PURPOSE OF THE STUDY.
Previous studies have investigated the association between early antibiotic exposure and the development of asthma, with inconsistent results and concern that any observed association was confounded by lower and upper respiratory tract illnesses in early childhood. Given the inconsistencies of existing data, the purpose of this study was to clarify if an association exists between antibiotic exposure in the first year of life and the development of asthma up to age 7 years.
From a retrospective cohort of children enrolled in a nationwide, employer-provided health insurance plan in the United States, this study examined 62 576 children who were continuously enrolled from birth to at least 5 years of age.
The children were evaluated for an association between antibiotic exposure during the first year of life and subsequent development of 3 asthma phenotypes: transient wheezing (began and resolved before 3 years of age), late-onset asthma (began after 3 years of age), and persistent asthma (began before 3 years of age and persisted through 4–7 years of age). Antibiotic exposure was defined as the receipt of at least 1 antibiotic prescription of 7 to 10 days’ length in the first year of life. Children were identified as having persistent asthma if at least 1 of the following criteria was met in the 2 years before the measurement year: (1) at least 1 emergency department visit with asthma as the principal diagnosis; (2) at least 1 acute care inpatient encounter with asthma as the principal diagnosis; (3) at least 4 outpatient asthma visits with asthma as one of the listed diagnoses and at least 2 asthma medication–dispensing events; and (4) at least 4 asthma medication–dispensing events. Exclusion criteria included having >1 physician-diagnosed lower and upper respiratory tract illness in the first year of life.
Antibiotic use in the first year of life was associated with the development of transient wheezing (odds ratio [OR]: 2.0 [95% confidence interval (CI): 1.9–2.2]; P < .001) and persistent asthma (OR: 1.6 [95% CI: 1.5–1.7]; P < .001). A dose–response effect was observed. When ≥5 antibiotic courses were received, the odds of persistent asthma doubled (OR: 1.9 [95% CI: 1.5–2.6]; P < .001). There was no association between antibiotic use and late-onset asthma.
Antibiotic use in the first year life is associated with an increased risk of early-onset childhood asthma before 3 years of age. The apparent effect has a clear dose response.
The exclusion of respiratory tract illnesses in the first year of life removes a significant potential confounding factor that has led to inconsistent conclusions in previous studies examining a link between antibiotic use in infancy and the development of asthma. The finding that more frequent antibiotic use leads to an increased risk of early-onset asthma seems to support the microbiota hypothesis, which postulates that antibiotic use in early life increases the risk of atopic disorders by altering the diversity and composition of the intestinal microbiota, thereby disrupting mucosal mechanisms of immune tolerance and increasing susceptibility to Th2 cytokine-dependent allergic inflammation. Antibiotic use in infancy should be limited to reduce the possibility of driving this process.
- Copyright © 2014 by the American Academy of Pediatrics