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Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children

Educational Objective
To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal bleeding, sepsis, pneumonia, and glaucoma, in children.
1 Credit CME
Key Points

Question  Are there potential harms associated with oral corticosteroid bursts (defined as the use of oral corticosteroids for 14 or fewer days) in children?

Findings  In this nationwide population-based study of 1 064 587 children who received a single corticosteroid burst, a burst was associated with 1.4- to 2.2-fold increased risk of gastrointestinal bleeding, sepsis, and pneumonia within the first month after corticosteroid initiation.

Meaning  This study suggests that clinicians should be aware of potentially severe adverse events associated with corticosteroid bursts 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.

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Article Information

Accepted for Publication: January 27, 2021.

Published Online: April 19, 2021. doi:10.1001/jamapediatrics.2021.0433

Correction: This article was corrected on July 6, 2021, to fix errors in the Abstract, Key Points, and text.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yao TC et al. JAMA Pediatrics.

Corresponding Authors: Tsung-Chieh Yao, MD, PhD, Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Hsin Street, Kweishan, Taoyuan 33305, Taiwan (yao@adm.cgmh.org.tw); Hui-Ju Tsai, MPH, PhD, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd, Zhunan, Miaoli County 35053, Taiwan (tsaihj@nhri.edu.tw).

Author Contributions: Drs Yao and H.-J. Tsai had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Yao, Wang, Wu, H.-J. Tsai.

Acquisition, analysis, or interpretation of data: Yao, Wang, S.-M. Chang, Y.-C. Chang, Y.-F. Tsai, Wu, Huang.

Drafting of the manuscript: Yao, Wang, H.-J. Tsai.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: S.-M. Chang, Y.-C. Chang, Y.-F. Tsai.

Obtained funding: Yao, H.-J. Tsai.

Supervision: Yao, Wang, Wu, H.-J. Tsai.

Conflict of Interest Disclosures: Dr Wu reported receiving grants from GlaxoSmithKline outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by grants from National Health Research Institutes, Taiwan (PH-109-PP-08, Dr Tsai), Ministry of Science and Technology of Taiwan (MOST 107-2314-B-400-031-MY3, Dr Tsai; and MOST 106-2314-B-182-051-MY3 and MOST 109-2314-B-182-042-MY3, Dr Yao); research grants from the Headquarters of University Advancement, National Cheng Kung University, Tainan, Taiwan (Dr Wang), Chang Gung Medical Foundation (CMRPG3F1711-3, CMRPG3F0361, CMRPG3J0121, and CMRPG3K1371, Dr Yao), and the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (1R01HD085993-01, Dr Wu).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance of the Ministry of Health and Welfare, Taiwan. The interpretation and conclusions contained in this article do not represent those of the Bureau of National Health Insurance or the Ministry of Health and Welfare.

Additional Contributions: We thank staff members in the Data Science Center of the Ministry of Health and Welfare, Taiwan, for their data management and maintenance.

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