Cooling for newborns with hypoxic ischemic encephalopathy

Abstract

Background: Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischemia in newborn infants may reduce neurological sequelae without adverse effects. Objectives: To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomized controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. Selection Criteria: We included randomized controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognizable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Data Collection and Analysis: Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). Main Results: We included 11 randomized controlled trials in this updated review, comprising 1,505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68-0.83); typical RD -0.15, 95% CI -0.20 to -0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5-10) (8 studies, 1,344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64-0.88), typical RD -0.09 (95% CI -0.13 to -0.04); NNTB 11 (95% CI 8-25) (11 studies, 1,468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63-0.94), typical RD -0.13 (95% CI -0.19 to -0.07); NNTB 8 (95% CI 5-14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia.