Hydrocortisone for evolving respiratory failure in preterm infants: predictors of treatment failure and associations with bronchopulmonary dysplasia. A retrospective cohort study

To identify predictors of hydrocortisone treatment failure and examine its association with bronchopulmonary dysplasia (BPD) in preterm infants. Retrospective single-centre cohort study including infants born at 24 0 –29 6 weeks' gestation (2013−2023) who received a standardized hydrocortisone course (cumulative dose 72.5 mg/kg) to facilitate extubation or avoid intubation. Treatment failure at day 21 was defined as death, ongoing mechanical ventilation, FiO₂ ≥ 0.40, inability to taper hydrocortisone according or escalation to dexamethasone. Logistic regression identified predictors of treatment failure. Longitudinal FiO₂ trajectories were analysed using linear mixed-effects models. n = 96 infants were included; at treatment initiation, on a median postnatal age of 19 days (IQR 14–24) and FiO₂ 0.40 (IQR 0.35–0.50), 31 (32%) received non-invasive ventilation. Treatment failure occurred in 32 infants (33%). Initiation during non-invasive respiratory support was independently associated with lower odds of treatment failure (aOR 0.34; 95% CI 0.12–0.99; p = 0.049). FiO₂ trajectories diverged from day 3 onward, remaining higher in infants with treatment failure. In survivors to 36 weeks postmenstrual age, treatment failure was strongly associated with severe BPD (OR 6.7; 95% CI 2.2–20.0; p = 0.01). Approximately two-thirds of preterm infants showed short-term respiratory improvement following hydrocortisone treatment. Treatment success was more frequently observed when hydrocortisone was initiated during non-invasive respiratory support. Early divergence in FiO₂ trajectories distinguished treatment success from failure and may serve as a pragmatic marker of short-term treatment response. Treatment failure was associated with adverse pulmonary outcome. These findings are hypothesis-generating and warrant further study. • Two-thirds of preterm infants treated with a hydrocortisone course for (imminent) respiratory failure showed short term improvement with hydrocortisone course. • Starting hydrocortisone during non-invasive support was associated with lower odds of treatment failure. • Infants with treatment failure could be separated by FiO₂-trajectory from day 3 onwards. • In survivors, hydrocortisone treatment failure was associated with a markedly increased risk on BPD.