Why are premature babies so susceptible to deadly infections?

Why are premature babies so susceptible to deadly infections?
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Researchers from Ludwig-Maximilians-Universitaet Muenchen (LMU) have discovered why the immune system of premature babies does not function properly after birth.

The earlier babies are born, the higher their risk of life-threatening health complications. Infections can often lead to sepsis, one of the most frequent causes of death for premature babies.

“In the case of very prematurely born infants, a bacterial infection can lead to death within hours,” said LMU physician and former paediatrician Professor Markus Sperandio.

The immune system of premature babies is often underdeveloped

Researchers at LMU’s Biomedical Centre in Munich examined the reasons behind this high susceptibility to infection in their study, titled ‘When life begins to early’. The team found that an immunostimulatory signalling pathway is suppressed in the developing immune system of premature babies.

Previous studies from LMU researchers have shown that important cells of the innate immune system, called neutrophils, do not work in foetuses and newborn babies as they do in adults. Foetal and neonatal neutrophils do not sufficiently attach to the walls of blood vessels and extravasate into inflamed tissue, as in adults. This process is necessary for triggering the inflammatory response required to initiate an immune defence.

The researchers collaborated with the Children and Women’s Clinic at the University of Munich Hospital to investigate the mechanisms behind this immaturity.

Using so-called transcriptomic analysis, the researchers compared the gene activity of neutrophils in the umbilical cord blood of premature babies to that of full-term babies with adult neutrophils. The researchers observed a lot of gene activity in premature and full-term infants that counteracted immune defence compared to adults. “In this case, these neutrophils act as if they were switched off,” said Sperandio.

The importance of signalling pathways

According to the researchers, this gene activity particularly affects signals transmitted via the NF-κB signalling pathway, which plays an important role in immune and inflammatory responses. There are two possible pathways for signals: one that promotes inflammation and one that can suppress inflammation. Therefore, the activity of these two pathways must be correctly balanced for the proper regulation of the immune response.

“Our experiments have shown that this balance is shifted towards the anti-inflammatory pathway in foetal and neonatal neutrophils,” said Sperandio.

“Whereas this regulation of neutrophil function is clearly a requirement for normal foetal growth in utero, it leads to immune defence problems in prematurely born infants who have to adapt ‘too soon’ to the world outside the uterus,” he continued.

The researchers say the extent to which these findings could be a springboard for new therapeutic approaches in the future remains to be seen.

“Due to the complex processes in the growing foetal and neonatal organism, maturation-adapted therapies are conceivable but remain a long way off at this stage,” concluded Sperandio.


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