Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children
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. 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. 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. 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. 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. When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.
FIG E1. Signal intensity of CD14 measurements and ‘‘no template controls.’’DRn values, which indicate the
magnitude of signal generated by the PCR reaction, are given for number of PCR cycles for 12 and 5
representative experiments, respectively.
FIG E2. Prevalences of atopic sensitization, hay fever, and asthma for farm (black bars) and reference
(gray bars) children.
FIG E3. The x-axis shows deciles of EPS load per square meter of mattress (n 5 322). The y-axis shows
geometric means (dots) of gene expression of TLR2, TLR4, and CD14, respectively, which were normalized by
dividing by gene expression of 18s rRNA. In addition, the linear ﬁt of the association (solid line), along with the
corresponding 95% CI (dashed line), is displayed. All analyses were adjusted for age, sex, family history of
atopy, parental education, environmental tobacco smoking, maternal smoking during pregnancy, number
of older siblings, contact with pets ever, child’s current exposure to a farming lifestyle, child’s exposure to
farm animals, and predominant farm milk consumption of the child.