Laptook Abbot R, Shankaran Seetha, Tyson Jon E, Munoz Breda, Bell Edward F, Goldberg Ronald N, Parikh Nehal A, Ambalavanan Namasivayam, Pedroza Claudia, Pappas Athina, Das Abhik, Chaudhary Aasma S, Ehrenkranz Richard A, Hensman Angelita M, Van Meurs Krisa P, Chalak Lina F, Khan Amir M, Hamrick Shannon E G, Sokol Gregory M, Walsh Michele C, Poindexter Brenda B, Faix Roger G, Watterberg Kristi L, Frantz Ivan D, Guillet Ronnie, Devaskar Uday, Truog William E, Chock Valerie Y, Wyckoff Myra H, McGowan Elisabeth C, Carlton David P, Harmon Heidi M, Brumbaugh Jane E, Cotten C Michael, Sánchez Pablo J, Hibbs Anna Maria, Higgins Rosemary D
Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode Island.
Department of Pediatrics, Wayne State University, Detroit, Michigan.
JAMA. 2017 Oct 24;318(16):1550-1560. doi: 10.1001/jama.2017.14972.
Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.
To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size.
Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C).
The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization.
Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively.
Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.
clinicaltrials.gov Identifier: NCT00614744.
出生后6小时内开始的低温治疗可降低孕36周及以后患有缺氧缺血性脑病婴儿的死亡或残疾风险。据我们所知，尚未对出生6小时后出现症状的婴儿进行低温治疗试验。
评估出生后6至24小时开始的低温治疗能否降低缺氧缺血性脑病婴儿18个月时的死亡或残疾风险。
设计、地点和参与者：2008年4月至2016年6月间，对出生后6至24小时入院的孕36周及以后患有中度或重度缺氧缺血性脑病的婴儿进行了一项随机临床试验。21个美国新生儿研究网络中心参与了该试验。鉴于预期样本量有限，预先设定了贝叶斯分析。
168名婴儿采用食管靶向温度监测。83名接受低温治疗的婴儿维持体温在33.5°C（可接受范围为33°C - 34°C）96小时，然后复温。85名未接受低温治疗的婴儿维持体温在37.0°C（可接受范围为36.5°C - 37.3°C）。
根据脑病程度和随机分组时的年龄调整后，18至22个月时死亡或残疾（中度或重度）的综合情况。
接受低温治疗和未接受低温治疗的婴儿均为足月儿（平均[标准差]，分别为孕39[2]周和39[1]周），83名中的47名（57%）和85名中的55名（65%）为男性。两组婴儿出生时均有酸中毒，主要以中度脑病转入治疗中心，接受低温治疗组和未接受低温治疗组的随机分组平均（标准差）时间分别为16（5）小时和15（5）小时。78名接受低温治疗的婴儿中有19名（24.4%）出现主要结局，79名未接受低温治疗的婴儿中有22名（27.9%）出现主要结局（绝对差异为3.5%；95%置信区间为-1%至17%）。使用中性先验的贝叶斯分析表明，与未接受低温治疗组相比，低温治疗降低死亡或残疾风险的后验概率为76%（调整后的后验风险比为0.86；95%可信区间为0.58 - 1.29）。接受低温治疗的婴儿死亡或残疾比未接受低温治疗的婴儿至少低1%、2%或3%的概率分别为71%、64%和56%。
在患有缺氧缺血性脑病的足月儿中，出生后6至24小时开始低温治疗与不进行低温治疗相比，有76%的概率可降低死亡或残疾风险，在18至22个月时有64%的概率使死亡或残疾风险至少降低2%。出生后6至24小时开始低温治疗可能有益，但效果存在不确定性。
clinicaltrials.gov标识符：NCT00614744。
