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expert reaction to antibiotic and antacid use in early childhood and risk of obesity

Research published in Gut demonstrates that prescriptions for antibiotics and antacid medications in the first 2 years of childhood are associated with the development of childhood obesity.

 

Prof Chris Butler, Professor of Primary Care, Clinical Director of the Primary Care Clinical Trials Unit, University of Oxford, said:

 “While interesting, these findings should be treated with a lot of caution: they cannot be taken as proof that antibiotic use in early childhood causes childhood obesity. The authors have identified an interesting hypothesis or association, but their findings are subject to several potential biases.  For example, less than half of the children in the database were included in the study analyses.  Children had to have valid body mass indices measured after the age of two before they could be included in the analysis. It is likely that children who did not consult often, or where there was no concern about their weight, were less likely to have these measurements taken, leading to a skewed pool of children for analyses.  Help seeking behaviour, family composition, birth order, smoking in the home, breastfeeding, parental depression and anxiety, and many other psycho-social variables could influence both the risk of being prescribed an antibiotic as well as the risk of childhood obesity. So while the authors were able to take military rank, caesarean section, and child sex into account, they were not able to control for the most important factors that drive both antibiotic use as well as childhood obesity.

“However, while it is clear that antibiotics are a lifesaving medicine when used under the right circumstances, and should always be treated with respect, they are often taken when they have little chance of benefiting patients.”

Prof Neil Thomas, Professor of Epidemiology and Research Methods, Institute for Applied Health Research, University of Birmingham, said:

“More generally, there is a growing body of evidence to support the role of the gut flora in health indicators. This is not really surprising given the wide variety of organisms in the gut (with 250-800 times more genes in gut bacteria than we have) and the chemicals they release have a lot of opportunity to come in contact with the large surface area of the gut lining and enter the circulation. There are studies that show the gut flora impacts on the body’s immune system. Some previous studies have shown that the flora can impact on obesity (particularly in rodent models).

“The data from this study are reasonable. It is a large study, although less than half of those potentially eligible were included in the study, and there is no data to show whether those excluded were different from those included and this could have potentially influenced the findings.”

“There are clearly limitations to the data. For instance, they showed lower socioeconomic groups (ie lower ranked soldiers’ children) had a greater risk of obesity. This could be influencing the findings and adjusting for that one variable (rank) would have removed this effect.

“Another confounder would be smoking. We know passive smoking impacts on childhood respiratory disease and is more common in lower socioeconomic groups; these individuals would likely also have a higher use of antibiotics. They have done a simple adjustment for mothers who smoke, but not fathers. Again, this could influence results.

“There are other factors that are more common in such families that might also contribute to the higher levels of adiposity such as a higher use of calorie-dense foods. There is therefore still a clear possibility that this these findings might be due to unmeasured or inaccurately addressed confounders.”

“The association with caesarean section shown in this study is an example of this. A recent RCT has shown no association between emergency caesarean section and obesity, yet did with emergency operations; which may be more likely in obese mothers, who are more likely to have obese children, so it might not be the gut flora that is causing the association. More evidence is needed to support this, but it is a potentially important area that might yield considerable benefits in future.

“The role of acid suppressants is less clear. In the UK these are rarely prescribed to children. They may be due to prescribing for reflux in babies, which is generally not the approach given in the UK. Young children who are given acid suppressants may be different from those who are not in multiple other ways so the association may not be linked to the use of acid suppressants specifically.

“The study is in no way representative of the general population, being conducted in military families. That said, there is no reason to suggest that these families would respond to antibiotic use etc in anyway differently from the general population, so the results found here are likely generalizable.

“This is interesting work and modifying the gut flora is being clinically trialled to treat a range of disorders, but more research in these areas is clearly warranted before we can state that antibiotic prescribing or the gut flora causes obesity.

“It is important to remember that many minor issues we face such as colds do not require and should not be treated with antibiotics. In addition to the major issues of antibiotic resistance we are facing, this study reminds us of other potential harmful consequences of inappropriate use of antibiotics we may not have considered, such as increasing obesity. Time will tell.”

 

Dr Matthew Child, Group Leader, Wellcome Trust & Royal Society Sir Henry Dale Fellow, Imperial College London, said:

 “This is a good retrospective study of a large dataset, with the analyses done rigorously and caveats duly noted. The researchers show an association between the exposure of very young children (0-2 years) to antibiotics and subsequent risk of that child being obese in later life (older than ~3 years). However, the researchers provide no data for specific changes in the gut microbiome as this is a retrospective analysis lacking any hard microbiome data. Therefore, while the hypothesis is sound and interesting, the link to the role of the microbiome cannot be established from this particular study. That said, it adds to a growing body of work linking early use antibiotics and body weight.

“It’s also worth remembering that they are reporting an increased risk of obesity. There are many risk factors and controlling for them to be able to discern cause versus effect is very challenging. It’s interesting to note that the authors find a stronger socioeconomic correlation with obesity than the headline association with antibiotics – “Military rank was evaluated as a proxy for socioeconomic status, and we found that children of lower ranking enlisted service members were more likely to develop obesity”.

 “The authors do not include adjustments for maternal factors – for instance the birth mothers’ weight is known to be associated with the weight of the child, but this is not incorporated into their analyses.

“Also, no attempt is made to address the underlying cause for the antibiotics being prescribed, i.e. a healthy baby will be one that doesn’t need antibiotics, versus the sick child being the one that does. Is the association with obesity the result of imbalance of the gut microbiome driven by antibiotics or in fact related to infections and sickness at a young age?

“Finally, assessment of obesity was made by BMI, and so cannot distinguish between fat mass and fat-free mass – which basically means that the children treated with antibiotics early in life could just be bigger, not fatter.

  

Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

 “This paper is interesting but I would not jump to the conclusion that antibiotics or acid suppressants cause obesity.   Far from it.  It is highly possible that children who are more often prescribed these medications have other lifestyle or social risk factors which increases their risks of obesity, rather than these medications.  For example, infections requiring antibiotics are likely more commonly prescribed in poorer households due to a variety of factors and the link between deprivation and obesity is very strong.   In this paper, they minimally adjusted for such factors so there is a very high probability of residual confounding whereby unmeasured factors, particularly those related to social class and related health behaviour, might explain this link rather than drugs examined.  For this reason, it is very premature to talk about gut microbiome changes as a possible explanation for this apparent link.”

 

Dr Max Davie, Officer for Health Promotion for the Royal College of Paediatrics and Child Health (RCPCH), said:

 “Although this is reported as the largest study of its kind, it has got its limitations – it is observational and so you can’t establish cause, information about the mother’s weight, whether they smoked or had other underlying conditions aren’t available and there are complex links between the environment and obesity that need to be taken into account.  That said, childhood obesity levels in the UK are at crisis point with one in three children overweight or obese by the time they leave primary school. We are also battling antibiotic resistance so any avoidable doses throughout the life-course is beneficial in tackling resistance. We therefore need to acknowledge these findings and would welcome further review.  In the meantime, children who are obese must receive tailored support to help them return to a healthy weight – we therefore call on the Government to ensure specialist obesity services are appropriately funded to prevent obese children today becoming obese adults in future.”

 

‘Antibiotic and acid-suppression medications during early childhood are associated with obesity’ by Christopher Stark et al. was published in Gut at 23:30 UK time on Tuesday 30th October.

 

Declared interests

Prof Naveed Sattar: No conflicts of interest.

No others received.

 

 

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