Early prophylactic low-dose hydrocortisone for bronchopulmonary dysplasia prevention in extremely preterm infants: a systematic review and meta-analysis

Background Early prophylactic low-dose hydrocortisone has been proposed to reduce inflammation and to compensate for relative adrenal insufficiency in extremely preterm infants. Its overall balance of benefit and risk remains uncertain. Objective To evaluate whether hydrocortisone initiated within the first 24–48 h after birth reduces bronchopulmonary dysplasia (BPD) and mortality in infants born before 30 weeks' gestation. Methods This systematic review and meta-analysis followed PRISMA 2020 guidance and was registered in PROSPERO. PubMed, Cochrane CENTRAL, Scopus, and Web of Science were searched from inception to May 2026. Eligible studies enrolled infants born before 30 weeks' gestation who received early prophylactic systemic hydrocortisone at a low dose. Low dose was defined as a starting dose of no more than 2.0 mg/kg/day, begun within 24–48 h of birth. The comparator was placebo or no hydrocortisone. Randomized and quasi-randomized trials, their follow-up reports, and comparative observational studies were eligible. Random-effects meta-analyses were performed using risk ratios (RRs) or mean differences with 95% confidence intervals (CIs). Results Fourteen studies with 3,416 infants were included. Early hydrocortisone did not significantly improve survival without BPD at 36 weeks' postmenstrual age (RR: 1.07, 95% CI: 0.97–1.19, p = 0.18). It also did not significantly reduce BPD at 36 weeks (RR: 0.94, 95% CI: 0.85–1.04, p = 0.25) or mortality before discharge (RR: 1.07, 95% CI: 0.77–1.49, p = 0.69). The duration of respiratory support and the need for oxygen at discharge were similar between groups. Subgroup analyses suggested a possible benefit in infants exposed to chorioamnionitis and in those born before 26 weeks, but these findings were exploratory. Hydrocortisone increased the risk of late-onset sepsis (RR: 1.19, 95% CI: 1.05–1.35, p = 0.01). Gastrointestinal perforation, necrotizing enterocolitis, major neonatal morbidities, and the available neurodevelopmental outcomes did not differ significantly between groups. Conclusion Current evidence does not support the routine use of early prophylactic hydrocortisone in all extremely preterm infants. Adequately powered trials and individual patient data analyses are needed to identify the subgroups most likely to benefit and to clarify long-term safety. Systematic Review Registration https://www.crd.york.ac.uk/prospero/view/CRD420261402317 , PROSPERO CRD420261402317.