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Nwaru B.I.,University of Tampere | Virtanen S.M.,University of Tampere | Virtanen S.M.,Finnish National Institute for Health and Welfare | Alfthan G.,Finnish National Institute for Health and Welfare | And 15 more authors.
Allergy: European Journal of Allergy and Clinical Immunology

Background: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. Objective: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. Methods: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). Results: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). Conclusions: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold. © 2013 John Wiley & Sons A/S. Source

Piemontese P.,University of Milan | Gianni M.L.,University of Milan | Braegger C.P.,University of Zurich | Chirico G.,Spedali Civili | And 7 more authors.

Background: the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy. Methodology/Principal Findings: this study was performed as a multi-center, randomized, double-blind, placebo-controlled trial including healthy term infants. Infants were recruited before the age of 8 weeks, either having started with formula feeding or being fully breast-fed (breastfeeding group). Formula-fed infants were randomized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Growth, tolerance and adverse events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control groups showed similar mean weight, length and head circumference, skin fold thicknesses, arm circumference gains and stool frequency at each study point. As far as the anthropometric parameters are concerned, the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point. The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants, whereas at 52 weeks were strikingly smaller. The stool consistency in the prebiotic group was softer than in the control group at 8, 16 and 24 weeks (p&0.001) and closer to that of the breastfeeding group. There was no difference in the incidence of adverse events between the two formula groups. Conclusions: our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants. Trial Registration: drks-neu.uniklinik-freiburg.de DRKS 00000201. © 2011 Piemontese et al. Source

Pfefferle P.I.,University of Marburg | Buchele G.,University of Ulm | Blumer N.,University of Marburg | Roponen M.,Finnish National Institute for Health and Welfare | And 15 more authors.
Journal of Allergy and Clinical Immunology

Background: Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection. Objectives: To investigate associations between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families. Methods: Supernatants from phorbol 12-myristate 13-acetate/ionomycin-stimulated CB mononuclear cells were assessed for the production of IFN-γ, TNF-α, IL-5, IL-10, and IL-12. Results: Significantly higher levels of IFN-γ and TNF-α in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-γ and TNF-α in umbilical blood. Conclusion: Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth. © 2010 American Academy of Allergy, Asthma & Immunology. Source

Michel S.,University of Regensburg | Michel S.,Hannover Medical School | Busato F.,French Atomic Energy Commission | Genuneit J.,University of Ulm | And 17 more authors.
Allergy: European Journal of Allergy and Clinical Immunology

Background Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases. Methods We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon-Mann-Whitney tests. Results In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P-value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P-value (IL13) = 1.57-rfit SUPPL10-8). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T-regulatory genes (FOXP3, RUNX3). Conclusions In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma- and allergy-related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Source

Roduit C.,University of Zurich | Wohlgensinger J.,University of Zurich | Frei R.,University of Zurich | Bitter S.,Swiss Tropical and Public Health Institute | And 16 more authors.
Journal of Allergy and Clinical Immunology

Background: Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. Objective: To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. Methods: A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. Results: Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. Conclusion: Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth. © 2010 American Academy of Allergy, Asthma & Immunology. Source

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