Celedon JC, Litonjua AA, Ryan L, Weiss ST, Gold DR. Am J Respir Crit Care Med. 2002;166:72–75
Purpose of the Study.
To examine the association between the frequency of use of antibiotics in the first year of life and the occurrence of asthma, allergic rhinitis, and eczema at 5 years. This was a prospective study that examined the association of antibiotic use and the development of allergic disease.
The study reports on 498 infants who had a history of allergy or asthma in at least 1 parent. At 2 months of life and subsequently every 2 months until age 2, a questionnaire was given to the primary caregiver. After the second year of life, the questions were asked every 6 months. Every 2 months questions were asked about the use of antibiotics. The multivariate analysis included a large number of variables including the child’s race, household income, and daycare attendance in the first year of life. Parental and familial factors included in utero cigarette smoke exposure, number of months of breastfeeding, parents’ history of asthma, allergic rhinitis, or eczema, number of siblings in the household, and the average number of cigarettes smoked by adults in the household. At 5 years of age, asthma was defined as a physician diagnosis and 1 or more episodes of wheezing in the previous 12 months. Similarly, allergic rhinitis was defined as a physician diagnosis of allergic rhinitis and a history of nasal symptoms in the past 12 months, and eczema had to be physician-diagnosed with the presence of a pruritic rash at least 6 months in the past year. Beginning with the second year of life, the primary caregiver was asked about the number of attacks of wheezing in the past 12 months. The children were categorized as having transient, late-onset, or persistent wheezing. Transient wheezing was defined as 1 or more episodes of wheezing before the age of 3 years but none between the ages 4 and 5. Late-onset wheezing was the occurrence of wheezing between the ages of 4 and 5 years, and persistent wheezing was the occurrence of wheezing before and after age 3 years.
Three hundred fifty-two (70.7%) of the 498 participants received 752 courses of oral antibiotics in their first year of life. These antibiotics were given for ear infections (62.1%), wheezing (21.4%), cough (10.9%), nasal congestion/discharge (3.9%), difficulty breathing (1%), and difficulty eating (0.7%). Ninety percent of the group were monitored up to age 5 years (n = 448). A subset of the group underwent an evaluation for total immunoglobulin E (IgE) (n = 230; 46.2%) at age 2 years. No significant association was found between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years. Among the 448 children, 90 had at least 1 allergic disorder at age 5 years. Within the group that developed these disorders, 30 (33.3%) received no antibiotic, 17 (18.9%) received 1 course, and 43 (47.8%) received 2 or more courses of antibiotics in the first year of life. Antibiotic use was significantly associated with transient wheezing; however, the association became weaker after adjustments for other variables. Transient wheezing was significantly associated with low household income. There was no association between antibiotic use in the first year of life and asthma in the persistent wheezing group. Persistent wheezing was more associated with male sex and a maternal history of asthma. A “reverse causation” was also looked into. When those children who were given antibiotics for wheezing were taken out of the analysis, there still was no association found. There was also no association in the late-onset wheezing group. Serum IgE levels were not different between those who had antibiotics and those who did not receive them in the first year of life.
In this prospective study of children from Boston, born to parents who had a history of allergy, there was no support for the theory that the use of antibiotics in early childhood is associated with the development of asthma or allergy at age 5 years.
This is a negative study and frequently such studies only tell us what did not work. I do think that although this is a “negative” study, it is important, well-done, and makes a significant contribution. Recently, a hypothesis has been put forth that suggests that the increase in the prevalence of allergic diseases may be associated with reduced exposure to infections and perhaps the use or frequent use of antibiotics in young children. The implication was that an antibiotic permits the immature immune system to remain in the allergy favoring TH-2 mode. The authors of this article point out that the support for the hypothesis had come from 5 retrospective studies. This may be the first prospective study on this issue and the conclusions are that antibiotic use in the first year of life does not seem to be associated with the subsequent development of asthma, allergic rhinitis, or eczema.