January 22, 2020

expert reaction to two studies looking at antibiotics in young children and while in the womb, and childhood obesity

Two studies, published in JAMA Network Open, report on the impact of antibiotics on the relationship between antibiotic exposure in early development and obesity later in life. 

Prof Neena Modi, Professor of Neonatal Medicine, Imperial College London, said:

“The question posed in these papers is whether antibiotic exposure early in human development increases the risk of later obesity.  The two reported studies – involving analyses of large pre-existing datasets – found an association between early antibiotic exposure and later obesity.  In one study the association disappeared when twins were analysed.  Twins have similar environmental exposures and lifestyles, suggesting that antibiotics are only indirectly related to obesity and do not cause the condition.

“However there is good evidence that antibiotics increase the weight of farm animals.  The mechanism is believed to be through alteration in intestinal bacteria leading to greater absorption of nutrients.

“The question of whether early antibiotics contribute to the growing epidemic childhood obesity therefore remains open.  Further careful studies using sophisticated analyses are required to disentangle whether antibiotics truly cause increased weight in humans, or are only indirectly associated with obesity.  It would also be useful to study very heavily antibiotic exposed groups such as premature babies as the effect may be more marked and hence easier to detect.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“These studies show a small association between antibiotic exposure in mothers and their children and subsequent obesity.  It is not possible with the design of these studies to show whether it is the antibiotics themselves or some other factor that causes the obesity.

“For example, a child being ill (and hence being prescribed an antibiotic) may reduce the capacity for regular exercise while not reducing the access to food.

“The within-family sibling study removes some of the factors that are associated with obesity and so that analysis, which “showed no associations between antibiotic exposure and obesity” is more reliable than the other analyses.  While this analysis may also have biases, the overall problem remains of whether it is the illness or the prescribing of the antibiotic that leads to obesity.  The within-sibling study, while subject to possible unknown bias, has removed some known bias and so suggests that it is definitely not the antibiotic exposure itself that is causing the childhood obesity.  Even if the results did show a causal effect, it is very small indeed and epidemiological studies with such small effects are vulnerable to other explanations for the association found.

“There is no doubt that for other reasons, especially antibiotic resistance, prescribing of antibiotics should be carefully controlled, so while there is no reason for anxiety, the studies should not be used to encourage antibiotic prescribing.”

Prof Alastair Sutcliffe, Professor of General Paediatrics, UCL, said:

“Obesity is said to be a normal physiological reaction to an abnormal environment but when does that environment start?

“A new Zealand group of epidemiologists have attempted to investigate whether antibiotic exposure antenatally and in early childhood is associated with childhood obesity.  In both studies they use the whole birth population of New Zealand and link it to their national prescribing dataset where records of antibiotic usage are recorded.  This is important as both datasets are likely to be reliable and complete.

“And the answer is yes.  In the paper describing singleton (single children) there appears to be a link between antibiotic use and obesity, with more use being associated with more fat.  But where is the rub?  In the sibling analyses (sibling and twin siblings) there is no such link.  The observers speculate that the reason why one sibling is obese and the other is not, is because of microbiome transfer between the non-obese healthy sibling (or twin) and the obese sibling.  (Children are not sterile and interact normally and naturally in households).  This makes sense as we know from previous research that the antibiotics effect the maternal microbiome during pregnancy and the infant young child microbiome after delivery.

“Antibiotics can be lifesaving but the general view about their prescribing is that less is more, and this set of reports add gist to the mill.

“Where is the study weak?  There is a simple lack of data not allowed for in the analyses – BMI in the women (mothers) during pregnancy this is a key missing confounder.

“Overall this pair of papers is one more brick in the wall around the importance of having the right microbiome at birth and going forwards.  We can expect more research to emerge in this exciting area of discovery.”

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“Antibiotics have been used to help fatten farm animals for a long time and experiments with mice have shown a similar effect, but the evidence for the same thing happening in humans is mixed.  It’s well established from the evidence-base in general that taking antibiotics alters the makeup of the bacteria in our guts, which is presumed to play a role in the potential for weight gain.

“These two new studies, on the face of things, have differing conclusions with the larger study showing no link between taking antibiotics in children up to the age of 4 and obesity.  However the smaller study, which does show such an association, is more focussed and consequently they’ve been able to show that there is an association between a child’s weight at the age of 4 and whether the child was exposed during its first year of life.

“While these robust studies are important contributions to understanding the obesity epidemic, they don’t go all the way to proving an effect, so it’s important that future studies are carried out to confirm these findings and to gain a better understanding of the finer effects that antibiotics have on the population of bacteria in our guts and the what impact this has on obesity.”

Paper 1: ‘Associations of prenatal and childhood antibiotic exposure with obesity at age 4 years’ by Karen S.W. Leong et al. was published in JAMA Network Open at 16:00 UK time on Wednesday 22 January 2020.

DOI: 10.1001/jamanetworkopen.2019.19681

Paper 2: ‘Association of repeated antibiotic exposure up to age 4 years with body mass at age 4.5 years’ by Carol Chelimo et al. was published in JAMA Network Open at 16:00 UK time on Wednesday 22 January 2020.

DOI: 10.1001/jamanetworkopen.2019.17577

Declared interests

Prof Neena Modi: “No disclosures in relation to these papers”

Prof Stephen Evans: “I have no conflicts of interest in relation to these papers.”

Prof Alastair Sutcliffe: “I have no conflict of interest with these papers.”

Dr Simon Clarke: “Absolutely no conflicts to declare.”