Longitudinal Growth Trajectories in Children with Cow's Milk Allergy: Effects of Elimination Diet and Post-Termination Period.

INTRODUCTION: The primary dietary approach for managing cow's milk allergy (CMA) is the elimination diet. We aimed to compare the growth patterns of children with CMA during and after the elimination diet with healthy peers and identify influencing factors. METHODS: We compared 74 CMA children with age-matched healthy peers. Anthropometric data were collected during the third month of cow's milk elimination (CME) diet (T1), 3 months after diet cessation (T2), and after ≥3 months of normal diet (T3). Control group measurements coincided. Nutrient intake was assessed by a 3-day record, and patient laboratory results were noted at T3. RESULTS: CMA children had consistently lower weight-for-age (WFA) and height-for-age (HFA) z-scores than controls. WtHt z-score of patients was lower than those of the healthy group at T2. HC z-scores of patients were lower than those of the healthy group at T0, T2, and T3. At T3, the HFA z-score of the CME group demonstrated a negative correlation with the duration of the elimination diet (p = 0.045). Inadequate intake of energy, vitamins A, E, B1, B6, C, folic acid, magnesium, and iron was significantly higher in CMA children (p < 0.05). T3 WFA z-score correlated positively with fiber, vitamin B1, magnesium, and iron intake (p < 0.05). T3 WtHt showed a positive moderate correlation with energy, protein, vitamin E, vitamin B1, vitamin B2, vitamin B6, calcium, magnesium, phosphor, iron intake (p < 0.05). CONCLUSIONS: Post-elimination diet, children with CMA need sustained monitoring and potentially micronutrient supplementation to match healthy peers' growth.

Single-food elimination of cow's milk as a treatment for eosinophilic esophagitis in children aged 2-18 years: A review of the literature.

Cow's milk elimination (CME) is an established treatment, similar to other forms of diet therapy, for eosinophilic esophagitis (EoE). However, there is limited research to support its efficacy as a primary treatment. This review evaluated studies published in the past 10 years that assessed the outcomes after CME on histologic remission, clinical findings, and quality of life (QoL) in children aged 2-18 years with EoE. The evidence demonstrated that CME was effective at achieving histologic remission of disease in 50%-65% of children. This intervention also improved clinical symptoms seen on endoscopy and resulted in increased QoL when self-reported by children. CME can be used as a primary treatment for some children with EoE.

Hydrolysed Formulas in the Management of Cow's Milk Allergy: New Insights, Pitfalls and Tips.

An allergy to cow's milk requires the avoidance of cow's milk proteins and, in some infants, the use of a hypoallergenic formula. This review aims to summarize the current evidence concerning different types of hydrolysed formulas (HF), and recommendations for the treatment of IgE- and non-IgE-mediated cow's milk allergy and functional gastrointestinal disorders in infancy, for which some dietary intervention and HF may be of benefit to both immune and motor mechanisms. Current guidelines recommend cow's milk protein (i.e., whey or casein) extensively hydrolysed formula (eHF) as the first choice for cow's milk allergy treatment, and amino acid formulas for more severe cases or those with reactions to eHF. Rice hydrolysed formulas (rHF) have also become available in recent years. Both eHF and rHF are well tolerated by the majority of children allergic to cow's milk, with no concerns regarding body growth or adverse effects. Some hydrolysates may have a pro-active effect in modulating the immune system due to the presence of small peptides and additional components, like biotics. Despite encouraging results on tolerance acquisition, evidence is still not conclusive, thus hampering our ability to draw firm conclusions. In clinical practice, the choice of hypoallergenic formula should be based on the infant's age, the severity, frequency and persistence of symptoms, immune phenotype, growth pattern, formula cost, and in vivo proof of tolerance and efficacy.

Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow's Milk Allergy.

Cow's milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.

A Clinical Perspective on the Dietary Therapies for Pediatric Eosinophilic Esophagitis: The Gap Between Research and Daily Practice.

Pediatric eosinophilic esophagitis (ped-EoE) is an immune-mediated pathology affecting 34 per 100.000 children. It is characterized by an esophageal inflammation caused by an immune response towards food antigens that come into contact with the esophageal lining. Depending on the age of the child, symptoms can vary from abdominal pain, vomiting and failure to thrive to dysphagia and food impaction. The diagnosis of this chronic disease is based on the symptoms of esophageal dysfunction combined with an infiltration of more than 15 eosinophils per high-power field and the exclusion of secondary causes. The treatment modalities include the 3Ds: Drugs, allergen avoidance by Diet and/or esophageal Dilation. In this review we focused on the efficacy of dietary approaches in ped-EoE, which currently include the elemental diet (amino acid-based diet), the empiric elimination diet and the allergy test-directed elimination diet. Although several reviews have summarized these dietary approaches, a lack of consistency between and within the elimination diets hampers its clinical use and differences in subsequent reintroduction phases present a barrier for dietary advice in daily clinical practice. We therefore conducted an analysis driven from a clinician's perspective on these dietary therapies in the management of ped-EoE, whereby we examined whether these variations within dietary approaches, yet considered to be similar, could result in significant differences in dietary counseling.

Vitamin D and iron status in children with food allergy.

BACKGROUND: Children with food allergy are at specific risk for nutritional deficiencies. OBJECTIVE: To retrospectively determine prevalence of vitamin D and iron deficiencies in children with or without food allergy (FA). METHODS: We compared the markers of vitamin D and iron status of 0 to 17-year-olds with cow's milk allergy (CMA) (n = 77), those with other FAs (n = 70), and those with atopy without FA (n = 87) at an academic pediatric allergy practice. Multiple linear regression analyses were performed to determine the impact of CMA and other FAs on vitamin D levels and iron markers. RESULTS: Vitamin D deficiency was detected in one-fourth and insufficiency in one-third of children with CMA and other FAs and in those with atopic diseases but no FA, respectively. Vitamin D levels were associated with vitamin D supplementation and consumption of breast milk, cow's milk, infant formula, or plant-based milk beverage, but not with CMA or other FAs. Older children with FA who did not consume any cow's milk or alternative milk beverage were at highest risk for vitamin D insufficiency. Children with CMA have a higher rate of iron deficiency anemia (8%) than children with other FAs (1%) or those with no FA (5%, P < .001); however, suboptimal levels of transferrin saturation and iron were detected in up to one-third of children with CMA or other FAs. CONCLUSION: Vitamin D deficiency and insufficiency is common in children with atopy overall, but children with CMA are at higher risk for iron deficiency anemia. Intensive nutritional counseling and nutrient intake monitoring, specifically for vitamin D and iron in those avoiding cow's milk, are necessary to optimize nutritional status.

The self-management work of food hypersensitivity.

BACKGROUND: Food hypersensitivity (FH) has received considerable attention in the scientific community in recent years. However, little attention has been given to the efforts people make to manage their FH. We aimed to explore these efforts by using Normalization Process Theory, which is a conceptual framework formerly used to describe the self-management 'work' of long-term conditions. METHODS: We carried out qualitative individual interviews with 16 women with FH. Transcripts from recorded interviews were analyzed using template analysis. RESULTS: 16 women participated; some had diagnoses from conventional medicine (celiac disease, lactose intolerance, food allergies, irritable bowel syndrome) and some did not. Participants described carrying out several tasks, some of which were time-consuming, to manage their FH. Women who had clarified once and for all what food(s) caused symptoms, described that they could concentrate on carrying out a restricted diet, which could become routine. Conversely, participants who had not achieved such clarification described carrying out tasks to identify what food(s) caused symptoms, and to implement and evaluate a tentative diet. Participants' descriptions also revealed a heightened vigilance when they ate food that others had prepared, and some made efforts to conceal their FH. CONCLUSIONS: Self-management of FH may, like the self-management of other long-term conditions, imply a large workload and burden of treatment. Efforts made to conceal FH may be considered part of this workload, while help in clarifying which food(s) cause symptoms has the potential to reduce the workload.

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.

OBJECTIVES: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Mare's Milk: Composition, Properties, and Application in Medicine.

Mare's milk is a highly valuable organic substance that has a great potential to replace cow's milk. Consumption of cow's milk causes digestive disorders in some individuals. Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is one of the most common food allergies among infants. Therefore, finding a protein substitute with the same nutritional value is a priority. Mare's milk can be a good substitute for cow's milk, especially for those suffering from CMA. Prerequisites for this study were the recent interest in mare's milk, as an ancient relic of the Turkic peoples which contains lots of nutrients. The present study aimed to systematize relevant information on the composition of mare's milk and its application in medicine. Google Scholar, PubMed, Cochrane, Elsevier, CyberLeninka were employed for a comprehensive literature search. The searched keywords for this study were mare's milk, saumal, composition, properties, use in medicine. A total of 77 sources were selected for reviewing the literature. Most sources were in English, except for one of the bottom 40 sources published in the last 10 years. Among the milk of many mammalian species, mare's milk is chemically similar to human milk so it can be used as a substitute. It is also used to feed people with various health conditions, especially in patients at risk, or suffering from tuberculosis, hepatitis C, psoriasis, and various types of immunodeficiency. The present study describes the rich composition, antibacterial and antiviral properties of mare's milk. A review of the literature revealed that mare's milk is an excellent thirst quencher, and has valuable nutrients necessary for the human body which is by no means inferior to human milk.

Dietary Vitamin D Supplementation Is Ineffective in Preventing Murine Cow's Milk Allergy, Irrespective of the Presence of Nondigestible Oligosaccharides.

INTRODUCTION: Cow's milk allergy (CMA) is one of the most common food allergies especially early in life. A mixture of nondigestible short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and pectin-derived acidic-oligosaccharides (GFA) may reduce allergy development and allergic symptoms in murine CMA. Recently, vitamin D (VitD) has been suggested to have beneficial effects in reducing allergy as well. OBJECTIVE: In this study, the immune modulatory effect on allergy prevention using the combination of GFA and VitD was investigated. METHODS: Female C3H/HeOuJ mice were fed a control or GFA-containing diet with depleted, standard (1,000 IU/kg), or supplemented (5,000 IU/kg) VitD content for 2 weeks before and during whey sensitization (n = 10-15). Mice were sensitized 5 times intragastrically with PBS as a control, whey as cow's milk allergen, and/or cholera toxin as adjuvant on a weekly interval. One week after the last sensitization, mice were intradermally challenged in both ear pinnae and orally with whey, subsequently the acute allergic skin response and shock symptoms were measured. After 18 h, terminal blood samples, mesenteric lymph nodes, and spleens were collected. Whey-specific immunoglobulin (Ig) E and IgG1 levels were measured by means of ELISA. T cell subsets and dendritic cells (DCs) were studied using flow cytometry. RESULTS: Additional VitD supplementation did not lower the allergic symptoms compared to the standard VitD diet. CMA mice fed the GFA diet supplemented with VitD (GFA VitD+) significantly decreased the acute allergic skin response of whey sensitized mice when compared to the CMA mice fed VitD (VitD+) group (p < 0.05). The effect of GFA was not improved by extra VitD supplementation even though the CMA mice fed the GFA VitD+ diet had a significantly increased percentage of CD103+ DCs compared to the VitD+ group (p < 0.05). The VitD-deprived mice showed a high percentage of severe shock and many reached the humane endpoint; therefore, these groups were not further analyzed. CONCLUSIONS: High-dose VitD supplementation in mice does not protect against CMA development in the presence or absence of GFA.

Effectiveness of allergy testing in milk induced eosinophilic esophagitis. Description and follow-up of patients.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated esophageal disease that has been on the increase lately. There is currently enough evidence to conclude that EoE is an allergic disorder triggered by food allergens, with cow's milk (CM) being the most frequent. Dietary intervention is the first-line approach. This study aimed to assess the clinical characteristics, the diagnostic method, and the prognosis of patients whose culprit food was CM, as opposed to other triggers. METHODS: Children with EoE evaluated in our pediatric Allergy Department were retrospectively studied from 2004 to 2017. We collected clinical variables, diagnostic protocol, treatment, and follow-up data. We compared patients whose culprit food was CM and patients with EoE due to other causative agents. RESULTS: We analyzed 31 children with EoE and found the causative food to be cow's milk in 14 (45%). Clinical characteristics were similar in patients with EoE due to milk or any other cause. Eight of 14 patients with milk-induced EoE (57.14%) presented positive skin prick test results against cow's milk. All patients had positive IgE against cow's milk. None of the patients had any other food as the trigger. The median follow-up was 2.68 years (6 months to 9 years) with initial remission of 100%. CONCLUSION: Testing-based elimination diets effectively treated all of the patients with milk-induced EoE. The advantage of this diagnostic protocol is that it required a mean of only two foods to be tested, significantly smaller number than in empiric diets.

A well-tolerated new amino acid-based formula for cow's milk allergy.

OBJECTIVES: Infants with cow's milk allergy (CMA) are in need of a substitute formula up to 2 years. The are three requisites for a substitute of milk in CMA: tolerability, nutritional adequacy, and cost-effectiveness. We evaluate here the tolerability of a new amino acid-based infant formula for the management of CMA. METHODS: In a phase III/IV prospective, multicentre, open-label, international study, infants and children with immunoglobulin E-mediated CMA were exposed to a diagnostic double-blinded, placebo-controlled food challenge with a new amino acid formula by Blemil Plus Elemental using Neocate as the placebo. If tolerant to it, the study formula was integrated into the patients' usual daily diet for 7 days. Efficacy on day 7 was assessed in terms of symptoms associated with CMA, amount of formula consumed, nutritional and energy intake, and anthropometric data. RESULTS: Thirty children (17 M and 13 F; median age, 1.58; range, 0.08-12.83 years) completed the open challenge and were able to consume the study formula for at least 7 days. No signs or symptoms of allergic reactions were recorded among children assuming either the test or the control formula, with a lower 95% one-sided confidence interval for the proportion of subjects who did not experience allergic reactions above 90%. Sixteen patient under the age of two continued with the optional extension phase. CONCLUSIONS: The study formula meets the American Academy of Pediatric criteria for hypoallergenicity and is well tolerated in short-term use. During optional phase, growth of the patients was not hindered by the study formula.

Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.

Several formulas are available for the dietary treatment of cow's milk allergy (CMA). Clinical data suggest potentially different effect on immune tolerance elicited by these formulas. We aimed to comparatively evaluate the tolerogenic effect elicited by the protein fraction of different formulas available for the dietary treatment of CMA. Five formulas were compared: extensively hydrolyzed whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (HRF), soy formula (SF), and amino acid-based formula (AAF). The formulas were reconstituted in water according to the manufacturer's instructions and subjected to an in vitro infant gut simulated digestion using a sequential gastric and duodenal static model. Protein fraction was then purified and used for the experiments on non-immune and immune components of tolerance network in human enterocytes and in peripheral mononuclear blood cells (PBMCs). We assessed epithelial layer permeability and tight junction proteins (occludin and zonula occludens-1, ZO-1), mucin 5AC, IL-33, and thymic stromal lymphopoietin (TSLP) in human enterocytes. In addition, Th1/Th2 cytokine response and Tregs activation were investigated in PBMCs from IgE-mediated CMA infants. EHCF-derived protein fraction positively modulated the expression of gut barrier components (mucin 5AC, occludin and ZO-1) in human enterocytes, while SF was able to stimulate the expression of occludin only. EHWF and HRF protein fractions elicited a significant increase in TSLP production, while IL-33 release was significantly increased by HRF and SF protein fractions in human enterocytes. Only EHCF-derived protein fraction elicited an increase of the tolerogenic cytokines production (IL-10, IFN-γ) and of activated CD4+FoxP3+ Treg number, through NFAT, AP1, and Nf-Kb1 pathway. The effect paralleled with an up-regulation of FoxP3 demethylation rate. Protein fraction from all the study formulas was unable to induce Th2 cytokines production. The results suggest a different regulatory action on tolerogenic mechanisms elicited by protein fraction from different formulas commonly used for CMA management. EHCF-derived protein fraction was able to elicit tolerogenic effect through at least in part an epigenetic modulation of FoxP3 gene. These results could explain the different clinical effects observed on immune tolerance acquisition in CMA patients and on allergy prevention in children at risk for atopy observed using EHCF.

Investigation of the Efficacy of Lactobacillus rhamnosus GG in Infants With Cow's Milk Protein Allergy: a Randomised Double-Blind Placebo-Controlled Trial.

This investigation has been performed to show the efficacy of Lactobacillus rhamnosus GG (LGG) together with milk-free diet in patients with cow's milk protein allergy (CMPA). This multicentre prospective investigation has been performed in 0-12 months of age children diagnosed as CMPA clinically and biochemically. Patients have been randomly divided in to two groups. Infants in probiotic group were received with cow's milk protein free diet and per oral (p.o.) daily 1X109 CFU LGG and in placebo group with milk-free diet and placebo. Mothers of all breast-fed patients have been put on milk-free diet and all patients fed with formula, offered to extensively hydrolysed formula. Symptoms like diarrhoea, vomiting, mucousy or bloody stool, abdominal pain or distension, constipation, dermatitis and restiveness were recorded at the beginning and weekly during the receiving dietary by the investigator. One-hundred infants diagnosed CMPA were included in this double-blind placebo controlled study. Forty-eight infants placed in probiotic group and 52 in placebo group. After 4 weeks of receiving dietary, infants in probiotic group have showed statistically significant improvement in symptoms of bloody stool, diarrhoea, restiveness and abdominal distension (p ≤ 0.001). Whilst statistically significant improvement was also observed in symptoms of mucousy stool (p = 0.038) and vomiting (p = 0.034), no significant improvement were observed in abdominal pain (p = 0.325), constipation (p = 0.917) and dermatitis (p = 0.071). In this study we observed significant improvement in symptoms of infants diagnosed CMPA receiving dietary LGG with cow's milk-free diet.

The use of amino acid-based nutritional feeds is effective in the dietary management of pediatric eosinophilic oesophagitis.

INTRODUCTION: Eosinophilic oesophagitis (EoE) is an immune-mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. METHODS: Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. RESULTS: Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%-100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%-81% and 40%-69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long-term impacts of each diet were not thoroughly explored. CONCLUSIONS: The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long-term management.

Testing the Cow's Milk-Related Symptom Score (CoMiSSTM) for the Response to a Cow's Milk-Free Diet in Infants: A Prospective Study.

The diagnosis of cow's milk allergy (CMA) is particularly challenging in infants, especially with non-Immunoglobulin E (IgE)-mediated manifestations, and inaccurate diagnosis may lead to unnecessary dietary restrictions. The aim of this study was to assess the accuracy of the cow's milk-related symptom score (CoMiSSTM) in response to a cow's milk-free diet (CMFD). We prospectively recruited 47 infants (median age three months) who had been placed on a CMFD due to persisting unexplained gastrointestinal symptoms. We compared data with 94 healthy controls (median age three months). The CoMiSSTM score was completed at recruitment and while on the exclusion diet. In 19/47 (40%) cases a response to the diet occurred. At recruitment CoMiSSTM was significantly higher in cases compared to controls (median score 8 vs. 3; p-value: <0.05), 9 cases had a score ≥12 and 8/9 normalized on CMFD. An oral milk challenge was performed in all 19 responders and six of these had a positive reaction to cow's milk (CM). In eight infants IgE allergy tests were positive. The receiver operation characteristic (ROC) curve identified a CoMISSTM score of 9 to be the best cut-off value (84% sensitivity, 85% specificity, 80% positive (PPV) and 88% negative predictive value (NPV)) for the response to CMFD. We found CoMiSSTM to be a useful tool to help identify infants with persisting gastrointestinal symptoms and suspected CMA that would benefit from CMFD.

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.

OBJECTIVE: 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). STUDY DESIGN: 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 12 months. 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. RESULTS: 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. CONCLUSIONS: These results confirm the increased risk for developing FGIDs in children with CMA and suggest that EHCF+LGG could reduce this risk.

Cow's Milk Substitutes for Children: Nutritional Aspects of Milk from Different Mammalian Species, Special Formula and Plant-Based Beverages.

Cow's milk and dairy are commonly consumed foods in the human diet and contribute to maintaining a healthy nutritional state, providing unique sources of energy, calcium, protein, and vitamins, especially during early childhood. Milk formula is usually made from cow's milk and represents the first food introduced into an infant's diet when breastfeeding is either not possible or insufficient to cover nutritional needs. Very recently, increased awareness of cow's milk protein allergy and intolerance, and higher preference to vegan dietary habits have influenced parents towards frequently choosing cows' milk substitutes for children, comprising other mammalian milk types and plant-based milk beverages. However, many of these milk alternatives do not necessarily address the nutritional requirements of infants and children. There is a strong need to promote awareness about qualitative and quantitative nutritional compositions of different milk formulas, in order to guide parents and medical providers selecting the best option for children. In this article, we sought to review the different compositions in terms of macronutrients and micronutrients of milk from different mammalian species, including special milk formulas indicated for cow's milk allergy, and of plant-based milk alternatives.

Formula supplementation remains a risk for cow's milk allergy in breast-fed infants.

BACKGROUND: Many breastfed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (a) impact of formula supplementation on the likelihood of developing cow's milk protein allergy (CMPA) and (b) current practice of formula supplementation (<24 hours) among mothers intending to breastfeed. METHOD: Fifty-five CMPA-diagnosed children, fed at <24 hours of age (breast only, formula only or breast with formula supplementation), were recruited, and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breastfeeding mothers. Linear regression (LiR) analysis was used to examine the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors. RESULTS: Two LoR examined the infant groups: exclusively breastfed, exclusively formula-fed or breastfed with formula supplementation. The first LoR model which showed only formula supplementation was significant in prediction of development of CMPA (χ2 (3) = 25.74, P < .05), with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breastfed infants given formula supplements were 7.03 (95% CI, 1.82-27.25) times more likely to exhibit CMPA than those who were exclusively breastfed. Formula supplementation was significant (OR 16.62, 95% CI 3.89-71.11), indicating that breastfed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (odds ratio 0.42, 95% CI, 0.16-1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breastfed in either model (P > .05). About 45.8% of breastfed infants (<24 hours) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170) = 66.95, P < .05) explaining 75% of total variance. The subjective factors 'no latch' and 'mum unwell' were the strongest predictors (ß > .45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant. CONCLUSION: Breastfed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the first 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and healthcare providers should be better educated on the benefits of exclusive breastfeeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.