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Early-life antibiotic use associated with childhood BMI

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January 30, 2017

Lifetime and first-year antibiotic use in children is associated with BMI at age 3 years, whereas prenatal antibiotic use is not, according to an analysis of more than 8,000 mother–child pairs.

“Our finding of an association between antibiotic use in the first year of life and child BMI is consistent with several past studies, and so this period of time may very well represent a critical exposure period,” Melissa N. Poulsen, PhD, MPH, postdoctoral fellow at the Johns Hopkins Bloomberg School of Public Health, told Endocrine Today. “However, we also found strong associations between cumulative antibiotic use through age 3 years and child BMI, which highlights the potential risk associated with multiple antibiotic exposures in childhood.”

Poulsen and colleagues analyzed electronic health records from 8,793 mothers and singleton children delivered at Geisinger Clinic in Pennsylvania between 2006 and 2012. Researchers assessed prenatal and childhood antibiotic orders from medication files for children through age 3 years, and used linear mixed-effects regression models to evaluate the associations of prenatal and childhood antibiotic use with child BMI z score.

Among mothers in the cohort, 60.4% had at least one antibiotic order during pregnancy; among children, 52.6% had at least one antibiotic order in their first year of life. By age 3 years, 82.2% of children had at least one antibiotic order.

Children of mothers who had three or more prenatal antibiotic orders had higher BMI z scores vs. children of mothers with no antibiotic orders, but results did not persist after adjusting for race, medical assistance for the mother, smoking status, parity and prepregnancy BMI.

After adjusting for prenatal antibiotics, children in the three highest categories of lifetime antibiotic orders had higher BMI z scores at age 3 years vs. children with no orders (P for trend < .001). In addition, children with three antibiotic orders during the first year of life had a higher BMI z score at age 3 years vs. children with no orders (beta = 0.104; 95% CI, 0.038-0.17), as did children with two antibiotic orders (beta = 0.088; 95% CI, 0.017-0.16) or one order (beta = 0.021; 95% CI, –0.038 to 0.081). Results persisted after excluding children with low birth weight from both prenatal and child lifetime antibiotic models, according to researchers.

“Strong associations between lifetime antibiotic orders and child BMI highlight the potential risk associated with cumulative exposure to antibiotics in childhood,” the researchers wrote. “By avoiding use of broad-spectrum antibiotics when feasible, limiting repeated antibiotic exposure, eliminating antibiotic use in cases that lack evidence of efficacy and recognizing the role of cumulative antibiotic exposure in weight gain throughout childhood, this common, population-wide exposure presents a modifiable factor for reducing obesity risk.” by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
De-Kun Li
De-Kun Li
In the current Obesity study, antibiotic users were compared with a control group of non-antibiotic users.   
This is an issue we discussed in a recent article in The Lancet Diabetes & Endocrinology, titled “Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study.” That is, what is the correct comparison group to use when attributing the risk of childhood obesity to antibiotic use?
Antibiotic users usually have both underlying infections (the cause for the prescription of antibiotics) and antibiotics exposure. The controls in this study, on the other hand, likely had neither an infection nor antibiotics exposure. Therefore, the observed association likely reflects the combined effects of underlying infections and antibiotic use, not just the effect of antibiotic use. In order to examine the true effect of antibiotics, one would need to compare antibiotic users to those with the same underlying infections (and similar severity as well), but who did not receive antibiotics (ie, untreated infection controls). When the correct comparison is used, as our study showed, the underlying infection, rather than antibiotics, was associated with increased risk of childhood obesity.

De-Kun Li, MD, PhD
Senior Research Scientist, Kaiser Foundation Research Institute, Oakland, CA
Disclosure: Li reports no relevant financial disclosures.