Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children

American Journal of Epidemiology December 29, 2010; Vol. 173, No. 3; pp. 310-318 Kari R. Risnes, Kathleen Belanger, William Murk, and Michael B. Bracken The authors are from Yale University This analyses of a cohort included 1,401 US children, assessed the associationbetween antibiotic use within the first 6 months of life and asthma and allergy at 6years of age. KEY POINTS FROM THIS STUDY 1) 25% of urban children in the developed world have asthma. 2) Many studies have reported that antibiotic use may be associated withincreased risk of childhood asthma. 3) Many studies report a positive association between antibiotic use andchildhood asthma, including a large prospective cohort study with more than 5,000cases of childhood asthma that determined early antibiotic exposure to be one ofthe most important predictors of childhood asthma. 4) The hygiene hypothesis is a frequently cited explanation for the increasingprevalence of allergic diseases, suggesting that reduced exposure to bacteria andviruses may delay development of the immune system and promote atopic immuneresponses. [including the use of antibiotics and vaccines] 5) Gastrointestinal flora are important for developing a healthy immune systemwith resistance to allergic sensitization, and antibiotic exposure in early life mightincrease the risk of atopic diseases through altered microbial exposure. RESULTS FROM THIS STUDY: 1) One third of the children had been exposed to antibiotics by 6 months ofage. 2) Nearly 70% of children with a history of lower respiratory infections andmore than 50% with otitis in the first year of life had received antibiotics. 3) Children of African-American or Hispanic mothers had twice the risk ofasthma compared with children of white mothers. 4) If one parent had a history of asthma, the increased risk of asthma was 140%compared with children with no history of parental asthma. If both parents had ahistory of asthma, the increased risk was 257%. 5) The number of antibiotic courses before 6 months of age and asthma showa dose-response relation. 6) One course of antibiotic exposure increased the risk of asthma by 40%. 7) Two or more courses of antibiotic exposure increased the risk of asthma by72%. 8) The increased risk for asthma in children who had no parental history ofasthma was 89%. DISCUSSION 1) The association of antibiotics and asthma in the present study wasparticularly strong in children with no family history of asthma. 2) The hygiene hypothesis suggests that microbial exposure [becominginfected] in early life enhances postnatal maturation of the immune system thatmay protect against development of allergic diseases. 3) Normal postnatal development incurs a change from fetal predominantly Thelper 2 (known as TH2) to more mature T helper 1 (known as TH1) immunity.This is important because Overexpression of TH2 responses to allergens is thehallmark of allergic diseases. 4) Microbial exposure, particularly in the intestinal tract, is necessary forpostnatal transition to a balanced immune response in healthy children. 5) The early postnatal period is particularly vulnerable to imbalances in immuneresponse, and that delayed postnatal maturation of TH1 cell function is a keycomponent of genetic risk for atopy. 6) Children with no family history of asthma are more susceptible to the effectsof antibiotics than children with a genetic predisposition to asthma. 7) We found a strong association between early antibiotic exposure withreported positive immunoglobulin E blood or skin test reactivity. 8) We conclude that antibiotic exposure before 6 months of age is associatedwith asthma and allergy at 6 years of age. 9) The adverse effect of antibiotics on asthma risk was particularly strong inchildren with no parental history of asthma, which should encourage physicians toavoid unnecessary antibiotic use in low-risk children with no genetic predispositionto asthma. 10) Antibiotic exposure is associated with increased risk of asthma by 52%.