181 Cooling for Newborns with Hypoxic Ischaemic Encephalopathy

Abstract

Background: Experimental studies suggest that hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae. Aims: To determine whether therapeutic hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and neurodevelopmental disability, without clinically important side effects. Methods: Randomised controlled trials (RCTs) evaluating therapeutic hypothermia in newborns with hypoxic ischaemic encephalopathy (HIE) were identified using the standard search strategy of the Neonatal Review Group of the Cochrane Library. The primary outcome was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling. Three reviewers independently selected, assessed the quality of and extracted data. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Results: Four RCTs were included in this review, comprising 349 term infants with HIE. Two studies (Gunn 1998, Gluckman 2005) achieved excellent follow-up rates at 18 months of age; one (Eicher 2005) had incomplete follow-up at 12 months (81.5%) and one (Shankaran 2002) has not reported long-term outcomes. The pooled analysis of the 2 higher quality studies showed no significant effect of therapeutic hypothermia on the combined outcome of death or major neurodevelopmental disability in survivors followed (RR 0.89 [95% CI 0.69, 1.05]). Inclusion of the poorer quality study (Eicher 2005) resulted in a significant reduction in death or major disability in infants allocated to therapeutic hypothermia (RR 0.80 [95% CI 0.66, 0.96]). No adverse effects of hypothermia on short term outcomes were detected. Conclusions: Four RCTs showed no evidence of harm from therapeutic hypothermia. Evidence of efficacy remains inconclusive. Therapeutic hypothermia for infants with HIE should continue to be evaluated in well designed RCTs. This abstract is a preliminary version of the update to be included in the Cochrane Library Issue 4 2005.