Every year thousands of babies born in the United States suffer from perinatal hypoxic-ischemic encephalopathy (HIE), a condition where a lack of oxygen and reduced blood supply during or shortly after birth causes brain damage and can lead to death or serious disability in later life. HIE results from a variety of causes, for example when the umbilical cord becoming wrapped around the child’s neck during birth, and until recently there was no specific treatment to help prevent injury in these cases. A report on the BBC highlights a promising therapeutic approach that may help doctors to reduce the damage.
In this clinical trial published in the New England Journal of Medicine members of the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY) study group lead by Dr Denis V Azzopardi at Imperial College London compared the effects of cooling the whole body of newborn babies to 33.5 degrees Celsius for 72 hours following HEI with a control group who underwent standard intensive care, and found that a significantly larger proportion of babies treated with hypothermia survived without signs of brain damage. This result builds that of two earlier clinical trials published in 2005 which reported that cooling could help to prevent brain damage in HIE babies, and since then one method, the Cool Cap system which cools the head rather than the whole body, has been approved by the FDA. Both the Cool Cap clinical trial and the TOBY trial report the most significant improvements for children who might have otherwise suffered mild-to-moderate injury, which is in agreement with the observation that damage to the brain in these cases occurs in two phases, one during oxygen starvation and a second in the following hours and days, with the hypothermia treatment helping to prevent the second phase of damage.
So where did this technique come from? Well the use of hypothermia in medicine in not entirely novel, indeed for the past fifty years induced hypothermia has been used to reduce oxygen use and slow the flow of blood during heart surgery, giving surgeons more time to perform delicate operations. This technique was first demonstrated by Dr. Wilfred G. Bigelow in 1949 when he demonstrated that hypothermia could increase the time available for open heart surgery in dogs. The use of hypothermia to treat HIE much more recent and is thanks mainly to Professor Marianne Thoresen, another member of the TOBY study group, who performed pioneering research in the mid 1990’s (1,2) which demonstrated that cooling the body by 3-4 degrees could reduce brain damage following oxygen starvation in newborn piglets and rats. Further animal studies by her research group and others (3) determined that the treatment needed to begin within 6 hours of birth and continue for a prolonged period of up to 72 hours for optimum results.
Thanks to the work of Prof. Thorsesen hypothermia is now a promising therapy for oxygen starved babies, but it can no doubt be improved further and studies in both animals and in the clinic are continuing in order refine these techniques.
1. Thoresen M. et al.”Mild hypothermia after severe transienthypoxia-ischemia ameliorates delayed cerebralenergy failure in the newborn piglet.” Pediatr Res Vol. 37, Pages 667-670 (1995) PubMed: 7603788
2. Bona E. et al. “Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome.” Pediatr Res Vol.43, pages 738-745 (1998) PubMed: 9621982
3. Gunn A.J. et al.. “Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.” J Clin Invest. Volume 99, Pages 248–256 (1997) DOI:10.1172/JCI11915