Enhanced levels of cow's milk antibodies in infancy in children who develop type 1 diabetes later in childhood

Background: Early exposure to cow’s milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM‐based infant formula in the trial to reduce insulin‐dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen‐conferred T1D susceptibility and had an affected first‐degree relative. After 7 years of follow‐up, 8 subjects had progressed to T1D, 15 had at least one disease‐associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta‐lactoglobulin (BLG), bovine serum albumin, and alpha‐casein and IgG antibodies to bovine insulin (BI) were measured with enzyme‐linked immunosorbent assays from sequential samples. Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody‐positive subjects than in autoantibody‐negative subjects at 18 months of age (p = 0.022). Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.     

Plasma Antibodies to Cow's Milk Are Increased by Early Weaning and Consumption of Unmodified Milk, but Production of Plasma IgA and IgM Cow's Milk Antibodies Is Stimulated Even during Exclusive Breast-Feeding

ABSTRACT. We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.     

Human breast milk contains bovine IgG. Relationship to infant colic?

Previous studies have suggested that an unidentified cow's milk protein, other than beta-lactoglobulin and casein, might play a pathogenetic role in infant colic. Therefore, a radioimmunoassay was used to analyze human breast milk and infant formula samples for the presence of bovine IgG. Milk samples from 88 of the 97 mothers tested contained greater than 0.1 micrograms/mL of bovine IgG. In a study group of 59 mothers with infants in the colic-prone 2- to 17-week age group, the 29 mothers of colicky infants had higher levels of bovine IgG in their breast milk (median 0.42 micrograms/mL) than the 30 mothers of noncolicky infants (median 0.32 micrograms/mL) (P less than .02). The highest concentrations of bovine IgG observed in human milk were 8.5 and 8.2 micrograms/mL. Most cow's milk-based infant formulas contained 0.6 to 6.4 micrograms/mL of bovine IgG, a concentration comparable with levels found in many human milk samples. The results suggest that appreciable quantities of bovine IgG are commonly present in human milk, that significantly higher levels are present in milk from mothers of colicky infants, and that bovine IgG may possibly be involved in the pathogenesis of infant colic.     

Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring

OBJECTIVE: To assess whether the maternal consumption of milk and milk products affects development of cow's milk (CM) antibodies in infants. DESIGN: A randomized pilot trial using food frequency questionnaires (mothers) and food records (infants). SETTING: Families with a newborn infant with increased HLA-DQB1-conferred risk of type 1 diabetes and at least one first-degree relative affected by type 1 diabetes from 16 hospitals in Finland between April 1995 and November 1997. Subjects and intervention: Infants randomized to receive a hydrolysed formula when breast milk was not available during their first 6-8 mo (n=112). Of these, 13 dropped out by the age of 3 mo and two were excluded due to incomplete CM antibody data. RESULTS: Maternal milk protein intake from cheese during pregnancy was inversely related to IgA-class antibody titres to beta-lactoglobulin (BLG) and casein (CAS) at 3 mo, and to IgA antibody titres to BLG at 6 mo. Maternal consumption of raw milk products during lactation was positively related to the development of IgA antibody titres to CAS at 6 mo, and inversely correlated to IgG antibody titres to bovine serum albumin (BSA) and IgA antibody titres to CAS at 2 y. Maternal cheese consumption was inversely related to the IgG antibody titres to CM formula and CAS and to the IgA antibody titres to CAS in early infancy. CONCLUSIONS: Few associations were established between maternal CM protein intake and CM protein antibody levels in the infants. The milk and milk products taken by the mother differed in their impact on the emerging CM antibody response in the offspring.     

Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants ≤31 weeks

Aim: To evaluate incidence, timing and clinical relevance of acquired human cytomegalovirus (HCMV) infection in preterm infants.
Methods: The prospective longitudinal study included preterm infants ≤31 weeks. Congenital HCMV infection was excluded by negative HCMV culture from urine or by HCMV-PCR-negative umbilical cord blood. Infants from HCMV-IgG-positive mothers received thawed frozen breast milk until 33 weeks. Urine samples were obtained weekly for HCMV culture. Data were collected regarding clinical course and milk-intake.
Results: Twenty-nine mothers (29/48, 60%) of 35 infants were HCMV-IgG-positive. Five of 35 infants (14%) excreted HCMV in urine. Three of five children remained asymptomatic. One child developed a respirator-dependent HCMV pneumonia, the other child an upper airway infection and a transient thrombocytopenia. HCMV infected children had a significant longer hospital stay (median 96 vs. 73 days, p = 0.025) and received more formula milk (89 vs. 44 mL/kg/day, p = 0.04). Mothers of infected children had significantly higher HCMV-IgG levels than those of non-infected children (mean 1557 vs. 921 AU/mL, p = 0.048).
Nineteen of 48 mothers (40%) with 23 infants were HCMV-IgG-negative. These children remained HCMV negative.
Conclusion: Feeding preterm infants ≤31 weeks of HCMV-IgG-positive mothers with thawed frozen breast milk until 33 completed weeks does not prevent symptomatic HCMV infection in all cases. These infections can be associated with a prolonged hospital stay.     

Breast milk from mothers of very low birthweight infants: variability in fat and protein content

While breast milk appears to be superior to formula for the development of very low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands of the rapidly growing premature infant. To estimate the nutritional variability of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method) and fat content (creamatocrit) were measured in breast-milk spot samples from mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of lactation. Protein content (median 1.9 g dl(-1), range 1.1-3.5 g dl(-1)) and fat content (3.8/1.0-14.6 g dl(-1)) were highly variable and lacked a normal distribution over all samples and in individual women's milk. There was only a weak correlation between fat and protein (rs=0.416, p < 0.001). Fat but not protein was lower in morning samples than in samples collected later in the day (p < 0.001). Protein but not fat content decreased during the weeks of lactation (rs =-0.446, p < 0.001). No impact of the baby's gestational age was observed. CONCLUSION: The fat and protein content of breast milk from mothers of VLBW infants is highly variable, calling into question the clinical feasibility of individualized supplementation of breast milk for VLBW infants based on spot sample measurements.     

Modulation by human milk of IgG subclass response to hepatitis B vaccine in infants

The influence of breast and formula feeding on specific anti-hepatitis B surface antigen (HBsAg) IgG subclass production and distribution has been investigated in 40 healthy infants, born to HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV). Twenty children were bottle fed and 20 were breast fed. Specific subclasses were detected at the 4th and 12th months using an enzyme-linked immunosorbent assay with monoclonal antibodies. A defect in total IgG and IgG subclasses was previously excluded. Significant differences were observed both at the 4th and 12th months for IgG1 and IgG2. Breast-fed infants had significantly higher levels of specific IgG2 (about three times higher), while IgG1 levels were significantly higher in formula-fed infants. Anti-HBsAg IgG4 levels were always higher in bottle-fed infants, but a statistical significance was never present. No difference was found in specific IgG3 levels. This study reports the evidence that breast feeding influences specific IgG subclass synthesis against a viral antigen and suggests an immunologic modulation of the response to vaccines dependent not only on age but also on factors present in human milk.     

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p?=?0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p?=?0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p?相似文献   

Insulin in human milk and the prevention of type 1 diabetes

Abstract: Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and β-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.     

Circulating levels of adiponectin in preterm infants

OBJECTIVE: To determine circulating levels of adiponectin in preterm infants and examine possible associations with anthropometric measurements, weight gain, and leptin and insulin levels. DESIGN: Prospective study. SETTING: A university hospital neonatal care unit. Study population: 62 preterm (mean (SD) gestational age 32.0 (2.1) weeks) and 15 full-term infants (reference group). INTERVENTIONS: Blood samples taken at discharge (40.9 (14.8) days of life) from the preterm infants and at a comparable postnatal age in full-term infants. All infants were fed the same commercial formula, but in nine preterms the formula contained long-chain polyunsaturated fatty acids (LCPUFAs). MAIN OUTCOME MEASURES: Serum levels of adiponectin, leptin and insulin. Associations of adiponectin levels were tested only in the preterm group. RESULTS: Serum levels of adiponectin were lower in preterm (40.9 (14.8) microg/ml) than full-term infants (53.1 (16.0) microg/ml, p<0.01). However, after adjustment for body weight, the influence of prematurity on adiponectin levels was no longer significant. In preterm infants, adiponectin levels independently correlated with being born small for gestational age (SGA) (beta=-0.35, p=0.01), weight gain (beta=0.28, p=0.03) and LCPUFA-supplemented formula (beta=0.34, p=0.009). Serum adiponectin levels did not correlate with insulin or leptin levels. However, insulin levels were higher in preterm than in full-term infants after adjustment for body weight. CONCLUSIONS: Adiponectin levels are lower in preterm infants at discharge than full-term infants probably due to decreased adiposity. The levels are influenced by being born SGA, weight gain and, possibly, by dietary LCPUFAs. The importance of these findings in the development of insulin or leptin resistance in children born prematurely needs to be further studied.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

Can the concentration of immunomodulating factors in mature breastmilk be associated with food alergy in breastfed children?

Objectives: The aim of the study was to determine the concentration of such immunomodulating factors as transforming growth factor beta1 (TGF-β1), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) in mature human milk and to relate the levels of the above mentioned cytokines in mature breast milk to the occurence of food allergy in children during the first 24 months of life. Materials and methods: Data on breastfeeding, symptoms of food allergy in children and breast milk samples were collected prospectively from birth to 24 months of age from 84 mothers participating in the Polish birth cohort of "EuroPrevall" study, in the years 2005-2007. Cytokine levels were measured in the whey with commercial enzyme-linked immunosorbent assays (ELISA) kits. Results: Ten out of the eighty four (11.9%) participating children had positive SPT and/or sIgE to food antigens. In 7 out of 84 (8.4%) children DBPCFC confirmed the diagnosis of food allergy. The median concentration of TGF-β1 was 21.94 pg/ml (range 10.47-83.19), TNF-α 1.46 pg/ml (range 0.35-16.50), IL- 101.83 pg/ml (range 0.58-31.04). There was a positive correlation between the concentration of IL-10 and TGF-β1. The level of TNF-α correlated positively with the duration of lactation (p=0.04). There was no significant difference between the concentration of IL-10, TGF-β1, TNF-α, in the mature breast milk of mothers of children with symptoms of allergy and positive SPT and/or sIgE, mothers of children with positive DBPCFC and in the milk of mothers of control children. Conclusions: There was no significant difference between the concentration of IL-10, TGF-β1, TNF-α, in the mature breast milk of mothers of children with food allergy and in the breast milk of mothers of control children.     

Carnitine during prolonged breast feeding

To assess carnitine levels during prolonged sole breast feeding we measured serum and breast milk carnitine concentrations in 37 lactating mothers and their healthy term infants from birth to the age of 1 yr. The number of solely breast-fed infants decreased to 31 at 2 months of age, to 28 at 6 months, and to seven at 9 months, because formula and/or solid food was added when there was not enough breast milk. In mothers the mean serum carnitine increased from 35 to 50 mumol/liter during the first 2 months after delivery and remained unchanged thereafter. Irrespective of the type of feeding, the mean serum carnitine in infants increased from 29 to 59 mumol/liter during the first 2 months, remained unchanged during 2-9 months, and decreased to the mean level of mothers thereafter. The mean carnitine concentration of breast milk was high (106 mumol/liter) immediately after delivery. During the first 2 months the mean carnitine concentration of milk decreased to the mean serum level of mothers and remained unchanged thereafter. The carnitine concentrations of serum and breast milk did not correlate, however. The mean daily carnitine intake of the breast-fed infants was 5.7 mumol/kg at 4 months of age, 4.7 mumol/kg at 6 months, and 6.0 mumol/kg at 9 months whereas the mean daily carnitine intake of the infants receiving formula was 28.9 mumol/kg at 1 month of age and 30.7 mumol/kg at 2 months. The serum concentration of carnitine in our infants did not correlate with carnitine intake. Our results indicate that serum carnitine concentrations are maintained during prolonged sole breast feeding.     

Erythrocyte membrane fatty acid content in infants consuming formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA): an observational study

In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percentage of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection: infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non-supplemented formula), breast milk, or non-supplemented formula plus breast milk. Membrane DHA (4.42 versus 1.79, P < 0.001) and omega-3 fatty acid (5.81 versus 3.43, P < 0.001) levels were higher in infants consuming supplemented versus non-supplemented formula. Omega-6 fatty acids were lower in infants consuming supplemented versus non-supplemented formula (26.32 versus 29.68, P = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, P < 0.001) and omega-3 fatty acids (5.81 versus 4.45, P = 0.008) than infants drinking breast milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega-3 and lower omega-6 fatty acid status.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Breast milk feeding and cognitive ability at 7-8 years

OBJECTIVE: To examine the association between duration of breast milk feeding and cognitive ability at 7-8 years in a birth cohort of very low birthweight infants. DESIGN: 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7-8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS: Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS: These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.     

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Transmission of cytomegalovirus from mothers to preterm infants by breast milk

OBJECTIVES: To assess the risk of transmission of cytomegalovirus (CMV) by breast milk from CMV-seropositive mothers to their breast-fed preterm infants and to evaluate their outcome. PATIENTS AND METHODS: The study population comprised breast-fed preterm infants with a birth weight of <1,500 g and gestational age of <35 weeks. Venous blood samples from the mothers and infants were tested for CMV IgG and IgM antibodies on the 5th and 30th day after birth. Breast milk was obtained for CMV DNA detection by polymerase chain reaction and viral culture on the 5th day and on the 3rd, 6th and 12th week. Urine samples of the babies were collected at the same time for CMV culture. Neurodevelopmental assessment was done at 6 months of age, corrected for preterm birth. RESULTS: Thirty-eight mothers and 42 infants (including 4 sets of twins) were enrolled in the study. A mother-infant pair was excluded because of inadequate breast milk collection. Thirty-six mothers (97.3%) were CMV-seropositive. CMV DNA of breast milk was detected in 35 seropositive mothers. Six infants of 5 mothers were infected (infected group) at a mean of 77 days after birth, and 34 infants of 31 mothers were not (noninfected group). In all the mothers of the infected group, CMV virus could be cultured from the milk whey. The average maternal CMV IgG on day 5 after delivery was higher in the infected than in the noninfected group. Sepsis-like symptoms and hyperbilirubinemia were more frequently noted in the infected infants than in the noninfected, but the difference was not statistically significant. Neurodevelopmental outcome did not significantly differ between the 2 groups. CONCLUSIONS: The risk of CMV infection in breast-fed premature infants was highest when the mothers shed viable virus in their breast milk. These mothers had high CMV IgG, which may help identify those mother-infant pairs at risk. Inactivation of the virus in milk by freezing may be a way of reducing the transmission of this virus via breast milk.     

Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study

The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population-based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast-feeding was associated with an odds ratio of 0.06 (95% CI 0.002-2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0-9.9) in favour of developing persistence of acute diarrhoea ( p = 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0-228.8) ( p = 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea.     

Does breast feeding protect from atopic diseases?

It is well established that food antigens can pass from mothers to infants via the breast milk. Bovine-beta-lactoglobulin has been detected in several breast milk samples from mothers with regular intake of cow's milk. Healthy breastfed infants can produce IgG antibodies against cow's milk protein and in infants at risk for atopic disease specific IgE antibodies were found before cow's milk based infant formula was introduced into the diet. However, several clinical studies in infants at risk for atopic disease indicate that exclusive breastfeeding decreases the incidence of atopic disease. The protective effect of breastfeeding is only relative and it is uncertain, how long protection lasts. Sensitization to food antigens may occur already in utero, because infants whose mothers avoid common allergenic foods during the whole pregnancy and then during the lactation period have a lower incidence of atopic eczema than infants whose mothers are on an unrestricted diet. Avoidance of common allergenic foods only during the last trimester of pregnancy had no effect, because the fetus is capable of forming IgE immune response.