The Indian Journal of Pediatrics

, Volume 79, Issue 10, pp 1342–1346 | Cite as

The Efficacy of Hypothermia in Hypoxic-Ischemic Encephalopathy at 18 Mo or More

  • Li Wu
  • Bin Yi
  • Yang Hu
  • Cunwei Ji
  • Tao Zhang
  • Youjie Wang
Original Article



To evaluate the efficacy of hypothermia in the treatment of hypoxic-ischemic encephalopathy (HIE) in neonates at 18 mo of age or more. Also to examine whether the severity of encephalopathy affects the efficacy of hypothermia on mortality and neurodevelopmental disability.


The authors recruited the trials that assessed the efficacy of therapeutic hypothermia in the treatment of HIE in neonates at 18 mo of age or older up to April 2011. The meta- analysis was performed using a fixed effect model.


Hypothermia significantly reduced the combined rate of death or neurodevelopmental disability (RR = 0.74, 95% CI: 0.67 to 0.82; RD = −0.13, 95% CI: −0.18 to −0.08; NNT = 7, 95% CI: 6 to 9) among infants at 18 mo of age or older. Hypothermia reduced the rate of death (RR = 0.75, 95% CI: 0.64 to 0.88), neurodevelopmental disability (RR = 0.65, 95% CI: 0.54 to 0.79), cerebral palsy (RR = 0.65, 95% CI: 0.53 to 0.80), developmental delay (RR = 0.72, 95% CI: 0.57 to 0.92), neuromotor delay (RR = 0.78, 95% CI: 0.61 to 0.99) and visual deficit (RR = 0.59, 95% CI: 0.36 to 0.99). Analysis of the severity of disease showed that hypothermia reduced the combined rate of death or neurodevelopmental disability not only in moderate encephalopathy infants (RR = 0.63, 95% CI: 0.53 to 0.76) but also in severe encephalopathy infants (RR = 0.82, 95% CI: 0.74 to 0.92).


Hypothermia has a beneficial effect in the treatment of HIE in neonates at 18 mo of age or older.


Hypothermia Hypoxic-ischemic encephalopathy Neonate Efficacy 



Hypoxic-Ischemic Encephalopathy


Selective Head Cooling


Whole Body Cooling


Confidence Interval


Relative Risk


Risk Difference


Number Needed to Treat



The authors thank Dr. Zhang (Southeast University) for providing them with additional data. They also thank Dr Liang (Tongji Medical College, Huazhong University of Science & Technology) for providing statistical advice.


YW: study design and manuscript drafting; LW: writing the manuscript; YH: analyzing the data; BY, YW: evaluating the methodological quality of the recruited studies; CJ and LW: collecting the data.

Conflict of Interest


Role of Funding Source

National Natural Science Foundation of China, Project No: 30671733, and NECT Program 07-0333.


  1. 1.
    Fatemi A, Wilson MA, Johnston MV. Hypoxic-ischemic encephalopathy in the term infant. Clin Perinatol. 2009;36:835–58. vii.PubMedCrossRefGoogle Scholar
  2. 2.
    Perlman JM. Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy. Pediatrics. 2006;117:S28–33.PubMedCrossRefGoogle Scholar
  3. 3.
    Gluckman PD, Pinal CS, Gunn AJ. Hypoxic-ischemic brain injury in the newborn: pathophysiology and potential strategies for intervention. Semin Neonatol. 2001;6:109–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Vannucci RC. Hypoxic-ischemic encephalopathy. Am J Perinatol. 2000;17:113–20.PubMedCrossRefGoogle Scholar
  5. 5.
    Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics. 1998;102:885–92.PubMedCrossRefGoogle Scholar
  6. 6.
    Shankaran S, Laptook A, Wright LL, et al. Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. Pediatrics. 2002;110:377–85.PubMedCrossRefGoogle Scholar
  7. 7.
    Amess PN, Penrice J, Cady EB, et al. Mild hypothermia after severe transient hypoxia-ischemia reduces the delayed rise in cerebral lactate in the newborn piglet. Pediatr Res. 1997;41:803–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Colbourne F, Corbett D, Zhao Z, Yang J, Buchan AM. Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model. J Cereb Blood Flow Metab. 2000;20:1702–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365:663–70.PubMedGoogle Scholar
  11. 11.
    Gunn AJ, Bennet L, Gunning MI, Gluckman PD, Gunn TR. Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res. 1999;46:274–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Guidelines for reviewers and editors. Cochrane Neonatal Review Group. 2009; [access date Dec. 30, 2011]
  14. 14.
    Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: A randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165:692–700.PubMedCrossRefGoogle Scholar
  15. 15.
    Palisano RJ, Hanna SE, Rosenbaum PL, et al. Validation of a model of gross motor function for children with cerebral palsy. Phys Ther. 2000;80:974–85.PubMedGoogle Scholar
  16. 16.
    Li T, Xu F, Cheng X, et al. Systemic hypothermia induced within 10 hours after birth improved neurological outcome in newborns with hypoxic-ischemic encephalopathy. Hosp Pract (Minneap). 2009;37:147–52.CrossRefGoogle Scholar
  17. 17.
    Simbruner G, Mittal RA, Rohlmann F, Muche R. Systemic hypothermia after neonatal encephalopathy: outcomes of RCT. Pediatrics. 2010;126:e771–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhou WH, Cheng GQ, Shao XM, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr. 2010;157:367–72.PubMedCrossRefGoogle Scholar
  19. 19.
    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;107:480–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic hypothermia (35.0 degrees C and 34.5 degrees C) after perinatal asphyxia. Pediatrics. 2003;111:244–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Gunn AJ, Hoehn T, Hansmann G, et al. Hypothermia: an evolving treatment for neonatal hypoxic ischemic encephalopathy. Pediatrics. 2008;121:648–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Kirpalani H, Barks J, Thorlund K, Guyatt G. Cooling for neonatal hypoxic ischemic encephalopathy: do we have the answer? Pediatrics. 2007;120:1126–30.PubMedCrossRefGoogle Scholar
  23. 23.
    Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010;340:c363.PubMedCrossRefGoogle Scholar
  24. 24.
    Shah PS. Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med. 2010;15:238–46.PubMedCrossRefGoogle Scholar
  25. 25.
    Rudan I, Chan KY, Zhang JS, et al. Causes of deaths in children younger than 5 years in China in 2008. Lancet. 2010;375:1083–9.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2012

Authors and Affiliations

  • Li Wu
    • 1
  • Bin Yi
    • 2
  • Yang Hu
    • 1
  • Cunwei Ji
    • 1
  • Tao Zhang
    • 1
  • Youjie Wang
    • 1
  1. 1.Department of Maternal and Child HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
  2. 2.Department of NeonatologyMaternal and Children Hospital of Gansu ProvinceLanzhouChina

Personalised recommendations