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Published on: June 21, 2024
Childhood outcomes after hypothermia for neonatal encephalopathy
Seetha Shankaran1, Athina Pappas, Scott A McDonald
1Department of Pediatrics, Wayne State University, Detroit, MI, USA. sshankar@med.wayne.edu
Insights
Whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy reduced death rates in children. Long-term outcomes showed a trend toward fewer deaths or low IQ scores, but results were not statistically significant.
Area of Science:
- Neonatalogy
- Pediatric Neurology
- Therapeutic Hypothermia
Background:
- Neonatal hypoxic-ischemic encephalopathy (HIE) is a serious condition in newborns.
- Early results showed whole-body hypothermia reduced death or disability at 18-22 months.
- Long-term outcomes up to 6-7 years of age are now reported.
Purpose of the Study:
- To evaluate the long-term neurodevelopmental and survival outcomes of neonatal HIE.
- To assess the efficacy of whole-body hypothermia compared to usual care up to 6-7 years of age.
Main Methods:
- A randomized trial comparing whole-body cooling (33.5°C for 72 hours) to usual care.
- Infants with moderate to severe HIE were enrolled.
- Long-term follow-up included cognitive, attention, executive, visuospatial function, neurologic, physical, and psychosocial assessments.
Main Results:
- The primary outcome (death or IQ < 70) occurred in 47% of the hypothermia group vs. 62% of the control group (P=0.06).
- Death rates were significantly lower in the hypothermia group (28% vs. 44%, P=0.04).
- Among survivors, rates of moderate/severe disability were similar between groups (35% vs. 38%).
Conclusions:
- Whole-body hypothermia showed a trend toward improved long-term outcomes (death or low IQ) in HIE survivors, though not statistically significant.
- Hypothermia significantly reduced mortality rates and did not increase severe disability in survivors.
- Therapeutic hypothermia is a potentially beneficial intervention for neonatal HIE.
Background:
We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available.
Methods:
In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70.
Results:
Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80).
Conclusions:
The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).
