High-Dose Omega-3s Linked to Reduced Cumulative Allergic Disease up to Age 2

The literature on the relationships between dietary fatty acids and the risk of allergy, especially in infants at high risk of developing eczema, asthma or allergic rhinitis, is fraught with inconsistencies. Omega-6 (n-6) and omega-3 (n-3) PUFAs have been associated with increased or reduced risk of allergic diseases, but the existing data do not permit firm conclusions. The effect of maternal supplementation with n-3 long-chain (LC) PUFAs in pregnancy is also unclear, although plausible reasons and evidence why these PUFAs might have anti-allergic effects, including lower sensitization to common food allergens, have been described. In general, fish oil or n-3 LC-PUFA supplementation during pregnancy has been associated with changes in several immune responses, but only modest effects on the occurrence or severity of allergic diseases. A recent systematic review of 5 randomized controlled trials reported that n-3 LC-PUFA supplementation during pregnancy reduced the 12-month prevalence of a positive egg skin prick test in 2 trials, reduced childhood asthma in 2 trials and significantly reduced cord blood interleukin-13 levels. The latter is a mediator of allergic inflammation and disease. All trials concluded that maternal fish intake in pregnancy was associated with protective effects. In contrast, researchers in Australia reported that breastfed infants born into families with a history of allergic disease had higher rates of food sensitivity with higher colostrum levels of n-3 LC-PUFAs. The investigators of the present study conducted a randomized controlled trial of n-3 LC-PUFA supplementation in 145 pregnant women affected by allergic disease or having a husband or previous child with allergies. The study provided a total of 2.7 g of n-3 LC-PUFAs (1.6 g EPA and 1.1 g DHA) per day from the 25^th week of gestation through 3 to 4 months’ breastfeeding. Food allergies were assessed by skin prick tests and serum IgE antibodies were measured. Initial results from the assessments in the infants at 6 and 12 months of age reported a significantly lower prevalence of positive egg skin prick tests and IgE-associated eczema in the infants of n-3 LC-PUFA-supplemented mothers compared with the soy oil control infants. This article reports the results in these children up to 2 years of age. From the original 145 participants, follow-up at 2 years was completed for 143, although 40 participants did not complete the entire intervention. The average duration of supplementation was 31 weeks. There was no difference in the prevalence or frequency of allergic symptoms between the intervention and control groups up to age 2 years. However, the cumulative incidence of IgE-associated disease and allergic sensitization was significantly lower in the n-3 LC-PUFA children compared with the control group (13% vs 30%, P = 0.01). As shown in the table, the odds of a child of an n-3 LC-PUFA-supplemented mother developing a positive skin prick response to egg, milk and/or wheat, or IgE-mediated food reactions or IgE-associated disease were significantly lower compared with infants of placebo mothers. These findings support those of Dunstan and colleagues for infants at 12 months of age. IgE-mediated food reactions, IgE-associated eczema and any IgE-associated disease were significantly less frequent in the children of n-3 LC-PUFA-supplemented mothers compared with the placebo group. TABLE Plasma n-3 LC-PUFAs were higher in the n-3 LC-PUFA-supplemented mothers and infants during the first year, but the difference disappeared by the age of 2 years. Likewise the cumulative incidence of IgE-associated disease was lower in the children of mothers in the highest plasma phospholipid DHA quartile at 12 months, but the difference was not sustained at 24 months. The occurrence of more than one allergic symptom, e.g., food allergy and eczema, in symptomatic infants was lower in the n-3 LC-PUFA infants (32%) compared with the placebo group (50%) during the first 2 years, but the difference was not statistically significant. Multiple symptoms were more frequent in infants with IgE-associated disease than in infants without sensitization. Severity of eczema symptoms assessed by SCORAD did not differ between the two groups, although the number of infants in each group was small. Further, infants with eczema were treated intensively once symptoms appeared. The investigators noted that dose is likely an important factor in the relationship between allergic symptoms and allergic sensitization. Studies supplementing high-risk mothers with approximately 3 g/day n-3 LC-PUFAs have tended to report significant reductions in allergic manifestations compared with studies using lower doses. They also commented that the relationship between n-3 LC-PUFA supplementation and clinical symptoms appears to be of greater biologic importance when combined with allergic sensitization than when considered solely on their own. Maternal history of allergy may also be an important factor in the anti-allergic and sensitization effects of n-3 LC-PUFAs. As observed by others, responses to n-3 LC-PUFAs in infants whose mothers had a history of allergy were less robust (IgE-associated disease 12% vs 26% in the placebo group) compared with infants whose mothers did not have allergic symptoms (7% vs 39%). A consistent observation in the literature is that dietary n-3 LC-PUFAs are not associated with a reduced occurrence of allergic disease, nor do they prevent it, but they may reduce its frequency and severity. This report suggests that the cumulative effects of these fatty acids on IgE-associated disease may persist until 2 years of age. We do not know what an optimal dose range might be, how long the fatty acids need to be consumed, or whether consumption continued into childhood might be beneficial. Guidance to parents for feeding infants at high-risk of allergic disease has been updated by the American Academy of Pediatrics and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Both organizations emphasize the importance of breastfeeding for about 6 months as a desirable goal, with the introduction of complementary foods by 26 weeks of age and not before 17 weeks. There are no recommendations to avoid or delay the introduction of potentially allergenic foods, such as fish or eggs. These guidelines do not offer recommendations for maternal diet during pregnancy and lactation, but two large German birth cohort studies reported evidence that high maternal intakes of margarine, vegetable oils and some allergenic fruits and vegetables were associated with a greater risk of infant allergies. Data may still be too sparse and inconsistent for recommendations to increase fish or n-3 LC-PUFA consumption for reducing the risk of infant allergies, but the topic warrants a close watch. Data such as these suggest that the current recommendation of at least 200 mg of DHA per day during pregnancy and lactation may be too low to reduce the risk of allergic disease in high-risk pregnancies.   Furuhjelm C, Warstedt K, Fagerås M, Fälth-Magnusson K, Larsson J, Fredriksson M, Duchén K. Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatr Allergy Immunol 2011;22:505-514. [PubMed]