A.L. Taylor

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.

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

Effects of probiotic supplementation for the first 6 months of life on allergen- and vaccine-specific immune responses

Background A reduction in microbial burden during infancy when allergen‐specific memory is evolving has become a prominent explanation for the allergy epidemic.

FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth

Factors that influence immune regulation in early life may be implicated in the rise in allergic disease, including reduced microbial burden. The aim of the study was to examine the infant regulatory T‐cell function in relation to (a) probiotic supplementation for the first 6 months of life and (b) the subsequent development of an early allergic phenotype. Two hundred and thirty‐one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic or placebo daily for the first 6 months of life. One hundred and seventy‐eight children completed the study, with blood samples available from 118 (60 placebo; 58 probiotic). CD4+CD25+CTLA4+T‐regulatory phenotype and allergen‐induced FOXP3 mRNA expression were compared in relation to this intervention as well as according to evidence of early disease (atopic dermatitis). The administration of probiotics was not associated with any significant differences in the proportion of circulating CD4+CD25+CTLA4+cells, or in the resting expression of FOXP3. There were also no relationships between these parameters and patterns of gut colonization, and this probiotic did not reduce the risk of atopic dermatitis. Children who developed atopic dermatitis (n = 36/118) had significantly higher induced FOXP3 expression following stimulation with both house dust mite (HDM) (p = 0.017) and ovalbumin (OVA) allergens (p = 0.021) than those that did not develop atopic dermatitis. Although this relationship was seen in both the probiotic and placebo groups, it was more pronounced in the probiotic group. However, regression analysis demonstrated that higher allergen‐induced FOXP3 expression was predicted by the presence of atopic dermatitis (p = 0.018) rather than probiotics supplementation (p = 0.217). The higher levels of allergen‐induced FOXP3 in atopic dermatitis suggest activation of these compensatory mechanisms rather than a primary defect in this pathway. Probiotic supplementation and gut colonization did not appear to substantially modify these regulatory pathways, or the risk of developing atopic dermatitis.

Evaluation of the effects of probiotic supplementation from the neonatal period on innate immune development in infancy

Background Activation of the innate immune system by microbial stimulation is believed to be critical for normal immune maturation, and there has been speculation that these pathways are important for inhibiting allergic‐immune responses.

Relationship between early intestinal colonization, mucosal immunoglobulin A production and systemic immune development

Background Variations in early intestinal colonization patterns have been implicated in the predispostion to allergic disease through effects on mucosal and systemic immune function.

Maternal reactivity to fetal alloantigens is related to newborn immune responses and subsequent allergic disease

Background Maternal allergy confers stronger allergy risk (than paternal allergy) suggesting that maternal patterns of immune response can directly influence immune development in offspring. Women prone to allergic immune responses to allergens may also have altered immune responses to other antigens including fetal antigens.

The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age

With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non‐smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin‐prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non‐typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty‐two mothers and their infants completed the 12‐month follow‐up period – 56 in the maternal non‐smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendalls tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti‐microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity.

Pregnancy IFN‐γ responses to foetal alloantigens are altered by maternal allergy and gravidity status

Background:  During pregnancy, variations in maternal–foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies.

Cytosine–phosphate–guanine motifs fail to promote T‐helper type 1‐polarized responses in human neonatal mononuclear cells

Background The T‐helper type 1 (Th1) trophic properties of bacterial cytosine–phosphate–guanine (CpG) motifs have made them logical adjuvants both for the suppression of Th2‐mediated allergic disease in early life and for promoting vaccine responses in neonates who have relatively immature Th1 function. However, little is known about their effects on immature immune responses in this period.