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

Abstract

Objectives: To clarify if systemic hydrocortisone, in protocols allowing to start it before the 15th day of life, prevents bronchopulmonary dysplasia (BPD) or other adverse outcomes in very preterm neonates, and to identify any possible effect size modifiers.

Study design: Systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Additional analyses included meta-regressions and review of biological plausibility.

Results: Seven trials were included, they were of general good quality and accounted for a total of 2193 infants. Hydrocortisone treatment did not reduce BPD (risk ratio (RR) 0.84 (95% CI 0.64 to 1.04)), but heterogeneity was evident (I²=51.6%). The effect size for BPD is greatest for 10-12 days duration of treatment (β=0.032 (0.01), p=0.007) and tended to be greater in patients with chorioamnionitis (β=-1.5 (0.841), p=0.07). Hydrocortisone treatment may significantly reduce mortality (RR 0.75 (95% CI 0.59 to 0.91)), there is no heterogeneity (I²=0) and the reduction tended to be greater in males (β=-0.06 (0.03), p=0.07). Hydrocortisone may significantly reduce necrotising enterocolitis (NEC; RR 0.72 (95% CI 0.53 to 0.92)); there is neither heterogeneity (I²=0%) nor any effect size modifiers. Hydrocortisone did not affect other adverse outcomes of prematurity.

Conclusions: Systemic hydrocortisone may be considered, on a case-by-case evaluation, to reduce mortality and NEC, while it does not affect BPD. There are some potential effect size modifiers for mortality and BPD which should be addressed in future explanatory trials.

Prospero registration number: CRD42023400520.

Keywords: intensive care units, neonatal; neonatology; respiratory medicine.