Vincenza Pezzella

Atopy patch tests are useful to predict oral tolerance in children with gastrointestinal symptoms related to non-IgE-mediated cow's milk allergy.

Atopy patch tests (APTs) have been proposed for the diagnostic approach in children with non‐IgE‐mediated cows milk allergy and gastrointestinal symptoms. We aimed to investigate the benefit of APTs in predicting oral tolerance in these patients. We prospectively evaluated 172 subjects with a sure diagnosis of non‐IgE‐mediated CMA and gastrointestinal symptoms (97 boys, 56.4%; age, 6.37 m; range, 2–12 m). At diagnosis, 113/172 (65.7%) children had positive APTs to cows milk proteins (CMP). After 12 months of exclusion, diet APTs were repeated immediately before OFC. APTs significantly correlated (P < 0.001) with the OFC outcome (r 0.579). Diagnostic accuracy was sensitivity of 67.95%, specificity of 88.3%, PPV of 82.81%, NPV of 76.85%, and a +LR of 5.80. APTs are a valuable tool in the follow‐up of children with non‐IgE‐mediated CMA‐related gastrointestinal symptoms by contributing in determining whether an OFC can safely be undertaken.

Diagnosing and Treating Intolerance to Carbohydrates in Children

Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment.

The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management

Food allergies (FAs) are an increasing problem in Western countries, affecting up to 10% of young children. FAs are frequently associated with gastrointestinal manifestations. The role of FAs as a potential causative factor for infantile colic (IC) is still controversial. We report the most recent evidence on the pathogenesis, clinical and diagnostic aspects of FA-induced infantile colic (IC) and suggest a stepwise diagnostic approach. We selected articles on clinical and immunologic features, pathogenesis and management of FAs and IC from of 1981 to 2015. Original and review articles were identified through selective searches performed on PubMed, using the following terms: colic, infantile colic, food allergy and infantile colic, infantile colic treatment. The possible relationship between FAs and IC derives from the presence of dysmotility with visceral hypersensitivity and dysbiosis, demonstrated in both conditions, and the clinical response to dietary interventions. Unfortunately, the design of the studies, poor characterization of atopy and different dietary approaches limit the understanding of the importance of FAs in subjects with IC. The role of FAs in IC subjects without other symptoms of atopy remains controversial. However, where there is a suspicion of FAs, a short trial with an extensively hydrolyzed cow’s proteins formula or, if breast fed, with maternal elimination diet may be considered a reasonable option.

Calcium and vitamin D intakes in children: a randomized controlled trial

BackgroundCalcium (Ca2+) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca2+ and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca2+ and VitD supplementation.MethodsDaily Ca2 + and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with <70% of dietary reference intakes (DRIs) of Ca2+ and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca2+ and VitD intake plus administration of a commercially available Ca2 + and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed.ResultsWe evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 μg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca2+ intake <70% of the DRIs in 82 subjects (55%). At baseline serum 25(OH)D levels were low (<30 ng/ml) in all study subjects and after 4 months of nutritional intervention, a normalization of serum 25(OH)D levels (≥30 ng/ml) was observed in all children in Group 1 and in only one subject in Group 2 [Group 1: T1 33.8 ng/ml (IQR 2.5) vs Group 2: T1 24.5 ng/ml (IQR 5.2), p <0.001].ConclusionsAdequate Ca2+ and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca2+ and VitD is a reliable strategy to prevent this condition.Trial registrationThe study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

Cow's milk and rice fermented with Lactobacillus paracasei CBA L74 prevent infectious diseases in children: A randomized controlled trial

BACKGROUND & AIM Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare. METHODS Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12-48 months) consuming daily cows milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and β-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated. RESULTS 377 children (193 males, 51%) with a mean (SD) age of 32 (10) months completed the study: 137 in group A, 118 in group B and 122 in group C. Intention-to-treat analysis showed that the proportion of children who experienced at least one CID was lower in group A (51.8%) and B (65.9%) compared to group C (80.3%). Per-protocol analysis showed that the proportion of children presenting upper respiratory tract infections was lower in group A (48.2%) and group B (58.5%) compared with group C (70.5%). The proportion of children presenting acute gastroenteritis was also lower in group A (13.1%) and group B (19.5%) compared with group C (31.1%). A net increase of all fecal biomarkers of innate and acquired immunity was observed for groups A and B compared to group C. Moreover, there was a negative association between fecal biomarkers and the occurrence of CID. CONCLUSION Dietary supplementation with cows milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.

The Potential Therapeutic Efficacy of Lactobacillus GG in Children with Food Allergies

Food allergy (FA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with 80–90% naturally acquiring tolerance by the age of five years. However, recent studies suggest that the natural history of FA is changing, with an increasing persistence until later ages. The pathogenesis of FA as well as oral tolerance is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by FA and healthy infants. These findings prompted the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells.

Investigation of chronic diarrhoea in infancy.

Diarrhoea in infants and young children is defined as >200g/day of stools, and occurs when there is an imbalance between intestinal fluids absorption and secretion. This may be caused by either a decreased absorption (osmotic diarrhoea) or an increased secretion (secretory diarrhoea). Chronic diarrhoea defines intestinal loss of water and electrolytes with increased stool frequency, reduced consistency and larger volume over more than 14days. This disorder in children shows a wide range of aetiologies depending on the age. The knowledge of common and rare aetiologies is important to optimize the diagnostic approach. A stepwise approach, starting with a comprehensive history, physical examination, inspection and collection of stool samples, helps to devise appropriate diagnostic and therapeutic management. In this article we discuss the pathophysiology, aetiology and possible approach to chronic diarrhoea in infancy.

Acceptability and efficacy of a gel hypotonic oral rehydration solution in children with acute gastroenteritis.

ObjectiveOral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. MethodsThis was a randomized-controlled trial of children (5–36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. ResultsEighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (<10 ml/kg/day) was lower in group 2 versus group 1 (P=0.001). The number of children presenting diarrhea after 72 h of treatment was lower in group 2 versus group 1 (P=0.028). Also, the mean duration of diarrhea was shorter in group 2 than in group 1 (P=0.001). The hypotonic super-ORS containing zinc in a gel formulation had a positive effect on the severity of diarrhea. No patient required hospitalization. No adverse events were observed in either of the two study groups. ConclusionThe new zinc-containing hypotonic super-ORS in a gel formulation is effective in the management of childhood acute gastroenteritis.

Twelve Novel Mutations in the slc26a3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea

Objectives: We aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and emphasize the importance of functional studies to define the effect of novel mutations. Methods: All member 3 of solute carrier family 26 (SLC26A3) coding regions were sequenced in 17 sporadic patients with CCD. Moreover, the minigene system was used to analyze the effect of 2 novel splicing mutations. Results: We defined the SLC26A3 genotype of all 17 patients with CCD and identified 12 novel mutations. Using the minigene system, we confirmed the in silico prediction of a complete disruption of splicing pattern caused by 2 of these novel mutations: the c.971+3_971+4delAA and c.735+4_c.735+7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of 6 novel missense mutations. Conclusions: We confirm the molecular heterogeneity of sporadic CCD adding 12 novel mutations to the list of known pathogenic mutations. Moreover, we underline the importance, for laboratories that offer molecular diagnosis and genetic counseling, to perform fast functional analysis of novel mutations.

New Insights and Perspectives in Congenital Diarrheal Disorders

Purpose of ReviewWe highlight new entities of congenital diarrheal disorders (CDDs) and progresses in understanding of functionally related genes, opening new diagnostic and therapeutic perspectives.Recent FindingsThe more significant advances have been made in field of pathogenesis, encouraging a better understanding not only of these rare diseases but also of more common pathogenetic mechanisms.SummaryCDDs represent an evolving group of rare chronic enteropathies with a typical onset early in the life. Usually, severe chronic diarrhea is the main clinical manifestation, but in other cases, diarrhea is only a component of a more complex systemic disease. The number of conditions has gradually increased, and many new genes have been indentified and functionally related to CDDs, opening new diagnostic and therapeutic perspectives. Advances in molecular analysis procedures have modified the diagnostic approach in CDDs, leading to a reduction in invasive and expensive procedures.