Increased Risk of Childhood Asthma From Antibiotic Use in Early Life

Anita L. Kozyrskyj; PhD, Pierre Ernst, MD; Allan B. Becker, MD


CHEST. 2007;131(6):1753-1759. 

In This Article

Abstract and Introduction


Background: To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, we undertook a cohort study of this association in a complete population of children.
Methods: Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children.
Results: Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these subpopulations of children.
Conclusions: Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.


Asthma is one of the most common chronic diseases worldwide, significantly impacts quality of life, and represents a significant cost to the health-care system.[1,2,3] The increasing prevalence of asthma in the industrialized world over the last quarter century has produced several theories on its origins.[4] In particular, the "hygiene hypothesis" postulates that growing up in a more hygienic environment with less microbial exposure may promote the fetal immune response, which is skewed in the atopic T-helper (Th) type 2 direction, whereas microbial pressure would drive the immune system toward a balanced Th-1 and Th-2 immunity.[5,6] Studies[7] of farmer children have suggested that exposure early in life to endotoxin from Gram-negative bacteria may be the key element of less hygienic environments, which results in a lower prevalence of allergy and asthma. However, many researchers have argued[8] that the regulation of the immune response is not likely to be dependent on external microbial exposure and have proposed the "microflora hypothesis" of allergic disease. This theory posits that the maturation of the mucosal immune system during infancy, namely, the development of immunologic tolerance via regulatory T cells, requires the presence of commensal microbial flora in the GI tract.[9] Evidence for this thesis comes from epidemiologic studies[10,11,12] that link variations in GI microflora and probiotic administration with less allergy and asthma, and from murine models[13,14,15] that document that antibiotic administration causes altered intestinal flora, impaired barrier function, diminished Th-1 immune responses, and allergic airway disease.

To date, the findings from epidemiologic studies have supported[16,17,18,19,20,21,22] and refuted[23,24,25] an association between antibiotic use in early life and the development of asthma. Since oral antibiotics are frequently prescribed for upper and lower respiratory tract infections in children,[26,27] an understanding of the relation between antibiotic use and asthma is critical to clinicians and health-care policymakers worldwide. Previous attempts to assess whether the relationship between antibiotic use in early life and asthma is causal have been hampered by cross-sectional or retrospective study design, in which it is difficult to discern whether the association is subsequent to antibiotic use for wheeze-related respiratory illnesses that precede asthma. A recent metaanalysis[28] of antibiotic use in the first year of life has reported a twofold increased risk of childhood asthma following antibiotic use, but no association among studies conducted prospectively. Further, some studies have been limited to high-risk cohorts[23,24] or to urban populations.[25] We examined the association between oral antibiotic use in the first year of life and asthma at age 7 years in a large cohort of children who were followed up from birth and were living in urban and rural environments with universal access to health-care insurance. As a secondary objective, we tested this association in subgroups of antibiotics and subgroups of children. Preliminary findings from this research have been published in an abstract.[29]


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