Antibiotic Use in Infancy May Play Role in Obesity

While it is easy to blame the childhood obesity epidemic on too many french fries and video games, it is likely that multiple factors such as genetics and environment also contribute to excessive weight gain. A retrospective study based on data from The Children’s Hospital of Philadelphia’s electronic health records identified another significant risk factor that may influence how tendencies toward obesity develop during infancy.

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.

They 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.

“As pediatricians, we’re interested in whether there is anything happening early in life that resets this ‘thermostat’ and has a long-term effect on how your body regulates its weight,” said L. Charles Bailey, MD, PhD, lead author of the study that appeared online Sept. 29 in JAMA Pediatrics. “The thought is that the microbiome may be critically dependent on what is going on during infancy.”

Dr. Bailey and colleagues observed an increased risk of obesity with greater antibiotic use, particularly for children with four or more exposures to broad-spectrum antibiotics in early childhood. 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 network of primary care practices affiliated with CHOP. They assessed the relationships between antibiotic prescription and related diagnoses before age 24 months and the development of obesity in the following three years.

“What this study is showing is that we can detect a connection between the antibiotics that you may have received as an infant and what your weight is going to look like later in childhood,” Dr. Bailey said, adding that it is important to note that the study does not directly examine cause and effect.

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.

“What we think we’re seeing here with these associations is that the more we choose to use narrow-spectrum antibiotics, the less likely it may be that we’re doing something that will affect a patient’s risk of obesity later on,” Dr. Bailey said.

One of the study’s advantages is that the researchers capitalized on CHOP’s wealth of information captured during regular medical care for a large group of patients without compromising individuals’ privacy. While the study did not assess children’s activity levels, dietary habits, family structure, or socioeconomics, the researchers’ conclusions were similar to those from a previous study that evaluated those factors and also found a connection between antibiotics in early childhood and higher risk of obesity.

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. The Children’s Hospital of Philadelphia’s Healthy Weight Program has a study underway that is following the changes of the microbiota of infants through the first year of life to see if it correlates with weight gain. As part of the study, they will track any babies who are prescribed antibiotics, in order to identify fluctuations in their microbial profiles.

Such research projects will add up to help give clinicians practical guidance on how to address the complexities of obesity.

“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,” Dr. Bailey said. “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.”

Christopher Forrest, MD, PhD; Peixin Zhang, PhD; Thomas M. Richards, MS; Alice Livshits, BS; and Patricia DeRusso, MD, MS, contributed to the article published in JAMA Pediatrics. The American Beverage Foundation for a Healthy America provided an unrestricted donation to support this Healthy Weight Program research study.