Newswise — Oxygen deprivation during birth, leading to brain damage, is a major cause of newborn mortality worldwide. Researchers from the University Hospital Bonn (UKB) and DZNE conducted a study using a small animal model to test the efficacy of 25 different active agents as treatments. Among them, seven substances showed greater effectiveness than the standard therapy of artificial cooling, with caffeine proving to be the most promising. These findings, published in the scientific journal Scientific Reports, have the potential to open up new avenues for treating newborns.
Newborns who experience oxygen deprivation during birth, a condition known as "birth asphyxia," require immediate treatment due to the resulting brain damage and life-threatening risks. Although such issues are rare in Germany, globally, birth asphyxia remains a leading cause of newborn mortality. Approximately one million newborns worldwide die annually as a result of birth asphyxia. To address this challenge, therapeutic hypothermia has been employed for several years. This approach involves reducing the infants' body temperature to around 33 degrees Celsius for several days, followed by a gradual increase. "Cooling down the body slows down metabolism and allows the brain to regenerate, thereby increasing the chances of survival and reducing the risk of long-term effects," explains Prof. Hemmen Sabir. Prof. Sabir is a research group leader at DZNE and a senior physician in the Department of Neonatology and Pediatric Intensive Care at UKB. "While the procedure is well-established in high-income countries, approximately 40 percent of treated children do not benefit from it. Moreover, the success rate is even lower in low- and middle-income countries. The reasons for this disparity are not fully understood, but they could be attributed to worse conditions for newborns in these countries due to the health status of their mothers and potential undetected infections. Therefore, there is an urgent need for alternative therapies, which is where our study comes into play."
Study with 25 Active Agents
Currently, therapeutic hypothermia stands as the sole established treatment for addressing the consequences of oxygen deprivation during childbirth. Various drug alternatives have been explored globally, primarily through animal studies. However, comparing the results of these investigations has proven challenging due to differences in research groups and settings. In light of this, Hemmen Sabir and his team set out to test a wide range of compounds under standardized conditions. Drawing from studies conducted by other research groups, they identified a total of 25 promising agents, which they then evaluated in a small animal model subjected to oxygen deprivation. The animals received treatment for a duration of up to six days, with specific dosages and administration conditions derived from previous studies. In certain cases, the initial dose of certain agents was given shortly before the onset of oxygen deprivation. "When applied to humans, this implies that these agents would be administered while the mother is still in labor, such as in situations involving apparent risks or complications," explained Sabir. "However, for this approach, only substances capable of crossing the placenta and reaching the unborn child through the mother's bloodstream are suitable. In a way, our study simulated this scenario.
Caffeine Was Most Effective
After a period of seven days following oxygen deprivation, the brains of the animal subjects were examined to assess any damage. "Among the treatments, caffeine exhibited the highest effectiveness, resulting in the least loss of brain tissue, even surpassing the effects of hypothermic treatment," Sabir reported. "Caffeine is known for its anti-inflammatory properties, and our study provides evidence of its remarkable neuroprotective abilities." Additionally, six other agents demonstrated superior performance compared to standard therapy. These included melatonin, a hormone known for its regulatory effects on sleep, a medication used for treating gout, an anti-allergy drug, and fish oil. The group of seven highly effective agents encompassed those administered prior to oxygen deprivation, such as caffeine, as well as those administered afterward.
Starting Point for Follow-Up Studies
"The benefit of drug treatment lies in its ability to bypass the need for complex medical equipment. If caffeine indeed proves to be the optimal drug, we would have an affordable and easily accessible agent. This form of therapy would be particularly suitable for developing countries. However, it could certainly be utilized in high-income nations if it outperforms hypothermic treatment," explained Sabir. Nevertheless, before proceeding to human trials, additional studies using animal models are required, along with in-depth investigations into the mechanisms of action of the different substances. This will help identify the most effective agent or potential combinations. The researchers from Bonn are actively collaborating with international partners for this purpose. "If subsequent laboratory studies yield positive results, I am optimistic that we can anticipate human clinical trials in the near future," Sabir concluded.
Funding
This study was funded by the “Bill and Melinda Gates Foundation”.
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