Objective To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA).Design... Show moreObjective To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA).Design Secondary analysis of a randomised placebo-controlled trial.Setting Dutch and Belgian neonatal intensive care units.Patients Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life.Intervention Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measures The 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treatment effect pattern plots.Results The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn).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.Conclusion This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by itscomponent death. There was insufficient evidence for other selected candidate effect modifiers. Show less
Halbmeijer, N.M.; Onland, W.; Cools, F.; Swarte, R.M.; Heide-Jalving, M. van der; Dijk, P.; ... ; STOP-BPD Study Grp 2023
ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected... Show moreObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years' corrected age (CA). DesignRandomised placebo-controlled trial. SettingDutch and Belgian neonatal intensive care units. PatientsInfants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life. InterventionInfants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). Main outcome measuresParent-reported behavioural outcomes at 2 years' CA assessed with the Child Behavior Checklist (CBCL 11/2-5). ResultsParents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalising and externalising problems, respectively; these scores were not significantly different between groups (mean difference -1.52 (95% CI -4.00 to 0.96), -2.40 (95% CI -4.99 to 0.20) and -0.81 (95% CI -3.40 to 1.77), respectively). In the subscales, we found a significantly lower T-score for anxiety problems in the hydrocortisone group (mean difference -1.26, 95% CI -2.41 to -0.12). ConclusionThis study found high rates of behaviour problems at 2 years' CA following very preterm birth, but these problems were not associated with hydrocortisone treatment initiated between 7 and 14 days after birth in ventilated preterm infants. Show less
Halbmeijer, N.M.; Onland, W.; Cools, F.; Kroon, A.; Heide-jalving, M. van der; Dijk, P.; ... ; SToP-BPD Study Grp 2022
Objective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term... Show moreObjective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week.Design Randomised placebo-controlled trial.Setting Dutch and Belgian neonatal intensive care units.Patients Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.Intervention Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measures Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models.Results Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH(2)O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure.Conclusions Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. Show less
Onland, W.; Cools, F.; Kroon, A.; Rademaker, K.; Merkus, M.P.; Dijk, P.H.; ... ; Data Safety Monitoring Comm 2019
