Background There are major concerns and uncertainty regarding a possible reduction in growth velocity and final height of children with asthma who are long-term users of inhaled corticosteroids (ICS). 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 June 2014. We used a combination of search terms involving drug names and adverse effects of interest (such as growth or height), and we also hand-searched reference lists of existing systematic reviews and trial reports. We selected RCTs and controlled observational studies of any ICS vs non-ICS control treatment in patients with asthma (treatment duration of at least 52 weeks). Meta-analysis of continuous outcomes (growth velocity in cm/year or final height in cm) was conducted using RevMan 5.3. We analysed mean differences using inverse variance method, random effects model. Heterogeneity was assessed using the I2 statistic.
Results We found 21 relevant studies (seventeen RCTs and four observational studies) after screening 1876 hits from the search. Meta-analysis of 16 RCTs showed a significant association between ICS use and reduction in growth velocity compared to controls (pooled Mean Difference -0.35cm/year, 95% CI -0.54 to -0.18). No significant reduction in growth velocity with ICS was reported in two observational studies of lower quality (pooled Mean Difference 0.03cm/year, 95% CI -0.61 to 0.67). Analysis of 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 found a non-statistically significant pooled mean reduction in final adult height of -0.85 cm (95% CI -3.35 to 1.65).
Conclusion Use of ICS for 12 months or more in children with asthma has a limited impact on annual growth velocity, with a slight reduction in final adult height. When interpreted in the context of the typical final adult height in the UK, ICS users may experience less than 0.7% reduction in height compared to non-ICS users.