Daily use of low- to medium-dose inhaled corticosteroids for mild to moderate persistent asthma suppresses growth to a "small" degree in children of all ages, according to a Cochrane review published online July 16 in the Cochrane Database of Systematic Reviews.
This level of use was associated with a mean reduction of 0.48 cm per year in linear growth velocity during the first year of treatment, against a background average growth rate of 6-9 cm per year. The growth suppression was less pronounced in subsequent years of treatment, and the magnitude of growth suppression was more strongly related to the particular drug used than to the dose or delivery device, said Dr. Linjie Zhang of the Federal University of Rio Grande (Brazil) and his associates.
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Daily use of low- to medium-dose inhaled corticosteroids suppresses growth to a "small" degree in children, according to the review.
"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimeter less during the first year of treatment. But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared with the known benefits of the drugs for controlling asthma and ensuring full lung growth," Dr. Zhang said in a press statement accompanying the report.
The investigators undertook this comprehensive review of the literature and metaanalysis because of persistent concerns about possible adverse effects of inhaled corticosteroids on children’s growth and because several recent randomized trials have examined the issue and have assessed newly available agents and modes of delivery. They identified 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children up to age 18, of whom 5,128 were treated with inhaled corticosteroids and 3,343 were treated with nonsteroidal anti-inflammatory drugs or placebo and served as controls.
Most of the trials were blinded, and most were multicenter. Seventeen of the 25 were funded by pharmaceutical companies.
The participating children used beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone, delivered by any type of inhalation device, and were followed for 3 months to 6 years.
All six inhaled corticosteroids were found to suppress linear growth velocity during 1 year of treatment, which was the primary outcome of interest. They all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time. These effects were less pronounced in subsequent years of treatment, but persisted until patients reached their adult height.
The one study that followed prepubescent participants into adulthood showed that those who used inhaled corticosteroids had a mean reduction of 1.2 cm in adult height, compared with those who did not.
Daily dose, delivery device, and patient age had had no significant impact on the magnitude of growth suppression. A small number of studies that compared the various corticosteroids against each other showed that beclomethasone and budesonide were somewhat more potent growth suppressors, compared with the other four agents. However, a meta-analysis is not the best method for exploring these issues, and data from more head-to-head randomized trials are required to confirm these findings, Dr. Zhang and his associates noted (Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]).
Their findings indicate that inhaled corticosteroids should be prescribed at the lowest effective dose. "Moreover, it is prudent to monitor linear growth in children treated with inhaled corticosteroids, given that individual susceptibility to these drugs may vary considerably," the investigators added.