Trial on Cooling Approach for Oxygen-deprived Newborns Supports Current Care Strategy

The current cooling approach to limit death and brain disorders — such as cerebral palsy — in infants deprived of oxygen during birth is the safest and should not be changed, researchers argue with the results of a clinical trial in hand.

The study found that infants who were treated with the current standard approach of having their body temperature lowered to 33.5 degrees Celsius (92.3 degrees Fahrenheit) for 72 hours had equally good outcomes — assessed as a combination of death or disability — as those treated with harsher cooling regimens.

But while fewer children died with the standard approach, data indicated that a harsher treatment might be linked to less severe motor disability and numerically lower rates of cerebral palsy.

“Neither longer cooling nor deeper cooling nor both were more superior to cooling for 72 hours at 33.5 degrees Celsius in reducing death or survival with disability at 18 months of age,” Seetha Shankaran, MD, a neonatologist at Detroit Medical Center’s Children’s Hospital who led the study, said in a press release.

The study, “Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial,” was published in the journal JAMA.

Hypoxic ischemic encephalopathy, or brain damage caused by a lack of oxygen during birth, affects thousands of U.S. infants each year, and about one-fourth of them will develop a permanent neuropsychological disorder such as cerebral palsy, mental retardation, visual or movement abnormalities, or epilepsy.

Cooling infants to 33.5 degrees Celsius for 72 hours has been the standard of care since 2005, when Shankaran published a study demonstrating the benefits of the approach. But an animal study suggested that cooling to 32 degrees Celsius (89.6 degrees Fahrenheit) for 120 hours might be better.

The trial (NCT01192776) randomly assigned 364 infants with oxygen-deprivation brain damage to be treated with either the standard of care cooling, or to cooling at a lower temperature for a longer time, or both. All children were born in week 36 of pregnancy or later (full-term). Those who survived were followed for 18 months after birth.

Results showed that longer or deeper cooling did not reduce death or disability at 18 months.

Looking specifically at mortality, infants cooled in the standard way had a death rate of about 9%, while the other approaches were linked to a mortality of 18% to 19%.

While not statistically significant, rates of moderate or severe disability did, however, appear to benefit from the harsher treatment, with 22 percent developing disability when treated for 72 hours, and 15 percent with the 120-hour treatment.

Similarly, those treated at the standard, higher temperature had a 21 percent disability rate, compared to 16 percent at the lower temperature.

For cerebral palsy, 19 percent of those treated for 72 hours developed the condition, compared to 13 percent of infants treated for 120 hours. There was no difference in rates of cerebral palsy with the different temperatures.

In addition, significantly fewer children developed severe motor symptoms when treated for 120 hours or at a lower temperature.

“In this trial we saw that the rate of death or disability was 29.3% with cooling for 72 hours at 33.5 C. This is even lower than the 44% rate we achieved with cooling for 72 hours at 33.5 C with our first trial published in the New England Journal of Medicine in 2005,” said Shankaran, who is also with the Hutzel Women’s Hospital and a researcher at Wayne State University School of Medicine.

“The reason for this reduced rate could be that the number of infants with severe encephalopathy was lower in this trial than our first trial, but other changes in care practices may also have helped to reduce this rate,” Shankaran added.

Although the research team said that the data obtained do not support a change in the current cooling approach, they cautioned that the study may have been too small to detect subtler differences and that further studies might be needed.

The team now plans to investigate whether this cooling approach used in combination with additional therapies might be even more beneficial. Such studies need to be larger than the current one, the researchers noted.