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Abstract
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 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 cmH2O (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.
Trial registration number Netherlands Trial Register (NTR2768; https://www.trialregister.nl/trial/2640) and European Union Clinical Trials Register (EudraCT, 2010-023777-19).
- Neonatology
- Respiratory Medicine
Data availability statement
Data are available upon reasonable request. Deidentified individual participant data (including data dictionaries) will be made available, in addition to study protocol, the statistical analysis plan and the analytical code. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to Professor Anton van Kaam (email: a.h.vankaam@amsterdamumc.nl).
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Data availability statement
Data are available upon reasonable request. Deidentified individual participant data (including data dictionaries) will be made available, in addition to study protocol, the statistical analysis plan and the analytical code. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to Professor Anton van Kaam (email: a.h.vankaam@amsterdamumc.nl).
Footnotes
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Presented at The short-term effects of the SToP-BPD Study were presented at the fourth joint European Neonatal Societies congress; live online congress; 15 September 2021.
Collaborators SToP-BPD Study Group members: Debbie H Nuytemans, Moniek van de Loo (Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands), Inez Vereeck (Department of Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium), Renate Swarte (Department of Neonatology, Sophia Children’s Hospital, Erasmus MC, Rotterdam, The Netherlands), Karin Rademaker (Department of Neonatology, University Medical Center, Utrecht, The Netherlands), Ellen de Kort (Department of Neonatology, Maxima Medical Center Veldhoven, The Netherlands), Eric Cavartorta, Anne Rassart (Department of Neonatology, Centre Hospitalier Universitaire Marie Curie, Charleroi, Belgium), An Eerdekens (Department of Neonatology, Universitair Ziekenhuis Leuven, Leuven, Belgium), Margriet Stuijvenberg (Department of Neonatology, University Medical Center Groningen, Beatrix Children’s Hospital, University of Groningen, Groningen, The Netherlands), René Matthijsse, Willem de Boode (Department of Neonatology, Radboud University Medical Center-Amalia Children's Hospital, Nijmegen, The Netherlands), Hendrik Niemarkt, Ilse van Hattum (Department of Neonatology, Medical University Center Maastricht, Maastricht, The Netherlands), Liesbeth Groot Jebbink, Susanne M Mulder-de Tollenaer (Department of Neonatology, Isala Medical Center, Zwolle, The Netherlands), Ratna Tan (Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands), Claire Theyskens (Department of Neonatology, Ziekenhuis Oost-Limburg, Genk, Belgium), Mirjam van Weissenbruch (Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands), Elke Dierckx (St Augustinus Ziekenhuis, Antwerp, Belgium). All members contributed to the design of the study protocol, data collection, data reporting and revision of the first draft of the manuscript. They received no compensation for their contributions.
Contributors FC, AK, MvdH-J, PD, HLMvS, ABtP, TM, EB, AFJvH, BK, AD, IAZ, YM, HB, KP and MO are local investigators at the participating centres, and made substantial contributions to the concept and design of the study, and interpretation of data. NMH performed the statistical analyses, prepared the data tables, drafted the initial manuscript and revised the manuscript. MPM made substantial contributions to the interpretation of data, and reviewed and revised the manuscript. WO and AHvK are local investigators, made substantial contributions to the concept and design of the study, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. AHvK accepts full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This trial was funded by a project grant from The Netherlands Organization for Health Research and Development ZonMW Priority Medicines for Children (no. 11-32010-02).
Disclaimer The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Competing interests AHvK reports grants from The Netherlands Organization for Health Research and Development ZonMW during the conduct of the study. No other disclosures were reported.
Provenance and peer review Not commissioned; externally peer reviewed.
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