Hydrolyzed Casein Formula Research Articles

Probiotics, prebiotics and food allergy: a review.

Background. The review was structured in the following sections: 1) Cow's Milk Proteins Allergy (CMA), 2) Food Allergy to Peanuts and 3) Prevention of Food Allergy. In CMA, studies indicate that extensively hydrolyzed casein formula supplemented with Lactobacillus Rhamnosus GG aids in acquiring tolerance to cow's milk proteins, resolving gastrointestinal symptoms and preventing of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with Lactobacillus Rhamnosus CGMCC 1.3724 appears to promote sustained desensitization. However, the evidence supporting probiotics for preventing food allergies lacks robustness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma Methods. A PubMed/Medline search was carried out on articles published between 2011 and 2021 with the following query: ("Food Hypersensitivity"[Mesh]) AND (("Probiotics"[Mesh]) OR ("Prebiotics"[Mesh])). Subsequently, the titles and abstracts were analysed and selected according to established criteria. After full reading of these articles, 54 were included and a narrative review was performed. Results. The review was structured in the following sections: 1) Cow's Milk Proteins Allergy (CMA), 2) Food Allergy to Peanuts and 3) Prevention of Food Allergy. In CMA, studies indicate that extensively hydrolyzed casein formula supplemented with Lactobacillus Rhamnosus GG aids in acquiring tolerance to cow's milk proteins, resolving gastrointestinal symptoms and preventing of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with Lactobacillus Rhamnosus CGMCC 1.3724 appears to promote sustained desensitization. However, the evidence supporting probiotics for preventing food allergies lacks robustness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma. Conclusions. The potential of probiotics to be used as therapeutic adjuvants in CMA and peanut OI is promising. However, there is inconsistency regarding the type of probiotic, the dose and duration of supplementation. Further studies are needed to clarify the role of probiotics and prebiotics in FA.

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.

Cost-effectiveness of therapeutic infant formulas for cow's milk protein allergy management.

Cow's milk protein allergy (CMPA) is children's most common food allergy. Therapeutic infant formulas for CMPA lead to symptom-free and potentially benefit early tolerance induction and reducing the allergic march in non-breastfed babies. This study assessed the cost-effectiveness of CMPA management with different therapeutic infant formulas in Thailand, which may reflect situations in developing countries throughout Asia. An analytic decision model was developed to simulate the occurrence of eczema, urticaria, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA over 36 months. Extensively hydrolyzed casein formula with added probiotic Lacticaseibacillus rhamnosus (previously Lactobacillus rhamnosus) strain GG (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), soy protein-based formula (SPF), and amino acid formula (AAF) were compared from the healthcare payer perspective. The results from a prospective cohort study were used for comparative effectiveness measures, while local experts were interviewed to estimate the healthcare resource used in the management of CMPA. The costs of healthcare resources were obtained from standard, publicly available sources. The direct medical cost of CMPA management was lowest for EHCF+LGG (USD 1,720), followed by SPF (USD 2,090), EHWF (USD 2,791), and AAF (USD 7,881). Compared with other formulas, EHCF+LGG was expected to save USD 370 (SPF), USD 1,071 (EHWF), and USD 6,161 (AAF) in the total cost of CMPA management over 36 months. In conclusion, EHCF+LGG was the most cost-effective strategy for managing non-breastfed infants with CMPA. This strategy was associated with more children developing immune tolerance to cow's milk and being symptom-free, contributing to overall cost-saving potential.

Cost-effectiveness of infant hypoallergenic formulas to manage cow’s milk protein allergy in France

ABSTRACT Background Clinician’s choice of hypoallergenic formulas in the first-line management of cow’s milk protein allergy (CMPA) should be informed by evidence on clinical efficacy and cost-effectiveness. Objective We compare the cost-effectiveness of amino acid-based formula (AAF), extensively hydrolyzed casein formula with Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), and rice hydrolyzed formula (RHF) in non-breastfed children in France. Methods Immunotolerance and atopic manifestations’ prevalence were based on a prospective non-randomized study with a 36-month follow-up. Resource utilization was sourced from a survey of French clinicians, and unit costs were based on national data. Costs and health consequences were discounted at 2.5% annually. Results were reported using the Collective and French National Health Insurance perspectives. Results Children receiving EHCF+LGG were predicted to require less healthcare resources, given their reduced prevalence of CMPA symptoms at 3 years. In the base case, EHCF+LGG led to savings of at least €674 per child compared to AAF, EHWF, and RHF at 3 years, from both perspectives. Nutrition had the highest economic burden in CMPA, driven by hypoallergenic formulas and dietetic replacements costs. Results were robust to one-way and probabilistic sensitivity analyses. Conclusions EHCF+LGG was associated with more symptom-free time, higher immune tolerance, and lower costs.

The anti-anxiety/depression effect of a combined complex of casein hydrolysate and γ-aminobutyric acid on C57BL/6 mice.

In view of a series of adverse side effects of drugs for anxiety/depression on the market at present, it is imminent to extract and develop novel anti-anxiety and depression drugs from plants and proteins (like casein hydrolysate) as adjuncts or substitutes for existing anti-anxiety and depression drugs. Consequently, this study investigated the improvement of the anxiety/depression function by the compound of casein hydrolysate and γ-aminobutyric acid (GABA) (casein hydrolysate: GABA = 4:1; CCHAA) on mice induced by chronic restraint stress-corticosterone injection. Animal experiments revealed that oral gavage administration of CCHAA significantly reversed the anxiety/depression-like behaviors. Compared to the model control group, body weights were increased after treatment with CCHAA groups [1.5, 0.75 mg/(g⋅d)]. As a diagnostic index of anxiety and depression, we assessed GABA and 5-HT levels in response to CCHAA ingestion. The GABA and 5-HT levels were increasingly enhanced by the CCHAA diet. In addition, histopathological changes in the hippocampus CA3 region of the anxious/depressed mice were also alleviated after the treatment with the CCHAA. Thus, the casein hydrolysate and GABA formula diets may induce beneficial effects on the mice with anxiety/depression.

Managing Cow's Milk Protein Allergy in Indonesia: A Cost-effectiveness Analysis of Hypoallergenic Milk Formulas from the Private Payers' Perspective.

Background: Cow’s milk protein allergy is very common in early childhood. Extensively hydrolyzed formulas are recommended in the first-line management of cow’s milk protein allergy in non-breastfed children. Choice of formulas should be informed by efficacy and cost data. Objectives: This study aims to compare the cost-effectiveness of extensively hydrolyzed casein formula with Lacticaseibacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), amino acid formula, and soy formula in the first-line management of cow’s milk protein allergy in non-breastfed children in Indonesia. Methods: A trial-based decision analytic cohort model was adapted to simulate the occurrence of cow’s milk protein allergy symptoms or being symptom free. The model was based on a prospective nonrandomized study that followed up children for 36 months. Costs and health consequences were discounted at 3% annually. Resources required to manage cow’s milk protein allergy and unit costs for clinical appointments and exams were based on a panel of 15 clinicians, from a private payers’ perspective. Other unit costs were based on publicly available national data. Results were reported as cost per additional child free from allergic manifestations or per additional immunotolerant child at 3 years, and per life-years under the same conditions. Uncertainty was assessed using deterministic and probabilistic sensitivity analysis. Results: Children receiving EHCF+LGG were associated with more symptom-free time, a higher probability of cow’s milk tolerance at 3 years, and lower healthcare resources and transportation use when compared with children receiving other formulas (with 38%-49% lower costs). Formula costs were lower for soy, but EHCF+LGG was predicted to save 9% and 54% of overall costs compared with extensively hydrolyzed whey formula and amino acid formula, respectively. Results were robust to sensitivity analyses. Conclusion: Use of EHCF+LGG resulted in more symptom-free time and the highest 3-year probability of cow’s milk tolerance. It also led to healthcare resource and transportation savings when compared with other hypoallergenic milk formulas. Soy formula remained an alternative if formula price represents a major constraint.

Managing Cow’s Milk Protein Allergy in Indonesia: A Cost-effectiveness Analysis of Hypoallergenic Milk Formulas From the Private Payers’ Perspective

Background: Cow’s milk protein allergy is very common in early childhood. Extensively hydrolyzed formulas are recommended in the first-line management of cow’s milk protein allergy in non-breastfed children. Choice of formulas should be informed by efficacy and cost data. Objectives: This study aims to compare the cost-effectiveness of extensively hydrolyzed casein formula with Lacticaseibacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), amino acid formula, and soy formula in the first-line management of cow’s milk protein allergy in non-breastfed children in Indonesia. Methods: A trial-based decision analytic cohort model was adapted to simulate the occurrence of cow’s milk protein allergy symptoms or being symptom free. The model was based on a prospective nonrandomized study that followed up children for 36 months. Costs and health consequences were discounted at 3% annually. Resources required to manage cow’s milk protein allergy and unit costs for clinical appointments and exams were based on a panel of 15 clinicians, from a private payers’ perspective. Other unit costs were based on publicly available national data. Results were reported as cost per additional child free from allergic manifestations or per additional immunotolerant child at 3 years, and per life-years under the same conditions. Uncertainty was assessed using deterministic and probabilistic sensitivity analysis. Results: Children receiving EHCF+LGG were associated with more symptom-free time, a higher probability of cow’s milk tolerance at 3 years, and lower healthcare resources and transportation use when compared with children receiving other formulas (with 38%-49% lower costs). Formula costs were lower for soy, but EHCF+LGG was predicted to save 9% and 54% of overall costs compared with extensively hydrolyzed whey formula and amino acid formula, respectively. Results were robust to sensitivity analyses. Conclusion: Use of EHCF+LGG resulted in more symptom-free time and the highest 3-year probability of cow’s milk tolerance. It also led to healthcare resource and transportation savings when compared with other hypoallergenic milk formulas. Soy formula remained an alternative if formula price represents a major constraint.

Cost-effectiveness Analysis of Hypoallergenic Milk Formulas for the Management of Cow's Milk Protein Allergy in the United Kingdom.

Background: Cow’s milk protein allergy (CMPA) is the most common food allergy in early childhood. In most children CMPA resolves by age 5 or 6; however, if not treated correctly can provoke nutritional deficiency resulting in poor growth. Management consists of excluding cow’s milk from the diet, with hypoallergenic formulas (or non-dairy alternatives) being introduced to meet nutritional requirements.Objectives: To compare the cost-effectiveness of hypoallergenic formulas in reducing allergic manifestations and promoting immune tolerance in infants with immunoglobulin E (IgE)-mediated symptoms of CMPA.Methods: A trial-based decision analytic cohort model was developed to simulate the occurrence of urticaria, eczema, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA in the United Kingdom. Amino acid-based formula (AAF), extensively hydrolysed casein formula containing Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolysed whey formula (EHWF), and soy formula (SF) were compared using the National Health Service (NHS) perspective, 3-year time horizon and 3.5% discount rate for cost and health consequences. Hypoallergenic formulas comparative efficacy was sourced from a prospective cohort study. Resources required to manage allergic symptoms were sourced from published literature, validated by a UK clinician, and applied to UK cost resources. Results were reported as cost per additional child free from allergic manifestations at 3 years and cost per additional immune tolerant child at 3 years.Results: In the base case, infants receiving EHCF+LGG were associated with lower NHS resource use and improved CMPA tolerance. Over the 3-year treatment period, savings of £119, £476, and £2645 were achieved with EHCF+LGG compared to SF, EHWF and AAF, respectively. Infant formula accounted for the largest proportion of resource consumption averaging 47% for all comparators, with a minimum of 31% for SF and a maximum of 69% for AAF over 3 years. General practitioners’ visits constituted the second highest cost component, approximately 16% of total costs across comparators. The results were robust to deterministic and probabilistic sensitivity analyses.Conclusions: Compared to AAF, SF, and EHWF hypoallergenic formulas, EHCF+LGG was the most cost-effective, associated with lower total costs and contributing to a higher proportion of children being symptom-free and developing immune tolerance 3-years after diagnosis.

The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF+LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF+LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF+LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P<.001) for rice hydrolyzed formula vs EHCF+LGG; 2.62 (1.63-4.22, P<.001) for soy formula vs EHCF+LGG; 2.31 (1.42-3.77, P<.001) for EHWF vs EHCF+LGG; and 3.50 (2.23-5.49, P<.001) for amino acid-based formula vs EHCF+LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF+LGG cohort. The use of EHCF+LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Effect of extensively hydrolyzed casein vs. conventional formula on the risk of asthma and allergies: The TRIGR randomized clinical trial

The role of hydrolyzed infant formulas in the prevention of asthma and allergies remains inconsistent. We tested whether extensively hydrolyzed casein formula compared to conventional cow's milk-based formula prevented asthma, allergic rhinitis, or atopic eczema. In the randomized double-blind Trial to Reduce IDDM in Genetically at Risk (TRIGR), comparing extensively hydrolyzed to standard cow's milk-based infant formula during the first 6-8months of life, we assessed the effect of the intervention on the incidence of asthma, allergic rhinitis, and eczema when the children were 9- to 11-years old. The asthma, allergic rhinitis, and eczema occurrence was assessed using online standardized and validated ISAAC questionnaire. Of the 1106 children who participated in this Ancillary study, 560 had been randomized to the experimental (extensively hydrolyzed casein formula) and 546 to the control arm (cow's milk-based formula). The risk of persistent asthma, allergic rhinitis, or atopic eczema did not differ by treatment, the hazard ratios (95% CI) being 1.00 (0.66-1.52), 0.95 (0.66-1.38), and 0.89 (0.70-1.15), respectively, in the intention-to-treat analysis. Neither were there any differences in the per-protocol analysis. Extensively hydrolyzed casein formula did not protect from asthma, rhinitis, or eczema in this population carrying genetic risk for type 1 diabetes.

Effectiveness of using an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG compared with an extensively hydrolysed whey formula in managing cow’s milk protein allergic infants

Aim: To assess the comparative effectiveness of two hypoallergenic formulae in managing cow's milk allergic infants. Materials & methods: This study retrospectively analyzed the case records of 940 formula-fed cow's milk allergic infants in the UK extracted from The Health Improvement Network database. Results: At 24 months after starting a formula, 77% of infants fed an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (eHCF LGG;n=470) were estimated to have been successfully managed compared with 63% of matched infants who were fed an extensively hydrolyzed whey formula (eHWF;n=470;p < 0.001). Additionally, significantly more eHWF-fed infants were estimated to be experiencing gastrointestinal symptoms, eczema and asthma (7.1 vs 3.1%; p < 0.02) at 24 months. Conclusion: First-line management of newly diagnosed cow's milk allergic infants with eHCF LGG may slow down the allergic march seen in cow's milk allergic children.

Dietary Treatment with Extensively Hydrolyzed Casein Formula Containing the Probiotic Lactobacillus rhamnosus GG Prevents the Occurrence of Functional Gastrointestinal Disorders in Children with Cow's Milk Allergy

To investigate whether the addition of the probiotic Lactobacillus rhamnosus GG (LGG) to the extensively hydrolyzed casein formula (EHCF) for cow's milk allergy (CMA) treatment could reduce the occurrence of functional gastrointestinal disorders (FGIDs). This cohort study included children with a positive history for CMA in the first year of life who were treated with EHCF alone or in combination with LGG and had evidence of immune tolerance acquisition to cow's milk for at least 12months. FGID was diagnosed according to the Rome III diagnostic criteria by investigators unaware of previous treatment. A cohort of consecutive healthy children was also evaluated as a control population. A total of 330 subjects were included, 110 per cohort (EHCF, EHCF+LGG, and healthy controls). The rate of subjects with ≥1 FGID was significantly lower in the EHCF+LGG cohort compared with the EHCF cohort (40% vs 16.4%; P<.05). In the EHCF+LGG cohort, a lower incidence was observed for all components of the main study outcome. The prevalence of FGIDs in the healthy cohort was lower than that in the EHCF cohort and similar to that in the EHCF+LGG cohort. The incidence rate ratio of FGIDs for the EHCF+LGG cohort vs the EHCF cohort (0.40; 95% CI, 0.25-0.65; P<.001) was unmodified after correction for age at CMA diagnosis, breastfeeding, weaning time, and presence of a first-degree relative with an FGID. These results confirm the increased risk for developing FGIDs in children with CMA and suggest that EHCF+LGG could reduce this risk.

Cost-effectiveness of using an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG in managing IgE-mediated cow’s milk protein allergy in the UK

Objective: To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula (eHCF) plus the probiotic Lactobacillus rhamnosus GG (eHCF plus LGG; Nutramigen* LGG®) compared to an eHCF alone as first-line dietary management for Immunoglobulin E (IgE)-mediated cow’s milk protein allergy (CMPA) in the UK.Methods: Decision modelling was undertaken to estimate the probability of IgE-mediated cow’s milk allergic infants being symptom free (i.e. not experiencing urticaria, eczema, asthma or rhinoconjunctivitis) and developing tolerance to cow’s milk by 5 years. The model also estimated the cost (at 2016/2017 prices) of healthcare resource use funded by the UK’s National Health Service (NHS) over 5 years after starting a formula, as well as the relative cost-effectiveness of the two dietary formulae.Results: At 5 years after the start of a formula the probability of being symptom free was estimated to be 0.97 and 0.76 among infants who were originally fed eHCF plus LGG and an eHCF alone, respectively. This encompassed the probability of children being asthma free at 5 years after the start of treatment, which was 0.99 and 0.91 in the eHCF plus LGG and eHCF alone groups, respectively. Additionally, the probability of acquiring tolerance to cow’s milk was estimated to be 0.94 and 0.66 among infants who were originally fed eHCF plus LGG and an eHCF alone, respectively. The estimated total healthcare cost over 5 years of initially feeding infants with eHCF plus LGG was less than that of feeding infants with an eHCF alone (£4229 versus £5136 per patient).Conclusions: First-line management of newly diagnosed infants with IgE-mediated CMPA with eHCF plus LGG instead of an eHCF alone improves outcome, releases healthcare resources for alternative use, reduces the NHS cost of patient management and thereby affords a cost-effective dietetic strategy to the NHS.

Randomized controlled trial on the influence of dietary intervention on epigenetic mechanisms in children with cow\u2019s milk allergy: the EPICMA study

Epigenetic mechanisms could drive the disease course of cow’s milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4+ T cells were assessed. At same study points IL-4, IL-5, IL-10, and IFN-γ methylation rate, expression and serum concentration, miRNAs expression were also investigated. 20 children (10/group) were evaluated. Baseline demographic, clinical and epigenetic features were similar in the two study groups. At 6 and 12 months, EHCF + LGG group showed a significant increase in FoxP3 demethylation rate compared to SF group. At the same study points, EHCF + LGG group presented a higher increase in IL-4 and IL-5 and a higher reduction in IL-10 and IFN-γ DNA methylation rate compared to SF group. A different modulation of miR-155, -146a, -128 and -193a expression was observed in EHCF + LGG vs. SF. Dietary intervention could exert a different epigenetic modulation on the immune system in CMA children.

P102 Dietary treatment with extensively hydrolyzed casein formula with the probiotic L. rhamnosus GG prevents the occurrence of functional gastrointestinal disorders in children with cow's milk allergy

P102 Dietary treatment with extensively hydrolyzed casein formula with the probiotic L. rhamnosus GG prevents the occurrence of functional gastrointestinal disorders in children with cow's milk allergy

Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow\u2019s milk allergy

Cow’s milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probiotic Lactobacillus rhamnosus GG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment of Bacteroides and Alistipes. Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase in Bacteroides from healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.

Attitudes towards cow's milk protein allergy management by Spanish gastroenterologist

Abstract Introduction Food allergy is an increasing health problem in the developed world. Cow's milk protein is the main cause of food allergy in infants. Without an appropriate diagnostic workup, there is a high risk of both over- and underdiagnosis and therefore, over and undertreatment. The objective of our study was to analyze the variability in cow's milk protein allergy (CMPA) management by pediatric gastroenterologists in Spain. Methods A 50 item questionnaire, including open and closed items in a Likert's scale from 0 to 5, was drafted and distributed through the Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) e-mail list. Results Seventy-three questionnaires were received back out of 321. Only 3 of the items achieved concordance greater than 90%. Thirty-three percent considered oral challenge to be necessary for the diagnosis of CMPA under any circumstance. Twenty-five percent considered that symptom improvement after cow's milk removal was enough for the diagnosis. Oral challenge was performed at home by 83.5% in non-IgE mediated cases. Extensively hydrolyzed casein formulas were the treatment of choice for 69.9%. Soy formulas were the last option. Almost all respondents were aware of the existence of clinical guidelines on CMPA, being European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines the most followed (64.4%). Twenty-three percent considered that their knowledge about allergy was inadequate. Conclusions Although CMPA is a prevalent condition that pediatric gastroenterologists have been treating for decades, we found a huge variability on its management. There is potential for improvement in this field among pediatric gastroenterologist in the future.

Manejo de la alergia a proteína de leche de vaca por los gastroenterólogos españoles

Food allergy is an increasing health problem in the developed world. Cow's milk protein is the main cause of food allergy in infants. Without an appropriate diagnostic workup, there is a high risk of both over- and underdiagnosis and therefore, over and undertreatment. The objective of our study was to analyze the variability in cow's milk protein allergy (CMPA) management by pediatric gastroenterologists in Spain. A fifty item questionnaire, including open and closed items in a Likert's scale from 0 to 5, was drafted and distributed through the Spanish Society for Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) e-mail list. Seventy-three questionnaires were received back out of 321. Only 3 of the items achieved concordance greater than 90%. Thirty-three percent considered oral challenge to be necessary for the diagnosis of CMPA under any circumstance. Twenty-five percent considered that symptom improvement after cow's milk removal was enough for the diagnosis. Oral challenge was performed at home by 83.5% in non-IgE mediated cases. Extensively hydrolyzed casein formulas were the treatment of choice for 69.9%. Soy formulas were the last option. Almost all respondents were aware of the existence of clinical guidelines on CMPA, being European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines the most followed (64.4%). Twenty-three percent considered that their knowledge about allergy was inadequate. Although CMPA is a prevalent condition that pediatric gastroenterologists have been treating for decades, we found a huge variability on its management. There is potential for improvement in this field among pediatric gastroenterologist in the future.

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes

Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. clinicaltrials.gov Identifier: NCT00179777.

A Double-Blind, Randomized, Crossover Allergy Study of an Extensively Hydrolyzed Casein Formula

Background: Extensively hydrolyzed formulas are used for the dietary management of cow’s milk allergy. There is a limited repertoire of commercially available formulas for infants with cow’s milk allergy. Methods: This was a multi-center, double-blind, randomized, crossover clinical study of 75 children younger than 12 years, 11 months with documented cow’s milk allergy. The primary outcome was the incidence of reactivity of a new extensively hydrolyzed casein formula and Nutramigen® during a Double-Blind Oral Food Challenge. A subset of subjects under the age of three years, 11 months at the time of enrollment received either the new formula or Nutramigen® for 16 weeks to investigate tolerance, taste preferences, growth and nutritional variables. Results: Sixty-one subjects completed both challenges in the per-protocol groups. The new formula was non-inferior to Nutramigen regarding allergic symptoms of reactivity in both per protocol and intent to treat analyses, the latter addressing risk of bias from attrition during DBOFC. Both formulas met the American Academy of Pediatrics criteria for hypoallergenicity and had similar adverse event profiles. The new formula was comparable to Nutramigen® in supporting growth and tolerance. Conclusion: The new hypoallergenic formula broadens access to formulations for dietary management of children with cow’s milk allergy. Intent to treat analyses should be included in DBOFC studies of hypoallergenicity to reduce risk of bias from early discontinuation.