Development of atopic dermatitis and its association with prenatal and early life exposures

Over 20% of children in industrialized countries are affected by atopic dermatitis. From epidemiological studies, it is quite obvious that the worldwide prevalence of atopic dermatitis has considerably increased over the past decades and constitutes a major public health problem. Atopic dermatitis is a chronic inflammatory skin disease that occurs in very early life and frequently precedes the development of asthma and allergic rhinitis during the first several years of life. Although a large numbers of researches were conducted, today there is no good evidence that measures for primary prevention of atopic dermatitis are effective. The aim of this work was to better understand which environmental factors and their timing of exposure might influence the development of atopic dermatitis in childhood, using data from a longitudinal study, the PASTURE/EFRAIM birth cohort. We focused on prenatal and early life exposures, as atopic dermatitis frequently occurs in the first years of life. We further analyzed which farm-related exposures during pregnancy and early life were associated with gene expression of innate immunity receptors in early life and whether there were differences in gene expression of those receptors at birth between children developing atopic dermatitis and the one who did not develop the disease. We found that contact to farm animals and to cats were negatively associated with atopic dermatitis already when these exposures occur during pregnancy. We also observed a dose-response of this protective effect with an increasing number of different farm animal species the mother had contact to during pregnancy. From the hygiene hypothesis, it was suggested that a reduced microbial stimulation of the innate immune system in early life may lead to the development of allergic diseases. In our study, we found that maternal farming during pregnancy was associated with an up-regulation of gene expression of innate immunity receptors at birth. An increased gene expression of those receptors measured at one year of age was positively associated with child’s consumption of raw milk during the first year of life. Moreover, children with a lower expression of innate immune receptors at birth had an increased risk of developing atopic dermatitis in the two first years of life compared to children with a higher expression of those receptors. Then, we could also show that, among early life exposures, infant’s feeding practices plays an important role on the development of atopic dermatitis. For those analyses, we excluded children with onset of the disease within the first year of life, in order to take into account the reverse causality. Introduction of milk products, especially yogurt, was negatively associated with atopic dermatitis. Furthermore, children with an increased food diversity introduced in the first year had a reduced risk of developing atopic dermatitis and also asthma, food allergy and sensitization. Taking together the results of this thesis, it can be concluded that the protective “farm effect” may also be effective on atopic dermatitis, especially when the exposure occurs during pregnancy. The role of the diversity of environmental exposures on atopic dermatitis has also been highlighted in this work. These results may contribute to the development of new strategies for primary prevention of atopic dermatitis among children.