Hypothermia: a systematic review and meta-analysis of clinical trials.

Hypothermia is a potential neuroprotective intervention to treat neonatal post-asphyxial (hypoxic-ischemic) encephalopathy (HIE). In this meta-analysis of 13 clinical trials published to date, therapeutic hypothermia was associated with a highly reproducible reduction in the risk of the combined outcome of mortality or moderate-to-severe neurodevelopmental disability in childhood. This improvement was internally consistent, as shown by significant reductions in the individual risk for death, moderate-to-severe neurodevelopmental disability, severe cerebral palsy, cognitive delay, and psychomotor delay. Patients in the hypothermia group had higher incidences of arrhythmia and thrombocytopenia; however, these were not clinically important. This analysis supports the use of hypothermia in reducing the risk of the mortality or moderate-to-severe neurodevelopmental disability in infants with moderate HIE.

[1]  C. Thompson,et al.  Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap. , 2006, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[2]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[3]  H. Sarnat,et al.  Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. , 1976, Archives of neurology.

[4]  P. Shah,et al.  Hypothermia to Treat Neonatal Hypoxic Ischemic Encephalopathy : Systematic Review , 2008 .

[5]  L. Doyle,et al.  Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. , 2004, The Journal of pediatrics.

[6]  H. Goodkin,et al.  Implementation of a ‘Hypothermia for HIE’ program: 2-year experience in a single NICU , 2008, Journal of Perinatology.

[7]  A D Edwards,et al.  Therapeutic hypothermia following perinatal asphyxia , 2006, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[8]  T R Gunn,et al.  Selective Head Cooling in Newborn Infants After Perinatal Asphyxia: A Safety Study , 1998, Pediatrics.

[9]  J. Tyson,et al.  Outcomes of Safety and Effectiveness in a Multicenter Randomized, Controlled Trial of Whole-Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy , 2008, Pediatrics.

[10]  A. Edwards,et al.  Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial , 2008, Archives of Disease in Childhood Fetal and Neonatal Edition.

[11]  A. Gunn,et al.  Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. , 1997, The Journal of clinical investigation.

[12]  M. Yalaz,et al.  Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. , 2003, Prostaglandins, leukotrienes, and essential fatty acids.

[13]  P. Jouvet,et al.  Whole-body cooling after perinatal asphyxia: a pilot study in term neonates. , 2003, Developmental medicine and child neurology.

[14]  T. Inder,et al.  Mechanisms of perinatal brain injury. , 2000, Seminars in neonatology : SN.

[15]  A. Edwards,et al.  Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial , 2010, Lancet Neurology.

[16]  M. Blennow,et al.  Passive induction of hypothermia during transport of asphyxiated infants: a risk of excessive cooling , 2009, Acta paediatrica.

[17]  C. Yun,et al.  Safety study of hypothermia for treatment of hypoxic-ischemic brain damage in term neonates , 2002 .

[18]  W. Phillips,et al.  Passive cooling to initiate hypothermia for transported encephalopathic newborns , 2007, Journal of Perinatology.

[19]  N. Marlow,et al.  Moderate hypothermia to treat perinatal asphyxial encephalopathy. , 2009, The New England journal of medicine.

[20]  S. Cousens,et al.  4 million neonatal deaths: When? Where? Why? , 2005, The Lancet.

[21]  W. T. Bass,et al.  Moderate hypothermia in neonatal encephalopathy: safety outcomes. , 2005, Pediatric neurology.

[22]  W. Silverman,et al.  The influence of the thermal environment upon the survival of newly born premature infants. , 1958, Pediatrics.

[23]  A. Stark,et al.  Hypothermia: A Neuroprotective Therapy for Neonatal Hypoxic-Ischemic Encephalopathy , 2006, Pediatrics.

[24]  R. A. Kilani.  The safety and practicality of selective head cooling in asphyxiated human newborn infants, a retrospective study. , 2002, Le Journal medical libanais. The Lebanese medical journal.

[25]  Shripada Rao,et al.  A systematic review of cooling for neuroprotection in neonates with hypoxic ischemic encephalopathy – are we there yet? , 2007, BMC pediatrics.

[26]  G. Simbruner,et al.  Induced brain hypothermia in asphyxiated human newborn infants: a retrospective chart analysis of physiological and adverse effects , 1999, Intensive Care Medicine.

[27]  A Whitelaw,et al.  Cardiovascular Changes During Mild Therapeutic Hypothermia and Rewarming in Infants With Hypoxic–Ischemic Encephalopathy , 2000, Pediatrics.

[28]  B. Westin.  Hypothermia in the resuscitation of the neonate: A glance in my rear‐view mirror , 2006, Acta paediatrica.

[29]  Kristian Thorlund,et al.  Cooling for Neonatal Hypoxic Ischemic Encephalopathy: Do We Have the Answer? , 2007, Pediatrics.

[30]  R. Palisano,et al.  Development and reliability of a system to classify gross motor function in children with cerebral palsy , 1997, Developmental medicine and child neurology.

[31]  A. Costello,et al.  Therapeutic hypothermia for birth asphyxia in low-resource settings: a pilot randomised controlled trial , 2008, The Lancet.

[32]  Carol L Wagner,et al.  Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. , 2005, Pediatric neurology.

[33]  N. Schor,et al.  Whole-Body Hypothermia for Neonates With Hypoxic–Ischemic Encephalopathy , 2007 .

[34]  Joy E. Lawn,et al.  4 million neonatal deaths: When? Where? Why? Neonatal survival 1. , 2005 .

[35]  F. Cowan,et al.  Pilot Study of Treatment With Whole Body Hypothermia for Neonatal Encephalopathy , 2000, Pediatrics.

[36]  A. Watkins,et al.  Hypothermia: A Neuroprotective Therapy for Neonatal Hypoxic-Ischemic Encephalopathy , 2007, Pediatrics.

[37]  Seetha Shankaran,et al.  Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. , 2006, The Journal of pediatrics.

[38]  P. Davis,et al.  Cooling for newborns with hypoxic ischaemic encephalopathy. , 2013, The Cochrane database of systematic reviews.

[39]  A. David Edwards,et al.  Assessment of Neonatal Encephalopathy by Amplitude-integrated Electroencephalography , 1999, Pediatrics.

[40]  T R Gunn,et al.  Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. , 2001, Pediatrics.

[41]  A. Gunn,et al.  Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  A. Gunn,et al.  Rebound Seizures During Rewarming , 2004, Pediatrics.

[43]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[44]  F. Mosca,et al.  Hypothermia Reduces Neurological Damage in Asphyxiated Newborn Infants , 2002, Neonatology.

[45]  M. Bhat.  Re: Therapeutic hypothermia following perinatal asphyxia , 2006, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[46]  A. Gunn,et al.  Treatment of Term Infants With Head Cooling and Mild Systemic Hypothermia (35.0°C and 34.5°C) After Perinatal Asphyxia , 2003 .

[47]  Andrew Whitelaw,et al.  Determinants of Outcomes After Head Cooling for Neonatal Encephalopathy , 2007, Pediatrics.

[48]  J. Low,et al.  Threshold of metabolic acidosis associated with newborn complications. , 1997, American journal of obstetrics and gynecology.

[49]  D. Deboutte,et al.  Child Sexual Behavior Inventory: A Dutch-speaking Normative Sample , 1999, Pediatrics.

[50]  Zhenlang Lin,et al.  Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit , 2006, Journal of Perinatology.

[51]  S. Jacobs,et al.  Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. , 2005, The Journal of pediatrics.

[52]  J. Tyson,et al.  Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for a randomized, controlled pilot study in term infants. , 2002, Pediatrics.

[53]  C. Thompson,et al.  Induced Hypothermia for Infants With Hypoxic- Ischemic Encephalopathy Using a Servo-Controlled Fan: An Exploratory Pilot Study , 2009, Pediatrics.