Early treatment with hydrocortisone may significantly improve the chances of survival without chronic lung disease for extremely premature infants, according to a new study led by researchers at Linköping University. The findings, published in the journal JAMA Network Open, similarly indicate the treatment is safe for use in this vulnerable population.
More than half of infants born extremely prematurely – before 28 weeks of gestation – develop a lung disease called bronchopulmonary dysplasia (BPD). BPD can have lifelong consequences, as the lungs of these infants are not fully developed at birth. Several factors can contribute to fragile lungs and hinder proper lung tissue development.
Regional Variations in Treatment
Inflammation, which damages lung tissue, is a key factor in the development of BPD. The hormone cortisol helps to reduce inflammation, but extremely premature infants often cannot produce enough cortisol on their own. Previous research has suggested potential benefits of preventative hydrocortisone treatment, but also raised concerns about possible severe side effects. The treatment is currently used in several countries.
In Sweden, some regions have implemented guidelines for hydrocortisone treatment starting within the first day of life, while others have chosen not to. This difference in approach created a unique opportunity for researchers.
“This created a natural experiment in Sweden, where some extremely premature infants received treatment and others did not,” said Ulrika Ådén, professor of pediatrics at Linköping University and Karolinska Institutet, and a neonatologist who led the study. “We took advantage of this in our study, looking at how this treatment works in real-world clinical practice in Sweden. You’ll see very few such studies in the world today.”
Early Intervention Improves Outcomes
The researchers analyzed data from the national neonatal registry, comparing 474 infants treated with hydrocortisone to 632 infants born in the same regions before the treatment was introduced. They also compared outcomes to regions that do not administer hydrocortisone. All infants were born between 22 and 27 weeks of gestation between 2018 and 2023.
“Our study shows that if extremely premature infants receive this treatment early in life, their chances of survival without lung disease increase,” said Veronica Smedbäck, a doctoral student at Linköping University and resident physician at Länssjukhuset Ryhov. “Hydrocortisone treatment is safe and does not increase the risk of serious side effects during the newborn period.”
Potential Impact on a Significant Number of Infants
Infants with BPD are at increased risk of infections and hospitalizations throughout childhood. The lung disease is also associated with poor weight gain and negative impacts on brain development. Researchers believe preventative treatment could benefit both children and their families, and potentially reduce healthcare costs.
“Given that more than half of all extremely premature infants are affected by this lung disease, this treatment, which can increase the chance of survival without the disease, could be valuable,” said Smedbäck. “Many countries are now saving infants born extremely prematurely, so it could potentially affect a very large number of children.”
Long-Term Effects Under Investigation
The current study focuses on the short-term safety of the treatment. Researchers are now investigating potential long-term effects, with a particular focus on brain development. While other studies have suggested a positive effect of the treatment on brain development, more research is needed to understand the long-term implications. The study was funded by, among others, the Joanna Cocozzas Foundation for Pediatric Research and ALF funding through Region Östergötland.
This research offers hope for improving outcomes for extremely premature infants, a population facing significant health challenges. Further investigation into the long-term effects of hydrocortisone treatment will be crucial to optimizing care for these vulnerable newborns.
