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.

The improvement in short-term outcomes without significant increase in side effects indicate the need for further trials to determine if there are long-term benefits of magnesium and to confirm its safety. Mortality was statistically insignificant between the magnesium and the control groups. However, the trend toward increase in mortality in the magnesium group is a major clinical concern and should be monitored closely in future trials.

Background: Therapeutic hypothermia provides up to 30% neuroprotection in moderate to severe hypoxic ischemic encephalopathy (HIE). Additional neuroprotection may be achieved by using concomitant pharmacologic neuroprotective agents. Aim: The aim was to evaluate the safety of concomitant neuroprotective therapy of therapeutic hypothermia and magnesium sulfate (MgSO 4) in the management of moderate and severe HIE in term and near-term infants. Study Design: Multicenter double-blind randomized controlled trial. Methodology: Term and near-term newborn infants (≥35 weeks) with a clinical diagnosis of moderate or severe HIE were randomized to either Arm A (therapeutic hypothermia plus MgSO 4) or Arm B (therapeutic hypothermia plus placebo) using a net-based randomization system. Both groups received, within 6 h of birth, standard hypothermia therapy (72 h of cooling to 33.5°C followed by slow rewarming over a period of 8 h) plus either MgSO 4 (250 mg/kg/dose ×3 doses) or placebo (normal saline). The groups were compared for short-term predischarge adverse outcomes. Results: A total of 60 patients were randomized (29 in Arm A and 31 in Arm B). Both groups had similar baseline characteristics (P > 0.05) including severity of HIE. There were no differences in the short-term adverse outcomes (death, seizures, thrombocytopenia, coagulopathy, renal failure, elevated liver function test's, hypotension, intracranial hemorrhage, necrotizing enterocolitis, pulmonary hemorrhage, persistent pulmonary hypertension, and pulmonary air leak syndromes) between the two groups (P > 0.05). Conclusions: The combined use of therapeutic hypothermia and MgSO 4 appears to be safe particularly with respect to maintaining normal blood pressure and coagulopathy. Long-term survival and neurodevelopmental outcomes remain to be evaluated.