Antibiotic exposure in the first year of life and later treated asthma, a population based birth cohort study of 143,000 children

Abstract

Several epidemiological studies reported an association between antibiotic consumption in the first year of life and later asthma, but results are conflicting and affected by potential biases. We examined this controversial issue in a population-based birth cohort. Using administrative data, we identified 143,163 children born in 1995-2011 in Friuli-Venezia Giulia (Italy) (median follow-up 5.25 years, 927,350 person-years). Antibiotic prescriptions in the first year of life and subsequent treated asthma (defined as ≥2 anti-asthmatic drug prescriptions within a 12-month period) were retrieved from drug prescription records. We estimated incidence rate ratios (IRR) using Poisson regression models, adjusted for perinatal variables and for hospitalizations for infections in the first year of life. We identified 34,957 new-onset asthma cases. Antibiotic consumption in the first year of life increased the risk of new-onset asthma [IRR 1.51, 95% confidence interval (CI) 1.48-1.54] with a dose-response relationship (p-trend <0.001). The risk was highest for asthma identified at 13-35 months of life (IRR 2.07, 95% CI 2.00-2.14), but remained statistically significant for asthma identified at 36-71 months (IRR 1.17, 95% CI 1.14-1.21) and at ≥72 months (IRR 1.15, 95% CI 1.08-1.22). Antibiotics increased the risk of current asthma at ≥6 years (IRR 1.35, 95% CI 1.30-1.41) and at ≥13 years of age (IRR 1.19, 95% CI 1.08-1.33). Antibiotic exposure in infancy is associated with an increased risk of asthma up to adolescence. The association detected at older ages is not explained by reverse causation; however, confounding by respiratory infections not leading to hospital admission cannot be excluded.

Reply to Bianchi et al.: In Italy anti-asthmatic drug prescription is not always a reliable proxy of asthma

“…Therefore, it should be tested in different settings before being considered the gold standard for pediatric asthma detection using healthcare databases in Italy or elsewhere. Anyhow, our previous [2] and present results consistently show an association between early antibiotic use and later pediatric treated asthma across a wide range of asthma definitions.…”

“…As suggested by Bianchi et al [1], we have conducted a sensitivity analysis of our previously published data [2], identifying treated asthmatics as those individuals with at least one prescription after the first year of life of any nonnebulised formulation of inhalatory anti-asthmatic drugs [3] Since nebulised formulations of anti-asthmatic drugs are frequently prescribed for respiratory infections [1], our previous definition may have misclassified as asthmatics a proportion of non-asthmatic subjects particularly in the 13-71 months groups and might have biased our results: children treated with antibiotics in the first year of life may be more predisposed to respiratory infections in early childhood; alternatively, antibiotic use may be a marker of parental tendency to seek medications for children.…”

Antibiotic treatment in infants: effect on the gastro-intestinal microbiome and long term consequences

“…Antibiotics during the first year of life are associated with an increased risk for wheezing and asthma up to the age of three and six years, independent of lower respiratory tract infections during the first year of life. [24][25][26][27][28] The strength of the association differs with the class of antibiotics, correlating with their effect on the gastrointestinal microbiome. 24 A dose-response effect was observed: when five or more antibiotic courses were administered, the risk to develop asthma increased significantly (p<001).…”

Viruses and bacteria in Th2‐biased allergic airway disease

“…In the absence of effective antiviral therapies, targeting pathogenic bacteria for manipulating the microbiome by antibiotics may be an alternative approach. In contrast, several epidemiological studies reported that antibiotic consumption in the first year of life was associated with a risk of asthma in later life (6,94). Due to the 'common mucosal response' concept, which introduces the idea that the alterations in immune function of the respiratory tract are linked to the immunomodulatory activity of the gut microbiome, oral administration of probiotics was used for treating allergic airway diseases by changing the gut microbiome.…”