The Journal of Pediatrics
Volume 157, Issue 3 , Pages 367-372.e3 , September 2010

Selective Head Cooling with Mild Systemic Hypothermia after Neonatal Hypoxic-Ischemic Encephalopathy: A Multicenter Randomized Controlled Trial in China

  • Wen-hao Zhou, MD

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • ,
  • Guo-qiang Cheng, MD

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • ,
  • Xiao-mei Shao, Prof

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • Corresponding Author InformationReprint requests: Xiao-mei Shao, 399 Wanyuan Rd, Shanghai, China.
    • ,
  • Xian-zhi Liu, MD

      Affiliations

    • Guangxi Maternity and Infant Health Hospital, Guangxi Province, China
    • ,
  • Ruo-bing Shan, Prof

      Affiliations

    • Qingdao Children's Hospital, Shandong Province, China
    • ,
  • De-yi Zhuang, MD

      Affiliations

    • Quanzhou Children's Hospital, Fujian Province, China
    • ,
  • Cong-le Zhou, MD

      Affiliations

    • The First Hospital of Beijing University, Beijing, China
    • ,
  • Li-zhong Du, Prof

      Affiliations

    • Children's Hospital of Zhejiang University, Zhejiang Province, China
    • ,
  • Yun Cao, MD

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • ,
  • Qun Yang, MD

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • ,
  • Lai-shuan Wang, MD

      Affiliations

    • Children's Hospital of Fudan University, Shanghai, China
    • ,
  • China Study Group

Received 3 October 2009 ,Revised 16 February 2010 ,Accepted 26 March 2010.

References 

  1. Phelan JP, Martin GI, Korst LM. Birth asphyxia and cerebral palsy. Clin Perinatol. 2005;32:61–76
  2. Shankaran S, Woldt E, Koepke T, Bedard MP, Nandyal R. Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants. Early Hum Dev. 1991;25:135–148
  3. Gunn AJ, Gunn TR, de Haan HH, Williams CE, Gluckman PD. Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest. 1997;99:248–256
  4. Tooley JR, Satas S, Porter H, Silver IA, Thoresen M. Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective. Ann Neurol. 2003;53:65–72
  5. Thoresen M, Penrice J, Lorek A, Cady EB, Wylezinska M, Kirkbride V, et al. Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet. Pediatr Res. 1995;37:667–670
  6. Ohmura A, Nakajima W, Ishida A, Yasuoka N, Kawamura M, Miura S, et al. Prolonged hypothermia protects neonatal rat brain against hypoxic-ischemia by reducing both apoptosis and necrosis. Brain Dev. 2005;27:517–526
  7. Sirimanne ES, Blumberg RM, Bossano D, Gunning M, Edwards AD, Gluckman PD, et al. The effect of prolonged modification of cerebral temperature on outcome after hypoxic-ischemic brain injury in the infant rat. Pediatr Res. 1996;39:591–597
  8. Wagner BP, Nedelcu J, Martin E. Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats. Pediatr Res. 2002;51:354–360
  9. Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics. 1998;102:885–892
  10. Thoresen M, Whitelaw A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics. 2000;106:92–99
  11. Azzopardi D, Robertson NJ, Cowan FM, Rutherford MA, Rampling M, Edwards AD. Pilot study of treatment with whole body hypothermia for neonatal encephalopathy. Pediatrics. 2000;106:684–694
  12. Battin MR, Dezoete JA, Gunn TR, Gluckman PD, Gunn AJ. Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics. 2001;107:480–484
  13. Shankaran S, Laptook A, Wright LL, Ehrenkranz RA, Donovan EF, Fanaroff AA, et al. Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics. 2002;110:377–385
  14. Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic hypothermia (35.0°C and 34.5°C) after perinatal asphyxia. Pediatrics. 2003;111:244–251
  15. Lin ZL, Yu HM, Lin J, Chen SQ, Liang ZQ, Zhang ZY. Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit. J Perinatol. 2006;26:180–184
  16. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365:663–670
  17. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–1584
  18. Azzopardi D, Strohm B, Edwards AD, Dyet L, Levene M, Halliday H, et al. Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy. N Engl J Med. 2009;361:1349–1358
  19. Jacobs S, Morley C. Infant Cooling Evaluation Trial. Available at: www.ctc.usyd.edu.au/6registry/PTO367.htm. Accessed November 29, 2005.
  20. Simbruner G, neo.nEuro.network. Induced systemic hypothermia in asphyxiated new-born infants: a randomized, controlled, multicenter study. Available at: http://neonatal-research/php/detail.php?artnr_4367&ukatnr_11237&ukatnameDepartment. Accessed November 29, 2005.
  21. Mei Qin, Shaozhen Fan. Protective effects of hypothermia in hypoxic-ischemic brain injury in newborn rats (Abstracts). Pediatric Res. 1998;44:421
  22. Cheng GQ, Shao XM, Huang HJ. Effects of selective head cooling on cerebral blood flow and cerebral metabolic rate in newborn piglets (in Chinese). Chin J Pediatr. 2005;43:748–752
  23. Lijun Yu, Laishuan Wang, Xiaomei Shao. Moderate hypothermia improves the cerebral energy metabolism of hypoxic-ischemic brain damage in the immature rat (English). Chin J Contemp Pediatr. 2003;5:192–195
  24. Wang LS, Yu LJ, Shao XM. Mild hypothermia attenuates neuronal apoptosis after cerebral hypoxia-ischemia in neonatal rats (in Chinese). Chin J Contemp Pediatr. 2007;9:37–41
  25. Wang LS, Shao XM, Yang Y, Chen L. Effects of moderate hypothermia on p-ERK/p38 MAPK signal pathway following hypoxic-ischemic brain injury in neonatal rats (in Chinese). Chin J Perinat Med. 2006;9:337–340
  26. Wang JM, Liu DL, Shao XM. Influence of mild hypothermia treatment on amplitude integrated electroencephalogram in newborn pigs with hypoxic-ischemic brain damage (in Chinese). Chin J Contemp Pediatr. 2005;7:159–162
  27. Zhou W, Shao X, Cao Y, Chen C, Zhang X, Fan S, et al. Safety study of hypothermia for the treatment of hypoxic-ischemic brain damage in term neonates. Acta Pharmacol Sin (Suppl). 2002;64–68
  28. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol. 1976;33:696–705
  29. Wei KL, Ji XC, Wu SM. Guideline of sclerdema neonatorum therapy (in Chinese). Chin J Pediatr. 1991;29:163–164
  30. Gesell AL. Gesell and Amatruda's developmental diagnosis: the evaluation and management of normal and abnormal neuropsychologic development in infancy and early. 3rd ed.. Hagerstown, ML: Harper & Row; 1974;
  31. Palisano R, Rosenbaum P, Walter S, Russel D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39:214–223
  32. Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2007;4:CD003311
  33. Naqeeb N, Edwards AD, Cowan FM, Azzopardi D. Assessment of neonatal encephalopathy by amplitude-integrated electroencephalography. Pediatrics. 1999;103:1263–1271
  34. Wyatt JS, Gluckman PD, Liu PY, Azzopardi D, Ballard R, Edwards AD, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics. 2007;119:912–921
  35. Ambalavanan N, Carlo WA, Shankaran S, Bann CM, Emrich SL, Higgins RD, et al. Predicting outcomes of neonates diagnosed with hypoxemic-ischemic encephalopathy. Pediatrics. 2006;118:2084–2093
  36. Perlman JM. Hyperthermia in the delivery: potential impact on neonatal mortality and morbidity. Clin Perinatol. 2006;33:55–63

 Supported by grants from Construction of Key Disciplines of 211 Engineering of Ministry of Education of People's Republic of China. The authors declare no conflicts of interest.

 Registration number at Clinicaltrials.gov: NCT00890409.

PII: S0022-3476(10)00284-2

doi: 10.1016/j.jpeds.2010.03.030

The Journal of Pediatrics
Volume 157, Issue 3 , Pages 367-372.e3 , September 2010

Article Tools

* Image Usage & Resolution