Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula-A Randomized Controlled Trial.

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study.

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

Guideline for wireless capsule endoscopy in children and adolescents: A consensus document by the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition) and the SEPD (Spanish Society for Digestive Diseases).

INTRODUCTION: Capsule Endoscopy (CE) in children has limitations based mainly on age. The objective of this consensus was reviewing the scientific evidence. MATERIAL AND METHODS: Some experts from the Spanish Society of Gastroenterology (SEPD) and Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP) were invited to answer different issues about CE in children. These sections were: a) Indications, contraindications and limitations; b) efficacy of CE in different clinical scenarios; c) CE performance; d) CE-related complications; e) Patency Capsule; and f) colon capsule endoscopy. They reviewed relevant questions on each topic. RESULTS: The main indication is Crohn's disease (CD). There is no contraindication for the age and in the event that the patient not to swallow it, it should be administered under deep sedation with endoscopy and specific device. The CE is useful in CD, for the management of OGIB in children and in Peutz-Jeghers syndrome (in this indication has the most effectiveness). The main complication is retention, which should be specially taken into account in cases of CD already diagnosed with malnutrition. A preparation regimen based on a low volume of polyethylene glycol (PEG) the day before plus simethicone on the same day is the best one in terms of cleanliness although does not improve the results of the CE procedure. CONCLUSIONS: CE is safe and useful in children. Indications are similar to those of adults, the main one is CD to establish both a diagnosis and disease extension. Moreover, only few limitations are detected in children.

Guideline for wireless capsule endoscopy in children and adolescents: a consensus document by the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition) and the SEPD (Spanish Society for Digestive Diseases)

INTRODUCTION: Capsule endoscopy (CE) in children has limitations based mainly on age. The objective of this consensus was reviewing the scientific evidence. MATERIAL AND METHODS: Some experts from the Spanish Society of Gastroenterology (SEPD) and Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP) were invited to answer different issues about CE in children. These sections were: a) Indications, contraindications and limitations; b) efficacy of CE in different clinical scenarios; c) CE performance; d) CE-related complications; e) Patency capsule; and f) colon capsule endoscopy. They reviewed relevant questions on each topic. RESULTS: The main indication is Crohn's disease (CD). There is no contraindication for the age and in the event that the patient not to swallow it, it should be administered under deep sedation with endoscopy and specific device. The CE is useful in CD, for the management of OGIB in children and in Peutz-Jeghers syndrome (in this indication has the most effectiveness). The main complication is retention, which should be specially taken into account in cases of CD already diagnosed with malnutrition. A preparation regimen based on a low volume of polyethylene glycol (PEG) the day before plus simethicone on the same day is the best one in terms of cleanliness although does not improve the results of the CE procedure. CONCLUSIONS: CE is safe and useful in children. Indications are similar to those of adults, the main one is CD to establish both a diagnosis and disease extension. Moreover, only few limitations are detected in children

Double-blind, randomised, placebo-controlled intervention trial to evaluate the effects of Bifidobacterium longum CECT 7347 in children with newly diagnosed coeliac disease.

Interactions between the immune system and the intestinal microbiota may play a role in coeliac disease (CD). In the present study, the potential effects of Bifidobacterium longum CECT 7347 in children with newly diagnosed CD were evaluated. A double-blind, randomised, placebo-controlled trial was conducted in thirty-three children who received a capsule containing either B. longum CECT 7347 (109 colony-forming units) or placebo (excipients) daily for 3 months together with a gluten-free diet (GFD). Outcome measures (baseline and post-intervention) included immune phenotype of peripheral blood cells, serum cytokine concentration, faecal secretory IgA (sIgA) content, anthropometric parameters and intestinal microbiota composition. Comparisons between the groups revealed greater height percentile increases (P= 0·048) in the B. longum CECT 7347 group than in the placebo group, as well as decreased peripheral CD3⁺ T lymphocytes (P= 0·004) and slightly reduced TNF-α concentration (P= 0·067). Within-group comparisons of baseline and final values did not reveal any differences in T lymphocytes and cytokines in the placebo group, while decreased CD3⁺ (P =0·013) and human leucocyte antigen (HLA)-DR⁺ T lymphocytes (P =0·029) and slightly reduced TNF-α concentration (P= 0·085) were detected in the B. longum CECT 7347 group. Comparison between the groups showed that the administration of B. longum CECT 7347 reduced the numbers of the Bacteroides fragilis group (P= 0·020) and the content of sIgA in stools (P= 0·011) compared with the administration of placebo. Although this is a first exploratory intervention with limitations, the findings suggest that B. longum CECT 7347 could help improve the health status of CD patients who tend to show alterations in gut microbiota composition and a biased immune response even on a GFD.

Influence of breastfeeding versus formula feeding on lymphocyte subsets in infants at risk of coeliac disease: the PROFICEL study.

PURPOSE: In addition to genetic risk, environmental factors might influence coeliac disease (CD) development. We sought to assess the effect of the interaction between milk-feeding practices and the HLA-DQ genotype on peripheral lymphocyte subsets and their activation markers in infants at familial risk for CD. METHODS: 170 newborns were classified in 3 different genetic risk groups (high risk, HR; intermediate risk, IR; and low risk, LR) after DQB1 and DQA1 typing. Lymphocyte subsets were studied at the age of 4 months by flow cytometry analysis. RESULTS: 79 infants were receiving exclusive breastfeeding (BF) and 91 partial breastfeeding or formula feeding (FF). Regarding genetic risk, 40 infants were classified in HR group, 75 in IR group and 55 in LR group. Two-way ANOVA did not show significant interactions between the type of milk feeding and genetic risk group on the lymphocyte subsets analysed. One-way ANOVA for milk-feeding practice alone showed that the percentage of CD4 + CD25+ cells was significantly higher in BF group than in FF group (BF, 10.92 ± 2.71; FF, 9.94 ± 2.96; p = 0.026), and absolute counts of CD4 + CD38+ cells were significantly higher in FF group than in BF group (FF, 2,881.23 ± 973.48; BF, 2,557.95 ± 977.06; p = 0.038). One-way ANOVA for genetic risk alone showed that absolute counts of NK cells were significantly higher in IR group than HR and LR groups (IR, 539.24 ± 340.63; HR, 405.01 ± 239.53; LR, 419.86 ± 262.85; p = 0.028). CONCLUSION: Lymphocyte subset profiles in the early stages of life could be modulated by milk-feeding practices and genetic risk separately. Breastfeeding might have a positive immunomodulatory effect on lymphocyte subsets in infants at risk of CD.

Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: the PROFICEL study.

Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder.

Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species.

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk.

Malaltia celíaca: entre el desig i la realitat / No disponible

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Safety and efficacy of granulocyte and monocyte adsorption apheresis in paediatric inflammatory bowel disease: a prospective pilot study.

OBJECTIVE: Selective granulocyte-monocyte adsorption (GMA) apheresis is a safe technique that has shown efficacy in inflammatory bowel disease (IBD), especially in adult steroid-dependent and steroid-refractory ulcerative colitis. GMA apheresis is performed with Adacolumn, a direct blood perfusion system that selectively adsorbs circulating granulocytes and monocytes. Studies on efficacy of GMA apheresis in paediatric IBD are scarce. Our aim was to evaluate efficacy, safety, and tolerability of GMA apheresis in paediatric IBD patients followed for 1 year. PATIENTS AND METHODS: Nine patients with a mild to moderate flare-up (6 boys, 3 girls; 5 ulcerative colitis [UC], 4 Crohn disease [CD]) were included. Mean age at inclusion was 13 years and 9 months, and mean disease duration before inclusion was 28 months. All of our patients with UC were steroid-dependent; patients with CD had been unsuccessfully treated with other therapies. GMA apheresis consisted of 5 consecutive weekly sessions lasting 60 minutes each. RESULTS: After the 5 sessions, 4 of 5 patients with UC and 1 of 4 patients with CD achieved remission. This remission was maintained in 2 of 4 patients with UC and in the single patients with CD. Patients taking steroids could begin to taper their daily doses after the second apheresis, and 3 of 5 of these patients reached the end of the study steroid-free. GMA apheresis was well tolerated and no severe side effects related to the technique were observed. CONCLUSIONS: GMA apheresis is a safe, well-tolerated technique in paediatric IBD. As previously reported, we have observed a better efficacy in promoting and maintaining remission, and reducing conventional drugs in patients with UC than in patients with CD.

Solitary rectal ulcer syndrome in childhood: a rare, benign, and probably misdiagnosed cause of rectal bleeding. Report of three cases.

Solitary rectal ulcer syndrome is an uncommon and often underdiagnosed condition that usually presents with hematochezia, mucous discharge, and tenesmus. Its etiology is unknown but it seems related to excessive straining with defecation. Prolonged efforts force the anterior rectal mucosa into the anal canal with strangulation and appearance of congestion, edema, and ulceration. Histologic findings (fibromuscular obliteration of lamina propria and disorientation of muscle fibers) are characteristic, which helps to differentiate these lesions from other rectal entities. Although solitary rectal ulcer syndrome is rarely reported in children, it must be suspected in patients with rectal discharge of blood and mucus and previous disorders of evacuation. We present three children (aged 9, 10, and 14 years) with solitary rectal ulcer syndrome that had presented with rectal bleeding. A careful inquiry about evacuation habits and a high index of suspicion in children presenting with hematochezia helps to diagnose this possibly unrecognized or misdiagnosed entity in children. Endoscopy and histologic examination confirms this condition.

Rectocolitis a proteïnes de llet de vaca / Rectocolitis a proteínas de leche de vaca / Proctocolitis secondary to intolerance to cow's milk protein

Introducció. La proctocolitis és una causa de rectorràgia en lactants inclosa dins les reaccions adverses a proteïnes alimentàries. L’objectiu d’aquest treball és revisar de manera prospectiva l’evolució en un grup de lactants amb aquesta sospita clínica. Mètode. Estudiar de manera prospectiva un grup de lactants visitats en el nostre centre amb clínica de rectorràgia i sospita de rectocolitis analitzant clínica, analítica i endoscòpia. Resultats. Vam visitar un total de nou pacients, dos dels quals van ser diagnosticats de colitis infecciosa i colitis ulcerosa, respectivament. La clínica es va manifestar amb rectorràgies acompanyades de bon estat general. La majoria dels restants (5/7) prenien lactància materna en el moment del debut. A tots se’ls va fer un estudi analític bàsic i una cerca de gèrmens en el coprocultiu. No van presentar anèmia (excepte un pacient), ni eosinofília perifèrica, ni hipoalbuminèmia. El diagnòstic es va fer sobre la base d’una bona història clínica i una hipòtesi diagnòstica. També se’ls va fer rectoscòpia amb presa de biòpsies en les quals es mostraven unes lesions característiques en la histologia (>20 eosinòfils per camp), però no patognomòniques. Conclusions. La rectocolitis a proteïnes de llet de vaca constitueix una entitat clínica pròpia que el pediatre general ha de reconèixer i incloure dins del diagnòstic diferencial dels lactants amb rectorràgia. Té una evolució clínica i una resolució excel•lents, i la rectoscòpia i la presa de biòpsies són necessàries per fer-ne la confirmació (AU)

Introducción. La proctocolitis es una causa de rectorragia en los lactantes, cuya naturaleza se encuentra dentro de las reacciones adversas a proteínas alimentarias. El objetivo del presente trabajo es revisar de forma prospectiva la evolución en un grupo de lactantes con sospecha de esta entidad. Método. Estudiar prospectivamente a un grupo de lactantes llegados a nuestro servicio con clínica de rectorragia y sospecha de rectocolitis analizando clínica, analíticas y endoscopia. Resultados. Visitamos a un total de nueve pacientes, dos de los cuales fueron diagnosticados de colitis infecciosa y colitis ulcerosa, respectivamente. La clínica se manifestó con rectorragias y buen estado general. La mayoría de los restantes (5/7) recibían lactancia materna en el momento del debut. En todos se realizó estudio analítico básico y búsqueda de gérmenes en los coprocultivos. No presentaron anemia (excepto un paciente), ni eosinofilia periférica, ni hipoalbuminemia. El diagnóstico se realizó en base a una buena historia clínica y una hipótesis diagnóstica. En todos se realizó rectoscopia con toma de biopsias, mostrando unas lesiones características en la histología (>20 eosinófilos por campo), pero no patognomónicas. Todos realizaron una dieta de exclusión materna de proteínas vacunas y suplementos con leches especiales (tres con hidrolizado y tres con fórmula elemental). Sólo uno mejoró con dieta de exclusión materna. La reintroducción se realizó sin problemas a partir del año de edad. Conclusiones. La rectocolitis a proteínas de leche de vaca constituye una entidad clínica propia que el pediatra general debe reconocer e incluir dentro del diagnóstico diferencial de los lactantes con rectorragia. Su evolución clínica y su resolución es excelente, y es conveniente y necesaria la rectoscopia y la toma de biopsias para su confirmación (AU)

Background. Proctocolitis is one of the causes of rectal bleeding in infants, and it is probably related to food protein intolerance. We prospectively reviewed the clinical course and outcome of a group of infants with rectal bleeding and suspected cow's milk protein intolerance. Method. We performed a prospective evaluation of a group of patients with rectal bleeding. We analyzed the clinical presentation, laboratory evaluation, and colonoscopy findings. Results. The group includes 9 infants; two of them were eventually diagnosed with infectious colitis and ulcerative colitis and were excluded from further analysis. Clinical presentation was characterized by rectal bleeding and a good general condition. Five of the 7 patients were breastfed at the time of presentation. Infectious etiology was excluded in all patients. One patient had mild anemia, and none of the patients presented with eosinophilia or hypoproteinemia. All patients underwent a rectoscopy with biopsy, and pathology showed eosinophilic infiltrates, suggestive of protein intolerance. All patients responded well to maternal restriction of cow protein and 6 patients also required supplementation with hydrolyzed (3 patients) or elemental (3 patients) formulas. After 12 months, cow's milk reintroduction was performed successfully in all cases. Conclusions. Food protein intolerance is one of the most common causes of rectal bleeding in infants, and this diagnosis should be included in the differential diagnosis of infants with bloody stools. Colonoscopy and biopsy are necessary for the diagnosis. Clinical course and outcome are excellent after exclusion of the offending protein (AU)

Sclerosing cholangitis secondary to hepatic artery ligation after abdominal trauma.

Several causes have been postulated as responsible for secondary sclerosing cholangitis (SSC), mainly in adults, and, although in very different situations, ischaemia seems to be one of the most important factors. The term 'ischaemic cholangitis' has been used as a collective label for all these ischaemia-induced bile duct lesions. The biliary epithelium is dependent on arterial blood flow, unlike the hepatic parenchyma, which receives a dual blood supply from the hepatic artery and the portal vein. This makes the biliary epithelium very susceptible to changes in arterial blood flow. We present one adolescent patient who developed SSC after abdominal trauma with hepatectomy and ligation of the right hepatic artery. Different factors could have helped in the development of SSC in our patient (septicaemia, bile duct destruction, cholecystectomy) but right hepatic artery ligation seems to be the most important aetiological factor in the development of secondary ischaemic cholangitis.

Malabsorption of carbohydrates and depression in children and adolescents.

BACKGROUND: Previous studies have shown an association between sugar malabsorption and depressive symptoms in adult women. Incompletely absorbed sugars may form nonabsorbable complexes with tryptophan, an amino acid precursor of serotonin, decreasing its availability. As serotonin is the most important neurotransmitter involved in depressive disorders, its depletion could lead to the onset of depression. METHODS: The authors' aim was to study the possible association between malabsorption of sugars (lactose and fructose) and depressive symptoms in adolescent patients of Spanish origin. The authors studied two groups of patients. Group G included 14 patients previously diagnosed with sugar intolerance. In these, the authors assessed depressive symptoms. Group P consisted of seven patients suffering from major depression. In these, the authors performed functional sugar absorption tests. The authors studied the metabolic pathway of tryptophan in both groups. RESULTS: In the group with sugar malabsorption, there was a 28.5% prevalence of depressive symptoms that was higher than expected in our population. In the group with depression, the authors found a higher than expected prevalence of sugar intolerance (71.42% versus 15% in controls). CONCLUSIONS: The unexpected prevalences obtained for the groups studied suggest that there may be an association between sugar intolerance and depressive symptoms during adolescence.

Implicació del reflux gatroesofàgic en els episodis aparentment letals / Gastroesophageal reflux and apparently lethal episodes

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Hepatitis per virus B i C en la infància (i II): hepatitis C / No disponible

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Hepatitis per virus B i C en la infància (I): hepatitis B / No disponible

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