Hydrocortisone Versus Dexamethasone Initiated in the Second Postnatal Week in Preterm Neonates at Risk of Bronchopulmonary Dysplasia: A Retrospective Exploratory Comparative Study

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and of long-term respiratory morbidity in preterm neonates, and inflammation is central to its pathogenesis.Corticosteroids are widely used for its prevention and treatment, but direct head-to-head comparisons of hydrocortisone and dexamethasone are limited.This exploratory study compared the two agents.Its primary objective was to compare death or BPD at 36 weeks postmenstrual age (PMA) in preterm neonates born at or before 34 weeks of gestation who received hydrocortisone or dexamethasone in the second postnatal week for evolving lung disease, and its secondary objectives were to compare respiratory weaning, duration of support and shortterm safety.Methodology: In this retrospective comparative observational study, the records of preterm neonates born at or before 34 weeks of gestation and admitted to a tertiary-care neonatal intensive care unit (NICU) in western India between October 2022 and April 2024, who required respiratory support during the second week of life and received either hydrocortisone or low-dose dexamethasone, were reviewed.Hydrocortisone was given as 1 mg/kg/day for seven days followed by 0.5 mg/kg/day for three days, and dexamethasone as a low-dose regimen with a cumulative dose of 0.89 mg/kg over 10 days.The primary outcome was death or BPD at 36 weeks PMA.Secondary outcomes were weaning from respiratory support, duration of ventilation and of hospital stay, and short-term adverse events.Categorical data were compared using the chi-square test or, for sparse data, Fisher's exact test.Data were analyzed by intention to treat using SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, USA), and all comparisons were treated as exploratory.Results: Of 37 neonates, 18 received hydrocortisone and 19 received dexamethasone, and baseline neonatal and maternal characteristics were comparable.Weaning from oxygen support (66.7% versus 73.7%, p = 0.641), BPD at 36 weeks PMA (16.7% versus 0%) and death at 36 weeks PMA (5.6% versus 10.5%) did not differ significantly, and the composite of death or BPD did not differ significantly (22.2% versus 10.5%, Fisher's exact p = 0.405; risk difference 11.7%, 95% CI -12.0% to 35.3%).The total duration of ventilation was shorter in the dexamethasone group (15.8 versus 19.1 days, t(35) = 2.17, p = 0.037; not significant after Bonferroni correction), whereas the duration of hospital stay (34.7 versus 29.1 days, t(35) = 1.39, p = 0.173) and the frequency of each short-term adverse event were comparable.Conclusions: In this small, retrospective exploratory study, no statistically significant difference was detected between hydrocortisone and dexamethasone initiated during the second postnatal week in death or BPD at 36 weeks PMA, respiratory weaning or short-term adverse events.Equivalence cannot be inferred.The wide confidence interval around the primary outcome is compatible with clinically important differences in either direction, so these findings are hypothesis-generating and require confirmation in adequately powered randomized trials with long-term neurodevelopmental follow-up.