Early Hydrocortisone Treatment Raises Survival Without Lung Disease in Extremely Premature Babies

More than half of babies born before 28 weeks of pregnancy develop bronchopulmonary dysplasia, a chronic lung disease that can affect them for the rest of their lives. The condition arises because extremely premature lungs are structurally and biochemically immature - vulnerable to injury from the very interventions needed to keep the baby alive, including mechanical ventilation and supplemental oxygen. Inflammation is a central driver, damaging lung tissue before it has fully formed.

Cortisol, the body's primary anti-inflammatory hormone, would normally help suppress that inflammation. But extremely premature babies cannot produce enough of it. That observation has long prompted interest in hydrocortisone - a synthetic form of cortisol - as a preventive treatment starting from birth. Previous clinical trials suggested benefits but also raised safety concerns, particularly around effects on brain development. The result was inconsistent adoption: some Swedish hospitals began using early hydrocortisone routinely, others did not.

A research team led by Ulrika Aden, professor of paediatric medicine at Linkoping University and Karolinska Institutet, recognized that this inconsistency created an opportunity. "This has led to a kind of natural experiment in Sweden, where some extremely premature babies have been treated and others not," said Aden. "We took advantage of this in our study, where we looked at how this treatment works in real healthcare situations in Sweden. There are almost no such studies in the world today."

How the study was designed

The researchers drew on Sweden's national neonatal registry to compare outcomes between treated and untreated groups. They identified 474 children who received hydrocortisone treatment - from hospitals that had introduced it as standard practice - and 632 children born in the same region before the treatment was introduced, as well as children from regions that had not adopted it. All babies were born between weeks 22 and 27 of pregnancy between 2018 and 2023.

This design - comparing contemporaneous patients from different regions alongside historical controls - is observational rather than randomized. It cannot fully control for all differences between treated and untreated populations. However, it captures real-world clinical practice across a large national sample, which randomized trials often cannot do.

What the data showed

Babies who received early hydrocortisone had higher rates of survival without bronchopulmonary dysplasia compared to untreated controls. The treatment also appeared safe by the measures examined: it did not increase the risk of serious adverse events during the newborn period.

"Our study shows that providing this treatment to extremely premature babies early in life increases their chance of surviving without lung disease. Hydrocortisone treatment is safe to administer and does not increase the risk of serious side effects during the newborn period," said Veronica Smedback, a PhD student at Linkoping University and physician who co-authored the research.

Why bronchopulmonary dysplasia matters beyond infancy

Bronchopulmonary dysplasia (BPD) is not a condition that resolves at hospital discharge. Children who develop it face elevated risks of respiratory infections throughout childhood, are more likely to be rehospitalized, and often show impaired growth and neurodevelopmental delays compared to premature babies who avoid BPD. The disease creates a cascade of downstream medical needs that extend years beyond the neonatal period.

"Given that more than half of all extremely premature babies are affected by this lung disease, this treatment may be valuable, as it increases the chance of survival without the disease," said Smedback. "Many countries today save extremely premature children, so this could potentially affect a very large number of children."

The open question: brain development

This study focused on short-term safety outcomes during the newborn period. It does not resolve the longer-term question of whether hydrocortisone affects brain development. Earlier concerns about corticosteroid treatments in premature babies centered partly on potential neurodevelopmental effects observed with dexamethasone, a different and more potent corticosteroid. Hydrocortisone has a different pharmacological profile, and some studies suggest it may actually be beneficial for brain development, but the evidence base remains incomplete.

The Linkoping team explicitly flagged this as the next research priority: investigating possible longer-term effects of the treatment, with neurodevelopment as a key outcome. Until those data are available, the study's conclusions about safety should be understood as applying to the neonatal period specifically.

The study was supported by the Joanna Cocozza Foundation for Child Medical Research and an ALF research grant through Region Ostergotland.