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 ω-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 ω-6) and α-linolenic acid (LNA, C18:3 ω-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 ω-6) and docosahexaenoic acid (DHA, C22:6 ω-3) as well as other ω-6 and ω-3 fatty acids increased significantly during the same time period. No correlations were found between ω-6 and ω-3 fatty acids and total IgE antibodies.

Proportions of ω-3 LCPUFA increased in the ω-3 supplemented group of mothers.

Lipopolysaccharide-induced prostaglandin E₂ secretion in whole blood culture decreased in a majority of ω-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 ω-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 (ω-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 ω-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. ω-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.

Background: A connection has been proposed between the increase of allergic disease and the altered composition of fatty acids in the diet in the westernised world. Less oily fish and more vegetable oil are consumed today compared to 50-100 years ago. Programming of the immune responses takes place very early in life and environmental factors, such as fish in the diet, have been suggested to protect from infant allergy.

Aim: The general aim of this thesis was to assess the effects of maternal dietary supplementation with ω-3 long chain polyunsaturated fatty acids (LCPUFA), i.e. fish oil, in pregnancy and lactation on the development of allergic symptoms and sensitisation in the infants as well as some immunological markers in mothers and infants.

Subjects and methods: This thesis is based on the results from a prospective double-blind placebo-controlled multi-centre trial comprising 145 families. Pregnant women, at risk of having an allergic infant, were recruited at the antenatal clinics and randomised to daily supplementation with 1.6 g eicosapentaenoic acid (EPA, C20:5ω-3) and 1.1 g docosahexaenoic acid (DHA, C22:6ω-3) or placebo, starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Phospholipid fatty acids in maternal and infant plasma were analysed to assess compliance. Maternal prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokines along with infant vaccine induced responses and chemokines were analysed with ELISA and Luminex techniques. Clinical outcomes were allergic disease and positive skin prick test/detectable circulating IgE antibodies to common allergens.

Results: Phospholipid proportions of ω-3 LCPUFA increased significantly in the ω-3 supplemented women and their infants. Lipopolysaccharide-induced PGE2 secretion from whole blood culture supernatants decreased in a majority of the ω-3-supplemented mothers (p<0.01). The decrease in PGE2 production was more pronounced among non-atopic than atopic mothers. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE associated eczema and IgE mediated food allergy was though reduced in the ω-3 group during the first two years (OR=0.2 and 0.3 compared to placebo, p<0.05 for both). The cumulative incidence of any IgE associated disease during the first two years of life was 13% in the ω-3 supplemented group compared to 30% in the placebo group (p=0.01, OR 0.3, p<0.05). This effect was most evident in infants of non-allergic mothers. Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05), in a dose dependent manner. In addition, no allergic symptoms as compared to multiple allergic symptoms in the infants, regardless of sensitisation, were related to higher maternal and infant ω-3 LCPUFA status (p<0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CC-chemokine ligand 17 (CCL17)/ CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p<0.05). Furthermore in non-allergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p<0.05), as well as increased IgG titres to diphtheria (p=0.01) and tetanus (p=0.05) toxins.

Conclusions: A decreased cumulative incidence of IgE associated disease in the infants was found after maternal ω-3 LCPUFA supplementation as well as a reverse dose response relationship between maternal ω-3 LCPUFA status and infant IgE associated disease. Higher plasma proportions of DHA and EPA in were also associated to less severe allergic disease. A tendency towards strengthened Th1 associated response after maternal ω-3 LCPUFA supplementation was indicated in the analysis of maternal and infant immunological markers. These effects, as well as the clinical outcomes, were more pronounced in non-allergic individuals, suggesting gene-by-environment interactions.