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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.
- intensive care units, neonatal
- neonatology
- respiratory medicine
Data availability statement
Data are available on reasonable request. Raw data are available from the authors on reasonable request.
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Data availability statement
Data are available on reasonable request. Raw data are available from the authors on reasonable request.
Footnotes
Contributors DDL conceptualised the work, performed the investigation and supervised it, performed data curation and provided resources for the work. He drafted the first manuscript and reviewed the final version. SF performed the investigation, contributed to data curation and performed the analysis. She critically reviewed the manuscript for important intellectual content and approved the final version. KLW performed the investigation and provided oversight and contributed to data curation. She critically reviewed the manuscript for important intellectual content and approved the final version. OB performed the investigation and provided oversight and contributed to data curation. She critically reviewed the manuscript for important intellectual content and approved the final version. MRG was responsible for methodology and investigation, performed the formal analysis. She critically reviewed the manuscript for important intellectual content and approved the final version. DDL is guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests DDL served in the advisory board for Chiesi farmaceutici, Airway Therapeutics and Ophirex. He received research grants or assistance from Chiesi farmaceutici, Vyaire and Getinge. He received speaker fees from Chiesi farmaceutici, Getinge, Vyaire, AstraZeneca, Medtronic, Masimo and BD. All these were unrelated to the present work. The other authors have no conflict of interest to declare.
Provenance and peer review Not commissioned; externally peer reviewed.
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