Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

The use of extensively hydrolysed and amino acid feeds beyond cow's milk allergy: a national survey.

BACKGROUND: Extensively hydrolysed formulas (EHFs) and amino acid formulas (AAFs) with proven hypoallergenicity are used for children suffering from cow's milk allergy, when breast milk is not available. However, these feeds are often used in other medical conditions where tolerance and absorption of whole protein is affected, frequently without assessment of efficacy. This practice survey assessed the use of these feeds in paediatric conditions other than cow's milk allergy; aiming to describe the population, growth parameters and micronutrient status. METHODS: Four National Health Service tertiary paediatric centres participated in this practice survey. Inclusion: children between 0 and 18 years, consuming >25% of their estimated energy requirements of an EHF/AAF for any condition other than allergic disease. Anonymised data were collected: (i) descriptive information; (ii) indications; (iii) type and route of feeding; (iv) growth status and nutritional deficiencies; and (v) medication and vitamin and mineral supplementation. RESULTS: One hundred-and-ninety-one children were included with a median age of 19 months (interquartile range 4-63]. Seventeen percent (33/191) were on AAFs and 83% (158/191) were on EHFs. The feeds were commonly used in cancer for 26% and in critical illness for 31%. The majority (73%) of children had enteral feeds via a nasogastric tube. Nutritional biomarkers were performed in 29% of children and 83% were on a vitamin or mineral supplement. CONCLUSIONS: This practice survey found that EHFs and AAFs were used in a variety of medical conditions. Indications for feed choice varied, and evidence-based research supporting the use was scarce. Awaiting further research, children on these types of feeds should have regular nutritional monitoring.

Symptoms and management of cow's milk allergy: perception and evidence.

Introduction: The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13). Methods: These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results: Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Discussion: Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

The use of amino acid formulas in pediatric patients with allergy to cow's milk proteins: Recommendations from a group of experts.

One of the most common food allergies in children is cow's milk allergy (CMA). In breast-fed infants with CMA, the mother is encouraged to avoid dairy products. If this is not possible, or in formula fed infants, use of hypoallergenic replacement formulas such as extensively hydrolyzed formulas (EHF) is recommended. However, in ∼5% of patients EHFs are not tolerated and/or allergy symptoms can persist. When EHFs are ineffective and in severe forms of CMA, amino acid-based formulas (AAF) should be considered. Six pediatric gastroenterologists with extensive experience in food allergy management reviewed scientific publications and international clinical practice guidelines to provide practical recommendations on AAF. The guidelines reviewed had discrepancies and ambiguities around the specific indications for using formulas as a milk substitute. The panel recommends AAFs as the first therapeutic option in anaphylaxis due to CMA, in acute and chronic severe food protein-induced enterocolitis syndrome, in CMA associated with multiple food allergy, and in cases of eosinophilic esophagitis not responding to an extended exclusion diet or not eating solids. The main benefit of AAF is its absence of residual allergenicity, making it a safe treatment option in severe CMA patients who do not tolerate or respond to an EHF.

Differences between peptide profiles of extensive hydrolysates and their influence on functionality for the management of cow's milk allergy: A short review.

Extensively hydrolyzed formulas (eHFs) are recommended for the dietary management of cow's milk protein allergy (CMPA) in non-exclusively breastfed infants. Studies show that peptide profiles differ between eHFs. This short review aims to highlight the variability in peptides and their ability to influence allergenicity and possibly the induction of tolerance by different eHFs. The differences between eHFs are determined by the source of the protein fraction (casein or whey), peptide size-distribution profile and residual ß-lactoglobulin which is the most immunogenic and allergenic protein in bovine milk for human infants as it is not present in human breastmilk. These differences occur from the hydrolyzation process which result in variable IgE reactivity against cow's milk allergen epitopes by subjects with CMPA and differences in the Th1, Th2 and pro-inflammatory cytokine responses elicited. They also have different effects on gut barrier integrity. Results suggest that one particular eHF-casein had the least allergenic potential due to its low residual allergenic epitope content and demonstrated the greatest effect on restoring gut barrier integrity by its effects on mucin 5AC, occludin and Zona Occludens-1 in human enterocytes. It also increased the production of the tolerogenic cytokines Il-10 and IFN-γ. In addition, recent studies documented promising effects of optional functional ingredients such as pre-, pro- and synbiotics on the management of cow's milk allergy and induction of tolerance, in part via the induction of the production of short chain fatty acids. This review highlights differences in the residual allergenicity, peptide size distribution, presence of optional functional ingredients and overall functionality of several well-characterized eHFs which can impact the management of CMPA and the ability to induce immune tolerance to cow's milk protein.

Clinical Observation of Extensively Hydrolysis Protein Formula With Feeding Intolerance in Preterm Infants.

Objective: To investigate whether feeding extensively hydrolysis protein formula during the NICU hospitalization was more beneficial for preterm infants with a gestational age (GA) ≤34 weeks when breastfeeding was not possible. Methods: In total, 587 preterm infants were randomly divided into two groups: observation groups fed with extensively hydrolyzed formula (EHF) milk and control groups fed with standard preterm formula (SPF) milk until discharge from the neonatal intensive care unit (NICU). The incidence of complications during hospitalization was recorded in both groups. Then, two groups were uniformly fed with 0-to-6-month infant formula milk and followed-up for 6 months after discharge. Results: The final study included 370 premature infants, including 185 babies in the observation group and 185 in the control group. In contrast to the SPF, feeding EHF among preterm infants of GA <34 weeks during NICU hospitalization significantly reduced the incidence of feeding intolerance (FI) (14.1 vs. 30.3%, p < 0.01). The incidence of necrotizing enterocolitis (NEC) was significantly reduced in the observation group (2.2 vs. 6.5%, p < 0.05), but there was no significant difference in the incidence of other related complications. At discharge, there was no difference in total serum protein (46.6 vs. 46.4 g/L), albumin (33.5 vs. 34.2 g/L), and calcium (2.37 vs. 2.35 mmol/L), but the serum phosphorus concentrations associated with skeletal mineralization (2.10 vs. 2.22 mmol/L, p < 0.05) was significantly reduced and alkaline phosphatase significantly rose (254 vs. 220 IU/L, p < 0.05) in the observation group. No significant difference was found in the growth rates of body weight, head circumference, or body length, either during the NICU hospitalization or during the 6-month follow-up after discharge (p > 0.05). Conclusions: Feeding premature infants of GA ≤34 weeks with EHF reduced the incidence of FI, but had no advantage in establishing whole intestinal nutrition, shortening parenteral nutrition (PN) time, or hospitalization time. It had little effect on physical growth or development during NICU hospitalization and within 6 months after discharge. However, it may increase the incidence of metabolic bone disease (MBD).

Managing Cow's Milk Protein Allergy with an Extensively Hydrolyzed Formula: Results from a Prospective, Non-Interventional Study in France (EVA Study).

Symptoms related cow's milk proteins allergy (CMPA) usually improve between two to four weeks following an elimination diet, firstly with extensively hydrolyzed formulas (eHF). The aim of the EVA study was to observe the evolution of CMPA-related symptoms in real life after initiation of a whey-based extensively hydrolyzed formula (w-eHF, Althéra®, Nestlé Health Science, Switzerland). This cross-sectional prospective non-interventional study was carried out alongside paediatricians in private practice in France between June 2019 and June 2020. Infants aged 0−3 years presenting with confirmed diagnosis or clinical symptoms suggesting CMPA were enrolled. Data were collected at enrolment (baseline visit) and three to five weeks later (follow-up visit). Symptoms were assessed using the Cow's Milk-related Symptom Score (CoMiSS®). The per protocol population included 135 infants. The average number of symptoms per infant significantly decreased under the study formula (from 2.81 to 1.36, p < 0.001) and the proportions of infants with any CMPA related symptoms decreased. Daily crying and regurgitation showed the largest decline, respectively −44.4% and −31.85% (p < 0.001). These results describe the early management of symptoms suspected to be related to CMPA in routine practice that was rarely described in the literature. The number and severity of symptoms decreased most of the cases after commencing the study formula.