Prenatal and Early-Life Anti-Infectives and Obesity at Age 7 Years

To examine associations of prenatal and early-life anti-infective exposures with obesity at 7 years.

In this nationwide, registry-based, prevalence study, we included all children with an anthropometric assessment at age 7 years from the Children's Database and linked their data with Danish population-based registries from 2001 to 2018. We defined exposure to anti-infectives (anti-bacterials, anti-virals, and anti-fungals) by outpatient dispensings or by infection diagnoses at hospital encounters. The earliest date defined the exposure timing category: prenatal (-9 months- < 0 months), infancy (0- < 2 years), and early childhood (2- < 5 years). We computed prevalence ratios (aPRs) for associations of anti-infective exposure with obesity prevalence at 7 years of age, adjusting for maternal and perinatal factors.

We included 460 363 children (51% boys). Prevalence of obesity at 7 years of age was 38% higher (aPR = 1.38, 95% confidence interval (CI): 1.27-1.49) among children exposed to any anti-infective, 21% higher (aPR = 1.21, 95% CI: 1.12-1.31) among children exposed to anti-infectives in infancy, and 14% higher (aPR = 1.14, 95% CI: 1.03-1.26) among children exposed to anti-infectives in early childhood. Exposure to anti-bacterials was associated with obesity in a similar time-dependent pattern [prenatal: aPR = 1.39 (95% CI: 1.29-1.50), infancy: aPR = 1.21 (95% CI: 1.12-1.30), and early childhood: aPR = 1.14 (95% CI: 1.03-1.25)]. For anti-virals and anti-fungals, exposure during infancy and early childhood was associated with larger aPRs than prenatal exposure. Furthermore, obesity prevalence increased monotonically with number of the anti-infective prescriptions.

These findings suggest that prenatal and early-life exposure to anti-infectives increases the risk of childhood obesity and that the magnitude of the associations depends on anti-infective type, timing, and dose.