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Safety of corticosteroids in young children with acute respiratory conditions: a systematic review and meta-analysis
  1. Ricardo M Fernandes1,2,
  2. Aireen Wingert3,
  3. Ben Vandermeer3,
  4. Robin Featherstone3,
  5. Samina Ali4,5,
  6. Amy C Plint6,
  7. Antonia S Stang7,
  8. Brian H Rowe8,9,
  9. David W Johnson10,
  10. Dominic Allain4,
  11. Terry P Klassen11,
  12. Lisa Hartling3,4
  1. 1 Pediatrics, Hospital de Santa Maria, Lisbon, Portugal
  2. 2 Faculty of Medicine, Instituto de Medicina Molecular, University of Lisbon, Laboratory of Clinical Pharmacology and Therapeutics, Lisbon, Portugal
  3. 3 Alberta Research Centre for Health Evidence, Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  4. 4 Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  5. 5 Women & Children’s Health Research Institute, Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  6. 6 Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  7. 7 Pediatrics, Emergency Medicine, and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  8. 8 Emergency Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  9. 9 School of Public Health, University of Alberta, Edmonton, Alberta, Canada
  10. 10 Pediatrics, Emergency Medicine, and Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  11. 11 Manitoba Institute of Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  1. Correspondence to Lisa Hartling; hartling{at}ualberta.ca

Abstract

Objective Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children.

Design Systematic review of primary studies.

Data sources Medline, Cochrane CENTRAL, Embase and regulatory agencies were searched September 2014; search was updated in 2017.

Eligibility criteria Children <6 years with acute respiratory condition, given inhaled (high-dose) or systemic corticosteroids up to 14 days.

Data extraction and synthesis One reviewer extracted with another reviewer verifying data. Study selection and methodological quality (McHarm scale) involved duplicate independent reviews. We extracted AEs reported by study authors and used a categorisation model by organ systems. Meta-analyses used Peto ORs (pORs) and DerSimonian Laird inverse variance method utilising Mantel-Haenszel Q statistic, with 95% CI. Subgroup analyses were conducted for respiratory condition and dose.

Results Eighty-five studies (11 505 children) were included; 68 were randomised trials. Methodological quality was poor overall due to lack of assessment and inadequate reporting of AEs. Meta-analysis (six studies; n=1373) found fewer cases of vomiting comparing oral dexamethasone with prednisone (pOR 0.29, 95% CI 0.17 to 0.48; I2=0%). The mean difference in change-from-baseline height after one year between inhaled corticosteroid and placebo was 0.10 cm (two studies, n=268; 95% CI −0.47 to 0.67). Results from five studies with heterogeneous interventions, comparators and measurements were not pooled; one study found a smaller mean change in height z-score with recurrent high-dose inhaled fluticasone over one year. No significant differences were found comparing systemic or inhaled corticosteroid with placebo, or between corticosteroids, for other AEs; CIs around estimates were often wide, due to small samples and few events.

Conclusions Evidence suggests that short-term high-dose inhaled or systemic corticosteroids use is not associated with an increase in AEs across organ systems. Uncertainties remain, particularly for recurrent use and growth outcomes, due to low study quality, poor reporting and imprecision.

  • corticosteroids
  • asthma
  • bronchiolitis
  • croup
  • paediatrics
  • safety

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors RMF, AW, BV, SA, ACP, ASS, BHR, DWJ, DA, TPK and LH critically reviewed and contributed to drafts of the report. RF conducted the literature searches. AW conducted screening, quality assessments and data extraction. AW and BV conducted data synthesis/analysis. RMF, AW, BV, SA, ACP, ASS, BHR, DWJ, DA, TPK and LH contributed to interpretation of results. All of the authors approved the final version of this report.

  • Funding This study was funded by a Knowledge Synthesis Grant from CIHR (funding reference number KRS134306). The funder had no role in the design of the study, the collection, analysis or interpretation of data, the writing of the report or the decision to submit the paper for publication.

  • Competing interests All authors declare funding from CIHR for the submitted work. LH was funded in part by a New Investigator Salary Award from the CIHR. ACP is supported by a Tier II University of Ottawa Research Chair Award. BHR was supported by a Tier I Canada Research Chair in Evidence-based Emergency Medicine from CIHR. The remaining authors have no financial relationships relevant to this manuscript to disclose. DWJ, TPK and ACP are also authors on some of the included studies.

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

  • Data sharing statement LH had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Data for this systematic review (using published data) are available from the corresponding author upon reasonable request.

  • Patient consent for publication Not required.

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