For decades, farmers have known that the quickest way to fatten up young, healthy livestock is to feed them antibiotics—the drugs will even plump animals on a diet. It’s unclear why the practice, called growth promotion, works. Scientists have a range of hypotheses, including that the drugs may kill off gut microbes that compete for calories or knock back mild infections that would otherwise take energy to fight off. Whatever the answer, one thing is certain: growth promotion spurs drug-resistance in bacteria. And with the rise of infections from such superbugs in people—a major threat to public health—the practice is now squarely discouraged.
Yet, despite the long-held practice in farms, researchers are just beginning to harvest data on whether the drugs have the same effect on human babies in clinics. So far, much of the data—but not all—shows some concerning similarities.
Looking at a population-representative sample of nearly 22,000 children in the United Kingdom, researchers found that giving children three or more courses of antibiotics within the first two years of life modestly increased the likelihood that they would be obese at age four. The study, being published in Gastroenterology, follows several smaller studies that hinted at such a connection, particularly for antibiotics used in the first six months of life.
“Collectively, we’re starting to recognize that maybe there’s more to avoiding antibiotics than just the antibiotic resistance problem,” gastroenterologist Frank Scott, of the University of Colorado-Denver, told Ars. “No doubt that that’s probably the biggest issue facing us right now,” he added. Still, Scott said it’s important to look at these subtler, potentially life-long health effects.
Past studies looking into this issue found similar effects on weight gain in childhood and beyond, but these often relied on parents' recall of how many antibiotics their children took, used much smaller pools of kids, or showed mixed results. Scott and colleagues set out to conduct a cleaner, larger study that relied on comprehensive electronic medical records that followed kids for years.
Of the 21,714 children with complete records in the study, about 64 percent were given antibiotics in the first two years of life. The researchers then adjusted the data for factors known to influence childhood obesity, including maternal and sibling obesity, maternal diabetes, mode of delivery (C-section, for example), socioeconomic status, year and country of birth, and urban dwelling.
At four years old, 5.2 percent of the antibiotic-free kids were obese (as defined by their body mass index). For those who did take antibiotics in their first two years, 6.4 percent were obese.
Overall, exposure to antibiotics in the first two years appeared to up the absolute risk of childhood obesity by 1.2 percent and the relative risk by 25 percent. The likelihood of obesity increased as the number of antibiotic courses increased from one-to-two, to three or more.
The association between the drugs and obesity is modest, Scott notes, but it’s clearly there.
Big fat pills?
The perspective is in stark contrast to views held by researchers who performed a similar study, published in The Journal of the American Medical Association (JAMA). In the study, researchers looked at data on nearly 39,000 children in Pennsylvania, New Jersey, and Delaware, and the team found that antibiotic exposure in the first two years of life led to a statistically significant boost in the rate of weight gain between the ages of two and five. However, that boost is small, the authors noted, only working out to about an additional 150 grams between two and five.
“The statistical significance likely reflects the robust statistical power afforded by the sample size instead of a clinically meaningful difference,” the author concluded. (Ars reached out to the lead author of the study, but he was unavailable for an interview.)
Additionally, the authors also noted that antibiotics given in the first six months of life didn’t affect weight gain despite other studies finding a connection. In all, these authors concluded: “There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.”
While the authors came to a different conclusion than Scott and his colleagues, Scott thinks that the data sets don’t conflict. And the two studies had a number of design differences, Scott noted. Scott’s study focused on BMI, since that is currently used in the clinical definition of obesity, while the JAMA looked at the rate of weight gain. The JAMA article also looked at different factors that may influence weight gain in children, such as demographics, but it didn’t look at things like maternal obesity specifically, for instance.
It’s a common problem, according to nutrition researcher Matthew Gillman at Harvard. Generally, the studies on the subject “not only have different findings, but they answer different questions,” he told Ars. Some compare zero versus any antibiotics, others breadth of exposure, others timing of antibiotics, and others number of courses. “Some have combined a couple of these attributes, but there is a need for a more comprehensive approach,” he emphasized.
Gillman, with colleagues, currently has a nearly $4.5 million grant to conduct what may be the biggest study of its kind into the subject—following 1.6 million children for 10 years through electronic medical records, noting details about the number, type, and duration of antibiotic use as well as how it links to obesity.
Scott, who is familiar with the project, says he’s excited to see the data. He notes that no matter what, none of the findings should be used to keep children who are clearly in need of antibiotics from getting the drugs. “When appropriate, antibiotics are still lifesaving,” he cautions. “But there’s still fairly rampant inappropriate use of antibiotics.” Perhaps, in those cases, the new data should give parents and doctors pause.
Gastroenterology, 2015. DOI:10.1053/j.gastro.2016.03.006