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  • Effect of systemic hydrocortisone in ventilated preterm infants on parent-reported behavioural outcomes at 2 years’ corrected age: follow-up of a randomised clinical trial

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Original research
Effect of systemic hydrocortisone in ventilated preterm infants on parent-reported behavioural outcomes at 2 years’ corrected age: follow-up of a randomised clinical trial
  1. Nienke Marjolein Halbmeijer1,2,
  2. Wes Onland1,2,
  3. Filip Cools3,
  4. Renate M Swarte4,
  5. Marja van der Heide-Jalving5,
  6. Peter Dijk6,
  7. Susanne Mulder-de Tollenaer7,
  8. Ratna N G B Tan8,
  9. Thilo Mohns9,
  10. Els Bruneel10,
  11. Arno F J van Heijst11,
  12. Boris Kramer12,
  13. Anne Debeer13,
  14. Mirjam M van Weissenbruch2,14,
  15. Yoann Marechal15,
  16. Henry Blom16,
  17. Katleen Plaskie17,
  18. Martin Offringa1,18,
  19. Aleid G van Wassenaer-Leemhuis1,2,
  20. Anton H van Kaam1,2,
  21. Cornelieke S H Aarnoudse-Moens1,2,19
  22. for the SToP-BPD study group
    1. 1 Neonatology, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
    2. 2 Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands
    3. 3 Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium
    4. 4 Section of Neonatology, Pediatrics Department, Erasmus MC Sophia Children’s Hospital, Rotterdam, Netherlands
    5. 5 Department of Neonatology, University Medical Center Utrecht, Utrecht, Netherlands
    6. 6 Neonatology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, Netherlands
    7. 7 Department of Neonatology, Isala Klinieken, Zwolle, Netherlands
    8. 8 Neonatology, Leiden University Medical Center, Leiden, Netherlands
    9. 9 NICU, Woman-Mother-Child Center, Màxima Medical Centre, Veldhoven, Netherlands
    10. 10 Department of Neonatology, Ziekenhuis Oost-Limburg, Genk, Belgium
    11. 11 Department of Neonatology, Amalia Children’s Hospital, Radboud Universiteit Nijmegen, Nijmegen, Netherlands
    12. 12 Pediatrics, Maastricht University Medical Center+, Maastricht, Netherlands
    13. 13 Neonatology, KU Leuven University Hospitals, Leuven, Belgium
    14. 14 Neonatology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
    15. 15 Department of Neonatology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium
    16. 16 Neonatology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium
    17. 17 Department of Neonatology, GZA Ziekenhuizen Campus Sint-Augustinus, Wilrijk, Belgium
    18. 18 Child Health Evaluative Sciences, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
    19. 19 Psychosocial Department, Universiteit van Amsterdam, Amsterdam, Netherlands
    1. Correspondence to Dr Cornelieke S H Aarnoudse-Moens, Neonatology, Amsterdam UMC, 1100 AZ Amsterdam, Netherlands; c.aarnoudse-moens{at}amsterdamumc.nl

    Abstract

    Objective To 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).

    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 Parent-reported behavioural outcomes at 2 years’ CA assessed with the Child Behavior Checklist (CBCL 1½−5).

    Results Parents 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).

    Conclusion This 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.

    Trial registration number NTR2768; EudraCT 2010-023777-19.

    • Neonatology
    • Child Development

    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 analytic 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 CSHA-M, email: c.aarnoudse-moens@amsterdamumc.nl.

    https://doi.org/10.1136/archdischild-2022-324179

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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 analytic 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 CSHA-M, email: c.aarnoudse-moens@amsterdamumc.nl.

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      Footnotes

      • Collaborators SToP-BPD study group members: Debbie H Nuytemans, CRC; Moniek van de Loo, MD (Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands); Ingrid van Limberghen, RN (Department of Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium); Andre Kroon, PhD; Nienke Rietema; Annette van der Kaa; Patricia Kalkman, MD (Department of Neonatology, Sophia Children’s Hospital, Erasmus MC, Rotterdam, The Netherlands); Karin Rademaker, PhD; Corine Koopman-Esseboom, PhD; Ingrid C van Haastert, PhD (Department of Neonatology, University Medical Center, Utrecht, The Netherlands); Ellen de Kort, PhD; Marieke Vervoorn, RN (Department of Neonatology, Màxima Medical Centre, Veldhoven, The Netherlands); Eric Cavartorta, MD; Anne Rassart, MD (Department of Neonatology, Centre Hospitalier Universitaire Marie Curie, Charleroi, Belgium); An Eerdekens, PhD; Isabelle Hermans, Julie Messiaen (Department of Neonatology, Universitair Ziekenhuis Leuven, Leuven, Belgium); Margriet Stuijvenberg, PhD (Department of Neonatology, University Medical Center Groningen, Beatrix Children’s Hospital, University of Groningen, Groningen, The Netherlands); René Matthijsse, MD; Willem de Boode, PhD; Wendy Jansen, RN (Department of Neonatology, Radboud University Medical Center-Amalia Children’s Hospital, Nijmegen, The Netherlands); Hendrik Niemarkt, PhD; Ilse van Hattum, MD (Department of Neonatology, Medical University Center Maastricht, Maastricht, The Netherlands); Astrid Giezen, RN; Henrica L van Straaten, PhD (Department of Neonatology, Isala Medical Center, Zwolle, The Netherlands); Arjan B Te Pas, MD; Romy Berkhout, RN (Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands); Claire Theyskens, PhD (Department of Neonatology, Ziekenhuis Oost-Limburg, Genk, Belgium); Inge Zonnenberg, PhD (Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands); Elke Dierckx, MD (Sint-Augustinus Ziekenhuis, Antwerpen, Belgium). All members contributed to the design of the study protocol, data collection and data reporting. They received no compensation for their contributions.

      • Contributors FC, RMS, MvdH-J, PD, SM-dT, RNGBT, TM, EB, AFJvH, BK, AD, MMvW, YM, HB, KP, MO, AGvW-L and CSHA-M 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. WO and AHvK are local investigators who 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. CSHA-M is guarantor.

      • Funding This trial was funded by a project grant from the Netherlands Organisation for Health Research and Development (ZonMw) Priority Medicines for Children (11-32010-02).

      • Disclaimer The funding agency had no role in the design and conduct of the study; collection, management, analysis and interpretation of data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.