1. Identifying effect modifiers of systemic hydrocortisone treatment initiated 7–14 days after birth in ventilated very preterm infants on long-term outcome: secondary analysis of a randomised controlled trial
- Author
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Halbmeijer, Nienke Marjolein, Sonnaert, Michel, Swarte, Renate M, Koopman-Esseboom, Corine, van Stuijvenberg, Margriet, Mulder-de Tollenaer, Susanne, Tan, Ratna N G B, Mohns, Thilo, Bruneel, Els, Steiner, Katerina, Kramer, Boris W, Debeer, Anne, van Weissenbruch, Mirjam M, Marechal, Yoann, Blom, Henry, Plaskie, Katleen, Offringa, Martin, Merkus, Maruschka P, Onland, Wes, Leemhuis, Aleid G, and van Kaam, Anton H
- Abstract
ObjectiveTo explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years’ corrected age (CA).DesignSecondary analysis of a randomised placebo-controlled trial.SettingDutch and Belgian neonatal intensive care units.PatientsInfants born <30 weeks’ gestational age (GA), ventilator-dependent in the second week of postnatal life.InterventionInfants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measuresThe composite of death or neurodevelopmental impairment (NDI) at 2 years’ CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots.ResultsThe composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups.ConclusionThis secondary analysis suggests that in infants <27 weeks’ GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.
- Published
- 2024
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