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

PLoS One. 2017 Jan 26;12(1):e0170259. doi: 10.1371/journal.pone.0170259. eCollection 2017.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Child
  • Child, Preschool
  • Chronic Disease / drug therapy
  • Cushing Syndrome / chemically induced
  • Cushing Syndrome / physiopathology*
  • Drug-Related Side Effects and Adverse Reactions / classification*
  • Drug-Related Side Effects and Adverse Reactions / physiopathology
  • Female
  • Herpes Zoster / chemically induced
  • Herpes Zoster / physiopathology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Osteoporosis / chemically induced
  • Osteoporosis / physiopathology*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiopathology
  • Respiratory System Agents / adverse effects*
  • Respiratory System Agents / therapeutic use
  • Weight Gain / drug effects

Substances

  • Adrenal Cortex Hormones
  • Respiratory System Agents

Grants and funding

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.