Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology

doi:10.1016/j.jaci.2005.09.042

Journal of Allergy and Clinical Immunology

Volume 117, Issue 1, January 2006, Pages 184-189

https://doi.org/10.1016/j.jaci.2005.09.042 Get rights and content

Background

Atopic dermatitis (AD) often develops in infancy as the first manifestation of the atopic phenotype. Wheezing is also common in infancy, but it is less clear whether infant wheezing should be considered as an atopic phenotype. If infant wheeze and AD share a common aetiology, this would indicate that infant wheezing is an atopic phenotype.

Objective

To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes, indicating a common etiology.

Methods

A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, and prenatal, perinatal, and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation, at 6 and 18 months of age, and by linkage to the Danish Medical Birth Register. Data were analyzed by binary and polytomous logistic regression models.

Results

The following variables had significantly differential effects on infant wheezing and AD: parental hay fever, parental asthma, parental AD, sex, maternal age, maternal occupation, smoking during pregnancy, season of birth, birth weight, gestational age, head circumference, breast-feeding, number of older siblings, day care attendance, and pets in the home.

Conclusion

The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology. Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease, and infant wheezing should not be used as an indicator of the atopic phenotype.

Section snippets

Participants

The study was based on mother-child pairs enrolled in the Danish National Birth Cohort (DNBC)⁸. Women were invited to participate when they first consulted their general practitioner about the pregnancy. Participation involved 4 computer-assisted telephone interviews at gestational weeks 12 and 30 (first and second interview) and when the child was 6 and 18 months old (third and fourth interview). The DNBC has consecutively recruited 100,000 pregnant women from 1997 to 2002. In April 2000, the

Results

“Wheeze ever” and AD were significantly associated (crude OR, 1.31; 95% CI, 1.21-1.42)). This association remained significant after adjustment for risk factors (adjusted OR, 1.28; 95% CI, 1.19-1.39). Thus, the cumulated incidence of “wheeze ever” was 32.6% and 26.9% among infants with and without AD, respectively. The cumulated incidence of “recurrent wheeze” was 11.4% and 7.3% among infants with and without AD, respectively (adjusted OR, 1.30; 95% CI, 1.20-1.41).

The estimates for the effects

Discussion

We found that the majority of risk factors had differential effects on the risk of wheezing and AD. Most risk factors even had opposite direction of their effects on wheeze and AD. For example, breast-feeding was associated with a decreased risk of wheezing but an increased risk of AD. Hence, these findings support the notion that infant wheezing and AD have a different etiology.

The association between infant wheeze and AD observed in the current study was relatively weak (OR, 1.3). However,

References (17)

S. Illi et al.
The natural course of atopic dermatitis from birth to age 7 years and the association with asthma
J Allergy Clin Immunol
(2004)
J.M. Spergel et al.
Atopic dermatitis and the atopic march
J Allergy Clin Immunol
(2003)
A.E. Tattersfield et al.
Asthma
Lancet
(2002)
S.J. Szefler et al.
Advances in pediatric and adult asthma
J Allergy Clin Immunol
(2005)
S.H. Sicherer et al.
Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects
J Allergy Clin Immunol
(2005)
R.S. Roberts et al.
An empirical demonstration of Berkson's bias
J Chronic Dis
(1978)
N. Pearce et al.
Asthma epidemiology
(1998)
R.A. Wood
Pediatric asthma
JAMA
(2002)

There are more references available in the full text version of this article.

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: The Danish National Research Foundation established the Danish Epidemiology Science Centre, which initiated and created the Danish National Birth Cohort. The cohort is a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort was obtained from the Pharmacy Foundation of 1991, the Egmont Foundation, the March of Dimes Birth Defects Foundation, and the Augustinus Foundation.

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Food allergy, dermatologic diseases, and anaphylaxisDifferential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology

Background

Objective

Methods

Results

Conclusion

Section snippets

Participants

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Chronic Dis

Asthma epidemiology

Pediatric asthma

JAMA

Food allergy, dermatologic diseases, and anaphylaxis
Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology