Inhaled corticosteroids and linear growth

26 July 2019    
Inhaled corticosteroids and linear growth

 

Question
What is the effect of inhaled corticosteroids on linear growth in children?

 

Answer
By Elham Hossny, MD, PhD. Pediatric Allergy and immunology Unit, Children’s Hospital, Ain Shams University, Cairo, Egypt &
Nelson Rosario, MD, PhD. Department of Pediatrics, Federal University of Parana, Brazil

Although inhaled corticosteroid (ICS) therapy is considered safe in children, its potential effect on linear growth remains a matter of concern. The effect of ICS on growth velocity and final adult height has been a subject of debate.1 Several reviews consistently describe small dose-dependent impairments to childhood growth velocity more evident during the first two years of therapy.2-6 Two Cochrane reviews of randomized clinical trials showed a small mean reduction in linear growth (-0.91cm/year for beclomethasone, -0.59 cm/year for budesonide, and -0.39 cm/year for fluticasone) in the first year of treatment in prepubertal children with persistent asthma.7

On the other hand, a 1-year follow-up study on guideline-recommended doses with high adherence in prepubertal children showed that the negative correlation between cumulative ICS dose and height velocity became non-significant after adjustment for age and sex in a multiple regression model.8 Another recent review showed that most of the "real-life" observational studies did not report significant effects of ICS on growth in children.7 Also, a retrospective study that included 284 asthmatic prepubertal children on long-term treatment with ICS did not reveal height reduction in low or medium dosage.9

The effect on target adult height is another matter of concern. Although several prospective studies denied such effect, ICs were reported to reduce final height (FH) in asthmatic children compared to controls, in a dose- and duration-dependent manner (2.5 ± 2.89 cm lower in boys and 2.0 ± 2.03 cm lower in girls than matched controls) and this effect was also dependent on the type of ICS.10 Data from the Childhood Asthma Management Program (CAMP) prospective trial showed that a larger daily dose of ICS in the first 2 years was associated with a lower adult height (−0.1 cm for each microgram per kilogram of body weight).11 Loke et al.12 noted a slight reduction of about one cm in final adult height which when interpreted in the context of average adult height in England represented a 0.7 % reduction compared to non-ICS users.

The concomitant use of intranasal corticosteroids (INC) raises concerns as well. Among a group who were prescribed more than 750 μg/d of beclomethasone dipropionate and an INC, a lower annual growth velocity from 3 to 5 years of age was demonstrated; however, this was followed by recovery of growth velocity so that the FH attained at the end of the follow-up period was comparable to children receiving lower doses of the same ICS with or without INC.13

A recent systematic review suggests that the drug molecule and delivery device may impact the effect of ICS on growth in children with persistent asthma. However, the evidence was not certain enough and further pragmatic trials and real-life observational studies were recommended.14

It is advisable that before increasing the dose of ICS, a physician should ensure that the child is actually taking the drug through an appropriate device with good technique and that the modifiable environmental triggers and co-morbidities such as environmental tobacco smoke, allergens and obesity have been addressed. It is also important to review the dosage regularly and reduce it whenever possible to the minimal effective dose.15 It is recommended that children be monitored for growth by stadiometry every 3 to 6 months.4

In spite of the measurable effects of ICS on the linear growth, it is important to keep in mind that the safety profile of all ICS preparation is markedly better than that of oral glucocorticoids. Also, asthma as a chronic disease by itself has growth-suppressing effects and this may confound research on the effect of ICS on growth.1 Nevertheless, physicians prescribing ICS to children should be aware of this possibility and carefully monitor linear growth especially with the concomitant use of nasal corticosteroids.

 

References

  1. Hossny E, Rosario N, Lee BW, Singh M, El-Ghoneimy D, Soh JY, Le Souef P. The use of inhaled corticosteroids in pediatric asthma: update. World Allergy Organ J 2016;9:26.
  2. Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Evid Based Child Health. 2014;9:829–930.
  3. Pruteanu AI, Chauhan BF, Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: dose–response effects on growth. Evid Based Child Health. 2014;9:931–1046.
  4. Skoner DP. Inhaled corticosteroids: effects on growth and bone health. Ann Allergy Asthma Immunol. 2016;117(6):595–600.
  5. Kapadia CR, Nebesio TD, Myers SE, Willi S, Miller BS, Allen DB, Jacobson-Dickman E; Drugs and Therapeutics Committee of the Pediatric Endocrine Society. Endocrine effects of inhaled corticosteroids in children. JAMA Pediatr. 2016;170(2):163-70.
  6. Gupta R, Fonacier L. Adverse effects of nonsystemic steroids (inhaled, intranasal, and cutaneous): a review of the literature and suggested monitoring tool. Curr Allergy Asthma Rep. 2016;16(6):1–11.
  7. Zhang L, Lasmar LB, Castro-Rodriguez JA. The impact of asthma and its treatment on growth: an evidence-based review. J Pediatr (Rio J). 2019;95 Suppl 1:10-22.
  8. Wardenier NR, Klok T, de Groot EP, Brand PL. Height growth in children with asthma treated with guideline-recommended dosages of fluticasone and electronically assessed adherence. Arch Dis Child. 2016;101(7):637-9.
  9. Hatziagorou E, Kouroukli E, Avramidou V, Papagianni M, Papanikolaou D, Terzi D, Karailidou M, Kirvassilis F, Panagiotakos D, Tsanakas J. A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids. J Asthma. 2018;55(4):437-42.
  10. De Leonibus C, Attanasi M, Roze Z, Martin B, Marcovecchio ML, Di Pillo S, Chiarelli F, Mohn A. Influence of inhaled corticosteroids on pubertal growth and final height in asthmatic children. Pediatr Allergy Immunol. 2016;27(5):499-506.
  11. Kelly HW, Sternberg AL, Lescher R, Fuhlbrigge AL, Williams P, Zeiger RS, Raissy HH, Van Natta ML, Tonascia J, Strunk RC, CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904–12.
  12. Loke YK, Blanco P, Thavarajah M, Wilson AM. Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis. PLoS One. 2015;10:e0133428.
  13. Lasmar L, Brand PL, Lima AC, Maciel MF, Camargos P. Growth velocity in prepubertal children using both inhaled and intranasal corticosteroids. Ann Allergy Asthma Immunol. 2016;116(4):368-70
  14. Axelsson I, Naumburg E, Prietsch SO, Zhang L. Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth. Cochrane Database Syst Rev. 2019;6:CD010126.
  15. Ohn M, Jaffe A, Selvadurai H. Persistent growth effects of inhaled corticosteroids. J Paediatr Child Health. 2016;52(10):964-6.

 

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