Impact of Inhaled Corticosteroids on Growth in Children with Asthma: Systematic Review and Meta-Analysis

PLoS One. 2015 Jul 20;10(7):e0133428. doi: 10.1371/journal.pone.0133428. eCollection 2015.

Abstract

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth.

Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic.

Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65).

Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy*
  • Body Height / drug effects*
  • Budesonide / therapeutic use
  • Child
  • Child Development / drug effects*
  • Child, Preschool
  • Humans

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Budesonide

Grants and funding

This manuscript presents a systematic review commissioned by Asthma UK (AUK-PG-2012-181), www.asthma.org.uk, and the authors are grateful to the Asthma UK Research team for their guidance. The views expressed in this paper are those of the authors, and the funders had no role in the data collection and analysis, decision to publish, or preparation of the manuscript.