Polyunsaturated fatty acids, maternal and infant immune responses and allergic disease in infancy

Abstract: Background: The incidence of allergic diseases in industrialized countries has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcome in the child.Aim: The aim of this thesis was to add knowledge on the relationship between long chain polyunsaturated fatty acids, sensitization and allergic disease and possible immunological events regulating this.Subjects: The thesis is based on results obtained from two cohorts. The first, including 300 cord blood samples collected from 1985-2005. The second, a double-blind placebo controlled multi-centre study comprising 145 families with allergic disease.Methods: Phospholipid fatty acids and total IgE antibodies were analyzed in cord blood samples with gas chromatography and Uni-CAP™, respectively.The families participating in the double-blind placebo controlled multi-centre study were recruited at antenatal units in Linköping and Jönköping and the mothers were supplemented with 2.6 g ?-3 long-chain polyunsaturated fatty acids (LCPUFA) or placebo daily from gestational week 25 until 3 months of breast feeding. Phospholipid fatty acids in maternal serum were analysed before and during the intervention to assess compliance. Prostaglandin E2, leukotrienes B4 and cytokines were analyzed with ELISA technique in supernatants from maternal LPS-stimulated whole blood cultures. Clinical outcome was allergic disease with positive skin prick test and/or specific circulating IgE to food allergens at one year of age. Cytokines, chemokines, SIgA antibodies and prostaglandin E2 were analyzed in breast milk with Luminex and ELISA techniques.Results: The proportions of cord serum linoleic acid (LA, C18:2 ?-6) and ?-linolenic acid (LNA, C18:3 ?-3) decreased significantly from 1985 to 2005. However, the LA/LNA ratio did increase, revealing a relatively larger decrease in LNA than in LA. The proportions of both arachidonic acid (AA; C20:4 ?-6) and docosahexaenoic acid (DHA, C22:6 ?-3) as well as other ?-6 and ?-3 fatty acids increased significantly during the same time period. No correlations were found between ?-6 and ?-3 fatty acids and total IgE antibodies.Proportions of ?-3 LCPUFA increased in the ?-3 supplemented group of mothers.Lipopolysaccharide-induced prostaglandin E2 secretion in whole blood culture decreased in a majority of ?-3 PUFA supplemented mothers (18 of 28, p < 0.002).The decreased prostaglandin E2 production was more pronounced among non-atopic than atopic mothers. Lipopolysaccharide induced cytokine and chemokine secretion was not affected. The period prevalence of food allergy was lower in the ?-3 group (1?52, 2%) compared to the placebo group (10?65, 15%, p <0.05) as well as the incidence of IgE-associated eczema (?-3 group: 4 ? 52, 8%; placebo group: 15 ? 63, 24%, p < 0.05) at one of year. There were no differences in breast milk cytokine, SIgA and PGE2 levels between the two intervention groups. However, the levels of several cytokines tended to be higher in colostrum from non-atopic ?-3 supplemented mothers as compared to non-atopic placebo supplemented mothers. Higher levels of TGFß2 and SIgA in 3 months milk were associated with allergic disease at one year of age both with and without detectable IgE.Conclusions: Cord blood LA proportions decreased and LA/LNA ratio increased over the 20 year period between 1985 and 2005 this was not related to total IgE. ?-3 fatty acid supplementation of pregnant and lactating mothers resulted in a lower period prevalence of IgE associated eczema and food allergy in the children at one year of age. This was most pronounced in children of non-allergic mothers. The underlying mechanism requires further clarification.