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Published: September 2001
MARC prescriber advice

Growth Retardation with Inhaled and Intranasal Corticosteroids

Prescriber Update 22: 14-16
September 2001

Medsafe Editorial Team

Recent studies have shown that growth suppression may occur in children after long-term exposure to inhaled and intranasal corticosteroids.  The Medicines Adverse Reactions Committee recommends that prescribers consider the risks and benefits of inhaled and intranasal steroids in children, and use the lowest effective dose.

Previously only systemic corticosteroids implicated

It is generally accepted that exposing children to systemic corticosteroids can impair normal growth even with relatively small doses.1  However, in the past this has not been thought to occur with steroids delivered via the inhaled or intranasal routes. 

Studies of growth suppression with inhaled2 and intranasal3,4 steroids have shown conflicting results.  Many of the studies have been hampered by poor design, insufficient follow-up (generally one year or less), poorly standardised measurement techniques and difficulties in predicting adult height.

FDA requires warnings about growth suppression

Nevertheless, in 1998 the United States Food and Drug Administration (FDA) recommended class labelling about growth suppression on all intranasal and inhaled corticosteroid products in the adverse reactions and precautions sections of the data sheets.5  This change reflected studies that showed a reduction in growth velocity in spite of the absence of hypothalamic-pituitary axis suppression (usually measured by the short ACTH stimulation test).  Advice was given to use the lowest effective dose, consider risk versus benefit, and monitor growth of paediatric patients.

Long-term studies show 1cm growth reduction in first year

Two long-term controlled studies6,7 of inhaled budesonide in children with asthma were published in 2000 (treatment durations averaging four and nine years, respectively).  Both studies demonstrated a reduction in growth in the inhaled steroid groups of approximately 1cm, predominantly in the first year of treatment.  However, as treatment continued, the growth rates approached that of the controls such that children were expected to attain6, or attained7, their projected or target adult height.  Agertoft and Pederson7 found that the initial growth retardation was significantly correlated with younger age (p=0.04).

Further research is needed to quantify the effects of inhaled/intranasal corticosteroids on growth in children to determine whether some patients are more sensitive to these effects.  Additionally, more needs to be known about whether the use of inhaled/intranasal corticosteroids at certain ages has a greater impact on growth retardation.

Consider risk versus benefit and use lowest effective dose

The Medicines Adverse Reactions Committee (MARC) advises prescribers that growth inhibition and other systemic effects8 may occur in children treated with these medicines.  In addition, be aware of the cumulative effect of co-prescribing various dose forms of corticosteroids (inhaled, intranasal, oral and topical preparations).

The MARC recommends that the risks and benefits be considered before prescribing inhaled or intranasal corticosteroids to children.  It is important to use the lowest effective dose but to balance this against adequate management of chronic conditions such as asthma, as poor control of these can themselves cause growth retardation.  If despite these measures, growth suppression still occurs then treatment with medicines other than corticosteroids should be considered.

If prescribers wish to monitor growth rate in children (e.g. those on long-term corticosteroid treatment or using several dose forms of corticosteroids), this can be recorded on growth charts.  Ask your local paediatrician which charts they use, or obtain them from the internet.9  Measurement of growth rate needs to be done at intervals by the same person using the same equipment and technique each time.

Competing interests (authors): none declared

References
  1. Corticosteroids. In Parfitt K (Ed) Martindale 32nd Edn. 1999: Massachusetts, p.1012.
  2. Skoner DP, Szefler SJ, Welch M, et al. Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma. J Allergy Clin Immunol 2000;105:259-268.
  3. Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000;105(2):e22.
  4. Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics 2000;105(2):e23.
  5. United States Food and Drug Administration. Class labeling for intranasal and orally inhaled corticosteroid containing drug products regarding the potential for growth suppression in children. FDA Talk Paper 1998. http://www.fda.gov/cder/news/cs-label.htm
  6. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Eng J Med 2000;343(15):1054-1063.
  7. Agertoft L, Pederson S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Eng J Med 2000;343(15):1064-1069.
  8. Havill S, Rademaker M. Poorly recognised adverse effects of inhaled corticosteroids. Prescriber Update 1998; April No.16:16-19. www.medsafe.govt.nz/Profs/PUarticles/2.htm
  9. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm

 

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