JMIR Publications

ABSTRACT

Background:

Childhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity.

Objective:

We evaluated the risk of developing obesity among children exposed to antibiotics early in life.

Methods:

An Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases and/or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12 and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, ≥3 prescriptions). Obesity was defined as a BMI z-score >3 for children aged ≤5 years and >2 for children aged >5 years, using the WHO Growth References. The obese incidence rate (IR) per 100 person-year and the relative 95% confidence intervals (95%CIs) were computed by infant sex, area of residence, preschool and school-aged, and area deprivation index, the covariates of interest. A mixed-effect Cox proportional-hazards model was used to estimate the Hazard Ratio (HR) and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months to 14 years of age considering the family pediatricians as a fixed factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results.

Results:

Among 121,540 children identified, 45% were prescribed at least an antibiotic within the first year of life, and 22% were classified as obese during follow-up with an IR of 4.05 cases (95% CI 4.01 to 4.10) x100 person-year. The risk of obesity remained consistent across different timing of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted HR 1.07, 95%CI 1.04 to 1.10; 1.06, 1.03 to 1.09; and 1.07, 1.04 to 1.10, respectively). Increasing the number of antibiotic exposures, the risk of obesity increased significantly (P for trend<.001). The individual-specific-age analysis showed that starting antibiotic therapy very early (between 0-5 months) had the greatest impact (1.12, 1.08 to 1.17) on childhood obesity with respect to what was observed among those who were first prescribed antibiotics after the fifth month of life. These results were consistent across subgroups and sensitivity analyses.

Conclusions:

The results from this large population-based study support the association between early exposure to antibiotics and an increased risk of childhood obesity. This relationship becomes more pronounced as the number of prescriptions increases and as the age-specific at the first prescription of antibiotics decreases.