Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy A Randomized Clinical Trial

被引:221
作者
Laptook, Abbot R. [1 ]
Shankaran, Seetha [2 ]
Tyson, Jon E. [3 ]
Munoz, Breda [4 ]
Bell, Edward F. [5 ]
Goldberg, Ronald N. [6 ]
Parikh, Nehal A. [7 ]
Ambalavanan, Namasivayam [8 ]
Pedroza, Claudia [3 ]
Pappas, Athina [2 ]
Das, Abhik [9 ]
Chaudhary, Aasma S. [10 ]
Ehrenkranz, Richard A. [11 ]
Hensman, Angelita M. [1 ]
Van Meurs, Krisa P. [12 ,13 ]
Chalak, Lina F. [14 ]
Hamrick, Shannon E. G. [15 ]
Sokol, Gregory M. [16 ]
Walsh, Michele C. [17 ]
Poindexter, Brenda B. [7 ,16 ]
Faix, Roger G. [18 ]
Watterberg, Kristi L. [19 ]
Frantz, Ivan D., III [20 ]
Guillet, Ronnie [21 ]
Devaskar, Uday [22 ]
Truog, William E. [23 ,24 ]
Chock, Valerie Y. [12 ,13 ]
Wyckoff, Myra H. [14 ]
McGowan, Elisabeth C. [1 ]
Carlton, David P. [15 ]
Harmon, Heidi M. [16 ]
Brumbaugh, Jane E. [5 ]
Cotten, C. Michael [6 ]
Sanchez, Pablo J. [25 ]
Hibbs, Anna Maria [17 ]
Higgins, Rosemary D. [26 ]
机构
[1] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA
[2] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA
[3] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Pediat, Houston, TX 77030 USA
[4] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA
[5] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[6] Duke Univ, Dept Pediat, Durham, NC 27706 USA
[7] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA
[8] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA
[9] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA
[10] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA
[11] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA
[12] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA
[13] Lucile Packard Childrens Hosp, Palo Alto, CA USA
[14] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA
[15] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA
[16] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA
[17] Case Western Reserve Univ, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA
[18] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA
[19] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[20] Floating Hosp Children, Tufts Med Ctr, Dept Pediat, Div Newborn Med, Boston, MA USA
[21] Univ Rochester, Sch Med & Dent, Rochester, NY USA
[22] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA
[23] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA
[24] Univ Missouri Kansas City, Sch Med, Kansas City, MO USA
[25] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA
[26] NICHHD, Eunice Kennedy Shriver, NIH, Bethesda, MD 20892 USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2017年 / 318卷 / 16期
基金
美国国家卫生研究院;
关键词
WHOLE-BODY HYPOTHERMIA; SERVICES TASK-FORCE; NEONATAL ENCEPHALOPATHY; SYSTEMIC HYPOTHERMIA; CARDIOVASCULAR-DISEASE; POSTISCHEMIC SEIZURES; MODERATE HYPOTHERMIA; CHILDHOOD OUTCOMES; CEREBRAL-PALSY; FETAL SHEEP;
D O I
10.1001/jama.2017.14972
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IMPORTANCE 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. OBJECTIVE To estimate the probability that hypothermiainitiated 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. INTERVENTIONS Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5 degrees C (acceptable range, 33 degrees C-34 degrees C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0 degrees C (acceptable range, 36.5 degrees C-37.3 degrees C). MAIN OUTCOMES AND MEASURES The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.
引用
收藏
页码:1550 / 1560
页数:11
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