Antibiotic Use in Early Life May Increase Risk for Childhood Asthma

News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

Posted: 6/15/2007

June 15, 2007 -- Use of antibiotics during the first year of life increases the risk for asthma by the age of 7 years, according to the results of a large longitudinal cohort study published in the June issue of Chest.

"Since oral antibiotics are frequently prescribed for upper and lower respiratory tract infections in children, an understanding of the relation between antibiotic use and asthma is critical to clinicians and health-care policymakers worldwide," write Anita L. Kozyrskyj, PhD, from the University of Manitoba in Winnipeg, Canada, and colleagues. "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."

Using the healthcare and prescription databases of Manitoba, Canada, the investigators evaluated the association between antibiotic prescription use during the first year of life and asthma at the age of 7 years in a 1995 birth cohort of 13,116 children.

In children who had received antibiotics in the first year of life, asthma was significantly more likely to develop at the age of 7 years, independent of well-known asthma risk factors. Increased risk for asthma was observed for antibiotic use in non–respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 - 3.37).

Children receiving more than 4 courses of antibiotics had the highest risk for asthma (adjusted OR, 1.46; 95% CI, 1.14 - 1.88), especially among rural children, in the absence of maternal asthma, or in the absence of a dog during the birth year. In these subpopulations of children, broad-spectrum cephalosporin use was more common.

"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 [broad-spectrum] cephalosporins," the authors write.

The authors note that the strongest evidence against reverse causation in this study is the finding of an association between asthma and antibiotic use for the treatment of non-respiratory-tract infections.

"While we have constructed our study to diminish the likelihood of reverse causation and confounding bias, and have implemented a validated definition of childhood asthma, we can neither confirm nor refute the causative role of antibiotics in the development of asthma," the authors conclude. "Further large-scale studies are required to determine the longitudinal associations between the composition of intestinal microflora, antibiotic use, and atopic dermatitis during infancy, and the development of asthma in low-risk and high-risk children. In the interim, it would be prudent to avoid the unnecessary use BS antibiotics in the first year of life when other antibiotics are available."

The Operating Grant, New Investigator Award, and New Emerging Team Programs of the Canadian Institutes of Health Research supported this study. The authors have disclosed no relevant financial relationships.

Chest. 2007;131:1753-1759.

Clinical Context

The evidence for an association between early antibiotic use and subsequent development of asthma is not clear. In the March 2003 issue of the Journal of Allergy and Clinical Immunology, Liu and Murphy reported on the hygiene hypothesis, which states that more hygienic childhood environments potentially exacerbate atopic T-helper type 2 immunity, whereas microbial pressure would provide a balanced immune system. According to Johnson and colleagues in the June 2005 issue of the Journal of Allergy and Clinical Immunology, children who required antibiotics and had less pet exposure during the first year of life were at higher risk for atopy. In the March 2006 issue of Chest, a meta-analysis by Marra and colleagues revealed that antibiotic use in the first year of life was linked to an increased risk for asthma in nonprospective studies.

This cohort study evaluates whether antibiotic use in the first year of life is associated with asthma at the age of 7 years and whether this association is affected according to subgroups of children and antibiotic use.

Study Highlights

  • Data for 13,116 children of a cohort of 13,980 children born in Manitoba and enrolled in universal health insurance were evaluated for asthma at age 7 years.
  • 864 children were excluded because of diagnosis of asthma in the first year of life.
  • Demographic data showed 50% were boys, 57% had urban residence (population > 40,000), 24% were low income, 90% had siblings, 6% had asthma at age 7 years, and 5% had mothers with history of asthma,
  • 65% had received at least 1 antibiotic in first year of life.
  • 3% received only narrow-spectrum antibiotics (penicillin, cloxacillin, cephalexin, cefadroxil, and erythromycin), 52% received only broad-spectrum antibiotics, and 10% received both narrow- and broad-spectrum antibiotics.
  • 55% received at least 1 broad-spectrum–type penicillin prescription.
  • Indications for antibiotics included otitis media in 40%, other upper respiratory tract infections in 28%, lower respiratory tract infection in 19%, and non–respiratory-tract infection in 7%.
  • Asthma diagnosis at age 7 years was based on at least 2 clinician visits, 1 hospitalization, or 2 medication prescriptions for asthma in the year after the seventh birthday.
  • After adjusting for asthma risk factors, antibiotic use during the first year was associated with greater risk for asthma at age 7 years.
  • The association between antibiotic use and asthma risk increased with number of antibiotic courses.
  • Children who took more than 4 antibiotic courses had highest asthma risk (OR, 1.46; 95% CI, 1.14 - 1.88).
  • Subgroup analysis showed asthma risk was associated with broad-spectrum antibiotic use (OR, 1.50; 95% CI, 1.16 - 1.93) and antibiotic prescription for non–respiratory-tract infections (OR, 1.86; 95% CI, 1.02 - 3.37).
  • There was no associated asthma risk for narrow-spectrum antibiotic use.
  • Association between antibiotic use and asthma risk was affected by the following:
    • Rural residence if more than 4 antibiotic courses (OR, 1.88).
    • Absence of maternal asthma, especially if more than 1 antibiotic course (OR, 1.57).
    • Absence of dog during birth year if more than 4 antibiotic courses (OR, 2.02).
  • In subgroup of 7517 urban children, the association between antibiotic use and asthma was not significant.
  • Broad-spectrum cephalosporin use was more common in rural children vs urban children, but there were no other differences in antibiotic type among groups.

 

Pearls for Practice

  • Children who receive oral antibiotics in the first year of life, especially more than 4 courses and for non–respiratory-tract infections, are more likely to have asthma at the age of 7 years.
  • The association between antibiotic use in the first year of life and asthma at the age of 7 years was especially strong in rural areas, in the absence of maternal asthma, in the absence of a dog during the birth year, and with broad-spectrum cephalosporin use.

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