Janet Dunstan

Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial.

Objective: To assess the effects of antenatal omega 3 long-chain polyunsaturated fatty acid (n-3 LC PUFA) on cognitive development in a cohort of children whose mothers received high-dose fish oil in pregnancy. Design: A double-blind randomised placebo-controlled trial. Setting: Perth, Western Australia, Australia. Patients: 98 pregnant women received the supplementation from 20 weeks’ gestation until delivery. Their infants (n = 72) were assessed at age 2½ years. Interventions: Fish oil (2.2 g docosahexaenoic acid (DHA) and 1.1 g eicosapentaenoic acid (EPA)/day) or olive oil from 20 weeks’ gestation until delivery. Outcome measures: Effects on infant growth and developmental quotients (Griffiths Mental Development Scales), receptive language (Peabody Picture Vocabulary Test) and behaviour (Child Behaviour Checklist). Results: Children in the fish oil-supplemented group (n = 33) attained a significantly higher score for eye and hand coordination (mean ((SD) score 114 (10.2)) than those in the placebo group (n = 39, mean score 108 (SD 11.3); p = 0.021, adjusted p = 0.008). Eye and hand coordination scores correlated with n-3 PUFA levels in cord blood erythrocytes (EPA: r = 0.320, p = 0.007; DHA: r = 0.308, p = 0.009) and inversely correlated with n-6 PUFA (arachidonic acid 20:4n-6: r = −0.331, p = 0.005). Growth measurements in the two groups were similar at age 2½ years. Conclusion: Maternal fish oil supplementation during pregnancy is safe for the fetus and infant, and may have potentially beneficial effects on the child’s eye and hand coordination. Further studies are needed to determine the significance of this finding.

Clinical effects of probiotics are associated with increased interferon‐γ responses in very young children with atopic dermatitis

Background We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate‐to‐severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits.

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition

Objective: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition.Design: A double-blind, randomised, placebo-controlled study.Setting: Subiaco, Western Australia.Subjects: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study.Interventions: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery.Main outcome measures: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth.Results: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group.Conclusions: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made.Sponsorship: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition

Background Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development.

Fish Oil Supplementation in Pregnancy Modifies Neonatal Progenitors at Birth in Infants at Risk of Atopy

Dietary n-3 polyunsaturated fatty acids (PUFA) may represent a mode of allergy prevention. Cord blood (CB) CD34+ hemopoietic progenitors are altered in infants at risk of atopy. We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at high risk of atopy. In a double-blind study, atopic, pregnant women were randomized to receive fish oil capsules or placebo from 20 wk gestation until delivery. At birth, CB CD34+ cells were isolated and analyzed by flow cytometry for expression of cytokine (IL-5Rα, IL-3Rα, granulocyte/macrophage colony-stimulating factor Rα) or chemokine (CXCR4 and CCR3) receptors. CB cells were also cultured in methylcellulose assays for eosinophil/basophil colony-forming cells. At age 1 y, infants were clinically assessed for atopic symptoms and skin tests. Percentages of CB CD34+ cell numbers were higher after n-3 PUFA than placebo. Co-expression of cytokine or chemokine receptors on CD34 cells was not altered by n-3 PUFA supplementation. However, there were significantly more IL-5-responsive CB eosinophil/basophil colony forming units (Eo/B-CFU) in the fish oil, compared with the control, group. Overall, there was a positive association between CD34+ cells and IL-5-responsive Eo/B-CFU in CB and 1 y clinical outcomes, including atopic dermatitis and wheeze. Dietary n-3 PUFA supplementation during pregnancy in atopic mothers alters infant cord blood hemopoietic progenitor phenotype. This may have an impact on development of atopic disease.

The Effects of Fish Oil Supplementation in Pregnancy on Breast Milk Fatty Acid Composition Over the Course of Lactation: A Randomized Controlled Trial

This study evaluated the longitudinal effect of fish oil in pregnancy on breast milk fatty acid composition and infant outcomes. In a randomized, controlled trial, 98 women received 2.2 g docosahexaenoic acid (DHA) and 1.1 g eicosapentaenoic acid (EPA) or olive oil from 20 wk of gestation until delivery. Fatty acid composition in breast milk (at 3 d, 6 wk, and 6 mo) and infant erythrocyte membranes (at 1 y) were determined by gas liquid chromatography. Breast milk fatty acids were examined in relationship to growth and development. Compared with control group, breast milk from women who received fish oil had proportionally higher DHA and EPA levels at 3 d and 6 wk after delivery, but this difference was no longer apparent by 6 mo. Infant DHA status at 1 y of age was directly related to DHA levels at 3 d, 6 wk, and 6 mo postpartum (but not to antenatal supplementation). Both EPA and DHA in breast milk were positively correlated with Griffiths developmental scores including hand and eye coordination. Thus, supplementation in pregnancy was associated with increased n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in breast milk, particularly in early lactation, and this was positively associated with infant DHA status at 1 y.

Fish oil supplementation in pregnancy lowers F2-isoprostanes in neonates at high risk of atopy

The anti-inflammatory properties of n-3 polyunsaturated fatty acids (n-3 PUFA) have suggested a potential role of these nutrients in dietary modification for prevention of allergic disease in early life. As oxidative stress is known to modify antigen presenting cell (APC) signalling and resulting immune responses, we examined the effects of maternal n-3 PUFA supplementation in pregnancy on markers of oxidative stress and APC function in neonates at high risk of allergy. Eighty-three pregnant atopic women were randomised to receive 4 g daily of either fish oil (n=40) or olive oil (n=43) capsules in a controlled trial from 20 weeks gestation until delivery. Plasma (cord blood) and urinary F2-isoprostanes were measured as markers of lipid peroxidation. Cord erythrocyte fatty acids and markers of APC function (HLA-DR expression and cytokine responses) were measured and related to levels of plasma F2-isoprostanes. Maternal fish oil supplementation lowered plasma (p<0.0001) and urinary (p=0.06) F2-isoprostanes. HLA-DR expression on APC was not different between the groups. In multiple regression analysis, 28.8% of the variance in plasma F2-isoprostanes was explained by positive relationships with erythrocyte arachidonic acid (AA) and monocyte HLA-DR expression and a negative relationship with erythrocyte eicosapentaenoic acid (EPA). This study shows that maternal supplementation with fish oil can attenuate neonatal lipid peroxidation. Clinical follow-up of these infants will help to determine if there are sustained effects on postnatal oxidative stress and expression of allergic disease.

Postnatal Fish Oil Supplementation in High-Risk Infants to Prevent Allergy: Randomized Controlled Trial

BACKGROUND AND OBJECTIVE: Relative deficiency of dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) has been implicated in the rising allergy prevalence in Westernized countries. Fish oil supplementation may provide an intervention strategy for primary allergy prevention. The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease. METHODS: In a double-blind randomized controlled trial, 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control (olive oil), from birth to age 6 months. PUFA levels were measured in 6-month-old infants’ erythrocytes and plasma and their mothers’ breast milk. Eczema, food allergy, asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age. RESULTS: At 6 months of age, infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher (both P < .05) and erythrocyte arachidonic acid levels were lower (P = .003) in the fish oil group. Although n-3 PUFA levels at 6 months were associated with lower risk of eczema (P = .033) and recurrent wheeze (P = .027), the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes. Specifically, between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization, eczema, asthma, or food allergy. CONCLUSIONS: Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease.

Early markers of allergic disease in a primary prevention study using probiotics: 2.5-year follow-up phase

Background:  We previously reported that a Lactobacillus acidophilus probiotic strain (LAFTI® L10/LAVRI‐A1) given for the first 6 months of life increased the risk of allergen sensitization at 1 year of age.

Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods

Background and objectives A reduced capacity of antigen presenting cells (APC) to provide pro‐T helper 1 (Th1) signals, such as IL‐12, to T cells during early life may be implicated in the development of T helper 2 (Th2)‐mediated allergic disease. In this study we examined the relationships between the capacity for IL‐12 responses in the neonatal period and atopic risk (family allergy), in vitro T cell responses to allergens, and the subsequent development of allergic disease at 6 years