Authors' objectives

To determine whether inhaled steroid therapy causes delayed linear growth in children with asthma.

Searching

MEDLINE from 1966 to 1998, EMBASE from 1980 to 1998 and CINAHL from 1982 to 1998 were searched (search terms listed). Additional studies (published and unpublished) were located through searching the reference lists of retrieved articles and contacting colleagues and researchers working in the field. No language restrictions were applied.

Study selection

Assessment of study quality

The Jadad scale was used (see Other Publications of Related Interest no.1). In addition each trial was evaluated for the adequacy of randomisation. The validity of studies was assessed independently by two reviewers. Agreement was assessed using kappa statistics (kappa=0.76) and disagreements were resolved through consensus. Points were awarded for each of the Jadad criteria fulfilled by the study (maximum number of points 5). Where there was uncertainty, study authors were contacted for further details and clarification.

Data extraction

Two reviewers independently abstracted the data using a standardised data extraction sheet. Where necessary, study authors were contacted for further details and clarification. The following data were abstracted: number of participants randomised, number enrolled, number completed study, specific medication used, dose and route of medication delivery, duration of intervention, compliance, number of withdrawals and reasons for withdrawal, and mean linear growth velocity for control and intervention groups. Descriptive data were also collected on patient baseline characteristics, study definition of asthma, inclusion criteria, and exclusion criteria. For each study the mean difference in linear growth velocity was calculated.

Methods of synthesis

Results of the review

Five double-blind RCTs (4 beclomethasone, 1 fluticasone) including 855 participants.

Some of the findings relating to beclomethasone have been published as a Cochrane Review (see Other Publications of Related Interest no.2).

Mean linear growth velocity (fixed-effect model, random-effects model not reported):

1. Beclomethasone (328-400 micrograms/day).

All trials (n=4 studies): WMD=-1.51cm/yr (95% CI: -1.159, -1.87).

Quality score >/=4 (n=3 studies): WMD=-1.65cm/yr (95% CI: -1.23, -2.06).

Quality score <=4 (n=1 study): WMD=-1.08cm/yr (95% CI: -0.35, -1.81).

Concealment adequate (n=3 studies): WMD=-1.65cm/yr (95% CI: -1.23, -2.06).

Concealment not adequate (n=1 study): WMD=-1.08cm/yr (95% CI: -0.35, -1.81).

Delivery method - diskhaler (n=3 studies): WMD=-1.54cm/yr (-1.15, -1.94).

Delivery method - metered-dose inhaler (n=1 study): WMD=-1.30cm/yr (95% CI: -0.38, -2.23).

Placebo-controlled (n=2 studies): WMD=-1.57cm/yr (95% CI: -1.15, -1.99).

Theophylline/salmeterol controlled (n=2 studies): WMD=-1.35cm/yr (95% CI: -0.66, -2.03).

2. Fluticasone (200 micrograms/day).

All trials (n=1 study): Mean difference=-0.43cm/yr (95% CI: -0.01, -0.85).

Heterogeneity:

Across all five studies the Q test produced a z value of 7.52 and a P value of >0.999, which revealed no evidence of significant heterogeneity between studies.

Quality of studies:

The mean Jadad score was 4.0 (SD=0.71) out of a possible maximum 5 points. Four of the five trials reported an adequate method of randomisation using an independent randomisation centre. Compliance was evaluated in four out of the five studies, withdrawal rates were low (10-33%) and each study adequately addressed the reasons for drop-out.

Publication bias:

A funnel plot of the four beclomethasone studies revealed no obvious exclusion of studies concluding a small measure of effect, although this should be viewed with caution considering the small number of studies and hence low power of the assessment.

Authors' conclusions

This meta-analysis suggests that moderate doses of beclomethasone and fluticasone in children with mild to moderate asthma cause a decrease in linear growth velocity of 1.51cm/yr and 0.43cm/yr, respectively. Similarly, a moderate dose of the inhaled steroid fluticasone significantly decreases the linear growth velocity of children with mild to moderate asthma. Caution must be used when generalising about fluticasone, however, because only one study was incorporated and the magnitude of effect was smaller than that of beclomethasone. The effects of inhaled steroids when given for >54wks, or on final adult height, remain unknown.

CRD commentary

This is a well-conducted and clearly presented review. A comprehensive search for both published and unpublished data was performed and studies were selected using clearly-defined inclusion/exclusion criteria. Although only one reviewer initially scanned the literature searches, two independent reviewers finally determined which studies were to be included in the review. Similarly, two reviewers were involved in assessing the validity of the studies and extracting data. Agreement between the reviewers was assessed at all stages of the review process.

Study details and individual study quality scores were clearly presented in tables. The authors used appropriate methods to combine the studies in a meta-analysis and also assessed the degree of heterogeneity between studies and the possibility of publication bias. However, with such small numbers of studies, such tests for heterogeneity and publication bias have little power and so their findings should be interpreted with caution. The results of various sensitivity analyses also appear to support the main study findings and the authors discuss in some detail the major limitations of the review. Overall, in view of the data presented, the conclusions and implications of the review appear to be reasonable.

Implications of the review for practice and research

Practice: The authors state that 'the negative effect on linear growth velocity needs to be weighed against the known positive effects of inhaled steroids on such outcomes as quality of life, symptom days, severity of exacerbations, decreased lung architectural changes, and health care utilisation before clinical significance in clear'. In addition 'this meta-analysis suggests that if inhaled steroids are required to control asthma in a child, then careful monitoring of height and an emphasis on using the lowest possible effective dose would be appropriate steps in minimising their effects on growth'.

Research: The authors state that 'whether inhaled steroids in doses presently used in children with asthma affect final adult height remains unanswered'.

Bibliographic details

Sharek P J, Bergman D A. The effect of inhaled steroids on the linear growth of children with asthma: a meta-analysis. Pediatrics 2000; 106(1): E8. [PubMed: 10878177]

Original Paper URL

http://pediatrics.aappublications.org/cgi/content/full/106/1/e8

Other publications of related interest

1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12. 2. Sharek PJ, Bergman DA. Beclomethasone for asthma in children: effects on linear growth (Cochrane Review). In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software.

Indexing Status

Subject indexing assigned by NLM

MeSH

Administration, Inhalation; Adolescent; Androstadienes /administration & dosage; Anti-Inflammatory Agents /administration & dosage; Asthma /drug therapy /physiopathology; Beclomethasone /administration & dosage; Body Height /drug effects; Budesonide /administration & dosage; Child; Child, Preschool; Fluocinolone Acetonide /administration & dosage /analogs & derivatives; Growth /drug effects; Humans; Infant; Infant, Newborn; Steroids /administration & dosage /therapeutic use; Triamcinolone /administration & dosage

AccessionNumber

12000008519

Database entry date

31/05/2001

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.