In a large nationwide study, no association was found between prenatal or early childhood exposure to antibiotics and obesity at 4 years of age in fixed-effects analyses of sibling and twin data, according to study results published in JAMA Network Open.

Studies have shown that antibiotics are associated with obesity in mice, but studies in humans have had conflicting results with regard to this association. There is some concern that previous research has not taken genetic and environmental factors into account; studies that did examine siblings or twins to account for possible confounders reported no associations between antibiotic exposure and childhood obesity, though the cohorts were small.

Cross-sectional national data from 150,699 children in New Zealand were used to analyze the association of exposure to antibiotics during pregnancy or early childhood with childhood obesity. In New Zealand, preschool-aged children are screened through a program called B4 School Check and their anonymized data are made available for research purposes. Prenatal antibiotic exposure was measured via pharmaceutical records of the mothers. The number of courses of antibiotics dispensed during each trimester, as well as the 3 months before conception, was noted. Postnatal antibiotic exposure data until 2 years of age were also collected.

Height and weight of the children were measured by registered nurses or nurse practitioners at age 4 or 5 years. Children with a body mass index (BMI) z score at or above the 95th percentile were classified as children with obesity.


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Nearly all the children in the study were singleton births (97.0%) of normal to high birth weight (94.2%). When BMI was calculated at age 4 or 5 years, 15.8% of children were obese (mean BMI z score, 0.68±1.05). In total, 35.7% of mothers were dispensed ≥1 course of antibiotics during pregnancy and 1.2% were dispensed ≥5 courses. In the postnatal period, 82.3% of children were dispensed ≥1 course of antibiotics before 2 years of age, 30.8% were dispensed ≥5 courses, and 8.4% were dispensed >10 courses.

The number of courses of antibiotics dispensed during (adjusted odds ratio [aOR], 1.06; 95% CI, 1.04-1.07) and after pregnancy (aOR, 1.04; 95% CI, 1.04-1.05) were independently associated with increasing prevalence of obesity at 4 years of age.

Analyses of 30,696 siblings and 4188 twins showed similar associations between antibiotic exposure and obesity (aORs, 1.04 [95% CI, 1.03-1.05] and 1.05 [95% CI, 1.02-1.09], respectively) as in the whole population (aOR, 1.04; 95% CI, 1.04-1.05). However, fixed-effect analyses of 6249 siblings and 522 twins with discordant outcomes were used to assess unmeasured family-level confounders and showed no statistically significant associations between antibiotic exposure and the odds of obesity for both maternal (aOR, 0.95; 95% CI, 0.90-1.00) and child’s (aOR, 1.02; 95% CI, 0.99-1.04) exposure in the sibling cohort and child’s exposure in the twin cohort (aOR, 0.91; 95% CI, 0.81-1.02).

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Taken together, these findings indicated that antibiotics are unlikely to be a major contributor to childhood obesity. Though the covariate-controlled analyses of siblings and twins showed similar magnitudes of associations between antibiotic exposure and obesity, the null findings in the fixed-effects analyses indicated that there may be unmeasured confounding factors that affect associations otherwise attributed to antibiotic exposure in analyses that do not account for family-level factors. Further research is needed to determine this unknown confounding.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Leong KSW, McLay J, Derraik JGB, et al. Associations of prenatal and childhood antibiotic exposure with obesity at age 4 years. JAMA Netw Open. 2020;3(1):e1919681.