Carol Chelimo, PhD, and Cameron Grand, MbChB, PhD, on the Association Between Early-Life Antibiotic Exposure and BMI and Obesity

The findings from a recent study published in JAMA Network Open suggest that early, repeated exposure to antibiotics is associated with higher body mass index (BMI) and likelihood of obesity.

For their study, the researchers analysed data from 5128 singleton children who were born during 2009 and 2010 and enrolled in the Growing Up in New Zealand prospective cohort study. Weight and height were measured at age 54 months, and data from a national database of community pharmacy prescribing was obtained.

Overall, 4886 (95%) of the participants had been prescribed antibiotics by age 48 months, and 437 (9%) had obesity at age 54 months. The researchers found that adjusted mean BMI-for-age z scores increased significantly in participants who received 4-6, 7-9, or more than 9 dispensings by age 48 months. Those children who received more than 9 dispensings also had an increased likelihood of obesity when compared with those participants with no antibiotic exposure.

In addition, those with first antibiotic exposure in the first year of life had higher adjusted mean BMI-for-age z scores than those without exposure, while participants with first exposure after the first year of life did not. Higher BMI was also observed in children whose mothers had 2 or more antibiotic prescriptions during pregnancy compared with no exposure, but this was not associated with overweight or obesity

Consultant360 reached out to authors Carol Chelimo, PhD, and Cameron Grant, MBChB, PhD, for more information about their study.

Dr Chelimo is a research fellow at the Department of Paediatrics: Child & Youth Health at the University of Auckland, and Dr Grant is the head of the Department of Paediatrics: Child & Youth Health at the University of Auckland.

Consultant360: What prompted you to explore the relationship between early-life antibiotic exposure and body mass index, and how did you choose this patient population?

Carol Chelimo and Cameron Grant: New Zealand has the third highest obesity prevalence among Organisation for Economic Co-operation and Development countries. Antibiotics can impact weight by altering gut microbiota, which is vital in the harvesting, storage and expenditure of energy from dietary sources. We used body mass index (BMI) from the

Growing Up in New Zealand study’s 54-month follow-up as this was most representative of preschool aged children. The age cut-off for antibiotic exposure assessment (48 months) ensured that, for all children, the period of exposure assessment preceded their BMI measurement. To our knowledge, this was the first study to explore both pregnancy and early childhood antibiotic exposure in relation to body mass.

C360: The results of your study suggested that repeated antibiotic exposure in early life was linked to higher BMI and an increased likelihood of obesity. How does this finding inform clinical practice?

CC, CG: The association between repeated antibiotic exposure and body mass suggests that repeated antibiotic exposure may be a potentially modifiable risk factor for childhood obesity. The scientific literature suggests that following antibiotic exposure, many children may not be able to have full recovery of microbiota as the duration required to achieve this exceeds the average interval between antibiotic courses (i.e. additional/repeated exposure). Therefore, although antibiotic stewardship programs are primarily designed to address concerns regarding antibiotic resistance, such programs may reduce repeated antibiotic exposure and its contribution in altering the microbiome; consequently, this could result in other benefits besides preventing antibiotic resistance.

C360: How do you think your findings add to the growing evidence of the harms of overprescription of antibiotics?

CC, CG: Compared to previous cohort studies examining the associations between antibiotic exposure and BMI/obesity in children, the main additional strengths of our study are that it: 1) accounted for antibiotic exposure during pregnancy (which was associated with higher BMI but not overweight/obesity); and 2) quantified antibiotic exposure using prescription data (as opposed to parental report or medical records). Findings from this research are consistent with the notion that the gut microbiota is susceptible to disruptions, particularly during infancy, which can occur via infant antibiotic exposure and possibly via maternal antibiotic exposure as infants acquire part of their early life microbiota from mothers.

C360: What knowledge gaps still exist in this area?

CC, CG: The present study and the other published studies examining associations between antibiotic exposure and BMI/obesity have been observational studies, which by design cannot determine causal relationships. It would be unethical to undertake randomized trials on this topic. Effective interventions to reduce overuse or unnecessary use of antibiotics should be implemented. Future research could examine whether interventions such as antibiotic stewardship programs, which are designed to reduce over-prescribing of antibiotics, also reduce early childhood obesity.

—Michael Potts

Reference:

Chelimo C, Camargo CA Jr, Morton SMB, Grant CC. Association of repeated antibiotic exposure up to age 4 years with body mass at age 4.5 years [published online January 3, 2020]. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2019.17577.