Hypoallergenic Infant Formulas Research Articles

Determination of αs1-Casein and αs2-Casein in hypoallergenic infant formula by extended specific peptide -isotope-labeled internal standard dilution-LC-MS/MS

The desensitization effect of the hypoallergenic infant formula products is critical for production quality, and establishment of sensitive and accurate determination method of allergens, such as αs1-casein and αs2-casein, remains challengeable in the field of infant formula industry. Therefore, the objective of this study was to identify specific peptides (YLGYLEQLLR and FALPQYLK) from αs1-casein and αs2-casein in infant formula by orbitrap high resolution mass spectrometry (Orbitrap MS), then establish an analytical method for the qualitative and quantitative determination of αs1-casein and αs2-casein based on extended specific peptide-isotope-labeled internal standard dilution-LC-MS/MS. Specific peptides obtained by trypsin enzymolysis of hypoallergenic infant formula were separated by Waters Acquity LC HSS T3 column, and analyzed under ESI positive ion mode using multi-reaction monitoring (MRM). The specific peptides of αs1-casein and αs2-casein exhibited linear relationships within the concentration range of 0.0025–1.5 μmol/L and correlation coefficients were above 0.99. The detection limits of αs1-casein and αs2-casein were 0.3 mg/kg, with quantification limits of 1.0 mg/kg, respectively. The average recoveries were 83.5%–87.3% (αs1-casein) and 80.1%–84.4% (αs2-casein), with RSDs of 2.3%–3.7% (αs1-casein) and 2.5%–5.0% (αs2-casein), respectively. Our results demonstrated that this method is capable of analyzing the content of αs1-casein and αs2-casein in hypoallergenic infant formula with excellent sensitivity and specificity.

Research progress on the mechanism of probiotics regulating cow milk allergy in early childhood and its application in hypoallergenic infant formula.

Some infants and young children suffer from cow's milk allergy (CMA), and have always mainly used hypoallergenic infant formula as a substitute for breast milk, but some of these formulas can still cause allergic reactions. In recent years, it has been found that probiotic nutritional interventions can regulate CMA in children. Scientific and reasonable application of probiotics to hypoallergenic infant formula is the key research direction in the future. This paper discusses the mechanism and clinical symptoms of CMA in children. This review critically ex- amines the issue of how probiotics use intestinal flora as the main vector to combine with the immune system to exert physiological functions to intervene CMA in children, with a particular focus on four mechanisms: promoting the early establishment of intestinal microecological balance, regulating the body's immunity and alleviating allergic response, enhancing the intestinal mucosal barrier function, and destroying allergen epitopes. Additionally, it overviews the development process of hypoallergenic infant formula and the research progress of probiotics in hypoallergenic infant formula. The article also offers suggestions and outlines potential future research directions and ideas in this field.

Allergenicity evaluation of an extensively hydrolyzed infant formula based on cow milk protein.

Cow milk protein allergy (CMPA) is the most common food allergy in infants. Currently, hypoallergenic infant formulas on the market are mainly divided into extensively hydrolyzed whey protein formulas and extensively hydrolyzed casein formulas. There are few extensively hydrolyzed infant formulas (EHFs) with a similar protein composition to breast milk. Therefore, we developed a hypoallergenic infant formula based on extensively hydrolyzed cow milk protein (whey protein-to-casein ratio of 6 : 4) and evaluated its allergenicity in vitro and in vivo. The results showed that the antigenicity of EHF was significantly decreased. The levels of Treg and Th1 cells were increased, while the levels of Th2 cells, IgE and IgG1, plasma histamine and serum mast cell enzymes were significantly decreased. At the same time, the allergic symptoms of the jejunum and lungs of mice were relieved. This study provides a solution for the development of cow milk protein based hypoallergenic infant formulas.

Aptamer-based stir bar sorptive extraction combined with MALDI-TOF-MS for the analysis of milk protein allergen β-lactoglobulin in foods

In this work, the preparation of an aptamer-based coating for stir bar sorptive extraction (SBSE) aimed at the selective clean-up and preconcentration of the allergenic milk protein β-lactoglobulin (β-LG) is described. To this end, a thiol-terminated aptamer was grafted onto a vinylized polytetrafluoroethylene stir bar via “thiol-ene” click chemistry. The aptamer affinity coating was characterized and several parameters that affect SBSE efficiency were evaluated. The optimized aptamer-based SBSE method combined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS) analysis provided suitable linearity (0.25–50 µg·mL−1), satisfactory limit of detection (LOD) (0.08 µg·mL−1 β-LG), and relative standard deviations below 5.2 % among the extraction units, which could be reused for 10 extraction cycles and were stable for at least one month. The applicability of the developed method was successfully demonstrated by analyzing low levels of β-LG in different dairy-free food samples (i.e. a 100 % cocoa dark chocolate, a hydrolyzed hypoallergenic infant formula, and a white bread) and in white breads with declared and undeclared contents of milk (84 %<recoveries < 93 %).

Assessment of the Efficiency of Technological Processes to Modify Whey Protein Antigenicity.

Whey is a by-product that represents a cheap source of protein with a high nutritional value, often used to improve food quality. When used as a raw material to produce hypoallergenic infant formulas (HIF), a processing step able to decrease the allergenic potential is required to guarantee their safe use for this purpose. In the present paper, thermal treatments, high hydrostatic pressure (HHP), and enzymatic hydrolysis (EH) were assessed to decrease the antigenicity of whey protein solutions (WPC). For monitoring purposes, a competitive ELISA method, able to detect the major and most allergenic whey protein β-lactoglobulin (BLG), was developed as a first step to evaluate the efficiency of the processes. Results showed that EH together with HHP was the most effective combination to reduce WPC antigenicity. The evaluation method proved useful to monitor the processes and to be employed in the quality control of the final product, to guarantee the efficiency, and in protein antigenicity reduction.

Relationship between antigenicity and allergenic epitopes of extensive hydrolyzed whey protein: LC-MS/MS-based analysis

Whey protein is the main protein in milk that causes allergic reactions in infants and children. In this work, Alcalase and Neutrase were combined to hydrolyze whey protein concentrate (WPC). The degree of hydrolysis (DH) and antigenicity reduction rate of WPC were 26.45% and 59.41% after hydrolyzed at the mass ratio of Alcalase and Neutrase of 1:1 and the enzyme to substrate ratio of 6000 U g−1 at pH 8.5, 50 °C for 3 h. HPLC results showed that when DH was about 26%, the molecular weight distribution of WPC hydrolysate less than 3000 Da exceeded 95%, and 18.33% of WPC hydrolysate was less than 180 Da (free amino acids). LC-MS/MS was used to detect peptides with 8–25 amino acid residues, the analysis indicated that most of the allergenic epitopes of β-lactoglobulin were destroyed, especially the major allergenic peptide fragments at positions 41–60 and 102–124. In conclusion, the combined hydrolysis of Alcalase and Neutrase significantly reduced the antigenicity of whey protein. This study could provide a potential value for the of WPC hydrolysates as a hypoallergenic infant formula.

Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity.

Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow's milk protein are increasingly considered for therapy and prevention of cow's milk allergy. The aim of this study was to investigate the allergenic activity and ability to induce T cell and cytokine responses of an infant formula based on extensively hydrolyzed cow's milk protein (whey) (eHF, extensively hydrolyzed formula) supplemented with Galactooligosaccharides (GOS) and Limosilactobacillus fermentum CECT5716 (LF) to determine its suitability for treatment and prevention of CMA. eHF and standard protein formula based on intact cow's milk proteins (iPF) with or without Galactooligosaccharide (GOS) and Limosilactobacillus fermentum CECT5716 (LF) were investigated with allergen-specific antibodies and tested for IgE reactivity and allergenic activity in basophil degranulation assays with sera from cow's milk (CM)-allergic infants/children. Their ability to stimulate T cell proliferation and cytokine secretion in cultured peripheral blood mononuclear cells (PBMC) from CM-allergic infants and children was studied with a FACS-based carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and xMAP Luminex fluorescent bead-based technology, respectively. An eHF supplemented with GOS and LF exhibiting almost no IgE reactivity and allergenic activity was identified. This eHF induced significantly lower inflammatory cytokine secretion as compared to an intact protein-based infant formula but retained T cell reactivity. Due to strongly reduced allergenic activity and induction of inflammatory cytokine secretion but retained T cell reactivity, the identified eHF may be used for treatment and prevention of CMA by induction of specific T cell tolerance.

Insight into the molecular-level details of αs1 casein interactions with IgG: Combining with LC-MS/MS and molecular modelling techniques

αs1-Casein (αs1-CN) is a major cow milk allergen, while the tertiary structure of αs1-CN and conformational epitopes of αs1-CN have not been clarified. Here, a reasonable three-dimensional structure of αs1-CN was established using ab initio methods, and hot-spot residues and epitopes were investigated by combining molecular dynamics simulation, peptides synthesis, and ELISA. Obtained results demonstrated that the binding mechanism between αs1-CN and IgG was located on three main regions: a helical structure zone (E77-Q97), the flexible loop zone (Y154-T174), and a flexible C-terminal (N190-L198), mainly connecting via hydrogen bond and ionic bonds. The hydrolysates produced by papain with lowest antigenicity (12.43%), which could considerably destroy the essential epitopes of αs1-CN confirmed by epitope synthesis, and LC-MS/MS. The results reported herein would provide novel insights into the interface interactions between αs1-CN and IgG, and prove valuable for developing hypoallergenic infant-formula and peptide vaccines for allergen-specific immunotherapy.

Alternatives to Cow's Milk-Based Infant Formulas in the Prevention and Management of Cow's Milk Allergy.

Cow’s milk-based infant formulas are the most common substitute to mother’s milk in infancy when breastfeeding is impossible or insufficient, as cow’s milk is a globally available source of mammalian proteins with high nutritional value. However, cow’s milk allergy (CMA) is the most prevalent type of food allergy among infants, affecting up to 3.8% of small children. Hypoallergenic infant formulas based on hydrolysed cow’s milk proteins are commercially available for the management of CMA. Yet, there is a growing demand for more options for infant feeding, both in general but especially for the prevention and management of CMA. Milk from other mammalian sources than the cow, such as goat, sheep, camel, donkey, and horse, has received some attention in the last decade due to the different protein composition profile and protein amino acid sequences, resulting in a potentially low cross-reactivity with cow’s milk proteins. Recently, proteins from plant sources, such as potato, lentil, chickpeas, quinoa, in addition to soy and rice, have gained increased interest due to their climate friendly and vegan status as well as potential lower allergenicity. In this review, we provide an overview of current and potential future infant formulas and their relevance in CMA prevention and management.

Dietary advanced glycation end-products, 2-monochloropropane-1,3-diol esters and 3-monochloropropane-1,2-diol esters and glycidyl esters in infant formulas: Occurrence, formulation and processing effects, mitigation strategies.

Infant formula contains thermal processing contaminants, such as dietary advanced glycation end-products (dAGEs), glycidyl esters (GEs), 2-monochloropropane-1,3-diol esters and 3-monochloropropane-1,2-diol esters (MCPDEs). This systematic review aimed to gain insights into the occurrence of these contaminants in different types of infant formula, to understand potential effects of the formulation and processing of infant formulas on these contaminants, as well as into possible mitigation strategies. The occurrence of dAGEs in infant formula depends on the recipes and processing conditions. Hydrolyzed protein formulations promote dAGEs formation in infant formula since peptides are more prone to glycation than intact proteins, which is reflected in high dAGEs concentration in hypoallergenic infant formula. Different carbohydrates in recipes result into different glycation extents of infant formula: maltodextrin containing formulas contained less dAGEs than those with lactose. Concerning mitigation strategies, applying ultra-high-temperature (UHT) treatment during milk processing leads to less dAGEs formation than using in-bottle sterilization. Although data are limited, evidence showed that encapsulation of raw ingredients or the use of antioxidants or enzymes in recipes is promising. The occurrence of MCPDEs and GEs in infant formula fully depends on the vegetable oils used in the recipe. High levels of these contaminants can be found when relatively high amounts of palm oils or fats are used. The mitigation of MCPDEs and GEs should therefore be performed on fats and oils before their application to infant formula recipes. Data and knowledge gaps identified in this review can be useful to guide future studies.

Exploring the Advantages of a Hydrolyzed Rice Formula in the Dietary Management of Infants with Cow's Milk Allergy in the Middle East, North Africa, and Pakistan Region.

Cow’s milk allergy (CMA) is the most common food allergy in early childhood, and its prevalence continues to rise. Exclusive breastfeeding is recommended for infants in the first 6 months of life, but this recommendation is poorly adhered to in many parts of the world, including the Middle East, North Africa, and Pakistan (MENAP) region. If the infant is affected by CMA, current guidelines recommend extensively hydrolyzed formulas (eHFs) or amino acid-based formulas (AAFs) in the case of severe symptoms, and hydrolyzed rice formulas (HRFs) where available. In recent years, HRFs have been proposed as a plant-based alternative to cow’s milk protein-based eHFs, and updates to current guidelines have been recommended. In 2014, a consensus statement and guidelines were published for the Middle East region on the prevention, diagnosis, and management of CMA. As new advances have been made in the extensively hydrolyzed hypoallergenic infant formula space, along with updated scientific evidence, a workshop of experts from the MENAP region focused on HRF was convened in 2021. This publication summarizes the insights from this meeting. During the consensus part of the meeting, a new approach was discussed and approved by all participants, and agreement was reached that HRF can be recommended as a first-line alternative to cow’s milk-based eHF in the dietary management of CMA.

Growth and tolerance of healthy, term infants fed lower protein extensively hydrolyzed or amino acid-based formula: double-blind, randomized, controlled trial

BackgroundOptimal protein level in hypoallergenic infant formulas is an area of ongoing investigation. The aim was to evaluate growth of healthy term infants who received extensively hydrolyzed (EH) or amino acid (AA)-based formulas with reduced protein.MethodsIn this prospective, multi-center, double-blind, controlled, parallel group study, infants were randomized to receive a marketed EH casein infant formula at 2.8 g protein/100 kcal (Control) or one of two investigational formulas: EH casein formula at 2.4 g protein/100 kcal (EHF) or AA-based formula at 2.4 g total protein equivalents/100 kcal (AAF). Control and EHF each had 2 × 107 CFU Lactobacillus rhamnosus GG/100 kcal. Anthropometrics were measured and recall of formula intake, tolerance, and stool characteristics was collected at 14, 30, 60, 90, 120 days of age. Primary outcome was weight growth rate (g/day) between 14 and 120 days of age (analyzed by ANOVA). Medically confirmed adverse events were recorded throughout the study.ResultsNo group differences in weight or length growth rate from 14 to 120 days were detected. With the exception of significant differences at several study time points for males, no group differences were detected in mean head circumference growth rates. However, mean achieved weight, length, and head circumference demonstrated normal growth throughout the study period. No group differences in achieved weight or length (males and females) and head circumference (females) were detected and means were within the WHO growth 25th and 75th percentiles from 14 to 120 days of age. With the exception of Day 90, there were no statistically significant group differences in achieved head circumference for males; means remained between the WHO 50th and 75th percentiles for growth at Days 14, 30, and 60 and continued along the 75th percentile through Day 120. No differences in study discontinuation due to formula were detected. The number of participants for whom at least one adverse event was reported was similar among groups.ConclusionsThis study demonstrated hypoallergenic infant formulas at 2.4 g protein/100 kcal were safe, well-tolerated, and associated with appropriate growth in healthy term infants from 14 to 120 days of age.Trial registrationClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT01354366. Registered 13 May 2011.

Lactose-Reduced Infant Formulas Are Over-Consumed Whereas Hypoallergenic Infant Formulas Are Not - When Compared to Medical Necessity

ObjectivesWe aimed to report the macronutrient composition of powdered infant formula purchased from major US physical-location retailers from 2017 through 2019. We then compared the percentage of lactose-reduced and hypoallergenic powdered infant formula consumed with the estimated prevalence of infant conditions necessitating a lactose-reduced or hypoallergenic formula. We also compared the proportion of formula consumed that was lactose-reduced between WIC and non-WIC purchases. MethodsAnnual powdered infant formula volume and purchase data from all major brick-and-mortar stores in the United States (excluding Costco) from 2017 through 2019 was obtained from IRi (Information Resources Inc). Protein, carbohydrate, fat composition and scoop size for each formula was obtained from formula companies and equivalent liquid ounces (“formula consumed”) was calculated. Small can sizes of “standard” (intact and partially hydrolyzed protein) formulas served as proxies for WIC purchases. Proportions were compared to published medical prevalence by calculating a z-ratio, t-test. ResultsAverage infant carbohydrate consumption consisted of 56.6% lactose, 37.7% glucose, and 5.7% sucrose. 21% of formula consumed contained sucrose. 55% of all formula and 47% of standard formula consumed was lactose-reduced, both higher than the estimated 7.5% prevalence of medical necessity (p < 0.0002). Lactose-reduced standard formula represented 51% of non-WIC sales which was greater than the 44% of WIC sales (p = 0.003). Protein consumption consisted of 5.0% soy protein, 74.1% intact dairy, 11.1% partially hydrolyzed dairy, 7.1% fully hydrolyzed protein, and 0.3% amino acid based. Hypoallergenic (fully hydrolyzed and amino acid-based) formula represented 7.4% of formula consumed, which did not differ from liberal estimates of cow’s milk allergy prevalence (7.5%). ConclusionsEstimated consumption of hypoallergenic formula in the US matches liberal estimates of medical necessity. However, a high proportion of formula-fed infants are consuming non-lactose-based carbohydrate; more than is medically warranted, necessitating further research into metabolic implications. Funding SourcesNone.

Determination of Casein Allergens in Extensively Hydrolyzed Casein Infant Formula by Liquid Chromatography-Tandem Mass Spectrometry.

BackgroundThe use of hypoallergenic infant formulas and the need for reliable tests to determine the presence of residual antigens have increased in parallel.ObjectiveAn LC-MS method for quantitation of casein was validated using incurred samples and a matrix-matched external standard curve.MethodPowdered infant formula samples were extracted in a buffer of sodium deoxycholate and ammonium bicarbonate at 60°C and filtered through 7 kDa desalting columns. Samples were digested overnight with trypsin and precipitated with acid prior to analysis of marker peptides by tandem mass spectrometry.ResultsBased on three marker peptides, the linear range for casein was 1.8–42 μg/g of powdered infant formula with an LOQ of 1.8 μg/g. The determination coefficients (R2) for each curve were ≥0.99 for casein peptides. Method repeatability was ≤22% RSD and intermediate precision was ≤23% RSD; recovery of casein from incurred material (2–20 µg/g) ranged from 78% to 118%.ConclusionsAn LC-MS/MS method was developed and validated for confirmation of casein allergens in hypoallergenic infant formula.HighlightsA method was developed to accurately and reliably quantify casein allergens in extensively hydrolyzed casein infant formula by LC-MS without the need for custom peptide standards.

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Pediatric provider knowledge of early peanut introduction recommendations

Peanut allergy affects approximately 2% of children in the United States. 1 Gupta R.S. Springston E.E. Warrier M.R. et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011; 128: e9-e17 Crossref PubMed Scopus (973) Google Scholar Delayed introduction of allergenic foods was recommended by the American Academy of Pediatrics in 2000 in an effort to reduce the incidence of allergic disease. 2 American Academy of PediatricsCommittee on Nutrition. Hypoallergenic infant formulas. Pediatrics. 2000; 106: 346-349 PubMed Google Scholar This recommendation was withdrawn in 2008 owing to insufficient evidence, and no specific guidance was provided on the timing of allergenic food introduction. 3 Greer F.R. Sicherer S.H. Burks A.W. American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008; 121: 183-191 Crossref PubMed Scopus (857) Google Scholar In January 2017, evidence-based recommendations for the early introduction of peanut were made. 4 Togias A. Cooper S.F. Acebal M.L. et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Allergy Asthma Clin Immunol. 2017; 13: 1 Crossref Scopus (25) Google Scholar The results of the Learning Early About Peanut (LEAP) trial suggest that early introduction of peanut may prevent peanut allergy among high-risk infants. 5 Du Toit G. Roberts G. Sayre P.H. et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015; 372: 803-813 Crossref PubMed Scopus (1226) Google Scholar Currently, the guidelines of the National Institute of Allergy and Infectious Diseases (NIAID) recommend the introduction of peanut around 6 months of age in infants with mild to moderate eczema. For infants with severe eczema, egg allergy, or both, it is recommended to strongly consider testing for peanut sensitivity, and if appropriate, introduce peanut as early as 4 to 6 months of age. 4 Togias A. Cooper S.F. Acebal M.L. et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Allergy Asthma Clin Immunol. 2017; 13: 1 Crossref Scopus (25) Google Scholar

Hypoallergenic infant formula lacks transforming growth factor beta activity and has a lower anti-inflammatory activity than regular infant formula

Hypoallergenic formulas are recommended for infants who are not breastfed and cannot tolerate cow milk formulas due to allergy. These formulas are hydrolyzed to break down larger protein chains into shorter, easy-to-digest, and potentially less allergenic proteins. Hydrolysis, however, possibly occurs at the expense of the transforming growth factor beta (TGF-β) and anti-inflammatory activity that is inherent in regular formula. Our objective was to determine the TGF-β and the anti-inflammatory activity of commercially available hypoallergenic and regular formulas. Human gingival fibroblasts were incubated with reconstituted formulas followed by detection of TGF-β target genes and activation of Smad2/3 signaling. Gingival fibroblasts and the oral squamous cell carcinoma cell line HSC-2 were also exposed to formulas before adding interleukin (IL)1β and tumor necrosis factor (TNF)α to provoke expression of pro-inflammatory cytokines. For murine bone marrow-derived macrophages, pro-inflammatory cytokine expression was stimulated with saliva. Changes in p65 nuclear translocation and phosphorylation of smad3 and p38 were analyzed by immunostaining. Our study demonstrated that regular formula, but not hypoallergenic formula, enhanced the expression of TGF-β target genes IL11, PRG4, and NOX4 in gingival fibroblasts. Hypoallergenic formulas also failed to initiate nuclear translocation of Smad2/3 and phosphorylation of Smad3. Moreover, regular formulas were more potent than hypoallergenic formulas in reducing the expression of pro-inflammatory cytokines in gingival fibroblasts, HSC-2 epithelial cells, and murine bone marrow macrophages. Hypoallergenic and regular formulas had a similar capacity to reduce p65 nuclear translocation and phosphorylation of p38 in fibroblasts. These findings suggest that hypoallergenic formulas lack in vitro TGF-β activity and have a lower anti-inflammatory activity compared with regular formulas.

Milk lactoperoxidase decreases ID1 and ID3 expression in human oral squamous cell carcinoma cell lines

Milk consumption may modify the risk of squamous cell carcinoma. The role of milk to modulate the gene expression in oral squamous cell carcinoma cells has not been investigated so far. Here, HSC2 oral squamous carcinoma cells were exposed to an aqueous fraction of human milk and a whole-genome array was performed. Among the genes that were significantly reduced by human and cow milk were the DNA-binding protein inhibitor 1 (ID1), ID3 and Distal-Less Homeobox 2 (DLX2) in HSC2 cells. Also, in TR146 oral squamous carcinoma cells, there was a tendency towards a decreased gene expression. Upon size fractionation, lactoperoxidase but not lactoferrin and osteopontin was identified to reduce ID1 and ID3 in HSC2 cells. Dairy products and hypoallergenic infant formula failed to decrease the respective genes. These data suggest that milk can reduce the expression of transcription factors in oral squamous carcinoma cells.

Comparison of the Allergenicity and Immunogenicity of Camel and Cow's Milk-A Study in Brown Norway Rats.

Background: When breastfeeding is impossible or insufficient, the use of cow’s milk-based hypoallergenic infant formulas is an option for infants suffering from or at risk of developing cow’s milk allergy. As the Camelidae family has a large evolutionary distance to the Bovidae family and as camel milk differs from cow’s milk protein composition, there is a growing interest in investigating the suitability of camel milk as an alternative to cow’s milk-based hypoallergenic infant formulas. Methods: The aim of the study was to compare the allergenicity and immunogenicity of camel and cow’s milk as well as investigating their cross-reactivity using a Brown Norway rat model. Rats were immunised intraperitoneally with one of four products: camel milk, cow’s milk, cow’s milk casein or cow’s milk whey fraction. Immunogenicity, sensitising capacity, antibody avidity and cross-reactivity were evaluated by means of different ELISAs. The eliciting capacity was evaluated by an ear swelling test. Results: Camel and cow’s milk showed similarity in their inherent immunogenicity, sensitising and eliciting capacity. Results show that there was a lower cross-reactivity between caseins than between whey proteins from camel and cow’s milk. Conclusions: The study showed that camel and cow’s milk have a low cross-reactivity, indicating a low protein similarity. Results demonstrate that camel milk could be a promising alternative to cow’s milk-based hypoallergenic infant formulas.

The German Infant Nutritional Intervention Study (GINI) for the preventive effect of hydrolysed infant formulas in infants at high risk for allergic diseases. Design and selected results

In the complex interaction between certain environmental factors and genetic disposition, the early allergen exposure plays a major role in the development of allergic diseases. In aiming to reduce the allergen burden for the infant at risk during early infancy, cow’s milk protein hydrolysate infant formulas (hypoallergenic infant formulas) are appropriate alternatives to breastfeeding for primary allergy prevention. The German Infant Nutritional Intervention-Program (GINI) was supported for the first 3 years by the German Ministry for Education and Research (BMBF) (FKZ 01 EE 9401-4). It is a birth cohort which was primarily scheduled until the children were 3 years old. The aim of the prospective, randomized, double-blind intervention study was to investigate the impact of different cow’s milk protein hydrolysate infant formulas in the first 4 – 6 months on the development of allergic diseases in children at risk due to at least one parent or biological sibling with a history of allergic disease. The allocation to one of the 4 intervention formulas (partial whey hydrolysate, extensive whey hydrolysate, extensive casein hydrolysate or standard cow’s milk formula) was randomised and stratified by family history (single/biparental) and the respective obstetric clinic. Recruitment was carried out by the three clinical centers (Research Institute Marien-Hospital Wesel, Children’s Department, Ludwigs-Maximilians-University Munich and Children’s Department Technical University Munich) in 18 obstetric clinics between 01.09.1995 and 30.06.1998. Along with the intervention study a non-interventional, complementary observational cohort of children with or without allergy risk was recruited and followed by annual self-reporting parental questionnaires. The GINI intervention study (GINI-I, N = 2.252) and the non-interventional observation study (GINI-NI, N = 3.739) are combined in the population-based GINIplus study (see article J. Heinrich et al. in this journal). The results of the GINI intervention study confirm that, cow’s milk protein hydrolysate infant formulas have a preventive effect on allergic manifestation compared with a standard cow’s milk formula, until school age. However, the dimension of the effect is different between the formulas. This effect, which is mainly driven by the effect on atopic eczema, develops in the first months of life and persists without rebound. In the formula groups the cumulative incidence of atopic eczema until school age is reduced between 26% and 45% compared with standard cow’s milk formula. A beneficial effect of the hydrolysate formulas on the respiratory manifestations asthma and rhinoconjunctivitis, however, could not be shown. By comparing the GINI intervention and non-intervention arm of the GINIplus study it was demonstrated, that a family history for allergy doubles the risk for eczema in the offspring. Early intervention with cow’s milk protein hydrolysate infant formulas is able to substantially compensate this risk for eczema until the age of 6 years. In contrast, by randomization to standard cow’s milk formula this risk showed a trend towards a higher incidence compared with children at risk from the non-intervention group. Thus, the results of the GINIplus study have contributed to answer some of the controversially discussed questions.