Association Between Early-Childhood Antibiotic Exposure and Subsequent Asthma in the US Medicaid Population

Melinda M. Rathkopf

doi:10.1542/peds.2020-023861K

E Fishma, G Crawfor, A DeVries. Ann Allergy Asthma Immunol. 2019;123(2):186–192.e9

PURPOSE OF THE STUDY:

To evaluate the association between antibiotic exposure in the first 2 years of life and incidence of asthma later in childhood among children insured by Medicaid.

STUDY POPULATION:

Children with continuous medical and pharmacy coverage from birth to 2.5 years of age whose claims were linked to their mothers’ claims. Children were excluded if they had complex chronic medical conditions, a diagnosis of asthma, a diagnosis of bronchiolitis, or another respiratory condition in the first 2.5 years of life.

METHODS:

Medical and pharmacy claims from 13 different Medicaid plans from geographically dispersed across the US were used to conduct this observational, longitudinal, retrospective cohort study. Claims from July 1, 2012 through November 30, 2018 were queried. The main exposure was the number of prescriptions filled for systemic antibiotics between 0-2 years of age. The span from 2-2.5 years of age was considered a wash-out period. The primary outcome was new cases of asthma. Asthma was defined as at least one inpatient diagnosis, at least 2 outpatient or emergency department diagnoses or at least 2 prescription fills for asthma medications.

RESULTS:

Out of a sample of 79 852 children, 2381 new asthma cases were observed, ∼2.7 new asthma cases per 100 person-years at risk. After adjustment for covariates, receipt of 1-2 prescriptions for antibiotics was associated with an increased risk of developing asthma compared with 0 (HR, 1.34; 95% CI, 1.21–1.49) antibiotics, and receipt of 3 or more was associated with a higher risk compared with 0 (HR, 1.71; 95% CI, 1.54–1.90) and 1–2 antibiotics (HR, 1.27; 95% CI, 1.15–1.41). Children born via cesarean section (HR 1.11; 95% CI, 1.02–1.21) or whose mothers had asthma (HR 1.68; 95% CI, 1.48–1.91) were more likely to develop asthma.

CONCLUSIONS:

Antibiotic dispensing in the first 2 years of life is associated with an increased risk of subsequent asthma in the Medicaid population, even after controlling for reverse causality and confounding.

REVIEWER COMMENTS:

This article adds to the data regarding effects of early antibiotic use. The early life exposure to antibiotics is hypothesized to increase risk of asthma through killing of commensal bacteria and alteration of the gut microbiome. This study tried to control for reverse causality and confounders by only looking at antibiotics in the first 2 years of life, excluding those with prior bronchiolitis and other respiratory infections and those with an early diagnosis of asthma and included a washout period. The findings of this study contribute to the need for health care providers to strongly consider the risks versus benefits of use of antibiotics early in life.