Background The role of dietary factors in the development of allergies is a topic of debate, especially the potential associations between infant feeding practices and allergic diseases. Previously, ...we reported that increased food diversity introduced during the first year of life reduced the risk of atopic dermatitis. Objective In this study we investigated the association between the introduction of food during the first year of life and the development of asthma, allergic rhinitis, food allergy, or atopic sensitization, taking precautions to address reverse causality. We further analyzed the association between food diversity and gene expression of T-cell markers and of Cε germline transcript, reflecting antibody isotype switching to IgE, measured at 6 years of age. Methods Eight hundred fifty-six children who participated in a birth cohort study, Protection Against Allergy Study in Rural Environments/EFRAIM, were included. Feeding practices were reported by parents in monthly diaries during the first year of life. Data on environmental factors and allergic diseases were collected from questionnaires administered from birth up to 6 years of age. Results An increased diversity of complementary food introduced in the first year of life was inversely associated with asthma with a dose-response effect (adjusted odds ratio with each additional food item introduced, 0.74 95% CI, 0.61-0.89). A similar effect was observed for food allergy and food sensitization. Furthermore, increased food diversity was significantly associated with an increased expression of forkhead box protein 3 and a decreased expression of Cε germline transcript. Conclusion An increased diversity of food within the first year of life might have a protective effect on asthma, food allergy, and food sensitization and is associated with increased expression of a marker for regulatory T cells.
Background Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective To assess the effect of supplementation of an infant ...and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life. Methods Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Results A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group ( P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants. Conclusion Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
Background Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly ...from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. Objectives We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. Methods The Protection Against Allergy—Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the “usually” consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. Results The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81). Conclusion Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators.
Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still ...not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
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.
Background In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of ...farming to asthma and wheeze have raised some doubt about a true protective effect. Objective We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes. Methods The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. Results Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio OR, 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. Conclusions The protective effect of being raised in a farm environment was ascribed to distinct exposures. Clinical implications The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.
Background Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal ...exposure is nutrition, although its association with allergic disease remains unclear. Objective We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality. Methods One thousand forty-one children who participated in the Protection Against Allergy–Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor's diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life. Results The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73). Conclusion As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis.
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.
Background There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. Objective We sought to determine environmental and nutritional exposures ...associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life. Methods For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n = 938) and year 1 (n = 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. Results Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers ( P for multifactorial multivariate ANOVA = .041), significantly so for TLR7 (adjusted geometric means ratio aGMR, 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. Conclusion Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.
Atopic sensitization in the first year of life Depner, Martin, PhD; Ege, Markus J., MD; Genuneit, Jon, MD ...
Journal of allergy and clinical immunology,
03/2013, Letnik:
131, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the ...first environmental exposures in infancy. Objective We sought to explore the course of atopic sensitization between birth and 12 months of age. Methods Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy–Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children’s health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. Results Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio OR, 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). Conclusion IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences.
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