Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children

Abstract

Importance: The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children.

Objective: To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children.

Design, setting, and participants: This study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020.

Exposure: Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days).

Main outcomes and measures: Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts.

Results: Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma.

Conclusions and relevance: This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.

Figure 1.. Graphic Presentation of Self-controlled Case Series Design

The observation periods are the baseline period and the 2 risk periods.

Figure 2.. Association Between Exposure to Corticosteroid Bursts and Gastrointestinal Bleeding, Sepsis, Pneumonia, and Glaucoma in Children

Incidence rate ratios (IRRs) and corresponding 95% CIs for 4 severe adverse events in 2 posttreatment periods (5-30 days and 31-90 days after initiation of a corticosteroid burst).

Figure 3.. Association Between Exposure to Corticosteroid Bursts and Gastrointestinal Bleeding, Sepsis, Pneumonia, and Glaucoma in Children Based on Alternative Inclusion and Exclusion Criteria and Different Durations of Observation Periods

IRR indicates incidence risk ratio. ^aWith inclusion of participants with prescriptions of topical corticosteroids prior to the study period. ^bWith 180 days as the maximum postexposure time (reference period defined as 5-180 days prior to initiation of a corticosteroid burst and 2 posttreatment periods defined as 5-60 days and 61-180 days after initiation of a corticosteroid burst).