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Hydrocortisone in very preterm neonates for BPD prevention: meta-analysis and effect size modifiers
Daniele De Luca1,2, Sara Ferraioli3, Kristi L Watterberg4
1Division of Pediatrics and Neonatal Critical Care, APHP, Paris Sac;ay University Hospitals, 'A. Beclere' Medical Centre, Paris, France dm.deluca@icloud.com.
Insights
Systemic hydrocortisone treatment in very preterm neonates did not prevent bronchopulmonary dysplasia but may reduce mortality and necrotizing enterocolitis. Further research is needed to explore potential effect modifiers for these outcomes.
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.
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.
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