Environmental and occupational respiratory disorders
Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children

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Background

There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role.

Objective

We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring.

Methods

In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information.

Results

Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively.

Conclusion

Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation.

Clinical implications

When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.

Section snippets

Population and study areas

The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style (PARSIFAL) study aimed at studying the determinants of childhood asthma and allergies in farming and anthroposophic populations, as described previously.12 A child who lived on a farm and whose family ran the farm was considered a farm child. Other children were termed farm reference children. The present analyses focus on 2823 farm and 5440 farm reference

Results

Of the 11,969 invited farm and farm reference children, 8402 (70%) returned the questionnaires. A total of 139 children were excluded because of missing values for sex and age or because they did not meet the age criteria of 5 to 13 years.

The prevalence of all outcomes (atopic sensitization, rhinoconjunctivitis symptoms and physician's diagnosis of seasonal rhinoconjunctivitis, and current wheezing and physician's diagnosis of asthma) was significantly lower in farm children compared with in

Discussion

The present study showed a clear inverse association of a farming environment (farm milk consumption, stable/barn visits, and contact with farm animals) with the prevalence of seasonal rhinoconjunctivitis, symptoms of seasonal rhinoconjunctivitis, and asthma. Maternal exposure to stables in pregnancy was associated with atopic sensitization and the expression of genes for receptors of the innate immune system (ie, TLR2, TLR4, and CD14). A dose-response relation was found between the extent of

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    Supported by a research grant from the European Union (QLRT 1999-01391) and by funding from the Swedish Foundation for Health Care Science and Allergy Research, the Swiss National Foundation (grant no. 32-100324), and the Kühne-Foundation.

    Disclosure of potential conflict of interest: D. Schram-Bijkerek has received grants from Parsifal EU projects. E. von Mutius has consultant arrangements with UCB and GlaxoSmithKline. All other authors—none disclosed.

    Both authors contributed equally to this work.

    The PARSIFAL study group: Tobias Alfvén, Johan Alm, Anna Bergström, Lars Engstrand, Helen Flöistrup, Niclas Håkansson, Gunnar Lilja, Fredrik Nyberg, Jackie Swartz, Magnus Wickman (Sweden); Marco Waser, Felix Sennhauser, Johannes Wildhaber, Alex Möller (Switzerland); Gert Doekes, Mirian Boeve, Jeroen Douwes, Machteld Huber, Mirjam Matze (the Netherlands); Waltraud Eder, Gertraud Weiss, Mynda Schreuer (Austria); and Karin B. Michels (United States).

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