The relationship between early fever and allergic sensitization at age 6 to 7 years

J Allergy Clin Immunol. 2004 Feb;113(2):291-6. doi: 10.1016/j.jaci.2003.11.010.


Background: The hygiene hypothesis suggests that early infections might protect against later allergic sensitization.

Objective: The purpose of this study was to determine whether fevers before age 1 year were associated with allergic sensitization at age 6 to 7 years.

Methods: Eight hundred thirty-five children from suburban Detroit, Michigan, were enrolled at birth. Clinic records from their first year were abstracted for episodes of fever, antibiotic use, and respiratory infections. Fever was defined as a rectal temperature of 38.3 degrees C (101 degrees F) or greater or its equivalent measured at another site. At age 6 to 7 years, 441 children underwent allergy testing. The primary outcome measures were atopy (>/=1 positive skin prick test result), seroatopy (>/=1 positive allergen-specific IgE level), and allergic sensitization (either seroatopy or atopy).

Results: By age 1 year, 207 (46.9%) of the 441 participants had a documented fever. Among children with 0, 1, or 2 or more fevers in the first year, 33.3%, 31.3%, and 26.0% demonstrated atopy at age 6 to 7 years, respectively (P =.504); 43.4%, 39.7%, and 25.0% had seroatopy, respectively (P =.032); and 50.0%, 46.7%, and 31.3% had allergic sensitization, respectively (P =.028). After adjusting for potential confounders, each febrile episode in the first year was associated with reduced odds for allergic sensitization (adjusted odds ratio, 0.69; 95% CI, 0.47-1.00). Febrile upper respiratory tract infections, in particular, were associated with lower odds of allergic sensitization (adjusted odds ratio, 0.55; 95% CI, 0.31-0.97) per episode.

Conclusion: This study provides direct support for the hygiene hypothesis because children with fevers before age 1 year were less likely to demonstrate allergic sensitivity at age 6 to 7 years.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Allergens / adverse effects*
  • Allergens / immunology*
  • Child
  • Cohort Studies
  • Female
  • Fever*
  • Humans
  • Hypersensitivity, Immediate / immunology*
  • Immunoglobulin E / blood*
  • Infant, Newborn
  • Skin Tests


  • Allergens
  • Immunoglobulin E