Whole-body cooling reduce the risk of death or disability among infants with encephalopathy

Among term infants, hypoxic-ischemic encephalopathy due to acute perinatal asphyxia remains an important cause of neurodevelopmental deficits. In particular, infants with moderate encephalopathy have a 10% risk of death, and those who survive have a 30% risk of disabilities. Among infants with severe encephalopathy, 60% die, and almost all survivors are handicapped.
Treatment is currently limited to supportive intensive care. Anyway, it has been demonstrated that reductions in brain temperature by 2-5°C can provide neuroprotection in newborn and adult animal models, up to 5.5 hours after brain ischemia. In fact, brain cooling has a favorable effect on multiple mechanisms which contribute to brain injury, such as excitatory amino acids, the cerebral energy state, cerebral blood flow and metabolism, nitric oxide production, and apoptosis. The feasibility of whole-body cooling in infants has already been proved in a pilot study of neonates with hypoxic-ischemic encephalopathy.
On these basis, the National Institute of Child Health and the Human Development Neonatal Research Network have recently conducted a randomized, controlled trial to evaluate if whole-body cooling initiated before 6 hours of age and continued for 72 hours in term infants with encephalopathy would reduce death or disability if compared with infants given usual care. The trial involved infants with a gestational age of at least 36 weeks, admitted to the hospital at or before six hours of age, with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group, n=103) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (hypothermia group, n=102). The primary outcome was a combined end point of death or moderate or severe disability. Neurodevelopmental outcome was assessed at 18 to 22 months of age.
Death or moderate or severe disability occurred in 44% of infants in the hypothermia group and in 62% of infants in the control group (p=0.01). In total, 24% of infants in the hypothermia group and 37% in the control group died. There was no increase in major disability among survivors; the rate of cerebral palsy was 19% in the hypothermia group and 30% in the control group. The rates of a Mental Development Index below 70 were 25% and 39% in the hypothermia and control group, respectively. Adverse events were similar in the two groups during the 72 hours of cooling.
As compared with usual care, whole-body cooling to an esophageal temperature of 33.5°C initiated within the first 6 hours after birth and continued for 72 hours reduced the rate of death or disability in term newborns with encephalopathy. A concern with any therapy that reduces mortality among infants is the possible increase in the number of infants who develop disabilities. In this study, there was no evidence of increased rates of moderate or severe disability at 18 to 22 months of age among infants treated with hypothermia.
In summary, this study can support the safety and effectiveness of whole-body cooling in reducing the risk of death or disability among infants with moderate or severe encephalopathy.

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