History of Brain Cooling

During gestation, an unborn child's brain is vulnerable to a wide range of threats, including placental or umbilical problems, severe illness with the mother, or a difficult delivery. When a newborn is asphyxiated before or during birth, the ensuing lack of oxygen to the brain can result in a condition termed hypoxic-ischemic encephalopathy, or HIE.

For hundreds of years, healthcare workers have tried to resuscitate babies after birth who have suffered from a sufficient supply of oxygen to the brain by altering body temperatures, usually to induce the onset of breathing. Almost no thought was given to brain protection. By the 1960's, physicians believed hypothermia after delivery was something to be avoided. The problem of babies who failed to breathe at birth had been solved by the invention of mechanical ventilation.

In fact, some influential clinical trials showed that keeping small and pre-term infants warm increased survival. These results, together with other study findings, made it an act of medical faith for decades that babies should not be allowed to get cold.

During the next two decades, studies of neonatal hypothermia in Europe and the U.S. were sporadic and often unsuccessful. An interest in brain cooling was beginning to emerge, but little progress was being made.

However, behind the Iron Curtain in the Soviet Union cooling was being applied following birth asphyxia, but due to cold war politics and other factors, there was almost total ignorance of this work outside that region.

It wasn't until the late 1980's that the development of a new set of concepts led to a re-examination of the heat is good, cold is bad thinking. A new generation of neonatal researchers were influenced by the growing evidence that protecting the brain against the effects of oxygen deprivation during labor might be possible.

Delayed brain injury was a critical new idea. If brain cells remained normal for a time and the mechanism of the delayed death could be implemented, then therapeutic intervention was possible. Researchers were on the verge of a breakthrough, but scientists did not immediately move to hypothermia.

Most neonatal researchers recognize work published in 1989 as a starting point of interest in post-insult hypothermia. As the experimental data continued to accumulate, studies were being conducted with trepidation because of the widespread belief that cold was dangerous for infants. Nevertheless, cooling was now becoming a topic of wider discussion.

Most importantly, cooling captured the attention of Jerry Lucey, editor of Pediatrics Magazine and one of the most influential figures in neonatal medicine. He had an extraordinary ability to identify new ideas and he became a proponent of brain cooling. He promoted hypothermia as a treatment for oxygen-deprived babies at every opportunity.

Olympic Medal, a small Seattle-based equipment company, constructed a brain-cooling device called the Olympic Cool-Cap System. Additionally, they underwrote a randomized controlled trial of hypothermic neural rescue therapy in newborns.

Researchers at University College London Hospitals joined forces with researchers in New Zealand, Bristol and Seattle to put theory into practice by using this water-cooled cap for babies' heads. In all, 234 babies from around the world took part in the trial. Half received cooling treatment, and the other half had standard intensive care. The cooled babies received 72 hours of treatment, followed by gradual re-warming and standard care. There was follow-up and assessment for the following 18 months by pediatricians who were unaware which infants were cooled and which weren't.

The cooled babies showed significant benefits. There was a reduction in both the number of babies who died and in how severely disabled they were at 18 months of age. However, those babies who had the most severe electrical deficits at birth, 20% of the total, did not respond to cooling.

The first results were reported at Lucey's annual "Hot Topics in Neonatology" meeting in December 2003, followed by full publication in The Lancet, a British medical publication, in 2005. An important question confronted the neonatal community: Should cooling become the standard of care?

In December 2006, the Food and Drug Administration approved the Olympic Cool-Cap System for clinical use. Detractors argued that results were statistically marginal and urged caution. A review meeting by the National Institute for Child Health and Human Development (NICHD) advised that cooling was an emerging therapy but not standard of care.

The last major trial, the Total Body (TOBY) hypothermia for prenatal asphyxia, collected the data needed to allow meta-analysis with both Cool Cap and the NICHD studies. This trial showed unequivocally that cooling increases an infant's chance of surviving without neurological deficits at 18 months and reduces neuro-developmental impairment in survival.

Today, most researchers and doctors regard hypothermic neural rescue therapy as an evidence-based clinical treatment that increases any individual child's chance of surviving without brain damage detectable at 18 months by about 50%.