The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials

Ethan K Gough, Erica E M Moodie, Andrew J Prendergast, Sarasa M A Johnson, Jean H Humphrey, Rebecca J Stoltzfus, A Sarah Walker, Indi Trehan, Diana M Gibb, Rie Goto, Soraia Tahan, Mauro Batista de Morais, Amee R Manges, Ethan K Gough, Erica E M Moodie, Andrew J Prendergast, Sarasa M A Johnson, Jean H Humphrey, Rebecca J Stoltzfus, A Sarah Walker, Indi Trehan, Diana M Gibb, Rie Goto, Soraia Tahan, Mauro Batista de Morais, Amee R Manges

Abstract

Objectives: To determine whether antibiotic treatment leads to improvements in growth in prepubertal children in low and middle income countries, to determine the magnitude of improvements in growth, and to identify moderators of this treatment effect.

Design: Systematic review and meta-analysis.

Data sources: Medline, Embase, Scopus, the Cochrane central register of controlled trials, and Web of Science.

Study selection: Randomised controlled trials conducted in low or middle income countries in which an orally administered antibacterial agent was allocated by randomisation or minimisation and growth was measured as an outcome. Participants aged 1 month to 12 years were included. Control was placebo or non-antimicrobial intervention.

Results: Data were pooled from 10 randomised controlled trials representing 4316 children, across a variety of antibiotics, indications for treatment, treatment regimens, and countries. In random effects models, antibiotic use increased height by 0.04 cm/month (95% confidence interval 0.00 to 0.07) and weight by 23.8 g/month (95% confidence interval 4.3 to 43.3). After adjusting for age, effects on height were larger in younger populations and effects on weight were larger in African studies compared with other regions.

Conclusion: Antibiotics have a growth promoting effect in prepubertal children in low and middle income countries. This effect was more pronounced for ponderal than for linear growth. The antibiotic growth promoting effect may be mediated by treatment of clinical or subclinical infections or possibly by modulation of the intestinal microbiota. Better definition of the mechanisms underlying this effect will be important to inform optimal and safe approaches to achieving healthy growth in vulnerable populations.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793643/bin/goue015813.f1_default.jpg
Fig 1 Flow diagram of search retrieval and trial selection
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793643/bin/goue015813.f2_default.jpg
Fig 2 Random effects meta-analyses and forest plots of antibiotic use and height. Point size reflects study weight
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793643/bin/goue015813.f3_default.jpg
Fig 3 Random effects meta-analyses and forest plots of antibiotic use and weight. Point size reflects study weight

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