IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and development of atopy by age 4

Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-beta in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (>3.5 or <0.5 mo); these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-beta1 and -beta2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4.     

Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms

de Meer G, Reijneveld SA, Brunekreef B. Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms.
Pediatr Allergy Immunol 2010: 21: 823–830.
© 2009 John Wiley & Sons A/S There is conflicting evidence for the relationship between parental socioeconomic position and their children’s asthma. The aim of this study was to investigate relationships between parental education and respiratory symptoms in their children, distinguishing atopic and non‐atopic symptoms. A cross‐sectional survey among 3262 elementary school children (age 8–13) was performed; data on parental education were obtained for 3213 children. Parents completed a questionnaire on their child’s allergic and respiratory symptoms, and potential explanatory variables including family history, indoor environment, and the child’s medical history. Subsets of children were tested for atopy (n = 1983), lung function (n = 2325), and airway hyperresponsiveness (AHR) (n = 880). Logistic regression was used to assess relationships of health outcomes with parental education. A high parental education was associated with an increased risk of atopic sensitization to indoor allergens (OR 1.31, 95% CI 1.02; 1.69). Studied explanatory variables did not influence the relationship. In contrast, a high parental education protected children from wheeze (OR 0.77, 95% CI 0.61; 0.97). This only applied to non‐atopic wheeze (OR 0.65, 95% CI 0.43; 0.99) and not to atopic wheeze (OR 0.89, 95% CI 0.60; 1.31). The protection from non‐atopic wheeze in children of highly educated parents declined after adjustment for household smoking and breastfeeding (OR 0.96, 95% CI 0.58; 1.57). Similar results were observed for non‐atopic and atopic rhinitis. We conclude that children from highly educated parents are protected from non‐atopic respiratory symptoms, which is largely explained by a lower rate of household smoking and a higher rate of breastfeeding.     

Self‐reported seafood intake and atopy in Japanese school‐aged children

Background: The effects of fish consumption and n‐3 poly‐unsaturated fatty acid (PUFA) levels on atopic disorders are inconsistent in previous reports, but few studies have investigated the effects of both fish and n‐3 PUFA. The aim of the present study was to investigate whether erythrocyte fatty acids and the consumption of fish are associated with atopic diseases in pre‐ and early adolescents. Methods: A total of 135 students with eczema, 136 students with asthma, and 137 healthy control students were selected from fifth and eighth grades in Shunan, Japan. Atopic disorders and dietary intake were evaluated with questionnaires, and total serum IgE was measured using an enzyme‐linked immunosorbent assay. In addition, erythrocyte membrane levels of PUFA were assessed via gas chromatography. Results: Total IgE was significantly elevated in the atopic subjects (P < 0.001). The intake of fatty and dried fish or seafood was significantly associated with eczema (odds ratios of the highest quartiles: 0.46, 95% confidence interval (95%CI): 0.22–0.94; 0.34, 95%CI: 0.16–0.71, respectively). Additionally, only erythrocyte eicosapentaenoic acid (EPA) level had a negative association with eczema (P= 0.048). For asthma, the effect of fish consumption was not significant. Conclusions: Fish consumption was related to a low prevalence of eczema, but not asthma in Japanese pre‐ and early adolescents. EPA may be involved in this mechanism.     

Polyunsaturated fatty acids in school children in relation to allergy and serum IgE levels

Altered composition of polyunsaturated fatty acids (PUFA) has been observed in allergic individuals and it has been proposed that this is due to an impairment of δ-6-desaturase activity. We have studied the composition of PUFA in serum phospholipids in twenty-two 12-15 year old children with asthma and/or allergic dermatitis and 23 non-atopic controls of similar age. The relative levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polyunsaturated fatty acids (LCP) were lower (1.46%± 0.54 vs. 1.90%± 0.58, P = 0.01 for DHA and 2.34%± 0.67 vs. 2.80%± 0.77, P <0.05 for total n-3 LCP) and the ratio of total n-6 to n-3 LCP was higher (P < 0.01) in the allergic children than in the controls. In addition to these differences, the relative levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to dihomo-γ-linolenic acid (DHGLA, C20:3n-6) were also lower in the 12 allergic children with positive skin prick test, as compared with the SIT negative children (both P < 0.05). In non-allergic children, the levels of total n-3 correlated with n-6 LCP (r = 0.76, p < 0.001). Furthermore, the n-3 LCP, i.e. EPA, DPA and DHA, correlated significantly with each other (r = 0.52-0.78, all p < 0.01) and correlated with n-6 LCP, i.e. C20:2, DHGLA and AA respectively (r = 0.56-0.83, all P < 0.01). Most of these correlations were absent in allergic children.
Higher levels of C20:2n-6 and lower levels of eicosapentaenoic acid (EPA, C20:5n-3) were recorded in 11 allergic children with serum IgE above the median level (56 kU/1), as compared to 11 with lower IgE levels (both P < 0.05). Furthermore, the levels of C20:2n-6 correlated with the IgE levels in the children (r = 0.65, P = 0.001).
The findings could not confirm an impaired δ-6-desaturase activity in allergic school children and suggest that a disturbance of LCP metabolism is associated with allergic diseases.     

Effect of breast milk of healthy and allergic mothers on in vitro stimulation of cord blood lymphocytes

Maternal milk has beneficial effects on the development and function of the newborn's immune system. Whether the milk of allergic mother has the same effects as the milk of healthy mothers is not yet quite clear. To contribute to the characterization of its immunomodulatory action, we tested the effect of milk of healthy and allergic mothers on the proliferation and immunoglobulin formation in cultures of cord blood mononuclear leucocytes (CBML) of newborns of healthy and allergic mothers. CBML proliferation was tested by (3)H-thymidine incorporation, IgM, IgG and IgA production by reverse ELISPOT. CBML response was examined in unstimulated cultures and after stimulation with polyclonal activators in the presence or absence of colostrum or milk. The cells of children of allergic mothers have a significantly higher proliferative activity than those of children of healthy mothers. Maternal colostrum/milk in high doses markedly suppresses cell proliferation after stimulation with polyclonal activators, whereas lower milk doses in the cultures have no such effect and exert a rather stimulatory action. Immunoglobulin production by cord blood lymphocytes is also different in the two groups of children. Low basal immunoglobulin formation is increased after stimulation with a strong polyclonal activator of B cells--Bacillus firmus, CBML of children of allergic mothers produce more IgA than those of children of healthy mothers. The stimulated production of all immunoglobulin classes in cells of children of healthy mothers is still enhanced by colostrum/milk. Children of allergic mothers show a markedly increased production of only IgM and IgA. The effect of healthy and allergic colostrum and milk on cell proliferation and immunoglobulin production is similar. The lymphocytes of children of allergic mothers differ from the lymphocytes of children of healthy mothers in their proliferative activity and the ability to form immunoglobulin already at birth.     

Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants

The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.     

Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non‐atopic children. We hypothesized that locally produced total IgE and allergen‐specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)‐specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non‐atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP‐specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL‐2 receptors (sIL‐2R), soluble CD23 (sCD23), and IL‐6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non‐atopic individuals. Median values of DP‐specific IgE and IgA antibodies were significantly higher in atopics than in non‐atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP‐specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non‐atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL‐2R, and IL‐6 levels. The levels of DP‐specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL‐2R, sCD23, and IL‐6. The presence of total IgE and DP‐specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally‐produced total IgE and DP‐specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.     

Serum immunoglobulin E,IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: Association with prognosis and clinical manifestations

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1–34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk‐specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme‐linked immunosorbent assay (ELISA). The results were compared to those of 30 non‐atopic age‐matched control children. On average, after 9.2 months (range 2–31 months) on a milk‐free diet, a repeated challenge was performed in 38 children. At the re‐challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom‐free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti‐α‐casein IgG level (of 2.10) in children with a positive reaction at the re‐challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re‐challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti‐BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti‐α‐casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.     

Clostridium difficile,atopy and wheeze during the first year of life

Differences have been suggested to occur in the composition of intestinal microflora from allergic and non‐allergic children. In this study we used a semi‐quantitative enzyme‐linked immunosorbent assay (ELISA) for the measurement of Clostridium difficile‐specific immunoglobulin G (IgG) (CDIgG). CDIgG was excellent in differentiating between adults with or without Cl. difficile colitis (absorbance levels, positive vs. negative controls: geometric mean (GM) 0.301, 95% CI: 0.289–0.314 vs. GM 0.167, 95% CI: 0.155–0.181; mean difference 1.8‐fold, 95% CI: 1.65–1.95; p < 0.0001). We used this technique to investigate whether there are any differences between atopic wheezy infants and non‐atopic non‐wheezy controls. In a prospective cohort study (n = 390) 10 patients were identified at 1 year of age (atopic, history of recurrent wheeze) and matched (gender, month of birth, exposure to Der p 1, Fel d 1 and Can f 1) with a control group of infants (non‐atopic, no history of wheeze). The patients had significantly higher Cl. difficile‐specific IgG absorbance levels (GM 0.298, 95% CI: 0.249–0.358) compared with controls (GM 0.235, 95% CI: 0.201–0.274; mean difference 1.27‐fold, 95% CI: 1.07–1.50; p = 0.01). These results suggest that there may be differences in the composition of intestinal microflora between allergic and non‐allergic infants at 1 year of age, with allergic children having higher Cl. difficile IgG antibody levels.     

Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers: diet, breast milk and infant growth

Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential dietary nutrients required for the optimal growth and development of infants, particularly of the brain and retina. It is important for exclusively breastfed infants to receive milk of a correct balance between omega-6 and omega-3 fatty acids. In this study, we compared the composition of LC-PUFAs in the diet and milk of mothers and their infants' growth between Chinese and Swedish. Twenty-three and 19 mother-term infant pairs from a rural area of northern Beijing, China, and Stockholm, Sweden, who were 3 mo old and exclusively breastfed, were studied. The Chinese diet was higher in carbohydrate (17% of energy) but lower in protein (4% of energy) and fat (12% of energy) than the Swedish diet. The intake of Chinese mothers contained more linoleic acid (LA, C(18 ratio 2 omega-6)) and less arachidonic acid (AA, C(20 ratio 4 omega-6)), eicosapentaenoic acid (EPA, C(20 ratio 5 omega-3)) and docosahexaenoic acid (DHA, C(22 ratio 6 omega-3)) than that of Swedish mothers. The breast milk of the Chinese mothers had significantly higher LA and lower EPA and DHA levels than that of the Swedish mothers. However, in Chinese breast milk the AA level was significantly higher than that in Swedish breast milk. The recommended ranges of the ratios of LA to alpha-linolenic acid (LNA, C(18 ratio 3 omega-3)) and of AA to DHA in human milk are 5-10 and 0.5-1 compared with 23.0 and 3.1 in the Chinese breast milk, and 7.5 and 1.6 in the Swedish breast milk, respectively.Conclusion: The diet of the studied Chinese mothers is less balanced with regard to the levels of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) than that of the Swedish mothers, which is also mirrored in the breast milk of these mothers. The clinical relevance of the difference between the levels of LC-PUFAs in the breast milk of Chinese and Swedish mothers may be elucidated by a follow-up study of the cognitive and visual functions of the infants involved.     

The relationships among immunoglobulin levels,allergic sensitization,and viral respiratory illnesses in early childhood

Possin ME, Morgan S, DaSilva DF, Tisler C, Pappas TE, Roberg KA, Anderson E, Evans MD, Gangnon R, Lemanske RF, Gern JE. The relationships among immunoglobulin levels, allergic sensitization, and viral respiratory illnesses in early childhood.
Pediatr Allergy Immunol 2010: 21: 990–996.
© 2010 John Wiley & Sons A/S IgE plays an essential role in type I allergy, however, there is less information about the relationship between other immunoglobulins (IgA and IgG) and atopic phenotypes in early childhood. We hypothesized that levels of circulating IgA in early childhood would be inversely related to the number of respiratory infections and the risk of becoming sensitized to allergens. Immunoglobulin levels were analyzed (ELISA) in plasma samples (IgG, IgA), and in nasal secretions (IgA) from children participating in a high‐risk birth cohort study. Samples were available from 264 children at age 2 yr and 257 children at age 4 yr, and results were compared to rates of respiratory illnesses, allergic sensitization, atopic dermatitis (AD), and asthma. Children who were sensitized to allergens had higher rather than lower levels of circulating IgA. A subgroup analysis showed that IgA levels were increased in relationship to foods sensitization (58 vs. 50 mg/dl, p = 0.003) but not aeroallergen sensitization (52 vs. 53 mg/dl, p = 0.11). IgA levels in the plasma correlated with levels of IgE levels (r_s =0.19, p = 0.003). Levels of IgE, but not IgG or IgA, were positively correlated with rates of respiratory illnesses, AD, and the risk of developing asthma. Finally, there were no significant relationships between IgA in nasal secretions and infectious outcomes. In conclusion, low‐normal concentrations of plasma IgA are associated with a reduced prevalence of allergic sensitization in infancy. Further, levels of IgA and IgG in plasma within the range of normal, and IgA in nasal secretions, do not appear to influence the risk of subsequent respiratory illnesses. Further studies to define relationships between IgA and allergic sensitization are likely to provide new insights into the pathogenesis of allergic diseases in infancy.     

Expression of and responses to CD2 and CD3 in 18‐month‐old children with and without atopic dermatitis

We hypothesize that atopy is associated with a reduced T‐cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by ³H‐thymidine incorporation in phytohaemagglutinin (PHA)‐ and anti‐CD3‐stimulated peripheral blood mononuclear cells (PBMC) of 18‐month‐old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)‐2 was added to compensate for possible functional differences in accessory cells. Anti‐CD3‐induced secretion of IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, and interferon‐γ (IFN‐γ) was analyzed by enzyme‐linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2⁺ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti‐CD3‐induced proliferation declined more rapidly with antibody dilution in the allergic than in the non‐allergic children. Atopic dermatitis was associated with high levels of anti‐CD3‐stimulated IL‐5 secretion. The IL‐4/IL‐10 and IL‐4/IFN‐γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test‐negative children with eczema produced higher levels of IL‐10 than skin prick test‐positive children. In conclusion, atopic children have a reduced T‐cell function. Atopic dermatitis is associated with increased IL‐5 production, while high total IgE levels are associated with high IL‐4/IFN‐γ and IL‐4/IL‐10 ratios.     

Fatty acid composition in colostrum and mature milk from non-atopic and atopic mothers during the first 6 months of lactation

The fatty acid composition of total lipids was analysed in colostrum and mature human milk samples obtained at 1, 3, 4 and 6 months from 17 non-atopic and at 1 and 3 months from 17 atopic mothers. The relative levels of linoleic acid and α-linolenic acid increased up to 3 months after delivery and then declined. In contrast, the levels of their metabolites were higher in colostrum than in mature milk. The levels of dihomo-γ-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid were all lower in atopic than non-atopic mothers in milk samples obtained after 1 month of lactation (all p < 0:05). The ratio of total n -6 to n -3 long-chain polyunsaturated fatty acids (LCP) in milk at 1 and 3 months was higher in atopic than non-atopic mothers (all p < 0:05). Lower levels of the monounsaturated fatty acids (MUFA) were also observed in atopic mothers, as compared to non-atopic mothers. In the non-atopic mothers, the levels of individual n -6 LCP correlated and also correlated with n -3 LCP in colostrum and early mature milk ( r = 0:60-0.92, all p < 0:01). These correlations within n -6 and between n -6 and n -3 LCP were mostly absent in atopic mothers. The findings suggest that the LCP metabolism in human milk is disturbed in atopic mothers, as indicated by the lower relative levels of some LCP at 1 month, higher ratios of n -6 to n -3 LCP and poor correlations between the levels of the various compounds during the first 3 months of lactation.     

Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies

Scott‐Taylor TH, Hourihane J, Strobel S. Correlation of allergen‐specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies.
Pediatr Allergy Immunol 2010: 21: 935–944.
© 2010 John Wiley & Sons A/S Cytokines can affect the quantity and class of allergen‐specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen‐specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food‐specific IgE, IgG1 and IgG4 to peanut, milk and egg than non‐atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age‐matched healthy children (p ≤ 0.05) and, in milk‐ and egg‐sensitized children, correlated with cytokine responses (p < 0.05). Peanut‐sensitized children additionally had elevated levels of IgG2 and IgG3 also which correlated inversely (p < 0.003 and p < 0.04, respectively) with IFNγ production. Elevated allergen‐specific IgG subclass antibodies in sensitized children correlated with total IgE levels (p ≤ 0.05) in all three food allergen groups. The ratio of specific IgG1 to IgG4 was highest in those with high IgE, inverted with resolution of allergy, and correlated with total IgE levels (p ≤ 0.01) in milk‐ and egg‐sensitized children. The correlation of TH2 responses with allergen‐specific antibodies would implicate polarized T cells in food allergic children in IgE hypersensitivity and overproduction of particular IgG subclasses alike. IgG1:IgG4 ratio declines with allergy sensitization and may denote emerging tolerance.     

Phospholipid fatty acids in cord blood: family history and development of allergy

The fatty acid composition of umbilical cord serum phospholipids was investigated by gas chromatography in 33 infants with allergic and 35 babies of non-allergic mothers. The relative levels of the linoleic acid metabolites C20:3, arachidonic acid (AA, C20:4) and C22:4n-6, and two α-linolenic acid metabolites, i.e. eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, C22:6) were significantly higher in infants of allergic mothers than in non-allergic mothers (all p < 0.05). Furthermore, an altered proportional relationship between the various fatty acids in n-6 series fatty acids and between n-3 and n-6 series fatty acids was present already at birth in infants who developed allergic disease during their first 6 years of life. These observations cannot be employed for the prediction of allergy, however, as the individual variations were considerable.     

Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years of age

Aim: Breastfeeding seems to be favorable for cognitive development. Could levels of polyunsaturated fatty acids (PUFA) explain this?Methods: Pregnant mothers were recruited consecutively at maternity care centres. PUFA were analysed in colostrum and breast milk at 1 and 3 mo. The product‐precursor ratios of n‐6+n‐3 PUFA were examined as measures of activity in respective steps in the fatty acid metabolic chain. Also, the quotient between DHA and AA was analysed. The children were tested with the full WISC‐III at 6.5 y. Results: First, the influence of length of breastfeeding was analysed by multiple regression together with relevant cofactors (except for PUFA). In the best models, 46% of the variation in total IQ was explained. Length of breastfeeding contributed significantly to total IQ (beta = 0.228, p= 0.021), verbal IQ (beta = 0.204, p= 0.040) and performance IQ (beta = 0.210, p= 0.056). There were no significant single correlations between PUFA and measures of cognitive development. However, in multiple regression analysis of colostrum, significant beta‐coefficients were found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p= 0.002). If length of breastfeeding and gestation week were added to steps 4+5, this three‐factor model could explain 67% of the variation of total IQ. Introducing length of breastfeeding and gestation week together with the quotient DHA/AA (beta = 0.510, p > 0.001) yielded a three‐factor model, which explained 76% of the variation in total IQ. Conclusion: Our findings could be interpreted as supporting the importance of high levels of PUFA for cognitive development. However, the sample is small and the results must be interpreted with caution.     

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.     

Cytokines in breast milk from allergic and nonallergic mothers

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo. milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-beta was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-beta, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-beta and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-beta, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.     

Low Colostral IgA Associated with Cow's Milk Allergy

ABSTRACT. During a nutritional study of 198 infants, seven became allergic to cow's milk. The seven infants showed acute cutaneous manifestations during cow's milk challenge tests in hospital and six had increased levels of IgE cow's milk-specific antibodies. Neither in the development of the levels of immunoglobulins G, A and M, nor in that of the cow's milk-specific antibodies of these isotypes did these seven patients differ from the remaining infants. Beta-lactoglobulin content and levels of cow's milk-, and beta-lactoglobulin-specific antibodies and of immunoglobulins A, G and M were measured in samples of colostrum and milk from the mothers of the seven infants with cow's milk allergy and from a comparison group (non-atopic mothers of non-atopic infants). The milk of the mothers whose infants became allergic to cow's milk contained less IgA through the lactation: 95% confidence intervals of the groups did not overlap. The difference was most marked in the colostrum. All other measurements were similar in the two groups. This suggests that an infant is more likely to develop cow's milk allergy if the mother's colostrum had a low total IgA content.     

Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin

We studied the levels of immunoglobulins in colostrum, milk and sera from two common variable immunodeficiency (CVID) mothers (M1 and M2), and in sera from their newborn infants. During pregnancy they continued intravenous immunoglobulin therapy (IVIG). Antibody levels from maternal and cord blood collected at delivery and colostrum and milk, collected on the 3rd and 7th post‐partum days, respectively, were analyzed. Although cord/maternal blood ratios of total immunoglobulins and subclasses, as well as specific antibodies differed between M1 and M2, both showed good placental transfer of anti‐protein and anti‐polysaccharide antibodies, despite lower cord/maternal blood ratios in M2. Anti‐Streptococcus pneumoniae antibody avidity indexes were similar between paired maternal and cord serum. Both mothers’ colostrum and milk samples showed only traces of IgA, and IgM and IgG levels in colostrum were within normal range in M1, whereas M2 presented elevated IgG and low IgM levels, when compared with healthy mothers. The study of colostrum and milk activity showed that they strongly inhibited enteropathogenic Escherichia coli adhesion in vitro. CVID patients must be informed about the relevance of regular IVIG administration during pregnancy, not only for their own health but also for their immune immature offspring. Breast‐feeding should be encouraged as colostra from these CVID patients strongly inhibited E. coli adhesion to human epithelial cells thus providing immunological protection plus nutritional and psychological benefits for the infant.