(25-01-08) Fish Oil Supplementation in Pregnancy Reduces Key Inflammatory Mediators in Neonates

Maternal consumption of fish oil during pregnancy not only increases the supply of long-chain omega-3 fatty acids (n-3 LC-PUFAs) to the infant for neurodevelopment, it also affects the maturation of the immune system and favors the infant?s neurodevelopment. It may lower the infant?s chance of developing allergic conditions, but findings are inconsistent. Omega-3 LC-PUFAs provided in childhood rather than during fetal development may reduce their potential effectiveness in deterring infant and childhood allergies. However, at least one report suggests that fish oil supplementation in late infancy may hasten the maturation of the immune system.

Susan Prescott and colleagues at the University of Western Australia in Perth have been investigating the effects of maternal consumption of n-3 LC-PUFAs in pregnancy on immune function in the offspring for several years. They reported that high doses of fish oil consumed in pregnancy reduce cytokine responses in the infants at birth and the severity of atopic dermatitis at age 1. In the study described here, these investigators examined the effect of maternal fish oil supplementation on the production of leukotrienes, potent mediators of inflammation, in the neutrophils of newborns.

Ninety-eight pregnant women with a clinical history of allergies and a positive skin prick test to one or more common allergens were randomized to consume either 3.7 g/day of n-3 LC-PUFAs from fish oil or a placebo (olive oil) for the final 20 weeks of pregnancy. Of these women, 83 completed the study and blood samples were available from 64 of them. Groups did not differ in maternal characteristics, gestation, birth weight or length. As expected, maternal and neonatal total and long-chain n-3 PUFAs were significantly higher in the red blood cell membranes of fish oil participants than in the placebo group; n-6 PUFAs were significantly lower.

Leukotriene production was measured in cultured cord blood fetal mononuclear cells stimulated with phytohemaglutinin mitogen. Leukotriene B4 production, especially for the leukotriene B4 isomer 2, was significantly lower in the neonates of mothers who had consumed fish oil compared with those in the placebo group. Another product of lipoxygenase activity, 5-HETE, was also appreciably lower in the neonates of the fish oil mothers, but the difference from the placebo group did not quite reach statistical significance (P=0.054). LTB4 was associated with higher maternal levels of adrenic acid (22:4n-6), but not significantly with arachidonic or linoleic acid levels. Leukotriene B5, the lipoxygenase product of eicosapentaenoic acid, was present at low levels in some samples of fish oil neonates, but not in placebo neonates. Its presence was consistently and significantly associated with higher levels of maternal n-3 LC-PUFAs and lower n-6 PUFAs in red blood cell phospholipids.

The investigators also looked at the neonatal antigen presenting cell responses to stimulation with interferon-? and lipopolysaccharide in mononuclear cells. These cells produced the proinflammatory mediator interleukin-6 and responses were correlated with LTB4, and 5-HETE production. Production of interleukin-10, which inhibits inflammatory responses, increased. The authors suggested that this might have been the cells? attempt to diminish the effects of inflammation. In the fish oil neonates, these responses were significantly down-regulated. Other assessments of immune function, T cell stimulation and up-regulation of antigen presentation, were consistent with these findings.

The key finding from this study is that maternal LC-PUFA status, as affected by fish oil consumption during pregnancy, significantly altered the pattern of neonatal red cell LC-PUFAs and eicosanoid metabolites, and inhibited neutrophil LTB4 production. This and other effects on immune function indicate that maternal fatty acid intake during pregnancy can modify the infant?s immune responses, with fish oil consumption having a dampening effect. Moderation of the production of pro-inflammatory cytokines may discourage or delay the development of allergic diseases which are characterized by inflammation. The observed immune responses were highly correlated with maternal and infant red blood cell LC-PUFA composition. These observations accord with previous studies in adults.

These studies have provided useful information in showing the various ways that maternal fatty acid intake and status can affect an infant?s maturing immune system. They underline the need to understand much more about neonatal and childhood immune responses to nutrient status, especially regarding LC-PUFAs, so that eventually we may lessen the burden and severity of immune-based diseases.
Prescott SL, Barden AE, Mori TA, Dunstan JA. Maternal fish oil supplementation in pregnancy modifies neonatal leukotriene production by cord blood derived neutrophils. Clin Sci (London) 2007;113:409-416

Source: PubMed - Clin Sci (Lond). 2007 Nov;113(10):409-16.

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