Adverse Events Following Short-Course Systemic Corticosteroids Among Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: Short courses of systemic corticosteroids are used in the management of a number of acute clinical conditions, including Bell palsy, croup, and pneumonia, but research on associations of corticosteroid use with adverse events (AEs) in children is limited. Objective: To document AEs associated with short-term (≤14 days) use of systemic corticosteroids in children and adolescents (1 to younger than 18 years) across different clinical conditions. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to February 2025. Reference lists of eligible articles and related systematic reviews were also searched. Study Selection: Randomized clinical trials evaluating AEs (any unfavorable and unintended signs, symptoms, or syndromes that occurred during the period of using an investigational product) after use of short-course systemic corticosteroids in children and adolescents were included. Data Extraction and Synthesis: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, pairs of reviewers independently reviewed abstracts, extracted data, and assessed risk of bias of eligible trials. Pairwise, fixed-effects meta-analyses were performed using Mantel-Haenszel methods with risk difference (RD). Main Outcomes and Measures: The primary outcomes were serious AEs (events resulting in death, life-threatening conditions, hospitalization, or substantial disability), AEs leading to discontinuation, hyperglycemia, sleep disturbances, change in behavior, and gastrointestinal bleeding. RDs were reported as AEs per 1000 patients with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence (high, moderate, low, or very low certainty). Results: A total of 45 eligible trials that included 6470 children (mean [SD] age, 5.57 [3.62] years; 3753 male [58%]) were identified. In pooled analysis, there was moderate certainty evidence that compared with usual care, corticosteroids were not associated with serious AEs (RD, 1 fewer AE per 1000 patients [95% CI], 9 fewer to 7 more AEs per 1000 patients]), AEs leading to discontinuation (RD, 4 more AEs per 1000 patients [95% CI, 3 fewer to 11 more AEs per 1000 patients]), or change in behavior (RD, 8 more AEs per 1000 patients [95% CI, 5 fewer to 21 more AEs per 1000 patients]). With moderate certainty evidence, corticosteroids were associated with an increased risk of hyperglycemia (RD, 38 more AEs per 1000 patients [95% CI, 11 to 64 more AEs per 1000 patients]) and sleep problems (RD, 15 more AEs per 1000 patients [95% CI, 1 to 28 more AEs per 1000 patients]). Corticosteroid use was also associated with an increased risk of gastrointestinal bleeding (RD, 13 more per AEs per 1000 patients [95% CI, 3 to 23 more AEs per 1000 patients]), but the certainty of evidence was low. Conclusions and Relevance: In this systematic review and meta-analysis of randomized trials, there was moderate certainty evidence that corticosteroids were associated with an increased risk of hyperglycemia and sleep problems and low certainty evidence that corticosteroids were associated with increased risk of gastrointestinal bleeding, but these AEs were very seldom serious. These findings suggest that an individualized approach to short-term corticosteroid use may be warranted and that further research is needed to obtain better quality of evidence.