University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• An 8-year-old boy with a history of asthma is seen in his primary care physician's office.  His mother expresses concern over information she read regarding the use of inhaled steroids.  She asks if her child will experience growth retardation as a result of this therapy.

Clinical Bottom Lines

1. The study summarized suggested that although there is a decrease in growth velocity during the first year of  using inhaled steroids, these changes in growth rate were not significantly associated with adult height (1). 
2. There did not appear to be any relationship between the mean daily dose of inhaled steroid, the cumulative dose of inhaled steroid, or the duration of treatment and the difference between measured and target adult heights (1).

Summary of Key Evidence

1. 211 children were enrolled in a prospective study: 142 budesonide-treated children with asthma, 18 children with asthma who never received inhaled steroids, and 51 healthy siblings of patients which served as controls (1).
2. Children were followed every six months for 13 years, measuring hospital admissions, age, height, weight, spirometry, dose and frequency of all medications and compliance (1).
3. Children in the test group received a mean daily dose of 412 micrograms (range, 110-877) and a mean cumulative dose of budesonide of 1.35 g (range, 0.41-3.99) (1).
4. The mean differences between the measured and target adult heights were +0.3 cm (95% CI, -0.6 to +1.2) for the treatment group, -0.2 cm (95% CI, -2.4 to +2.1) for control group with asthma, and +0.9 cm (95% CI, -0.4 to +2.2) for the healthy siblings (1).
5. In the budesonide group, there was a statistically significant 1 cm decrease in the mean growth rate during the first year of treatment only (5.1 cm per year with 95% CI, 4.7-5.5, P<0.001) versus 6.1 cm per year (95% CI, 5.7-6.5) during the run-in period and 5.9 cm (95% CI, 5.5-6.3) during the third year.  The initial growth retardation was significantly correlated with age (P<0.04) with a more pronounced reduction in younger children (1).
6. The adult height did depend significantly on the child's height before budesonide treatment and the severity of asthma (1).
7. Weaknesses in the study include the lack of a randomized control study and insufficient controls which isolate the variable of inhaled steroid use.  Also, additions were made to the control group after the initiation of the study.

Additional Comments

• Many studies in the past have shown that inhaled steroids can cause growth retardation in the first year of use (1,2,3).  This article supports findings reported previously in a double-blind, randomized, parallel group, multicenter study who were treated with fluticasone and their heights measured for one year which show no significant effect on adult height (5).
• The study also supports the findings in the CAMP study which was a randomized treatment trial for more than 4 years in 1000 children with mild to moderate asthma.  It also noted that most of the difference in growth amongst the budesonide-treated group occurred during the first year of treatment.  One weakness of that study is that it did not report the child's pubertal status prior to entry or during the study (2).
• This study was consistent with previous studies which showed a growth rate reduction of 1.5 cm during the first year of receiving 400 micrograms of inhaled beclomethasone per day.
• Many previous studies which demonstrated decreased adult height were flawed in that they observed the decrease in velocity after one year of use and then postulated further loss based on the trend (1,3).
• The CAMP study also shows that symptoms improved markedly in the budesonide-treated group although there was no change in the FEV1 (2,3).
• The studies do not comment on the growth of other organs, such as the brain or lung.  Alveoli continue to be formed in the early postnatal years up until the age of eight, with most of it occurring during the first two years.  Corticosteroids, accelerate the development of lung features.  When applied during a period of alveolar development, this may result in decreased lung cell mass and too few abnormally large alveoli (3).

Citation

1. Agertoft L, Pedersen S.  Effect of long-term treatment with inhaled budesonide on adult height in children with asthma.  The New England Journal of Medicine, 2000; 343:1064-1069.
2. The Childhood Asthma Management Program Research Group.  Long-term effects of budesonide or nedocromil in children with asthma.  The New England Journal of Medicine, 2000: 343:1054-1063.
3. Wohl M, Majzoub J.  Asthma, steroids, and growth (editorial).  The New England Journal of Medicine, 2000; 343:1113-1114.
4. Freedman D, et al.  Statistics (W. W. Norton & Company, Inc., New York) 1991; 485-598.
5. Mohr B.  No long-term effects on growth in asthmatic children using Flovent (CAT).  University of Michigan Pediatric EBM Web Site, 1999.

CAT Author: John P. Schmidt, MD

CAT Appraisers: Katherine Layton, MD

Date appraised: October 25, 2000