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Review Article |

Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy:  An Updated Systematic Review and Meta-analysis

Mohamed A. Tagin, MB BCh; Christy G. Woolcott, PhD; Michael J. Vincer, MD; Robin K. Whyte, MB; Dora A. Stinson, MD
Arch Pediatr Adolesc Med. 2012;166(6):558-566. doi:10.1001/archpediatrics.2011.1772.
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Objective  To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy (HIE).

Data Sources  Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews.

Study Selection  Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE.

Intervention  Therapeutic hypothermia.

Main Outcome Measures  Death or major neurodevelopmental disability at 18 months.

Results  Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability (RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93, respectively).

Conclusion  Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE. Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns.

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Figure 1. Publication bias funnel plots for the primary outcome. A, Publication bias funnel plot for death or severe disability in newborns with moderate hypoxic ischemic encephalopathy. B, Publication bias funnel plot for death or severe disability in newborns with severe hypoxic ischemic encephalopathy.

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Figure 2. Forest plot of the composite primary outcome of death or major disability in survivors. Diamond indicates overall summary estimate for the analysis (width of the diamond represents the 95% CI). M-H indicates Mantel-Haenzel test.

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Figure 3. Forest plot of components of the composite primary outcome. Blindness and deafness were not reported in the study by Zhou et al.22 M-H indicates Mantel-Haenzel test.

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Figure 4. Forest plot of survival with normal neurological function (“events”). Diamond indicates overall summary estimate for the analysis (width of the diamond represents the 95% CI). M-H indicates Mantel-Haenzel test.

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Figure 5. Forest plot of the primary outcome of death or major disability in survivors in newborns with moderate to severe hypoxic ischemic encephalopathy. Diamond indicates overall summary estimate for the analysis (width of the diamond represents the 95% CI). M-H indicates Mantel-Haenzel test.

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Figure 6. Forest plot for the primary outcome of death or major disability by method of cooling in newborns with moderate to severe encephalopathy. Diamond indicates overall summary estimate for the analysis (width of the diamond represents the 95% CI). M-H indicates Mantel-Haenzel test.

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