Association of Infant Antibiotic Exposure With Childhood Health Outcomes

Abstract

Objective: To investigate the extent to which antibiotic exposure in the first 2 years of life is associated with the risk of immunological, metabolic, and neurobehavioral health conditions with childhood onset.

Patients and methods: In this population-based cohort study, we identified all children born in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2011, through the Rochester Epidemiology Project medical records-linkage system. Demographic characteristics, antibiotic prescriptions, and diagnostic codes through June 30, 2017, were retrieved using the Rochester Epidemiology Project infrastructure. Time-to-event analysis was performed to assess the impact of antibiotic exposure on the risk of several adverse health conditions.

Results: This study included 14,572 children (7026 girls and 7546 boys), of whom 70% (10,220) received at least 1 antibiotic prescription during the first 2 years of life. Early antibiotic exposure was associated with an increased risk of childhood-onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, and attention deficit hyperactivity disorder (hazard ratios ranging from 1.20 to 2.89; P<.05 for all). The associations were influenced by the number, type, and timing of antibiotic exposure. Moreover, children exposed to antibiotics had a higher probability of having combinations of conditions, particularly when given multiple prescriptions.

Conclusion: The present study finds significant associations between early life antibiotic exposure and several distinct health conditions with childhood onset. Additional research is warranted to establish practical guidelines to optimize the benefit and minimize the risk of antibiotics in children.

Figure 1.. Kaplan-Meier Curves of Time to Event for Health Conditions with Childhood Onset Stratified by Sex and Antibiotic Exposure in the First 24 Months of Life.

The numbers (No.) of females unexposed (F-No), females exposed (F-Yes), males unexposed (M-No), and males exposed (M-Yes) to antibiotics and at risk for (A) asthma, (B) allergic rhinitis, (C) overweight, and (D) attention-deficit hyperactivity disorder (ADHD) are reported below the x-axis for the specified ages. The total numbers of events for each group are reported in the legend for each condition.

Figure 2.. Associations between Antibiotic Exposure in the First Two Years of Life and Risk of Several Common Health Conditions with Childhood Onset.

(A) Hazard ratios (HR) and 95% confidence intervals (95% CI) for antibiotic exposure and risk of health conditions with childhood onset, after adjustment for child confounders (male sex, birth weight, ethnicity, and cesarean section) and maternal confounders (age, education, smoking, and antibiotic use during pregnancy). HRs and CIs highlighted in red are statistically significant. Attention-deficit hyperactivity disorder is abbreviated as ADHD. (B) Cumulative probability of developing 1, 2, and 3 or more health conditions in children unexposed or exposed to antibiotics stratified by number of prescriptions. (C) Number of years spent with 0, 1, 2, or 3 or more health conditions during the first 14.5 years of life stratified by number of prescriptions.