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Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

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      Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.


      A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included.


      One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths).


      Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

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      Most cited references 122

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      The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

      Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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          Population-based assessment of adverse events associated with long-term glucocorticoid use.

          The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. Using linked administrative and pharmacy claims, adults receiving >or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE (70% of the individuals), cataracts (15%) and fractures (12%) were among the most serious. After multivariable adjustment, all AEs demonstrated a strong dose-dependent association with cumulative glucocorticoid use. Among users of low-dose therapy (

            Author and article information

            Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom
            York University, UNITED KINGDOM
            Author notes

            Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Imti Choonara is an Academic Editor of the journal.

            • Conceptualization: IC SC.

            • Data curation: FA.

            • Formal analysis: FA.

            • Investigation: FA.

            • Methodology: IC SC FA.

            • Project administration: IC SC FA.

            • Resources: IC SC.

            • Supervision: IC SC.

            • Validation: IC SC FA.

            • Visualization: IC SC FA.

            • Writing – original draft: IC SC FA.

            • Writing – review & editing: IC SC FA.

            Role: Editor
            PLoS One
            PLoS ONE
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            26 January 2017
            : 12
            : 1
            © 2017 Aljebab et al

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Figures: 5, Tables: 5, Pages: 18
            The authors received no specific funding for this work. Fahad Aljebab is a postgraduate student and would like to acknowledge his sponsor the Saudi Arabian government (Prince Mohammed Medical City). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Research Article
            Research and Analysis Methods
            Research Design
            Cohort Studies
            Medicine and Health Sciences
            Child Development
            Child Growth
            Growth Restriction
            Research and Analysis Methods
            Research Design
            Clinical Research Design
            Case Series
            Biology and Life Sciences
            Physiological Parameters
            Body Weight
            Weight Gain
            Medicine and Health Sciences
            Physiological Parameters
            Body Weight
            Weight Gain
            Medicine and Health Sciences
            Adverse Reactions
            Research and Analysis Methods
            Database and Informatics Methods
            Database Searching
            Research and Analysis Methods
            Research Assessment
            Systematic Reviews
            Medicine and Health Sciences
            Drug Therapy
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            All relevant data are within the paper and its Supporting Information files.



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