 72 successive newborns within 6 hours of an HI event, and randomly assign them to hypothermia (33 C) or normothermia (37.5 C) for 48 hours after HI insult. This study will test a degree of systemic hypothermia which may have the greatest neuroprotective effect with few adverse effects based on studies in human infants and our preliminary feasibility study of 5 term newborns. We will address measures of efficacy and safety, refine the treatment protocol and the target population for the full-scale clinical trial. We will show that systemic hypothermia can be safely and uniformly begun at outlying hospitals and during transport of newborns to a tertiary care center. The use of hypothermia in this disease process may be groundbreaking and profoundly change the way asphyxiated newborns are treated even in the most rural areas. Questions regarding measures of safety and efficacy of hypothermia, novel methods for identification of neonates in first few hours after the insult, and outcome predictions for these newborns need to be better defined prior to a definitive clinical trial.

围产期缺氧 - 疾病（HI）仍然是新生儿护理的严重问题。 向大脑供应血液的供应中断可能导致神经元损伤，脑病和可能死亡。 新生儿脑病（NE）发生在每1000名婴儿中的3-9中。 体温过低会减少或抑制许多细胞事件，从而导致再灌注后神经元损害，并在潜在的灾难性疾病过程中提供了早期且相对简单的干预措施的优势。在接受心脏和神经外科手术的成人和新生儿种群中，已经在HI期间建立了短期全身性体温过低的安全性和功效。 长期全身性体温过低（1-5天）的安全性和功效已在成年头部外伤患者和17个具有连接性心律失常的新生儿中得到证实，但在这一新生儿人群中没有证实。 在设计和进行此干预措施的全面临床试验之前，我们需要验证干预方案的均匀性并定义结果指标。在这项试点研究中，我们将在HI事件发生6小时内将72个新生儿录入，并将其随机分配给体温过低（33 C）或Normothermia（37.5 C），持续48小时后HI侮辱。这项研究将测试一定程度的系统性体温过低，这可能具有最大的神经保护作用，而基于人类婴儿的研究以及我们对5个新生儿的初步可行性研究，几乎没有不良影响。 我们将解决疗效和安全性，完善治疗方案以及全尺度临床试验的目标人群。 我们将表明，系统的体温过低可以安全，统一开始，并在将新生儿运送到三级护理中心期间。 在这种疾病过程中，体温过低可能是开创性的，甚至在大多数农村地区也对窒息新生儿的治疗方式深刻地改变了。 有关体温过低的安全性和有效性测量的问题，侮辱后的最初几个小时内鉴定新生儿的新方法以及对这些新生儿的结果预测需要在确定的临床试验之前更好地定义。

项目成果

Vitamin D insufficiency in neonatal hypoxic-ischemic encephalopathy.

• DOI: 10.1038/pr.2017.13
• 发表时间: 2017-07
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Lowe DW;Hollis BW;Wagner CL;Bass T;Kaufman DA;Horgan MJ;Givelichian LM;Sankaran K;Yager JY;Katikaneni LD;Wiest D;Jenkins D
• 通讯作者: Jenkins D