Asthma, Rhinitis, Other Respiratory Diseases
The relationship between early fever and allergic sensitization at age 6 to 7 years☆

https://doi.org/10.1016/j.jaci.2003.11.010Get rights and content

Abstract

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°C (101°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.

Section snippets

Setting and participants

The data are derived from the Childhood Allergy Study, which has been previously described.13 All pregnant women belonging to a Detroit area health maintenance organization and residing in a contiguous geographic suburban region were eligible to enroll their children at birth between April 15, 1987, and August 31, 1989. Informed consent was obtained, and the study was approved by the institutional human rights committee at Henry Ford Health System. During the prenatal interview, participating

Results

Of 1194 eligible pregnant women, 953 consented to enroll their children, and 835 children with cord blood IgE measurement were enrolled. Clinical records were missing for 27 children, 24 had missing temperature readings, and 71 did not have a complete year of follow-up (presumably because of change of insurance, clinician, or residence). Of the 713 remaining children, 441 (62%) participated in the clinical evaluation at age 6 to 7 years, 171 children were unavailable, and 101 did not undergo

Discussion

Epidemiologic studies have consistently demonstrated that children with siblings, particularly an older sibling, are less likely to have atopy18, 19, 20 and atopic diseases.3, 21, 22, 23 In addition, early exposure to daycare appears to lower the risk of allergic sensitization,24, 25 whereas belonging to a higher socioeconomic stratum20 and being breast-fed26 are associated with an increased risk. Although these studies indirectly suggest that infections influence the development of allergies,

Acknowledgements

We acknowledge the work of all the staff who made this study possible and would like to extend especial thanks to Drs Manel Pladevall and Edward Zoratti for their thoughtful review of the manuscript.

References (41)

  • SL Prescott et al.

    Development of allergen-specific T-cell memory in atopic and normal children

    Lancet

    (1999)
  • R Shtrichman et al.

    The role of gamma interferon in antimicrobial immunity

    Curr Opin Microbiol

    (2001)
  • R Beasley et al.

    Prevalence and etiology of asthma

    J Allergy Clin Immunol

    (2000)
  • DM Mannino et al.

    Surveillance for asthma—United States, 1960-1995

    MMWR Morb Mortal Wkly Rep

    (1998)
  • DP Strachan

    Hay fever, hygiene, and household size

    BMJ

    (1989)
  • FD Martinez et al.

    Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels

    Group Health Medical Associates. Thorax

    (1995)
  • PM Matricardi et al.

    Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus

    BMJ

    (1997)
  • JJ Cogswell et al.

    Respiratory infections in the first year of life in children at risk of developing atopy

    BMJ

    (1982)
  • F Forastiere et al.

    Socioeconomic status, number of siblings, and respiratory infections in early life as determinants of atopy in children

    Epidemiology

    (1997)
  • C Bodner et al.

    Childhood exposure to infection and risk of adult onset wheeze and atopy

    Thorax

    (2000)

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    ☆

    Supported by Blue Cross Blue Shield Foundation of Michigan; National Institutes of Health grants AI 24156, AI 50681, and HL 67427; the Fund for Henry Ford Hospital; and grant PO3ES06639 from the National Institute of Environmental Health Sciences.

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    Copyright © 2004 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.