casein-hydrolysate and Milk-Hypersensitivity

Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease.. We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life.. Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease.. In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.

Topics: Autoantibodies; Autoimmunity; Biopsy; Caseins; Celiac Disease; Child; Child, Preschool; Diabetes Mellitus, Type 1; Double-Blind Method; Duodenum; Finland; Gliadin; GTP-Binding Proteins; Humans; Infant; Infant Formula; Milk Hypersensitivity; Milk Proteins; Protein Glutamine gamma Glutamyltransferase 2; Risk Assessment; Risk Factors; Serologic Tests; Time Factors; Transglutaminases; Treatment Outcome

Cow's milk allergy (CMA) is treated in formula-fed infants with an extensive protein hydrolysate. This study aimed to evaluate the nutritional safety of a non-thickened and thickened extensively casein hydrolyzed protein formula (NT- and T-eCHF) in infants with CMA.. Infants younger than 6 mo old with a positive cow milk challenge test, positive IgE, or skin prick test for cow milk were selected. Weight and length were followed during the 6 mo intervention with the NT-eCHF and T-eCHF.. A challenge was performed in 50/71 infants with suspected CMA and was positive in 34/50. All children with confirmed CMA tolerated the eCHF. The T-eCHF leads to a significant improvement of the stool consistency in the whole population and in the subpopulation of infants with proven CMA. Height and weight evolution was satisfactory throughout the 6 mo study.. The eCHF fulfills the criteria of a hypoallergenic formula and the NT- and T-eCHF reduced CMA symptoms. Growth was within normal range.

Topics: Animals; Body Height; Body Weight; Caseins; Child Development; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Double-Blind Method; Energy Intake; Female; Humans; Immunoglobulin E; Infant; Infant Formula; Laryngopharyngeal Reflux; Male; Milk; Milk Hypersensitivity; Prospective Studies; Protein Hydrolysates; Viscosity

Children with cows' milk protein allergy (CMPA) are at risk of insufficient length and weight gain, and the nutritional efficacy of hypo-allergenic formulas should be carefully assessed. In 2008, a trial assessed the impact of probiotic supplementation of an extensively hydrolysed casein-based formula (eHCF) on acquisition of tolerance in 119 infants with CMPA. First analysis of the study results showed that the studied formula allowed improvement of food-related symptoms. The scoring of atopic dermatitis (SCORAD) index was assessed at randomisation and after 6 months of feeding. A post hoc analysis was performed using WHO growth software's nutritional survey module (WHO Anthro version 3.2.2). All infants who were fed the study formula tolerated it well. The SCORAD index significantly improved from randomisation to 6 months of feeding with the study formula. Anthropometric data indicated a significant improvement in the weight-for-age, length-for-age and weight-for-length z scores, as well as in the restoration of normal BMI. The probiotic supplementation did not show any impact on these parameters. The present data showed that this eHCF was clinically tolerated and significantly improved the SCORAD index and growth indices.

Topics: Bifidobacterium; Body Mass Index; Caseins; Child Development; Dermatitis, Atopic; Double-Blind Method; Female; Follow-Up Studies; Foods, Specialized; Humans; Immune Tolerance; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Lacticaseibacillus casei; Lost to Follow-Up; Male; Milk Hypersensitivity; Netherlands; Patient Dropouts; Probiotics; Risk; Thinness

Observational studies have shown that allergic infants, irrespective of the type of diet, show various degrees of growth depression in the first year of life. We investigated whether the type of milk in the complementary feeding period (6-12 months of age) is associated with differences in the increase of standardized growth indices (weight-for-age, WA; length-for-age, LA; and weight-for-length, WL, z-scores) in infants with cow's milk allergy (CMA). Infants with immunoglobulin E-mediated CMA breastfed at least 4 months and progressively weaned in the 5- to 6-month period were randomly assigned to three special formulas, a soy formula (n = 32), a casein hydrolysate (n = 31), and a rice hydrolysate (n = 30). A fourth, non-randomized group was made up by allergic infants still breastfed up to 12 months (n = 32). Groups were compared for WA, LA, and WL z-scores at 6, 9 and 12 months of age. All groups showed low WA and LA z-scores at 6 months of age. Infants fed hydrolyzed products showed a trend toward higher WA z-score increments in the 6- to 12-month period. The use of casein- and rice-based hydrolyzed formulas resulted in higher changes in WA compared with soy formula. Further research should be aimed at optimizing the dietary needs and feeding regimens for infants with CMA.

Topics: Body Height; Body Weight; Breast Feeding; Caseins; Child Development; Female; Humans; Immunoglobulin E; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Male; Milk Hypersensitivity; Oryza; Prospective Studies; Protein Hydrolysates; Skin Tests; Soy Milk

Early nutrition may influence the development of food allergies later in life. In the absence of breastfeeding, hydrolysates from cow's milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP. The additional nonspecific effect of the probiotic. PBS pretreated mice were efficiently sensitized and demonstrated elicitation of allergic reaction after OFC, whereas mice pretreated with MPI were durably protected from allergy to CMP. eHC+/-LGG pretreatments had no protective effect on sensitization to casein (specific) or BLG (non-specific), nor on CMP-induced allergic reactions. Surprisingly, eHC+LGG mice demonstrated significantly enhanced humoral and cellular immune responses after sensitization with CMP. Only some subtle changes were evidenced by flow cytometry.. Neither specific nor nonspecific preventive effects of administration of casein-derived peptides on the development of CMP food allergy were evidenced in our experimental setup. Further studies should be conducted to delineate the mechanisms involved in the immunostimulatory potential of LGG and to clarify its significance in clinical use.

Topics: Animals; Antibodies; Caseins; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Gastrointestinal Tract; Immunity, Cellular; Immunity, Humoral; Lacticaseibacillus rhamnosus; Mice, Inbred C57BL; Milk Hypersensitivity; Probiotics; Spleen; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Cow's milk allergy (CMA) is a common diagnosis in infants, requiring the exclusion of cow's milk until tolerance is recovered. In the present study, we aim to determine which factors are associated with the development of tolerance.. Retrospective, observational study of subjects who underwent the same clinical follow-up methodology. We studied 245 cases of CMA (125 IgE-mediated and 120 non-IgE-mediated). The following variables were analysed: age at diagnosis, gender, type of delivery, type of feeding received, feeding during the first months of life, clinical features, and type of feed received as treatment: casein hydrolysates or casein hydrolysates with Lactobacillus rhamnosus GG (LGG).. Factors associated with earlier tolerance were non-IgE-mediated CMA (HR = 2.92; 95% CI: 2.20-3.88) and patients receiving casein hydrolysate with LGG (HR = 1.79; 95% CI: 1.33-2.42). Later tolerance was associated with caesarean delivery (HR = 0.78; 95% CI: 0.58-1.05) and breastfeeding for a period of at least 3 days (HR = 0.64; 95% CI: 0.44-0.93). The multivariate study shows that the type of formula (HR = 1.61; 95% CI: 1.19-2.18) and the type of CMA (HR = 2.82; 95% CI: 2.12-3.85) have an effect on the recovery time. Casein hydrolysates with LGG reduces the recovery time in IgE-mediated (HR = 1.88; 95% CI: 1.17-3.01) and non-IgE-mediated CMA (HR = 1.46; 95% CI: 0.98-2.17).. Tolerance acquisition is faster in non-IgE-mediated CMA subjects and in those who received casein hydrolysate with LGG.

Topics: Allergens; Animals; Caseins; Cattle; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immune Tolerance; Immunoglobulin E; Male; Milk Hypersensitivity; Milk Proteins; Retrospective Studies; Risk Factors; Spain

Topics: Administration, Oral; Allergens; Caseins; Cells, Cultured; Desensitization, Immunologic; Humans; Milk Hypersensitivity; Milk Proteins

Infants with milk protein intolerance are usually switched to a casein hydrolysate or amino acid-based formula, which they continue to receive until 1 year of age, when they are rechallenged with a cow's-milk or soy protein formula. To investigate whether some of these infants actually become tolerant sooner, this study gathered preliminary data for establishing an empirical timetable for the resolution of milk protein intolerance.. This prospective, longitudinal cohort study enrolled infants <4 months of age receiving either breast milk or a cow's-milk or casein hydrolysate formula who presented to a pediatric subspecialty practice during an 18-month period and had a positive stool guaiac test. After having been successfully switched to a casein hydrolysate or amino acid formula, infants who had guaiac-negative stools for at least 2 consecutive months were rechallenged with the formula that had necessitated the most recent switch.. Of the 25 patients enrolled in the study, 16 completed the food challenge and data collection protocol. Negative stool guaiac tests following rechallenge indicated resolution of milk protein intolerance by the time subjects reached an average age of 6.7 ± 1.0 months (mean ± standard deviation). By the age of 7 months, milk protein intolerance was resolved in 12 of the 16 infants, the remainder having resolved by 10 months.. It may be reasonable to treat infants with milk protein intolerance for 2 to 3 months with a hypoallergenic formula, then rechallenge them at 6 months of age, usually without causing recurrence of the hematochezia. Rechallenging before 12 months old could result in cost savings to families and insurers.

Topics: Amino Acids; Animals; Caseins; Female; Humans; Infant; Infant Formula; Infant, Newborn; Longitudinal Studies; Male; Milk; Milk Hypersensitivity; Milk Proteins; Milk, Human; Prospective Studies; Protein Hydrolysates

Around 2.5% of neonates experience hypersensitivity reactions to cow's milk protein during the first year of life, which is highly associated with early exposure to cow's milk. To prevent early allergy development, cow's milk proteins in infant formulas were modified by hydrolyzation processes for use in children at high atopic risk who need milk supplementation in the first months of life. Dependent on the degree of modification, hydrolyzed cow's milk formulas are differentiated into extensively and partially hydrolyzed whey or casein hydrolysates (pHF, eHF). However, their allergy-preventive potential seems not only to dependent on the degree but also on the process of hydrolysis. pHF and eHF can be used for primary prevention of allergy in infants at high atopic risk, while only eHFs are indicated for secondary prevention in patients with manifest cow's milk allergy. In clinical trials a consistent trend to a reduction in atopy, mainly atopic eczema and food allergy, by certain pHFs and eHFs could be demonstrated in children with a familial risk of atopy until the age of 6 years. Because more than 50% of allergic children do not have a family history of atopy, it would be worthwhile to consider primary allergy prevention with hydrolysates for all children who need supplementation to breastfeeding.

Topics: Animals; Caseins; Child; Child, Preschool; Clinical Trials as Topic; Dermatitis, Atopic; Food Hypersensitivity; Humans; Hypersensitivity; Immune Tolerance; Infant; Infant Formula; Infant, Newborn; Milk Hypersensitivity; Milk Proteins; Models, Animal; Nutrition Policy; Protein Hydrolysates

A 10-day-old male neonate was admitted with bilious vomiting and gross hematochezia. Peripheral eosinophilia, delayed positive skin prick test to artificial milk, and elevated eosinophil cationic protein levels suggested cow's milk allergy. Fluid infusion with prohibition of oral intake improved the digestive symptoms. Breast-feeding was resumed on hospital day 3 and only casein hydrolysate formula was fed from day 7 onward. Nevertheless, eosinophilia and elevated transaminase levels developed on day 14. Liver dysfunction associated with casein hydrolysate formula was suspected and the infant was transferred to soy formula. Eosinophil counts decreased and transaminase levels were normalized on day 19. A cow's milk protein-specific lymphocyte proliferation test was positive for alpha-casein, beta-lactoglobulin, and bovine serum albumin, indicating sensitization of T cells to cow's milk proteins. These observations suggest that careful attention should be paid to liver dysfunction in non-immunoglobulin E-mediated cow's milk allergy, even when hypoallergenic formula is used.

Topics: Caseins; Eosinophilia; Humans; Immunoglobulin E; Infant Formula; Infant, Newborn; Liver Diseases; Male; Milk Hypersensitivity

Food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated food allergy in which digestive symptoms such as severe vomiting and diarrhea are induced by cow's milk and/or soy protein in infants. Generally, a food-specific IgE is not detected, and FPIES may be caused by inadvertent exposure to allergenic foods.. The patient in our case was a male infant in whom vomiting had been induced by ingestion of a cow's milk-based formula and bloody diarrhea had been caused by ingestion of breast milk during the neonatal period. Accidental ingestion of a new and extensively hydrolyzed casein/whey formula, MA-mi, caused watery diarrhea at 8 months of age, and FPIES was diagnosed based on these symptoms. In antigen-specific lymphocyte stimulation tests, New MA-1 was negative, but MA-mi and cow's milk antigens were positive. The only causative antigens were derived from cow's milk, and the symptoms were not induced by another extensively hydrolyzed casein formula, New MA-1. The patient grew and developed normally thereafter, and no symptoms were induced by solid food during the course of the condition.. MA-mi is likely to be used increasingly for allergic infants, but it is not necessarily a substitute for other hydrolyzed milk formulae in all cases, and care should be taken regarding its use and possible misuse.

Topics: Animals; Caseins; Enterocolitis; Humans; Infant; Infant Formula; Male; Milk; Milk Hypersensitivity; Syndrome

Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce.. To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life.. A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated.. One-way analysis of variance and Student's t-test were used for statistical comparison. Significance was set at p<0.05.. No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo-1 y (p=0.025) and 1-1.5 y (p=0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower (p=0) in the first trimester of life.. Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.

Topics: Allergens; Animals; Antigens, Plant; Body Weight; Caseins; Cattle; Child, Preschool; Dermatitis, Atopic; Energy Intake; Humans; Infant; Infant Formula; Infant, Newborn; Milk; Milk Hypersensitivity; Plant Proteins; Protein Hydrolysates; Research Design

Atopic eczema/dermatitis syndrome (AEDS) is often the first manifestation of atopic disease in children. Food hypersensitivity should be considered in approximately 40% of these patients. AEDS children with cow's milk allergy are commonly prescribed a hydrolyzed formulas or amino acid-based formulas for an alternative protein source. The aim of this study was to investigate hypersensitivity to extensive hydrolyzed casein and whey proteins in AEDS children with cow's milk protein allergy (CMA).. The study included 67 hospitalized children with AEDS (m/f--43/24), aged 1-28 months (mean 11.34 +/- 8.52) and CMA confirmed by oral food challenge. All patients were treated with extensively hydrolyzed formulas: 48/67 children with casein hydrolysates and 19/67 children with whey hydrolysates.. In most of studied children we recognized severe AEDS (SCORAD Index: mean 55.41 +/- 17.4; 95% CI 51.17-59.66) with elevated total IgE (mean 432.98 +/- 1030.46; 95% CI 181.63-684.33). In 22/67 children (32.8%) we established diagnosis of hypersensitivities to hydrolyzed formula (HHF): in 17/22 to casein hydrolysates, in 4/22 to whey hydrolysates and in 1/22 to amino-acid based formula. Children with HHF did not differ in the severity of AEDS evaluated by SCORAD (57.18 +/- 16.59 vs 54.56 +/- 17.90), the serum level of total IgE (603.9 +/- 1253 vs 349.4 +/- 906.1) and the time of breast-feeding (4.4 +/- 4.0 months vs 6.8 +/- 7.28). They differ in the number of plasma eosinophils and positive correlation between number of eosinophils and serum level of total IgE (p<0.05, r=0.46 vs r=0.07).. Children with moderate or severe atopic eczema/dermatitis syndrome can demonstrate hypersensitivity to hydrolyzed formula recommended for therapeutic indications.

Topics: Allergens; Animals; Caseins; Cattle; Child; Child, Preschool; Dermatitis, Atopic; Eosinophils; Female; Humans; Hydrolysis; Infant; Infant Formula; Male; Milk Hypersensitivity; Milk Proteins; Syndrome; Whey Proteins