Hydrocortisone in very preterm neonates for BPD prevention: meta-analysis and effect size modifiers

Area of Science:

• Neonatal Medicine
• Pediatric Pharmacology
• Critical Care

Background:

• Bronchopulmonary dysplasia (BPD) remains a significant challenge in extremely preterm infants.
• Early administration of systemic hydrocortisone is being explored to mitigate adverse outcomes.
• Optimal timing and effects of hydrocortisone in this vulnerable population require clarification.

Purpose of the Study:

• To evaluate the efficacy of early systemic hydrocortisone in preventing BPD and other adverse outcomes in very preterm neonates.
• To identify potential effect modifiers influencing hydrocortisone's impact on neonatal outcomes.
• To synthesize evidence from existing trials on hydrocortisone use in preterm infants.

Main Methods:

• Systematic review and meta-analysis adhering to PRISMA guidelines.
• Inclusion of seven high-quality trials involving 2193 very preterm neonates.
• Meta-regression analyses to explore effect size modifiers and biological plausibility.

Main Results:

• Hydrocortisone did not significantly reduce BPD rates (RR 0.84), with heterogeneity observed (I²=51.6%).
• Treatment duration (10-12 days) and chorioamnionitis appeared to modify BPD effects.
• Significant reductions were observed in mortality (RR 0.75) and necrotizing enterocolitis (NEC; RR 0.72) with no heterogeneity.
• Mortality reduction trended higher in males; no effect modifiers identified for NEC.

Conclusions:

• Systemic hydrocortisone may be considered for reducing mortality and NEC in very preterm infants on a case-by-case basis.
• Hydrocortisone does not appear to prevent BPD.
• Future trials should investigate identified effect modifiers for mortality and BPD.