Treating brain damage can cause damage in low- and middle-income countries

A procedure widely used to treat birth-related brain damage in newborns in low- and middle-income countries (LMICs) may increase the risk of death.

This is the conclusion of research conducted by Imperial College London, in collaboration with several large hospitals in South Asia, published in the journal The Lancet Global Health.

The study, involving 408 babies suspected of birth-related brain damage in India, Sri Lanka and Bangladesh, used a technique called therapeutic hypothermia. This technique cools a baby’s body temperature by four degrees, placing it on a kind of cooling mat.

Previous evidence suggests that cold temperatures may help reduce brain cell damage and cell death.

The cooling treatment is widely used around the world, and evidence from several trials in high-income countries suggests that the treatment reduces mortality and disability in babies.

However, although the treatment is also widely used in LMICs, so far there have been few trials analyzing the effectiveness of the treatment in LMICs.

All of the babies in the new study were believed to have suffered brain damage during birth and had a condition called neonatal encephalopathy. This condition means that a baby has abnormal brain function and is normally caused by a lack of oxygen.

Neonatal encephalopathy is the cause of one million deaths each year worldwide, 99% of which occur in LMICs.

In the new trial, funded by the Garfield Weston Foundation, 206 babies with suspected brain damage received cooling therapy after birth, while 202 babies received no treatment after birth.

The study, called the HELIX trial, was a randomized controlled trial. After the babies’ families agreed to participate in the trial, the babies were randomly assigned to receive the cooling therapy, widely used in many parts of the world, or not to receive the cooling therapy.

Babies in both groups received full treatment in intensive care units. The cooling treatment was started within six hours of birth and continued for 72 hours, while the babies were closely watched.

Advanced MRI has been used to assess the health of their brains at two weeks of age and the general health of babies at 18 months. It is difficult to assess the level of development and disability of a child before this age.

The results of the trial showed that 50 percent of the infants in the group who received the cooling treatment died or had moderate or severe disability.

In the control group, where the babies did not receive the cooling treatment, 47 percent of the infants died or had moderate or severe disability.

The results also showed that 42% of the children in the cooling treatment group died, while 31% of the infants in the control group died.

All study sites were closely monitored by the team at Imperial College London, who have extensive experience in therapeutic hypothermia, using daily real-time video conferences to discuss the health of the babies. The test team also made site visits every three to four months and provided training during the recruitment period.

The cooling treatment was administered using the same cooling device used in the UK, and core body temperatures were tightly within the target range of 33-34 degrees.

Professor Sudhin Thayyil, lead author of the Imperial’s Department of Brain Sciences, said: “These data, from the HELIX trial, suggest that therapeutic hypothermia, combined with intensive care treatment high quality, does not reduce the risk of brain injury or death in LMICs. The results also suggest that the treatment may increase the risk of death, compared to babies who did not receive the treatment. Therefore, the treatment of hypothermia should no longer be used as a treatment for neonatal encephalopathy in low- and middle-income countries. International guidelines (ILCOR “International Liaison Committee on Resuscitation) on cold therapy in LMICs should be immediately amended. “

The study team says more research is now urgently needed to understand why the cooling treatment was ineffective and harmful.

The team suggests that the babies in the trial, and LMICs more generally, may have had a different type of brain injury than the type of brain injury seen in trials in high-income countries. Scans of babies’ brains suggested damage to connecting fibers in the brain rather than deep brain structures. One suggestion is that the brain damage may have occurred at an early stage of birth, or earlier in pregnancy.

Professor Jayshree Mondkar, senior author and professor of neonatology and former dean of Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, said: “The results of the HELIX trial were surprising as many centers in India regularly cool babies. . But the test was carried out. at a very high level, and the results are convincing. “

Professor Mohammed Shahidullah, senior author and professor of neonatology at Bangabandhu Sheikh Mujib University Medical Hospital, Dhaka, said: “The HELIX trial is a prime example of North-South collaboration between Imperial College and other centers of excellence in South Asia for the benefit of babies in LMIC. “

Study co-investigator Professor Seetha Shankaran of Wayne State University said: “While cooling is safe and effective in term babies with moderate to severe encephalopathy in high-income countries, The HELIX trial stresses the importance of conducting high-quality clinical trials before using for untested indications, for example in babies with milder brain damage or premature infants, even in high-income countries. “

Professor Thayyil adds, “COVID 19 has exposed how certain diseases affect disadvantaged populations differently. It is possible that ethnicity, socioeconomic status, infection, and nutritional status, for example, can influence birth-related brain injury, even in high-income countries, and therefore not all will respond to the problem. same treatment. Extensive research into how these factors cause brain damage in unborn babies is important for preventing and developing new treatments for birth-related brain damage. ”