Hydrocortisone for prevention or treatment of bronchopulmonary dysplasia: long-term neurodevelopmental safety and efficacy-a meta-analysis of randomized clinical trials

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Shehab K. A., Almatrafi R. M. N., Ali E., Albargi Y., Saabi S., Aljohani H. A., ...More

FRONTIERS IN PEDIATRICS, vol.14, 2026 (SCI-Expanded, Scopus)

Abstract

Background: Postnatal systemic steroids can reduce inflammation that contributes to bronchopulmonary dysplasia (BPD) in extremely preterm infants; however, prior experience with dexamethasone raised concerns regarding long-term neurodevelopmental harm. As a result, hydrocortisone has been proposed as a potentially safer alternative. Methods: We conducted a meta-analysis of randomized controlled trials comparing hydrocortisone with placebo/routine care in preterm infants, stratified by early prophylaxis (<7 days) or late treatment (>= 7 days). We searched major databases through February 2026. The primary outcome was the composite of death or neurodevelopmental impairment (NDI) at 2 years of corrected age. Results: We included 17 studies representing seven distinct trials and their follow-up publications, comprising a total of 2,213 infants (1,096 receiving hydrocortisone and 1,117 receiving placebo). At 2 years, death/NDI occurred in 53.5% (531/993) of infants in the hydrocortisone group and 56.8% (581/1,023) of infants in the placebo group, with no significant effect observed with either early administration [risk ratio (RR) 0.89, 95% CI 0.70-1.13; I & sup2;=0%] or late administration (RR 0.97, 95% CI 0.80-1.17; I & sup2;=0%). Hydrocortisone was not associated with significant differences in death at 2 years (17.1% vs. 20.8%) or NDI at 2 years (42.5% vs. 43.9%) nor in cerebral palsy, hearing impairment, or visual impairment. Exploratory analyses showed no significant reduction in death or BPD at 36 week of postmenstrual age overall, and available school-age outcomes did not demonstrate differences in neurocognitive measures. Conclusion: Across randomized trials with long-term follow-up, postnatal hydrocortisone was not associated with improved survival free of NDI at 2 years nor was it associated with an increased risk of major neurodevelopmental or sensory impairments. These findings do not demonstrate an increased neurodevelopmental risk with hydrocortisone as used in current regimens, but its use should still be individualized based on respiratory phenotype, timing, and short-term monitoring for steroid-related adverse effects. Systematic Review Registration: PROSPERO CRD420261280132