Among children aged ≤6 years, short-term high-dose inhaled or systemic corticosteroid use does not appear to correlate with increased adverse events across organ systems. However, evidence is inconclusive regarding long-term use and effects on growth, according to study results published in BMJ Open.
This systematic review included 85 studies including 11,505 young children treated with corticosteroids for acute respiratory conditions. Because safety terminology was not uniform across studies, data were collected on all drug-related adverse events. All initial screening of titles and abstracts was performed by 2 independent reviewers, as was a more in-depth review of potentially eligible full texts. Data were extracted by one reviewer and verified by another, with adverse events categorized by organ sections.
The McMaster Quality Assessment Scale for Harms was used to assess quality. For the meta-analysis, Peto odds ratios (pORs) were used to pool binary data, while the DerSimonian Laird inverse variance random-effects method was used to pool growth data. Cochran’s Q (α=0.05) was used to examine statistical heterogeneity in subgroup analyses of respiratory condition and dose.
There was notable heterogeneity among the studies for corticosteroid type, dose, and administration, but the studies had poor overall methodological quality due to inconsistent standardization of adverse event reporting. Among 6 studies (n=1373) focusing on asthma and croup, vomiting was less common with dexamethasone treatment (12/663 cases) vs other corticosteroids (51/710 cases; pOR, 0.29; 95% CI, 0.17-0.48; I²=0%). Placebo and systemic corticosteroids were associated with a pOR of 1.44 for tremor/jitteriness, 0.11 for headache, and 1.95 for behavior change, with no statistically significant differences.
Changes in linear growth with inhaled corticosteroid vs placebo were examined in 2 studies (n=263), which reported a mean difference of 0.10 cm (95% CI, -0.47 to 0.67; I²=9%) from baseline. Due to large heterogeneity, further results on growth from 5 studies could not be pooled.
In a randomized controlled trial examining high-dose (1500 μg/d) inhaled fluticasone propionate vs placebo in children with recurrent wheeze, a smaller mean change in height z-score was observed in one year (mean difference, -0.24; 95% CI, -0.40 to -0.08). Other adverse events had no significant associations with inhaled or systemic corticosteroid use, although small sample sizes and low number of events made data difficult to interpret.
Limitations to this meta-analysis included inconsistencies in adverse event reporting and data collection throughout the included studies and notable interstudy inconsistencies in corticosteroid dosage and formulation.
Despite the lack of an observed association between increased adverse events and short-term high-dose inhaled or systemic corticosteroids, the researchers concluded that “uncertainties remain due to low quality of studies, poor reporting, and lack of precision of results.” Future research should include growth and behavioral metrics to better guide decisions in the cases of young children with acute respiratory conditions.
Fernandes RM, Wingert A, Vandermeer B, et al. Safety of corticosteroids in young children with acute respiratory conditions: a systematic review and meta-analysis [published online August 1, 2019]. BMJ Open. doi:10.1136/bmjopen-2018-028511