Children who receive antibiotics before their first birthday might be at an increased risk of developing asthma, new research published in The Lancet Respiratory Medicine has confirmed. However, the findings suggest that it is impaired viral immunity and genetic variants on a region of chromosome 17 that increase the risk of both antibiotic use in early life and later development of asthma rather than the antibiotics themselves, as previously thought.
Importantly, the longitudinal study did not find a link between early antibiotic prescription and the development of atopy (allergic diseases), contradicting the prevailing theory that early antibiotic exposure, via changes in gut flora, alters the development of a child's immune system, increasing susceptibility to allergic asthma later on.
In children, antibiotics are routinely used to treat respiratory infections, ear infections, and bronchitis, and several studies have reported a link between the use of antibiotics during early childhood and the subsequent development of asthma. However, systematic reviews have reported conflicting results and called for additional longitudinal studies to provide definitive answers.
In this study, UK researchers examined data from the Manchester Asthma and Allergy Study (MAAS) which has followed over 1000 children from birth to 11 years. Information on antibiotic prescription, wheeze, and asthma exacerbations were taken from medical records. Skin reaction tests that show whether a child is sensitized to allergens were done at ages 3, 5, 8, and 11 years. At age 11, blood was collected from children who had received at least one course of antibiotics or children who had received no antibiotics in the first year of life to compare their immune-system cell response to viruses (rhinovirus; the virus responsible for the common cold, and respiratory syncytial virus; RSV) and bacteria (Haemophilus influenzae and Streptococcus pneumoniae). Genetic testing was also done to look at the links between common genetic variations on chromosome 17, known as 17q21, and antibiotic prescription.
The study's findings are believed to be the first to show that children with wheezing who were treated with an antibiotic in the first year of life were more than twice as likely as untreated children to experience severe wheeze or asthma exacerbations and be hospitalized for asthma.
Of particular interest was that these children also showed significantly lower induction of cytokines, which are the bodies' key defense against virus infections such as the common cold. However, no differences were noted in antibacterial responses.
The researchers also identified two genes in the 17q21 region that were associated with an increased risk of early life antibiotic prescription.
According to lead author Professor Adnan Custovic from the University of Manchester in the UK, "We speculate that hidden factors which increase the likelihood of both antibiotic prescription in early life and subsequent asthma are an increased susceptibility to viral infections due to impaired antiviral immunity and genetic variants on 17q21. However, further studies will be needed to confirm that the impaired immunity was present at the time of the early childhood respiratory symptoms and predated antibiotic prescribing rather than as a consequence of the antibiotics."
Commenting on the study, Professor Julian Crane and Dr Kristin Wickens from Otago University in New Zealand discuss whether we can be sure that early antibiotic use is not linked with the development of asthma, writing that, "A randomized trial is required to settle the conflicting evidence. Very similar issues apply to paracetamol and its association with asthma. But, is a randomized trial of antibiotics feasible? This trial would need to be large and would be ethically difficult, but perhaps not impossible, at least in terms of restricted versus usual antibiotic prescriptions. In view of the concerns over the rapidly waning efficacy of antibiotics, partly from overprescription, the fact that many are prescribed for disorders that they cannot benefit and the disquiet many parents express about overmedicating their children, the proposal for a randomized control trial is perhaps worthy of some consideration."
- Aida Semic-Jusufagic, Danielle Belgrave, Andrew Pickles, Aurica G Telcian, Eteri Bakhsoliani, Annemarie Sykes, Angela Simpson, Sebastian L Johnston, Adnan Custovic. Assessing the association of early life antibiotic prescription with asthma exacerbations, impaired antiviral immunity, and genetic variants in 17q21: a population-based birth cohort study. The Lancet Respiratory Medicine, 2014; DOI: 10.1016/S2213-2600(14)70096-7
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