An Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides Modifies the Fecal Microbiome and Metabolome in Infants with Cow's Milk Protein Allergy.

Cow's milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.

Characterization of Upper Gastrointestinal Motility in Infants With Persistent Distress and Non-IgE-mediated Cow's Milk Protein Allergy.

BACKGROUND: Persistent crying in infancy is common and may be associated with gastroesophageal reflux disease (GERD) and/or non-IgE-mediated cow's milk protein allergy (CMPA). We aimed to document upper gastrointestinal motility events in infants with CMPA and compare these to findings in infants with functional GERD. METHODS: Infants aged 2 to 26 weeks with persistent crying, GERD symptoms and possible CMPA were included. Symptoms were recorded by 48-hour cry-fuss chart and validated reflux questionnaire (infant GERD questionnaire [IGERDQ]). Infants underwent a blinded milk elimination-challenge sequence to diagnose CMPA. GERD parameters and mucosal integrity were assessed by 24-hour pH-impedance monitoring before and after cow's milk protein (CMP) elimination. C-octanoate breath testing for gastric emptying dynamics, dual-sugar intestinal permeability, fecal calprotectin, and serum vitamin D were also measured. RESULTS: Fifty infants (mean age 13 ±â€Š7 weeks; 27 boys) were enrolled. On the basis of CMP elimination-challenge outcomes, 14 (28%) were categorized as non-IgE-mediated CMPA, and 17 (34%) were not allergic to milk; 12 infants with equivocal findings, and 7 with incomplete data were excluded. There were no baseline differences in GERD parameters between infants with and without CMPA. In the CMPA group, CMP elimination resulted in a significant reduction in reflux symptoms, esophageal acid exposure (reflux index), acid clearance time, and an increase in esophageal mucosal impedance. CONCLUSIONS: In infants with persistent crying, upper gastrointestinal motility parameters did not reliably differentiate between non-IgE-mediated CMPA and functional GERD. In the group with non-IgE-mediated CMPA, elimination of CMP significantly improved GERD symptoms, esophageal peristaltic function, and mucosal integrity.

Pediatric Collagenous Gastritis and Colitis: A Case Series and Review of the Literature.

INTRODUCTION: Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date. OBJECTIVE: We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition. METHODS: A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted. RESULTS: A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine. CONCLUSIONS: Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the "'adult" phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.

Food Allergy Prevention and Treatment by Targeted Nutrition.

In view of the dramatic rise in the prevalence of food allergy globally, effective prevention strategies have become a public health priority. Several models have emerged around the etiology of food allergy, including the hygiene hypothesis, dual allergen exposure hypothesis, and vitamin D hypothesis. These form the basis for current and potential prevention strategies. Breastfeeding remains a key pillar of primary allergy prevention. Other nutritional interventions, including the use of whey-based, partially hydrolyzed formula in non-breastfed infants, also play an important role. In recent years, there has been a shift away from prolonged food allergen avoidance to the proactive allergen introduction from 4 months of age. This approach is supported by 2 pivotal randomized clinical trials showing that the early introduction of peanut and other food allergens significantly reduces the risk of food allergy. However, the implementation of this strategy at the population level still raises significant logistic problems, including patient selection and development of suitable food formats for young infants. Other prevention strategies, including vitamin D supplementation, are currently under evaluation. Maternal elimination diets during pregnancy and lactation are not recommended for allergy prevention. The treatment of food allergies has also seen major transformations. While strict allergen avoidance is still the key treatment principle, there is a greater focus on desensitization and tolerance induction by oral and epicutaneous immunotherapy. In addition, specialized hypoallergenic infant formulas for the treatment of infants with cow's milk allergy have undergone reformulation, including the addition of lactose and probiotics in order to modulate the gut microbiome and early immune responses. Further research is needed to inform the most effective food allergy prevention strategies at the population level. In addition, the wider application of food allergen immunotherapy may provide better health outcomes and improved quality of life for families affected by food allergies.

Eosinophilic oesophagitis: A paediatric update.

Eosinophilic oesophagitis (EoE) is a key differential for gastro-oesophageal reflux (GOR) in children. It can be difficult for clinicians to decide which patients need referral for the assessment of EoE, which can only be confirmed by histological analysis of endoscopic biopsies. Recent guidelines recommend that EoE can only be diagnosed following the exclusion of GOR through empiric treatment with proton pump inhibitors prior to endoscopy. Some aspects of history are strongly suggestive of EoE: red flags for referral include poor weight gain in the context of reflux symptoms, choking during eating or food impaction. Therapeutic options include dietary allergen elimination or swallowed aerosolised corticosteroids. Other novel therapies have failed to demonstrate benefit, but novel diagnostic biomarkers to enable non-invasive disease ascertainment and follow-up show some promise.

Clinical audit results in earlier nutritional intervention in malnourished children with cystic fibrosis with improved outcome.

AIM: The association between nutritional status, pulmonary function and survival in cystic fibrosis (CF) is well established. A previous case series from the Royal Children's Hospital, Melbourne (RCH), demonstrated suboptimal referral practices and highlighted the importance of early nutritional interventions in children with CF. Various qualitative changes were made to our CF service, and this study assesses the effects of these practice changes timing of gastrostomy and clinical outcome in patients who underwent gastrostomy insertion. METHOD: Clinical audit of all CF patients who had undergone gastrostomy insertion from 2002 to 2010 at Royal Children's Hospital. Clinical data, including nutritional parameters, respiratory function and survival, were collected at 2 years prior and 2 years post gastrostomy insertion. Data were compared with the previous study from 1989 to 1997. RESULTS: Patients with CF who underwent gastrostomy insertion between 2002 and 2010 (n = 22) had higher weight-for-age scores (-1.5 ± 0.68 vs. -2.67 ± 1.06; P = 0.0001) and higher forced expiratory volume in 1 s (68% ± 22 vs. 52% ± 18.5; P = 0.006), compared with the cohort from 1989 to 1997 (n = 37). These differences were maintained at 2-year follow-up. Pseudomonas aeruginosa colonisation rate was 100% in 1989-1997 vs. 41% in 2002-2010; P = 0.0001. The 2-year survival post-gastrostomy insertion improved from 70% to 100%; P = 0.004. CONCLUSION: Earlier referral of patients in the recent cohort resulted in sustained improvements in weight-for-age and lung function. Survival at 2 years post-procedure was significantly improved. This study confirms the value of clinical audits and subsequent re-evaluation of clinical services.

Medical intervention in parent-reported infant gastro-oesophageal reflux: A population-based study.

AIM: To report the cumulative incidence, health-seeking behaviour and medical intervention of infants with gastro-oesophageal reflux (GOR) in the first year of life. METHODS: The HealthNuts study is a longitudinal, population-based study. At 12 months of age, infants underwent skin prick testing to food allergens, including cows milk. Parents completed a questionnaire on GOR symptoms, food allergy and treatments. Factors associated with seeking health care for infants with GOR were modelled using logistic regression. RESULTS: Of 4674 infants, parents reported GOR in 1054 (23%; 95% confidence interval (CI) 21.4-23.8). Parents consulted a medical practitioner in 662 (64%) cases. Symptoms commenced in the first month in 411 (48%) and resolved within 6 months in 703 (75%) infants. Factors associated with doctor consultation for GOR were prematurity (adjusted odds ratio (aOR) 1.94; 95% CI 1.43-2.63) and family history of atopy (aOR 1.64; 95% CI 1.1-2.43). Eight per cent of infants (371/4674; 95% CI 7.2-8.7) received anti-reflux medication and 6% (296/4674; 95% CI 5.7-7.1) changed formula. Parents were more likely to seek treatment if they perceived their infant to be unsettled (aOR 2.55; 95% CI 1.26-5.17) and if the duration of GOR was prolonged (aOR 3.36 for symptoms >6 months; 95% CI 1.83-6.17). CONCLUSIONS: In the first year of life, approximately 14% of the population seek medical advice for GOR symptoms. The use of anti-reflux medication in the general community remains high, despite the absence of evidence that it is appropriate or effective for uncomplicated GOR.

Can celiac serology alone be used as a marker of duodenal mucosal recovery in children with celiac disease on a gluten-free diet?

OBJECTIVES: Assessment of treatment response in children with celiac disease (CD) after commencing a strict gluten-free diet (GFD) is generally based on the resolution of clinical features and normalization of serology. Recent adult studies have shown that serologic markers do not correlate with mucosal recovery. We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are sensitive and specific markers of mucosal recovery in children with CD on a GFD for at least 12 months, and (ii) to determine whether a validated dietary questionnaire of compliance can identify patients with mucosal recovery. METHODS: A total of 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies at ≥12 months on GFD, paired with repeat tTG and DGP serology. The biopsies were reviewed in a blinded manner by two histopathologists and graded by Marsh criteria. A validated questionnaire of dietary compliance was also administered. RESULTS: Of 150 children recruited, 27 (18%) had positive serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the 27 patients with positive serology, only 6 had Marsh type 3 changes. The sensitivity and specificity of serology as a marker of significant mucosal pathology was 75 and 85%, respectively, with a positive predictive value of 22% but a negative predictive value of 98%. Of the 129 (86%) questionnaires completed, 88% reported good or excellent compliance with a GFD (negative predictive value 97%). CONCLUSIONS: This study suggests that follow-up using two serological tests in children with CD on a GFD may obviate the need for repeat mucosal biopsy in the majority of patients. A standardized dietary questionnaire may be useful in identifying patients who require further evaluation.

Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary disease and bronchiectasis.

BACKGROUND AND OBJECTIVE: The aims of this observational study were (i) to examine the prevalence of symptomatic and clinically silent proximal and distal gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and (iii) to explore the possible clinical significance of this comorbidity in these conditions. METHODS: Twenty-seven participants with COPD, 27 with bronchiectasis and 17 control subjects completed reflux symptom evaluation and dual-channel 24 h oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum samples were measured using enzyme-linked immunosorbent assay, with disease severity (lung function and high-resolution computed tomography) also measured. RESULTS: The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in control subjects was 18% (P = 0.005). Of those diagnosed with GOR, clinically silent reflux was detected in 20% of participants with COPD and 42% with bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis participants, the presence of pepsin in sputum was not related to a diagnosis of GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis of GOR nor the presence of pepsin was associated with increased severity of lung disease in COPD or bronchiectasis. CONCLUSIONS: The prevalence of GOR in COPD or bronchiectasis is twice that of the control population, and the diagnosis could not be based on symptoms alone. Pepsin was detected in sputum in COPD and bronchiectasis, suggesting a possible role of pulmonary aspiration, which requires further exploration.

Tolerability and safety of a semi-elemental enteral formula with partially hydrolyzed guar gum (PHGG) in tube-fed children aged 1-4 years: An open-label, single-arm study.

BACKGROUND AND AIMS: Partially hydrolyzed guar gum (PHGG) is a water-soluble fiber supporting digestive health with well-established safety and efficacy. This open-label, single-arm, multicenter trial aimed to assess the tolerability and safety of a semi-elemental enteral formula containing PHGG at 12 g/L in tube-fed young children. METHODS: Children aged 1-4 years with stable conditions requiring tube feeding to provide ≥80% of their nutritional needs received the study formula for seven days. Tolerability, safety, adequacy of energy/protein intake, and weight change were assessed. RESULTS: Of 24 children (mean age 33.5 months; 10 [41.7%] female), 23 (95.8%) commenced treatment and 18 (75%) completed the study. All children had underlying neuro-developmental disabilities, often in association with gastrointestinal comorbidities requiring treatment for constipation (70.8%) or gastroesophageal reflux (66.7%). The formula was well-tolerated by 19 (82.6%) subjects, while 4 (17.4%; 95% CI: 5%, 39%) subjects withdrew early from the study due to gastrointestinal intolerance. The mean (SD) percentage energy and protein intake across the 7-day period were 103.5% (24.7) and 139.5% [50], respectively. Weight remained stable over the 7-day period (p = 0.43). The study formula was associated with a shift towards softer and more frequent stools. Pre-existing constipation was generally well controlled, and 3/16 (18.7%) subjects ceased laxatives during the study. Adverse events were reported in 12 (52%) subjects and were deemed 'probably related' or 'related' to the formula in 3 (13%) subjects. Gastrointestinal adverse events appeared more common in fiber-naïve patients (p = 0.09). CONCLUSION: The present study indicates that the study formula was safe and generally well tolerated in young tube-fed children. GOV IDENTIFIER: NCT04516213.

Probiotics to improve outcomes of colic in the community: protocol for the Baby Biotics randomised controlled trial.

BACKGROUND: Infant colic, characterised by excessive crying/fussing for no apparent cause, affects up to 20% of infants under three months of age and is a great burden to families, health professionals and the health system. One promising approach to improving its management is the use of oral probiotics. The Baby Biotics trial aims to determine whether the probiotic Lactobacillus reuteri DSM 17938 is effective in reducing crying in infants less than three months old (<13.0 weeks) with infant colic when compared to placebo. DESIGN: Double-blind, placebo-controlled randomised trial in Melbourne, Australia. PARTICIPANTS: 160 breast and formula fed infants less than three months old who present either to clinical or community services and meet Wessel's criteria of crying and/or fussing. INTERVENTION: Oral once-daily Lactobacillus reuteri (1x108 cfu) versus placebo for one month. PRIMARY OUTCOME: Infant crying/fussing time per 24 hours at one month. SECONDARY OUTCOMES: i) number of episodes of infant crying/fussing per 24 hours and ii) infant sleep duration per 24 hours (at 7, 14, 21, 28 days and 6 months); iii) maternal mental health scores, iv) family functioning scores, v) parent quality adjusted life years scores, and vi) intervention cost-effectiveness (at one and six months); and vii) infant faecal microbiota diversity, viii) infant faecal calprotectin levels and ix) Eschericia coli load (at one month only). ANALYSIS: Primary and secondary outcomes for the intervention versus control groups will be compared with t tests and non-parametric tests for continuous data and chi squared tests for dichotomous data. Regression models will be used to adjust for potential confounding factors. Intention-to-treat analysis will be applied. DISCUSSION: An effective, practical and acceptable intervention for infant colic would represent a major clinical advance. Because our trial includes breast and formula-fed babies, our results should generalise to most babies with colic. If cost-effective, the intervention's simplicity is such that it could be widely taken up as a new standard of care in the primary and secondary care sectors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95287767.

Upright positive expiratory pressure therapy and exercise: effects on gastroesophageal reflux in COPD and bronchiectasis.

BACKGROUND: Patients with COPD and patients with bronchiectasis undertake airway clearance therapy and exercise as part of management, but the effect of these activities on gastroesophageal acid exposure is unknown. This study aimed to determine if positive expiratory pressure (PEP) therapy and standardized exercise tasks were associated with increased gastroesophageal reflux. METHODS: During dual-probe 24 hour esophageal pH monitoring, all participants undertook a single session of PEP therapy, a measure of submaximal exercise capacity (6-min walk test [6MWT]), and a functional upper limb task (grocery shelving task [GST]). The number of reflux episodes and fractional reflux time (reflux index [RI]) were recorded during each intervention and compared to equivalent background time (BGT). RESULTS: Fifty-seven participants (30 with bronchiectasis, 27 with COPD, mean ± SD age 61 ± 13 y, FEV(1) 61.2 ± 24.6% predicted) completed the study. Episodes of isolated distal esophageal reflux occurred in 30% of participants during PEP therapy, 22% during the 6MWT, and 20% during the GST. However, there was no significant difference in distal RI during 6MWT or PEP therapy, compared to BGT (all P > .05). The number of reflux episodes was decreased, compared to BGT during the GST (P = .001) and 6MWT (P = .001), but not during PEP therapy (P = .71). CONCLUSIONS: Episodes of gastroesophageal reflux may occur during physiotherapy tasks, including airway clearance therapy using mouthpiece PEP, the 6MWT, and a measure of upper limb movement. However, as these activities did not increase the frequency of these events, no modifications to these tasks to minimize the occurrence of gastroesophageal reflux are necessary.

International Cross-Sectional Survey among Healthcare Professionals on the Management of Cow's Milk Protein Allergy and Lactose Intolerance in Infants and Children.

Purpose: The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow's milk protein allergy (CMPA) and lactose intolerance (LI) in infants. Methods: A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) disease-specific knowledge and potential educational needs. Results: Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area. Conclusion: The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow's Milk Protein Allergy.

This open-label, non-randomized, multicenter trial (Registration: NCT03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow's milk protein allergy (CMPA). Term infants aged 1-8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from -0.31 at the baseline to +0.28 at the 4-months' follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.

Assessment of the Cow's Milk-related Symptom Score (CoMiSS) as a diagnostic tool for cow's milk protein allergy: a prospective, multicentre study in China (MOSAIC study).

OBJECTIVES: The MOSAIC study aimed to evaluate if the Cow's Milk-related Symptom Score (CoMiSS) can be used as a stand-alone diagnostic tool for cow's milk protein allergy (CMPA). DESIGN: Single-blinded, prospective, multicentre diagnostic accuracy study. SETTING: 10 paediatric centres in China. PARTICIPANTS: 300 non-breastfed infants (median age 16.1 weeks) with suspected CMPA. INTERVENTIONS: After performing the baseline CoMiSS, infants commenced a cow's milk protein elimination diet with amino acid-based formula for 14 days. CoMiSS was repeated at the end of the elimination trial. Infants then underwent an open oral food challenge (OFC) with cow's milk-based formula (CMF) in hospital. Infants who did not react during the OFC also completed a 14-day home challenge with CMF. A diagnosis of CMPA was made if acute or delayed reactions were reported. PRIMARY OUTCOME MEASURES: A logistic regression model for CoMiSS to predict CMPA was fitted and a receiver-operator characteristic (ROC) curve generated. An area under the curve (AUC) of ≥0.75 was deemed adequate to validate CoMiSS as a diagnostic tool (target sensitivity 80%-90% and specificity 60%-70%). RESULTS: Of 254 infants who commenced the OFC, 250 completed both challenges, and a diagnosis of CMPA made in 217 (85.4%). The median baseline CoMiSS in this group fell from 8 (IQR 5-10) to 5 (IQR 3-7) at visit 2 (p<0.000000001), with a median change of -3 (IQR -6 to -1). A baseline CoMiSS of ≥12 had a low sensitivity (20.3%), but high specificity (87.9%) and high positive predictive value (91.7%) for CMPA. The ROC analysis with an AUC of 0.67 fell short of the predefined primary endpoint. CONCLUSIONS: The present study did not support the use of CoMiSS as a stand-alone diagnostic tool for CMPA. Nevertheless, CoMiSS remains a clinically useful awareness tool to help identify infants with cow's milk-related symptoms. TRIAL REGISTRATION NUMBER: NCT03004729; Pre-results.

Effects of an Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety and Infection Risk in Infants with Cow's Milk Protein Allergy: A Randomized, Multi-Center Trial.

This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content (2.20 g/100 kcal) supports normal growth in infants with cow's milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.

Eosinophilic esophagitis: trials and tribulations.

Eosinophilic esophagitis (EE) is a recently recognized form of pan-esophagitis, which is characterized by the presence of at least 15 eosinophils per high power field on esophageal histology. EE is closely associated with atopic disorders and occurs predominantly in male patients. Young children are more likely to be sensitized to food allergens whilst aeroallergen sensitization predominates in older children and adults--a pattern reminiscent of the "atopic march". EE presents with a diverse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or refusal in infancy, in addition to dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained incidentally in patients undergoing gastroscopy for other suspected gastrointestinal conditions, such as gastroesophageal reflux disease or celiac disease. Complications mainly relate to subepithelial remodeling and fibrosis which may result in dysmotility, dysphagia and esophageal strictures. The proportion of EE patients at risk of these complications is unknown due to a paucity of data on the natural history of EE. There are only few randomized controlled trials assessing the efficacy of treatment modalities for EE, which currently either involve food allergen elimination or use of swallowed aerosolized corticosteroids. This article aims to discuss the complex issues of the diagnosis and long-term management that confront clinicians who care for children with EE.