The authors of this study in a previously published randomized controlled trial reported that whole-body hypothermia of neonates with hypoxic-ischemic encephalopathy initiated within 6 hours of birth was associated with significant reductions in the rate of combined outcome of death or moderate or severe disability at 18 to 22 months of age. Until now, long-term data on outcomes beyond 2 years have not been available.
This study was designed to determine whether benefits of hypothermia for neonatal encephalopathy persist after 2 years of age. In the earlier trial, 208 infants with moderate or severe encephalopathy had been randomized to receive usual care (the control group, n = 106) or undergo whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group, n = 102). In the present study, outcomes evaluated in the surviving children at 6 to 7 years of age included cognitive, attention, and executive and visuospatial function, as well as neurologic outcomes and physical and psychosocial health. The primary study outcome was death or an IQ score less than 70.
Primary outcome data were available for 91% (190/208) of the children enrolled in the trial: 95% (97/102) in the hypothermia group and 88% (93/106) in the control group. Among the 190 participants, death or an IQ score less than 70 at 6 to 7 years of age occurred in 47% (46/97) of the children in the hypothermia group and 62% (58/93) in the control group (P = 0.06). Death occurred in 28% (27/97) of children in the hypothermia group and 44% (41/93) of those in the control group (P = 0.04). Death or severe disability occurred in 41% (38/93) of children in the hypothermia group and 60% (53/90) of those in the control group (P = 0.03). Among the 122 survivors, 27% (19/70) in the hypothermia group and 33% (17/52) in the control group had an IQ score less than 70. Moderate or severe disability occurred in 35% (24/69) in the treated group and 38% (19/50) of the controls (P = 0.87). There was no significant difference between the groups in the proportion of children with attention and executive function scores (P = 0.19) or visuospatial scores less than 70 (P = 0.80).
These findings show that the rate of composite end points of death or an IQ score less than 70 is lower, although not quite significantly reduced, in children at 6 to 7 years of age who had undergone neonatal whole-body hypothermia; the lack of significant difference is likely due primarily to the sample size and some underpowering of the long-term outcome. Although hypothermia reduces death rates, it again did not increase the rates of a low IQ score or severe disability among survivors significantly, although all adverse outcomes were lower in the cooling group.