title: Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study.
abstract: OBJECTIVE
  Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in infancy.
  
  
  METHODS
  Information on antibiotic use in the first 6 months and eczema and wheeze until age 2 was collected by repeated questionnaires in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) Birth Cohort Study in The Netherlands. Antibiotic intake was evaluated both as maternal antibiotic use during breastfeeding and infant oral medication. Venous blood samples taken from 815 infants at 2 years of age were analyzed for total and specific immunoglobulin E against common food and inhalant allergens using a radioallergosorbent test. Multivariate logistic regression analysis was used to adjust for confounding factors.
  
  
  RESULTS
  During the first 2 years, eczema was present in 32% of all infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old, 27% of children were sensitized against > or = 1 allergen. At 6 months old, 11% had been exposed to antibiotics through breast milk and 20% directly through medication. The risk for recurrent wheeze, and prolonged wheeze was higher in infants directly exposed to antibiotics through medication, also after excluding from the analyses children who wheezed in the same period as an antibiotic had been used (avoiding reverse causation). Antibiotic use through breastfeeding was associated with recurrent wheeze, but prolonged wheeze was not. Eczema and sensitization were not associated with antibiotic exposure.
  
  
  CONCLUSIONS
  We demonstrated that early antibiotic use preceded the manifestation of wheeze but not eczema or allergic sensitization during the first 2 years of life. Different biological mechanisms may underlie the etiology of wheeze compared with eczema or sensitization. Antibiotic exposure through breastfeeding enhanced the risk for recurrent wheeze, but this needs further confirmation.
authors.affiliation: Department of Epidemiology, Maastricht University, PO Box 616, 6200 Maastricht, The Netherlands. Ischa.Kummeling@epid.unimaas.nl
authors.forename: Ischa
authors.initials: I
authors.lastname: Kummeling
authors.forename: Foekje F
authors.initials: FF
authors.lastname: Stelma
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.forename: Bianca E P
authors.initials: BE
authors.lastname: Snijders
authors.forename: John
authors.initials: J
authors.lastname: Penders
authors.forename: Machteld
authors.initials: M
authors.lastname: Huber
authors.forename: Ronald
authors.initials: R
authors.lastname: van Ree
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: Carel
authors.initials: C
authors.lastname: Thijs
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001942:Breast Feeding; D015331:Cohort Studies; D004485:Eczema / Q000209:etiology*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology* / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D012135:Respiratory Sounds / Q000209:etiology*; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D007073:Immunoglobulin E