Malin Barman

High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development

Background Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18∶1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (Ptrend<0.001), n-6 LCPUFA (Ptrend = 0.001), and total LCPUFA (Ptrend<0.001) and decreased linearly with the proportions of total MUFA (Ptrend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infants immune system.

No association between allergy and current 25-hydroxy vitamin D in serum or vitamin D intake

Vitamin D may be involved in allergy development, but there is conflicting evidence. We investigated if dietary intake of vitamin D and levels of 25OHD in serum differed between allergic and nonallergic adolescents and if serum 25OHD correlated with dietary intake of vitamin D or season of blood sampling.

Fat intake and breast milk fatty acid composition in farming and nonfarming women and allergy development in the offspring.

Background:Children growing up on small family farms are at much lower risk of developing allergy than other children. We hypothesized that low intake of margarine and polyunsaturated fats among farming families could contribute to this protection.Methods:Twenty-eight mother–infant pairs living on small dairy farms and 37 nonfarm rural resident pairs were recruited in the FARMFLORA birth cohort. Food items expected to affect dietary fat composition were recorded by food frequency questionnaires during pregnancy and by 24-h recalls followed by 24-h food diaries during lactation. Allergy was diagnosed by doctors, using strict predefined criteria. Maternal diet and breast milk fat composition were compared between farming and nonfarming mothers and related to children’s allergy at age 3 y.Results:Farming mothers consumed more butter, whole milk, saturated fat, and total fat than nonfarming mothers, who consumed more margarine, oils, and low-fat milk. Farming mothers’ breast milk contained higher proportions of saturated and lower proportions of polyunsaturated fat. Allergy was eight times more common in nonfarm children. Mothers of allergic children consumed more margarine and oils than mothers of nonallergic children.Conclusion:Low maternal consumption of margarine and vegetable oils might contribute to the allergy-preventive effect of growing up on small dairy farms.

Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema

Long‐chain polyunsaturated fatty acids (LCPUFAs) are immunomodulatory, but their role in allergy development is controversial. We investigated whether proportions of LCPUFAs in serum phospholipids were related to allergic diagnosis, seafood intake and LCPUFA proportions in cord blood.

Serum fatty acids in infants, reflecting family fish consumption, were inversely associated with allergy development but not related to farm residence.

In this study, differences in serum fatty acid patterns between farm and nonfarm infants were investigated and related to subsequent allergy development. We also related allergy‐related serum fatty acids to maternal diet and breast milk fatty acids.

Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort).

Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.

Diet in 1-year-old farm and control children and allergy development: results from the FARMFLORA birth cohort

Background A farming environment confers strong protection against allergy development. We have previously shown that farming mothers consume more full-fat dairy than control mothers, who instead consume more low-fat dairy, margarine, and oils; margarine and oil intake was associated with increased risk of allergy development in their children. Objectives The aims of this study were to investigate the differences in diet between children in farming and control families at 1 year of age, to investigate the relation between the diets of the mothers and their children, and to relate the childrens diet to allergy development. Design The diet of 1-year-old children from dairy farming families (n=28) and from control families in the same rural area (n=37) was assessed by 24-h dietary recalls, followed by 24-h food diaries. Allergy was diagnosed by pediatricians at 3 years of age using strict predefined criteria. Results Farm children had a higher intake of farm milk, whole cream, cholesterol, saturated fat, and fat in total and tended to eat more butter, while controls consumed more carbohydrates and poultry and tended to eat more margarine. Farm children also had higher intakes of homemade porridge/gruel, oily fish, and iodine. The intake of butter and whole milk in children and mothers correlated significantly in farm families but not in controls. A weak negative association was found between seafood intake and allergy development, while allergy was positively associated with the intake of pork as well as zinc in the control group; these intakes also correlated with each other. Conclusions Consistent with mothers in farming families, the children consumed more full-fat dairy and saturated fat than did controls, but this could not be linked to the low risk of allergy in the farming group. Seafood intake might protect against allergy development, in accordance with earlier findings.

Late introduction of fish and eggs is associated with increased risk of allergy development – results from the FARMFLORA birth cohort

ABSTRACT The prevalence of allergy is markedly low in children growing up on farms. An increasing number of studies indicate that the timing of food introduction may affect allergy development. We aimed to investigate if protection against allergy in farm environments may be mediated through differences in food-introduction practices between farm and non-farm families, using an explorative approach. Twenty-eight farm and 37 non-farm children were included in the FARMFLORA birth cohort. Practices of breastfeeding and introduction of formulas and complementary foods were collected by questionnaires at 6, 12, and 18 months of age. Allergy was diagnosed by pediatricians at 3 years of age. The only difference in food-introduction practices observed between farm and non-farm children was an earlier introduction of nuts in farmers (median month: 11 [IQR: 8–6] in farmers, 15 [12–19] in non-farmers). One farm child (4%) and 10 non-farm children (27%) were allergic at 3 years of age. Lower risk of allergy development was associated with early exclusive breastfeeding (continuous variable; OR = 0.59, 95% CI: 0.39–0.89), but also having received eggs (OR = 0.08, 95% CI: 0.13–0.54) and fish (logistic regression not applicable, P = 0.01 in likelihood ratio testing [χ2]) at 10 months of age or earlier compared to later. Our results were not affected by reverse causation, as judged by a questionnaire sent to the families in retrospect. Timing of introduction of complementary foods is unlikely to contribute to the lower risk of allergy among farm children. Although early exclusive breastfeeding was associated with a lower rate of allergy development, postponed introduction of complementary foods might increase the risk of developing allergy. Owing to the limited sample size, our results are only indicative, but support prior findings.

Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden

Introduction Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, ‘Nutritional impact on Immunological maturation during Childhood in relation to the Environment’ (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures—diet, microbes and environmental toxicants—during pregnancy and early childhood, on the maturation of the infant’s immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health. Methods and analysis The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015–2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health. Ethics and dissemination The NICE cohort has been approved by the Regional Ethical Review Board in Umeå, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.

Effect of maternal supplementation with fish oil during pregnancy and lactation on allergy development in childhood

Allergic diseases have increased rapidly during the past few decades, and both environmental and genetic factors appear to play a role. For example, observational studies have found associations between maternal fish intake during pregnancy and protection against allergic disease in their offspring (1). Oily fish is rich in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), and several attempts has been made to influence allergic development in offspring by providing maternal supplementation with fish oil during pregnancy and/or lactation. In a double-blind randomised controlled trial in Link€oping, Sweden, from 2003 to 2005, 145 pregnant mothers at risk of having infants with allergies were given either omega-3 LCPUFA supplementation or a soya bean oil placebo from gestational week 25 until three months after they gave birth. The children were followed up clinically at three, six, 12 and 24 months of age (2). At 12 months of age, maternal fish oil supplementation was associated with a lower prevalence of food allergy, immunoglobulin E (IgE)-associated eczema, sensitisation to egg and any positive skin prick test. At 24 months of age, no associations were found between maternal fish oil supplementation and allergic diseases or sensitisation (2). In this issue of Acta Paediatrica, a followup study by Warstedt et al. (3) aimed to examine the association between maternal omega-3 LCPUFA supplementation, omega-3 LCPUFA proportions in breast milk and allergic diseases at two years of age. Higher proportions of omega-3 LCPUFAs were observed in the breast milk of the supplemented mothers and were associated with lower levels of IgE-associated eczema and food reactions in the first two years of life. This randomised controlled study was conducted more than 10 years ago, yet only allergy diagnoses at two years of age were reported. It is well known that allergic phenotypes may change throughout the first years of life and that eczema and food allergies are most prevalent around one and two years of age, while respiratory allergy usually appears for the first time after four years of age. In young children, wheezing phenotypes are often caused by viral respiratory infections rather than allergies. For example, a child diagnosed with eczema at two years of age may be free from allergic symptoms later in childhood. Hence, it would have been of great interest to evaluate the association between maternal omega-3 LCPUFA supplementation and allergy in these children when they were older than two years of age. Furthermore, the authors conclude that the proportions of the omega-3 LCPUFAs eicosapentaenoic acid and docosahexaenoic acid in breast milk were related to a protective effect of the development of IgE-associated allergic diseases in infancy. Based on their results, they suggest that supplementation must occur both during pregnancy and lactation (3). We have previously proposed that the perinatal period of life is of high importance for later allergy development (4). In the study by Warstedt et al. (3), the effect of supplementation of omega-3 LCPUFA on allergy was not evaluated separately during pregnancy and lactation. Hence, it is difficult to draw conclusions about the role of the omega-3 LCPUFA content in breast milk per se. The effect of supplementation may be set already during pregnancy, and there is no clear evidence from this study of a direct effect of supplementation during lactation, as children who received high breast milk proportions of omega-3 LCPUFA also received high levels of omega-3 LCPUFA during pregnancy.