Antibiotic exposure in infancy linked to childhood obesity

Repeated exposure to broad-spectrum antibiotics in the first two years of life is associated with early childhood obesity, say researchers from The Children's Hospital of Philadelphia in a retrospective study based on data from electronic health records from the extensive CHOP Care Network.

The researchers found that children with four or more exposures to broad spectrum antibiotics during infancy were particularly more likely to be at risk for obesity. The study, published online September 29, 2014 in JAMA Pediatrics, did not directly examine cause and effect, said Charles Bailey, M.D. Ph.D. lead author of the study, but he added, "as pediatricians, we're interested in whether events that happen early in life might reset the baseline and have a long-term effect on how the body regulates weight."

The researchers were intrigued by the emerging idea that the microbial population that begins to colonize in infants' intestines shortly after birth, known as the microbiome, plays an important role in establishing energy metabolism. Previous studies have shown that antibiotic exposure influences the microbiome's diversity and composition. "The thought is that the microbiome may be critically dependent on what is going on during infancy," Bailey added.

The study team analyzed electronic health records from 2001 to 2013 of 64,580 children with annual visits at ages 0 to 23 months, as well as one or more visits at ages 24 to 59 months within the CHOP Care Network. They assessed the relationships between antibiotic prescription and related diagnoses before age 24 months and the development of obesity in the following three years.

The investigators saw the association with broad-spectrum drugs, but they reported no significant association between obesity and narrow-spectrum drugs. For this study, they classified first-line therapy for common pediatric infections, such as penicillin and amoxicillin, as narrow-spectrum. They considered broad-spectrum antibiotics to include those recommended in current guidelines as second-line therapy.

"Treating obesity is going to be a matter of finding the collection of things that together have a major effect, even though each alone has only a small effect," said Patricia DeRusso, M.D., director of the Healthy Weight Program and vice president of Medical Staff Affairs at Children's Hospital who was the senior author of the study. "Part of what we are exploring in this study is one of those factors that we can possibly modify in the way we take care of kids and make it better."

Future investigations are needed involving multiple large pediatric health systems that will take a broader look at several populations and how adopting guidelines that accentuate the use of narrow-spectrum antibiotics might affect patients' risk of obesity, Dr. Bailey said. In addition to supporting this type of research locally, CHOP is also a key contributor to networks such as PEDSnet that link many children's hospitals to make more effective clinical research possible. Researchers also are looking at ways the microbial communities living in infants' intestines are swayed by dietary and environmental factors.

Childhood obesity has more than doubled in children over the past 30 years, according to the Centers for Disease Control and Prevention. Many will remain obese into adulthood and be susceptible to heart disease, type 2 diabetes, stroke, several types of cancer, and osteoarthritis. Medical researchers at CHOP want to identify ways to intervene as early as possible, in order to avert the lifetime of medical, developmental, and social problems associated with obesity.

"Association of Antibiotics in Infancy With Early Childhood Obesity" JAMA Pediatrics, published online on September 29, 2014 doi:10.1001/jamapediatrics.2014.1539