Antibiotics are valuable, potentially life-saving tools that have significantly reduced human morbidity and mortality. Unfortunately, antibiotics may also have unintended consequences from their off-target effects that may increase the risk of many long-term conditions. Now, a study published in JAMA Pediatrics finds that the use of broad-spectrum antibiotics in children under 2 years old may increase the risk of obesity in early childhood.
Currently, 1 in 3 children and adolescents in the US are either overweight or obese. What’s more, youth obesity is not simply a consequence of unhealthy behaviors in adolescence – by the age of 24 months, 10% of children are obese.
Early childhood obesity is thought to be influenced by a number of factors, including maternal pre-pregnancy body mass index (BMI), nutritional intake, physical activity, sleep duration and screen time. However, researchers have now begun to investigate the influence that colonies of microbes residing in the gut might have on early childhood obesity.
From the moment we are born, the colonization of our intestines by a variety of bacteria begins. Recent evidence has suggested that different intestinal bacteria may differently affect the growth of the host.
Recent studies have also shown that antibiotic exposure can influence the diversity and composition of the gut-dwelling microbes. Therefore, the researchers behind the new study – from the Children’s Hospital of Philadelphia, PA – wanted to investigate what influence antibiotic use might have on early childhood obesity.
Children prescribed antibiotics on four or more occasions by 24 months have a higher risk of obesity
The team examined electronic health records from a network of primary care clinics, spanning the period 2001-13. In total, the analysis included 64,580 children who had annual visits at a clinic at the ages of 0-23 months, as well as one or more visits at ages 24-58 months. The study followed the children up until the age of 5 years old.
The analysis revealed an increase in the prevalence of overweight/obesity in the children across the study period:
- At 2 years of age, 10% of the children were obese and 23% were overweight
- At 3 years – 14% obesity, 30% overweight
- At 4 years – 15% obesity, 33% overweight.
More than two-thirds (69%) of the children had received antibiotics before the age of 24 months, with an average of 2.3 antibiotic episodes per child. Examining obesity rates among these children, the researchers found that exposure to antibiotics was linked with obesity risk.
Specifically, children who got broad-spectrum antibiotics in their first two years were about 11% more likely to be obese between ages 2 and 5 than were those who got no such drugs. Babies who had four or more courses of any antibiotics in the first two years were also 11% more likely to be obese in early childhood than those who’d had fewer exposures to antibiotics.
But among children who had four or more antibiotics prescriptions, including at least one wide-spectrum antibiotic, the risk of obesity rose to 17%. And the earlier a baby’s exposure to wide-spectrum antibiotic medications, the more likely he or she was, on average, to be obese between age 3 and 5.
Complex causes of obesity
The new findings add to a growing body of evidence indicating that the mix of bacteria in the gut plays a potent role in obesity. Numerous studies have shown that the diversity of the gut’s population of bacteria appears to confer protection from obesity, while an impoverished microbiotic environment in the gut has been linked to higher risk.
In this latest study, the researchers report no association between obesity and narrow-spectrum antibiotics, which are prescribed to kill only a narrow range of bacteria; the obesity risk was associated only with broad-spectrum antibiotics.
“Because obesity is a multifactorial condition, reducing prevalence depends on identifying and managing multiple risk factors whose individual effects may be small but modifiable,” the authors write. “Our results suggest that the use of broad-spectrum outpatient antibiotics before age 24 months may be one such factor.”
Broad-spectrum antibiotics — including amoxicillin, tetracycline, streptomycin, moxifloxacin and ciprofloxacin — are intended for treatment of major systemic infections, in cases where the bacteria causing the illness has not been identified, or where a patient is under attack by a strain of bacteria resistant to standard antibiotics. While they can be highly effective, their antibiotic action is indiscriminate, and beneficial bacteria can be killed off as collateral damage.
“This [study] provides additional support for the adoption of treatment guidelines for common pediatric conditions that emphasize limiting antibiotic use to cases where efficacy is well demonstrated and preferring narrow-spectrum drugs in the absence of specific indications for broader coverage,” the authors add.
The findings also suggest that very early childhood may be a pivotal period in creating a rich and complex mix of microbiota in the gut, the researchers say.
“Because the first 24 months of life comprise major shifts in diet, growth and the establishment of intestinal microbiome, this interval may comprise a window of particular susceptibility to antibiotic effects,” the authors write. They went on to speculate that by knocking off-course the normal development of bacterial populations inside a child’s gut, the repeated use of antibiotics may alter his or her long-term ability to control weight gain.
Furthermore, the research underscores the fact that, for some, obesity may have origins in decisions made long before food preferences, eating habits, and lifestyle decisions are developed or established. It also demonstrates the complexity of obesity, showing that maintaining a healthy body weight is not as simple as ‘moving more, eating less.’