Three articles are reviewed that lend support to the usefulness of one or more techniques of hypothermia in the prevention of death and cerebral palsy among term babies born with evidence of hypoxic-ischemic encephalopathy. The study conducted under the auspices of the National Institute of Child Health and Human Development contains the most significant data.
Previous Research Fact Sheets (April 1998 and February 2003) have commented on the potential role of hypothermia in preventing cerebral palsy and have reported on encouraging animal research models. Cooling inhibits a number of potentially damaging chemical reactions in the hypoxic brain and is ready for human trials. Two approaches are under evaluation: whole body cooling and selective cooling of the head using a device called the Cool-Cap®.
Seetha Shrankaran and her many colleagues report on a multicenter study on whole body infant cooling financed by the National Institute of Child Health and Human Development1. They studied newborn infants with evidence of hypoxic-ischemic brain injury randomized within 6 hours of birth to either traditional care plus whole body hypothermia for 72 hours (hypothermia group) or traditional care without hypothermia (control group). 102 infants were assigned to the hypothermia group and 106 to the control group. The authors followed the surviving babies in both groups out to 18-22 months of age. Follow-up was available on all the babies treated with hypothermia and all but 5 of the babies in the control group.
Their statistics clearly showed that fewer babies in the hypothermia group died or survived with severe disabilities. The difference was statistically significant, although individual outcome measures showed only trends. However, the trends within the study were very encouraging. 76% of the hypothermic treated babies survived compared to 63% of the controls. Concerns that the increased survival rate might translate into increased numbers of severely handicapped children, proved to be unfounded. In the control group, 30% of surviving children in the control group had disabling cerebral palsy compared to only 19% of the hypothermic babies. Only 55% of the control babies had IQ’s of 85 or better compared to 62% of the hypothermic babies. Similar reductions were seen in severe vision and hearing impairment.
Some months earlier, Gluckman and his associates2 reported a similar study cooling only the heads of the babies using the Cool-Cap®. They applied EEG criteria to divide infants into those with moderate and those with severe brain injury. 66% of babies in the control group died or had severe disabilities compared to 55% in the hypothermic group. Among the survivors, 31% of controls have severe neurosensory deficits compared to 19% of the babies treated with head cooling. Although these numbers did not reach statistical significance, their findings reinforce those of the whole body cooling study. The trend is encouraging.
In a smaller study, Inder and her group3 demonstrated that among 26 infants randomized to control and hypothermic treatment, the hypothermic babies had much less abnormality in the cortical grey mater than did the controls.
Term babies with hypoxic-ischemic encephalopathy are at risk for spastic hemiplegic cerebral palsy as well as other forms. Although statistically significant results are most convincing, the trends reported in these three studies are certainly encouraging. Historically, one would hope we would soon see additional studies showing improved outcomes after technical fine tuning. It is just possible that we are on our way to a management strategy capable of preventing cerebral palsy in a significant number of children.
1 Whole body hypothermia for neonates with hypoxic-ischemic encephalopathy. New England Journal of Medicine 2005; Vol 353: Pg. 1574-84.
2 Gluckman PD et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicenter, randomized trial. The Lancet 2005; Vol 365: Pg. 632-634.
3 Inder, TE et al. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. J. Pediatrics 2004; Vol 145:Pg 835-7.
© UCP Research & Educational Foundation, November 2005