British Medical Journal
19 April 2014 (Vol 348, Issue 7954)
http://www.bmj.com/content/348/7954

The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials
BMJ 2014;348:g2267 (Published 15 April 2014)

Editorial
Excerpt
Worth studying in highly selected children, with a close eye on potential harms
Overt infections are a leading cause of death worldwide in children under 5,1 and strategies to prevent and treat infections are a cornerstone of child survival programmes. Recent assessments suggest that despite a net increase in the size of birth cohorts, the number of children dying before their fifth birthday has fallen to 6.6 million (uncertainty range 6.3-7.0 million) per year, a 45% reduction from almost 12 million deaths in 1990.2 In contrast, the fall in undernutrition has been modest at best. An estimated 165 million children under 5 were stunted in 2011 and an estimated 52 million severely wasted; almost 45% of the current burden from child mortality in under 5s can be attributed to malnutrition.3 Although many risk factors for early child mortality are well recognised, the mechanisms underlying chronic enteropathy and growth failure among children in low and middle income countries remain uncertain.4
In a linked paper, Gough and colleagues (doi:10.1136/bmj.g2267) report a systematic review of 10 trials looking for associations between antibiotics, given for a variety of indications, and growth in childhood.5 The review included 4316 children (age range 1 month to 12 years) from low and middle income countries. The authors’ analysis using random effects models suggests that antibiotic use was associated with increased mean height or linear growth (extra linear growth 0.04 cm/month, 95% confidence interval 0.00 to 0.07) and an extra 23.8 g weight gain per month (95% confidence interval 4.3 to 43.3 g). The authors recommend further evaluation of the growth promoting effect of antibiotics and speculate that the effects may operate through reduction in subclinical infections and beneficial effects on intestinal microbiota…
…There is a clear need for further research in this area to help us understand precisely how antibiotics might promote growth in children. Researchers could start by characterising high risk groups of children who might benefit, such as those with clearly defined subclinical or overt infections, HIV, or severe acute malnutrition. Further trials should be done to confirm the interesting findings from Malawi.7 But extending trials of antibiotics to other categories of children, such as those at risk of malnutrition and growth failure, may not be justifiable at this stage. Researchers should instead exploit existing observational cohorts to explore the relation between infections, antibiotic treatment, and nutrition outcomes, including growth patterns, where data are available. The large multicentre Mal-ED studies assessing patterns of growth among infants 0-24 months of age across eight countries (www.fnih.org/work/key-initiatives/mal-ed) are an excellent example of an opportunity to assess the potential impact of antibiotic treatment on linear growth and weight gain using standardised data and definitions. In the interim, continued focus on the 10 recommended evidence based nutrition interventions to promote growth15 must be prioritised.

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.