Antibiotics in Early Childhood Have Small Effect on BMI Milestones

Exposure to antibiotics in early childhood had little effect on attaining body mass index (BMI) milestones and should not be a significant factor in pediatrician’ prescribing decisions, according to investigators who followed a large cohort receiving antibiotics within 48 months of birth.

"The small associations with BMI trajectory patterns after antibiotic exposure would likely have minimal clinical importance and should not affect the individual decision to prescribe antibiotics," Izzuddin Aris, PhD, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, and lead author of the study, commented to Contagion.

"Nevertheless, it remains unclear whether antibiotics causally influence obesity development in humans and whether particular antibiotic types are especially detrimental," Aris pointed out."From a public health perspective, excessive antibiotic exposure during early life remains a valid concern and antibiotic stewardship is an urgent priority, regardless of its potential role in obesity prevention."

The possibility that antibiotic use may be a modifiable risk factor for later childhood obesity has emerged from studies finding a small dose-response association with antibiotic exposure. It has been hypothesized that antibiotic effects on gut microflora result in altered energy metabolism and homeostasis, according to Aris and colleagues.

While previous studies have examined antibiotics and weight outcomes, it remains to be determined if, and how the age of exposure factors into an association, Aris remarked."Most of these studies have primarily focused on antibiotic exposures before 24 months of age, and few studies have investigated whether antibiotic after 24 months of age is associated with greater weight or alters longitudinal BMI trajectory patterns,"he said.

Aris and colleagues accessed the PCORnet, a collaborative data network from approximately 75 large health systems in the US, to identify a cohort of 183,444 children, 78.1% of whom had received antibiotics before 48 months of age, and whose records of height and weight allowed for estimable BMI peak and rebound in multiple age brackets, from 0-5 months, to 60-131 months.

"We chose to examine BMI growth milestones—BMI peak and rebound—as our outcomes because of its clinical significance and importance," Aris explained."An altered timing of these growth milestones—later age at BMI peak in infancy and earlier age at BMI rebound in early childhood—has been associated with excessive weight gain and cardiometabolic risk in later childhood."

The investigators report that exposure to any antibiotics at 0 to 5 months of age compared to no exposure was associated with later age (β coefficient, 0.05 months [95% CI, 0.02-0.08 months]) and higher BMI (β coefficient, 0.09 [95% CI, 0.07- 0.11]) at peak.Exposure to any antibiotics at 0 to 47 months of age compared to no exposure was associated with an earlier age (-0.60 months [95% CI, -0.81 to -0.39 months]) and higher BMI at rebound (β coefficient, 0.02 [95%CI, 0.01=0.03]).

Aris and colleagues found the strongest association for children with at least 4 episodes of antibiotic exposure.The association was stronger for those exposed to antibiotics at 24 to 35 months of age or 36 to 47 months of age than for those exposed at 0 to 5 months or 6 to 11 months of age.

"Effect estimates for associations with age at BMI rebound were larger for antibiotic exposure periods closer to the trajectory milestone," the investigators noted."The type of antibiotics—broad or narrow spectrum—did not substantively affect the pattern of the observed associations."

The apparently stronger association with antibiotic exposure closer to the trajectory milestone suggests to Aris that there may be "a short-term effect of antibiotic exposure on weight in infancy and childhood.

"This effect may not be sustained over the long term." he posited.