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- Materials and methods
Background: Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role. However, methodological limitations in the studies make conclusions uncertain. The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4.
Methods: A prospective birth cohort of 4089 new-born infants was followed for 4 years using parental questionnaires at ages 2 months, 1, 2 and 4 years to collect information on exposure and health effects. The response rate at 4 years was 90%. A clinical investigation was performed at age 4 years, which included blood sampling for analysis of specific IgE to common food and airborne allergens.
Results: Parental allergic disease and onset of eczema or wheeze during the first year of life delayed introduction of fish in the child's diet. After exclusion of such children to avoid disease-related modification of exposure, regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age 4, ORadj 0.76 (95% CI 0.61–0.94) and sensitization, ORadj 0.76 (0.58–1.0). The reduced risk appeared most pronounced for multiple disease, ORadj 0.56 (0.35–0.89). IgE-sensitization to fish was only present among 18 of the 2614 children.
Conclusion: Regular fish consumption before age 1 appears to be associated with a reduced risk of allergic disease and sensitization to food and inhalant allergens during the first 4 years of life.
In recent decades consumption of omega-3 polyunsaturated fatty acid has decreased, whereas the consumption of vegetable oil-based products, rich in omega-6 polyunsaturated fatty acid, has increased (1, 2). Omega-3 fatty acids, prevalent in fish and especially in oily fishes, seem to have anti-inflammatory effects in contrast to omega-6 fatty acids which seem to promote inflammation (3, 4). Changes in the fatty acid content of the diet have been proposed to contribute to the increased prevalence of allergic diseases among children (5–8). For several autoimmune diseases such as rheumatoid arthritis, Crohn's disease and ulcerative colitis the omega-3 fatty acids appear to be beneficial in both prevention and treatment (2, 3).
Fish consumption has been associated with a decreased risk of childhood asthma and rhinitis in some studies but the evidence is not conclusive (9–12). In parallel, to reduce the risk for allergic diseases in children parents in many countries have been advised to postpone the introduction of fish for infants with heredity of allergy or early symptoms of allergic diseases (13). In Sweden, allergy-preventive advice regarding avoidance of egg and fish during the first year of life has been given to families with allergic disease during 1979–2001 (14). If such recommendations are followed, a bias resulting from disease-related modification of exposure is likely to be introduced in aetiological epidemiological studies. However, such bias has not been controlled for in previous studies on this topic.
The aim of this study was to investigate the association between fish consumption during the first year of life and development of allergic diseases by age 4 in a prospective birth cohort (BAMSE) controlling for disease-related modification of exposure.
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- Materials and methods
In this prospective cohort study, we observed a reduced risk of asthma, eczema, allergic rhinitis and sensitization at age 4 years among children who consumed fish at least twice a month during the first year of life. After exclusion of children with early symptoms of eczema and/or recurrent wheeze, to control for disease-related modification of exposure, a reduced risk was indicated primarily for eczema, allergic rhinitis and sensitization. The risk reduction seemed to be most pronounced for allergic rhinitis. The lower risk for sensitization was only seen in children without heredity for allergic disease.
The strengths of our study include the large sample size and the population-based design, reasonable numbers of exposed children, and fairly detailed data for fish consumption. We have also been able to assess a large number of potential confounders. After testing several models only parental allergic disease, maternal age, maternal smoking during pregnancy or at enrolment and breastfeeding were identified as confounders. Despite this, we cannot entirely rule out that other, unmeasured dietary factors such as use of cooking oil and intake of trans fatty acids may affect our findings. Furthermore, children with early symptoms of allergic disease or parental allergy had a later introduction of fish in the diet and consumed less fish at 12 months of age. This clearly shows that disease-related modification of exposure and parental allergy need to be controlled in epidemiological studies on fish consumption and allergic disease. However, excluding children with very early symptoms of eczema or recurrent wheeze may be a limitation with regard to generalization of data. The fact that some of our associations, such as the reduced risk of sensitization, in children with regular fish consumption were seen in children without heredity for allergic disease speaks against a residual confounding effect by parental allergy.
One weakness of our study is the absence of data about maternal diet during pregnancy and lactation as fatty acids may be stored for a long time in the human body. But it is probable that the diet of the child reflects the diet in the family and thus regular fish consumption at age 1 may serve as a proxy for the maternal dietary habits during pregnancy and lactation. It would also have strengthened the study if the exposure assessment had been more precise regarding both amount and type of ingested fish, but such information was not available.
Although, the potential association between early fish consumption and allergy has been addressed in several studies, data are not conclusive (8–11). In a Norwegian birth cohort, Nafstad et al. reported a reduced risk of asthma and allergic rhinitis among children who consumed fish during the first year of life (11). However, they did not account for disease-related modification of exposure. The association between omega-3 fatty levels and allergic disease, measured as asthma and atopy, has not been confirmed in some cross-sectional studies among teenagers and adults (21, 22).
In recent years several intervention studies with fish oil supplementation during pregnancy have been published, suggesting an immunomodulating effect (23–25). This is supported in our study where a protective effect of fish consumption on sensitization was indicated.
It is possible that dietary polyunsaturated fatty acids might influence the development of allergic sensitization by increasing the formation of prostaglandin E2, which in turn promotes a Th2 response and stimulates the formation of IgE (1). There is only limited evidence regarding supplementation with fish oil during childhood. In a recent publication of the 3-year follow up of the Australian Childhood Prevention Study, there was a 10% significant reduction in the prevalence of atopic cough associated with such supplementation, but with no effect on other manifestations of allergic disease (26). Intervention with supplementation of omega-3 has not been shown to reduce the severity of concurrent allergic disease in several studies (27, 28). However, in a study from Cardiff, UK supplementation of fish oil markedly reduced the severity of exercise-induced broncho-constriction in elite athletes (29).
IgE sensitization to fish was rare at age 4 years. Only 18 of 2614 tested children had specific IgE antibodies to fish, indicating that fish is probably not an important allergen in the population. This is supported by results of others. In a population-based cohort of children followed up to 7 years of age, only one of 2061 children had a positive skin prick test to cod (30). A low prevalence of sensitization to fish has also been reported from Germany, where less than 1% of children up to 17 years of age had a positive skin prick test to herring (31).
The discrepancy between the marked effects on fish consumption and onset of allergic disease in epidemiological studies compared with the generally limited effects seen in intervention studies may have several explanations. Firstly, the role of polyunsaturated fatty acids in the pathogenesis of allergic disease remains unclear, e.g. absolute and relative quantities of different polyunsaturated and saturated fatty acids may be important. Secondly, it is possible that regular fish consumption is a parallel phenomenon to other exposures and lifestyle factors that may protect from onset of allergic disease. Fish consumption in early life might be a proxy for a lifestyle that reduces the risk of allergic disease. Thirdly, to our knowledge no other previous epidemiological studies have controlled for disease-related modification of exposure. In many populations, parental allergy and early symptoms of allergy are likely to alter both the time for introduction of fish and regular consumption, such as in our cohort.
In conclusion our results indicate that early and regular fish consumption at 1 year of age is associated with a reduced risk of allergic disease (primarily allergic rhinitis and eczema), and sensitization to food and airborne allergens at 4 years of age in children. A risk reduction was also seen for severity of allergic disease such as persistent disease or multiple allergic disease at the age of 4. Sensitization to fish is rare, even among those with early introduction to fish.