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.

围产期缺氧缺血（HI）仍然是新生儿护理中的一个严重问题。 大脑含氧血液供应中断可能会导致神经元损伤、脑病，甚至可能导致死亡。 每 1000 名足月婴儿中就有 3-9 名患有新生儿脑病 (NE)。 低温可减少或抑制再灌注后导致神经元损伤的许多细胞事件，并在潜在的破坏性疾病过程中提供早期且相对简单的干预的优势。 HI期间短期全身低温的安全性和有效性已在接受心脏和神经外科手术的成人和新生儿人群中得到证实。 长期全身低温（1-5 天）的安全性和有效性已在成人头部外伤患者和 17 名患有交界性快速心律失常的新生儿中得到证实，但在这一 HI 新生儿群体中尚未得到证实。 在设计和进行这种干预的全面临床试验之前，我们需要验证干预方案的一致性并定义结果测量。在这项试点研究中，我们将在 HI 事件发生后 6 小时内连续招募 72 名新生儿，并在 HI 损伤后 48 小时内将他们随机分配到低温 (33°C) 或常温 (37.5°C) 组。这项研究将测试一定程度的全身低温，根据对人类婴儿的研究和我们对 5 足月新生儿的初步可行性研究，这种低温可能具有最大的神经保护作用，且副作用很少。 我们将讨论有效性和安全性的衡量标准，完善治疗方案和全面临床试验的目标人群。 我们将证明，在边远医院以及将新生儿运送到三级护理中心期间，可以安全、统一地开始全身低温治疗。 在这种疾病过程中使用低温可能是开创性的，并且深刻地改变了窒息新生儿的治疗方式，甚至在大多数农村地区也是如此。 在进行最终的临床试验之前，需要更好地确定有关低温安全性和有效性的措施、在损伤后最初几个小时内识别新生儿的新方法以及这些新生儿的结果预测等问题。

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