Blood poisoning can be fatal. Premature babies who develop sepsis sometimes die from it within a few hours. If the infants survive, they may be particularly susceptible to diseases, often many years afterwards. Because it is currently difficult to predict which newborns will contact sepsis, most premature infants – as many as 85 percent – are given antibiotics as a precaution. The drugs are life-saving for many of the infants, but they also have their drawbacks. For example, they may promote antibiotic resistance and permanently disrupt the infants’ gut flora – which, in turn, can lead to chronic inflammatory diseases, allergies, obesity and diabetes later in life.
Alarmins are very important for the newborn’s immune system
As part of a research project called PROSPER (Prevention of Sepsis by Personalized Nutritional S100A8/A9 Supplementation to Vulnerable Neonates), a team led by Professor Dorothee Viemann of the Clinic for Pediatric Pneumology, Allergology and Neonatology at the Hannover Medical School (MHH) is preparing to study whether a nutritional supplementation – an alarmin – can also protect premature babies from blood poisoning. The German Federal Ministry of Education and Research (BMBF) is supporting the project with a grant of approximately €1.9 million.
Alarmins are primarily a marker for inflammation in adults. However, Viemann, along with Dr. Sabine Pirr, a senior physician at the MHH intensive care unit for premature and newborn infants, previously discovered that alarmins have a positive influence on the development of gut flora and the immune system in newborns. These proteins are found, for example, in breast milk in large quantities.
“In addition, unlike a cesarean section, vaginal delivery appears to stimulate the body’s production of alarmins in newborns,” says Dr. Sofia Forslund, head of the Host-Microbiome Factors in Cardiovascular Disease Group at the Experimental and Clinical Research Center (ECRC), a joint institution of the Berlin-based Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité – Universitätsmedizin Berlin. Forslund is involved in the PROSPER project as a bioinformatician, with a particular focus on the statistical analysis of the microbiome.
Calprotectin deficiency increases the risk of sepsis in premature babies
We plan to use bioinformatics methods to explore in greater depth the mechanism by which calprotectin protects the infants.
In an earlier project called PRIMAL (Priming Immunity at the Beginning of Life), the three researchers, along with other colleagues, already showed that a high level of the alarmin calprotectin positively influences the microbiome and immune system of newborns who were born by cesarean section and cannot be breastfed. “We now also know that the risk of sepsis increases significantly when premature infants lack calprotectin,” says Forslund.
So the PROSPER project now aims to find out whether administration of the protein protects preterm infants with low calprotectin levels from sepsis. In addition to experts from the MHH and the ECRC, researchers from the Department of Pediatrics at the University Hospital of Würzburg and the Institute of Immunology at the University of Münster are also involved in the project. “At the ECRC, we will follow in detail how the microbiome develops in premature infants and also provide our statistical and data analysis expertise,” says Forslund. “We also plan to use bioinformatics methods to explore in greater depth the mechanism by which calprotectin protects the infants.”
The common goal of everyone involved in PROSPER is to set the groundwork for a larger clinical trial – in order to make the widespread use of antibiotics in premature infants unnecessary as soon as possible.
Text: MHH / Anke Brodmerkel