New Approaches to Addressing the Effects of Oxygen Deprivation During Birth

Babies born with oxygen deprivation require immediate treatment, as this condition damages the brain and poses an acute threat to life. While such complications are rare in this country, globally, oxygen deprivation at birth is one of the leading causes of death among newborns. Worldwide, 1 million newborns die from it each year. To counteract this, so-called therapeutic hypothermia has been used for several years. The newborns’ body temperature is lowered to around 33 degrees Celsius for several days and then gradually raised again. “The cooling slows down the metabolism and gives the brain a chance to regenerate. This increases the chances of survival and reduces the risk of long-term complications,” explains Prof. Hemmen Sabir. The scientist and physician is a research group leader at the DZNE and a senior physician in the Department of Neonatology and Pediatric Intensive Care Medicine at the UKB. “While the procedure is established in industrialized nations, around 40 percent of the children treated do not benefit from it. And in developing countries, the success rate is even lower. The reasons for this are not entirely clear, but could be related to the fact that newborns there have poorer conditions than in industrialized nations due to their mothers’ health status and possibly undetected infections. Given this, there is an urgent need for alternative therapies. That is exactly where our study came in.”

Hypothermia is currently the only established treatment for the consequences of oxygen deprivation during birth. Although drug-based alternatives have been tested worldwide – mostly in animal studies. However, the results of these studies are difficult to compare because they were conducted by different research groups and mostly under varying conditions. Hemmen Sabir and his team therefore set out to test a whole range of active compounds under identical conditions. Based on studies by other research groups, they identified a total of 25 promising substances, which they then tested in small animal models under oxygen deprivation. The animals were treated for up to six days: depending on the specific active ingredient and its application conditions, which were derived from earlier studies. For some active ingredients, an initial dose was administered shortly before oxygen deprivation. “Applied to humans, this means that these active ingredients are administered shortly before or during the mother’s delivery, for example in cases of obvious risks or complications,” says Sabir. “However, only substances that can cross the placenta and thus pass from the mother’s bloodstream to the unborn child are suitable for this. We essentially simulated this situation in our study.”

Seven days after the oxygen deprivation, the animals’ brains were examined for damage. “Treatment with caffeine was the most effective; in this case, the loss of brain tissue was the lowest and also significantly lower than with cooling therapy,” says Sabir. “Caffeine is known to have anti-inflammatory effects. Our study demonstrates that caffeine is also extremely neuroprotective. ” Six other active ingredients also performed better than standard therapy. These include, among others, the Hormone melatonin, a gout medication, an anti-allergy drug, and fish oil. Among the seven particularly effective agents are both those administered before the oxygen deprivation – such as caffeine – and those administered afterward.

“The advantage of drug therapy is that it does not require complex medical equipment. If caffeine does indeed prove to be the treatment of choice, we would also have an active ingredient that is inexpensive and readily available. This form of therapy would be particularly well-suited for developing countries. But of course, it could also be used in industrialized nations if it proves superior to cooling therapy,” said Sabir. Before testing in humans, however, additional studies in animal models are necessary, and the mechanisms of action of the various substances must be examined in greater detail to identify the best possible active ingredient or potential combinations. The Bonn researchers are in contact with international partners regarding this. “If further laboratory studies yield positive results, I am confident that we can expect clinical trials in humans very soon,” says Sabir.

Original publication

Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia–ischemia in newborn rats: a multi‑drug randomized controlled screening trial, Hemmen Sabir et al., Scientific Reports (2023)
DOI: https://doi.org/10.1038/s41598-023-36653-9