Norma D. Diaper

Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood

Mononuclear cells in umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs in utero is unknown. We investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (> or =37 weeks of gestation). Der p 1 was detectable in 24 of 43 amniotic fluid samples where it was also present in maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 in the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.

Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review.

There are two main families of polyunsaturated fatty acids (PUFAs), the n−6 and the n−3 families. It has been suggested that there is a causal relationship between n−6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n−6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n−3 PUFAs and these fatty acids act to oppose the actions of n−6 PUFAs. Thus, it is considered that n−3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n−3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n−3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.

Increased intake of oily fish in pregnancy: effects on neonatal immune responses and on clinical outcomes in infants at 6 mo

BACKGROUND Long-chain n-3 PUFAs found in oily fish may have a role in lowering the risk of allergic disease. OBJECTIVE The objective was to assess whether an increased intake of oily fish in pregnancy modifies neonatal immune responses and early markers of atopy. DESIGN Women (n = 123) were randomly assigned to continue their habitual diet, which was low in oily fish, or to consume 2 portions of salmon per week (providing 3.45 g EPA plus DHA) from 20 wk gestation until delivery. In umbilical cord blood samples (n = 101), we measured n-3 fatty acids, IgE concentrations, and immunologic responses. Infants were clinically evaluated at age 6 mo (n = 86). RESULTS Cord blood mononuclear cell (CBMC) production of interleukin (IL)-2, IL-4, IL-5, IL-10, and tumor necrosis factor-α in response to phytohemagglutinin (PHA) and of IL-2 in response to Dermatophagoides pteronyssinus allergen 1 (Derp1) was lower in the salmon group (all P ≤ 0.03). In the subgroup of CBMCs in which an allergic phenotype was confirmed in the mother or father, IL-10 production in response to Toll-like receptor 2, 3, and 4 agonists, ovalbumin, salmon parvalbumin, or Derp1 and prostaglandin E(2) production in response to lipopolysaccharide or PHA was lower in the salmon group (all P ≤ 0.045). Total IgE at birth and total IgE, incidence and severity of atopic dermatitis, and skin-prick-test positivity at 6 mo of age were not different between the 2 groups. CONCLUSION Oily fish intervention in pregnancy modifies neonatal immune responses but may not affect markers of infant atopy assessed at 6 mo of age. This trial is registered at clinicaltrials.gov as NCT00801502.

Immunoregulatory molecules during pregnancy and at birth

Regulation of the maternal immune response to the fetal allograft is essential for the success of pregnancy and delivery of a well-developed neonate. Numerous mechanisms have been postulated to mediate this. We hypothesised that the potent immunosuppressive molecules TGF-beta1 and IL-10 could contribute to this regulation in the mother and neonate during gestation. In comparison to non-pregnant women, TGF-beta1 and cortisol levels were increased significantly in mid (16-18 weeks) and late pregnancy (>37 weeks, no labour), with levels of both highest in late gestation. In contrast, IL-10 levels were significantly lower in maternal plasma in mid-gestation compared with that from late pregnancy and from non-pregnant women. TGF-beta1, IL-10 and cortisol were all detectable in umbilical cord blood plasma with TGF-beta1 levels significantly decreased in association with labour in contrast to cortisol levels that increased with labour. IL-10 levels in cord plasma were comparable to those of adults and did not change with mode of delivery. Elevated levels of TGF-beta1, but not IL-10, in the maternal and neonatal circulation could have a role in immunoregulation of the maternal response to the fetal allograft as well as growth and development of the fetus.

Salmon Consumption during Pregnancy Alters Fatty Acid Composition and Secretory IgA Concentration in Human Breast Milk

Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-β (TGFβ)1, TGFβ2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P ≤ 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P < 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1-28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear.

Effect of salmon consumption during pregnancy on maternal and infant faecal microbiota, secretory IgA and calprotectin

The gut microbiota plays an important role in the development of the immune and gastrointestinal systems of infants. In the present study, we investigated whether increased salmon consumption during pregnancy, maternal weight gain during pregnancy or mode of infant feeding alter the markers of gut immune defence and inflammation. Women (n 123) who rarely ate oily fish were randomly assigned to continue consuming their habitual diet or to consume two 150 g portions of farmed salmon per week from 20 weeks of pregnancy to delivery. Faecal samples were collected from the mothers (n 75) at 38 weeks of gestation and from their infants (n 38) on days 7, 14, 28 and 84 post-partum. Fluorescence in situ hybridisation was used to determine faecal microbiota composition and ELISA to measure faecal secretory IgA (sIgA) and calprotectin concentrations. There was no effect of salmon consumption on maternal faecal microbiota or on maternal or infant faecal sIgA and calprotectin concentrations. The degree of weight gain influenced maternal faecal microbiota, and the mode of infant feeding influenced infant faecal microbiota. Faecal samples collected from infants in the salmon group tended to have lower bacterial counts of the Atopobium cluster compared with those collected from infants in the control group (P=0·097). This difference was significant in the formula-fed infants (P< 0·05), but not in the exclusively breast-fed infants. In conclusion, the impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences are associated with maternal weight gain during pregnancy and mode of infant feeding.

Plasma Inflammatory and Vascular Homeostasis Biomarkers Increase During Human Pregnancy but Are Not Affected by Oily Fish Intake

The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.

The effect of labor on neonatal T-cell phenotype and function

With increasing interest in the role of fetal programing in child and adulthood diseases, and therefore interest in the measurement of various factors at birth, it is essential to ascertain whether the factors of interest show any gestation- or parturitionassociated changes. We have investigated whether mode of delivery influenced T-cell phenotype and function (CD4+) as has been described for monocytes and neutrophils. Interferon-γ production in response to either the mitogen phytohemagglutinin or anti-CD2/CD3/CD28 F(ab′)3 was significantly reduced by neonatal mononuclear cells compared with adult cells but did not differ with mode of delivery at term (normal vaginal delivery versus elective lower-segment cesarean section). Likewise, anti-CD2/CD3/CD28-stimulated IL-2 production by the neonate was lower than adult levels but did not differ with mode of delivery. The expression of common T-cell activation markers (CD25, MHC class II, CD69, CD62L, CD11a, CD44, and CD49d) was examined. Only CD62L (L-selectin) expression was significantly different, with fewer adult T cells expressing this surface antigen compared with neonatal T cells (p < 0.0003), and significantly more T cells from lower-segment cesarean section than normal vaginal delivery were positive for CD62L (p = 0.012). sCD62L levels were significantly lower in cord plasma compared with adult plasma but did not differ with mode of delivery. Thus the phenotype and function of cord blood T cells did not differ greatly with mode of delivery, but possible differences for the marker of interest should always be assessed. Furthermore, although there was no significant difference with mode of delivery for all markers, except CD62L, the variation in the normal vaginal delivery samples, as for the adults, was greater than in the lower-segment cesarean section samples, indicating that the effects of length of labor and stress at delivery may well be relevant.

Does Consumption of Two Portions of Salmon Per Week Enhance the Antioxidant Defense System in Pregnant Women

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, β-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.

Phenotypic analysis of circulating dendritic cells during the second half of human gestation

Dendritic cells (DCs) have been characterized as having an immature phenotype in infants when compared with adults; but it is unclear whether the phenotype or function of these populations changes during human intrauterine development. Three‐colour flow cytometry was used to phenotype fetal/neonatal circulating DCs during the second half (>20‐wk gestation) of pregnancy, (n = 34) and adults (n = 9). DCs were identified from peripheral blood mononuclear cells (PBMCs) or cord blood mononuclear cells (CBMCs) as staining brightly for HLA‐DR but negative for T cell, B cell, monocyte, and NK cell lineage markers. The surface molecule of interest was detected in a third colour. During gestation CD34, a marker of immaturity was significantly higher, and CD4, a differentiation marker, was significantly lower than adult levels. The percentage of CD11c+ cells did not differ significantly at any age, although a trend to reduced intensity of expression at earlier stages of gestation was observed. Significantly fewer DCs expressed the IgG receptors CD32 and CD64 at all gestations. The percentage of HLA‐DR+/lin‐ cells expressing CD40 was lowest at 20–23 wks and was always significantly lower on DCs from cord blood vs. adult blood. Similarly, the percentage of CD86+ and CD54+ DCs was significantly lower than adults throughout gestation. Thus, immaturity of cord blood DCs is likely to arise as a consequence of decreased ability to take up antigen (at least via IgG‐mediated mechanisms) and reduced provision of co‐stimulation.