Early antibiotics and childhood obesity: link remains uncertain

By Will Boggs MD

NEW YORK (Reuters Health) - Are multiple courses of antibiotics in the first two years of life linked with an increased risk of childhood obesity? Two different studies found contrasting results.

In the March 19 online issue of Gastroenterology, Dr. Frank I. Scott from the University of Colorado Denver, Aurora, and colleagues examined the association between antibiotic use before age two and obesity, as determined by body mass index (BMI) z-scores, in 21,714 UK children.

At age four, obesity rates were 5.2% in children without antibiotic exposure and 6.4% in those with antibiotic exposure. Any prescription antibiotic use in the first year of life was associated with a 21% increased risk of obesity.

After adjusting for other factors, the risk of obesity was 41% higher among children receiving three or more antibiotic prescriptions and 47% higher among those receiving more than five prescriptions, compared with no antibiotic exposure.

The association between antibiotic use and childhood obesity was evident only for anti-anaerobic antibiotics and not for antibiotics without anti-anaerobic activity or for antifungal agents.

"While early antibiotic use has been associated with a number of rare long-term health consequences, these data link antibiotics to one of the most important and growing public health problems worldwide," the researchers concluded.

But Dr. Jeffrey S. Gerber from Children's Hospital of Philadelphia, Pennsylvania, and colleagues reached different conclusions in their March 22/29 JAMA report.

They evaluated the association between antibiotic exposure in the first 24 months of life and growth trajectory up to age seven in 38,614 children, including 92 twins discordant on antibiotic exposure in their first six months of life.

"Our feeling is that growth trajectory is less prone to finding spurious associations," Dr. Gerber told Reuters Health by email.

Fourteen percent of children were exposed to antibiotics in the first six months, and by 24 months of age, two-thirds of children had been exposed to any antibiotic.

There was no significant association between antibiotic use in the first six months of life and the rate of change of weight to age five. Exposure to any antibiotic in the first 24 months was associated with greater weight gain between ages two and five, but the average difference amounted to only 0.15 kg.

In sensitivity analyses, the maximum weight gain difference attributable to antibiotic exposure was 0.26 kg.

In the comparison of 46 twin pairs, there was no association between antibiotic exposure in the first six or 24 months and subsequent weight gain.

"These findings do not support a clinically meaningful association of early-life antibiotic use with childhood weight gain," this group concluded.

"I'm not sure that there is a big message here for clinicians (who should always prescribe antibiotics judiciously for reasons other than the fear of obesity)," Dr. Gerber said.

Dr. Leonardo Trasande, from NYU School of Medicine, New York, who has also investigated links between antibiotic use and obesity, told Reuters Health by email, "These papers do very little to resolve the basic question as to the contribution of antibiotics to childhood obesity. There are still substantial and better studies in the laboratory that support the effect."

"Compared to past studies, these two have substantial flaws," he said. "In particular, the absence of prenatal data in both studies speaks to the challenges of big data - often, big data sets have huge holes. Missing breastfeeding data, and data about prenatal risks (smoking, just to name one) known to influence postnatal growth were missing. We need better designed studies that capture these factors and interrogate mechanism (studying the microbiome as an intermediate factor), such as through the Environmental Influences on Child Health Outcomes program."

Dr. Anita Kozyrskyj from the University of Alberta, Edmonton, Alberta, Canada, another expert in the link between antibiotic use and childhood obesity, told Reuters Health by email, "Note that the U.S. study measured weight gain, while the UK study implemented a more standard (and accepted) measure of overweight based on BMI calculated for weight and height (or length for infants)."

"In both studies, antibiotic use was determined from health care records, which is a more accurate assessment than parent report," she said. "The UK study adjusted for a variety of covariates (i.e., family history of overweight), none of which change the reported risk for antibiotic use."

Dr. Kozyrskyj concluded, "My take-home message is that treatment of infants with multiple courses of antibiotics at a time when their gut microbiome is being developed places them at increased risk of becoming overweight."

Dr. Antti Saari, from the University of Eastern Finland, Kuopio, recently found an association between early antibiotic exposure and early life overweight. He told Reuters Health by email, "I was quite surprised in results that were reported in JAMA. According to the research evidence prior to this study, the association between early antibiotic exposure and weight gain was pretty evident. Thus, I found their findings interesting."

"In spite of the findings of the JAMA paper, antibiotics should be used judiciously in infants, but we need more research in this field," Dr. Saari concluded.

Dr. Scott did not respond to a request for comments.

The National Institutes of Health supported the first study; three coauthors reported disclosures. The authors of the second story reported no funding or disclosures.

SOURCES: http://bit.ly/1U7USb4

Gastroenterology 2016.

http://bit.ly/22vWvnP

JAMA 2016.

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