Long term outcomes of intestinal rehabilitation in children with neonatal very short bowel syndrome: Parenteral nutrition or intestinal transplantation.

BACKGROUND & AIMS: Intestinal rehabilitation is the preferred treatment for children with short bowel syndrome (SBS) whatever the residual bowel length, and depends on the accurate management of long-term parenteral nutrition (PN). If nutritional failure develops, intestinal transplantation (ITx) should be discussed and may be life-saving. This study aimed to evaluate survival, PN dependency and nutritional status in children with neonatal very SBS on PN or after ITx, in order to define indications and timing of both treatments. PATIENTS AND METHODS: This retrospective cross-sectional study enrolled 36 children with very SBS (<40 cm) who entered our intestinal rehabilitation program from 1987 to 2007. RESULTS: All the children on long-term PN (n = 16) survived with a follow-up of 17 years (9-20). Six of them were eventually weaned off PN. Twenty children underwent ITx: eight children died (40%) 29 months (0-127) after Tx. The others 12 patients were weaned off PN 73 days (13-330) after Tx. Follow-up after transplantation was 14 years (6-28). Seven out of 8 (88%) patients with a history of gastroschisis required ITx. Patients who required ITx had longer stoma duration. CONCLUSION: Survival rate of children with very short bowel was excellent if no life-threatening complications requiring transplantation developed. Gastroschisis and delayed ostomy closure are confirmed as risk factor for nutritional failure. Intestinal rehabilitation may allow a total weaning of PN before adulthood. A follow-up by a multidisciplinary team is necessary to avoid PN complications in order to minimize indications for ITx.

ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis.

The aim of the present article was to perform a systematic review with meta-analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition-associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short-term use (following surgery or bone marrow transplantation), 1 in neonates with long-term use, and 3 in infants and children receiving long-term parenteral nutrition (PN). Meta-analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short-term use of different ILEs. Because of high heterogeneity of the long-term studies no meta-analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)-containing ILE compared with pure soya bean oil (SO), ILE-reduced liver enzymes, and bilirubin levels in noncholestatic children on long-term PN and one other RCT found that FO-based ILE-reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short-term use in neonates. The use of multicomponent FO-containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well-designed RCTs are, however, lacking and long-term effects have not been determined.

Weaning Off Prognosis Factors of Home Parenteral Nutrition for Children With Primary Digestive Disease.

OBJECTIVES: The aim of the present study was to describe the indications for home parenteral nutrition (HPN) in children with primary digestive diseases and to identify factors associated with weaning off. METHODS: All the children initially discharged on HPN between January 1, 2000, and December 31, 2009, for chronic intestinal failure (IF) were included. The associations between clinical factors and weaning off of HPN were assessed using a multivariable Cox regression model. RESULTS: Among the 151 children (boys = 58%) included in this study, 98 (65%) presented with short bowel syndrome (SBS), 17 (11%) with digestive neuromuscular disorders, 14 (9%) with mucosal diseases, 13 (9%) with inflammatory bowel disease, and 9 (6%) with other primary digestive diseases. The probability of survival was ∼100%. At the end of the follow-up, the probability for weaning off of HPN was 0.73 (95% confidence interval 0.54-0.84) but varied according to the underlying cause of IF (for example, SBS and inflammatory bowel disease had a better prognosis). The median time until weaning off was 21 months (95% confidence interval 18-38 months). Unfavourable prognostic factors for weaning off of HPN included a bowel remnant of <40 cm, the presence of <50% of the colon, and daily lipid intakes >1.5 g · kg · day. Underlying disease was also associated with weaning off. CONCLUSIONS: HPN is a safe therapeutic option for children with chronic IF requiring long-term nutritional management. Prognostic factors for weaning off of HPN were identified, and they highlight the relevance of SBS anatomy and parenteral nutrition caloric intake. The outcome of children on HPN was primarily dependent on the underlying disease.

Arsenic in rice: a cause for concern.

Inorganic arsenic intake is likely to affect long-term health. High concentrations are found in some rice-based foods and drinks widely used in infants and young children. In order to reduce exposure, we recommend avoidance of rice drinks for infants and young children. For all of the rice products, strict regulation should be enforced regarding arsenic content. Moreover, infants and young children should consume a balanced diet including a variety of grains as carbohydrate sources. Although rice protein-based infant formulas are an option for infants with cows' milk protein allergy, the inorganic arsenic content should be declared and the potential risks should be considered when using these products.

Intestinal failure-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation.

Intestinal failure-associated liver disease is the most prevalent complication affecting children with intestinal failure receiving long-term parenteral nutrition. This paper reviews the definition, diagnostic criteria, pathogenesis, and risk factors. The authors discuss the role of enteral nutrition, parenteral nutrition, and its components, especially lipid emulsions. The authors also discuss the surgical treatment, including intestinal transplantation, its indications, technique, and results, and emphasise the importance of specialised intestinal failure centres.

Anastomotic ulcerations after intestinal resection in infancy.

OBJECTIVE: Anastomotic ulceration (AU) is a rare complication after intestinal resection and anastomosis, described mostly in children. The main symptom is occult bleeding, leading to iron-deficiency anemia, which is life threatening. METHODS: The present survey reports a series of patients with AU after intestinal resection in infancy, focusing on predictive factors, medical and surgical treatment options, and long-term outcomes. Eleven patients (7 boys) born between 1983 and 2005 with AU after an intestinal resection and anastomosis in infancy were included in this retrospective review. RESULTS: The diagnosis of AU was often delayed for several years. No predictive factor (including the primary disease, the length of the remnant bowel, and the loss of the ileocaecal valve) could be identified. Numerous treatment options, including antibiotics and anti-inflammatory drugs, proved to be ineffective to induce prolonged remission. Even after surgical resection, relapses were observed in 5/7 children. CONCLUSIONS: The mechanism leading to AU remains unknown. Contrary to previous reports with limited follow-up, no medical or surgical treatment could prevent recurrences. Because relapses may occur several years after treatment, long-term follow-up is needed.

Syndromic (phenotypic) diarrhoea of infancy/tricho-hepato-enteric syndrome.

OBJECTIVES: Syndromic diarrhoea/tricho-hepato-enteric syndrome (SD/THE) is a rare congenital syndrome. The main features are intractable diarrhoea of infancy, hair abnormalities, facial dysmorphism, intrauterine growth restriction and immune system abnormalities. It has been linked to abnormalities in two components of the putative human ski complex: SKIV2L and TTC37. The long-term outcome of this syndrome is still unknown. We aim to describe the long-term outcome, in the French cohort of patients born since 1992. DESIGN: Review of the clinical and biological features of the 15 patients with SD/THE, followed in France and born between 1992 and 2010. RESULTS: All patients presented typical SD/THE syndrome features, of intractable diarrhoea in infancy requiring parenteral nutrition, a facial dysmorphism with hair abnormalities, and immunological disorders. Half of them also had liver and skin abnormalities. Five children died, among which 3 died due to infections. Probabilities of survival according to the Kaplan-Meier method were 93.3%, 86.7%, 74.3 and 61.9%, respectively at 1 year, 5 years, 10 years and 15 years of age. 3/15 were weaned from parenteral nutrition (PN) with likelihood of weaning being 10% at 5 years and 40% at 10 years. At birth 80% were small for gestational age and the short stature persisted in 60%. Haemophagocytic syndrome was noted in 60% and mild mental retardation was present in 60%. CONCLUSIONS: SD/THE is a rare disease with high morbidity and mortality. Management should be focused on nutrition and immunological defects.

Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form.

Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.

Iron requirements of infants and toddlers.

Iron deficiency (ID) is the most common micronutrient deficiency worldwide and young children are a special risk group because their rapid growth leads to high iron requirements. Risk factors associated with a higher prevalence of ID anemia (IDA) include low birth weight, high cow's-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status. The aim of this position paper was to review the field and provide recommendations regarding iron requirements in infants and toddlers, including those of moderately or marginally low birth weight. There is no evidence that iron supplementation of pregnant women improves iron status in their offspring in a European setting. Delayed cord clamping reduces the risk of ID. There is insufficient evidence to support general iron supplementation of healthy European infants and toddlers of normal birth weight. Formula-fed infants up to 6 months of age should receive iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6-1.2 mg(-1) · kg(-1) · day(-1)). Marginally low-birth-weight infants (2000-2500 g) should receive iron supplements of 1-2 mg(-1) · kg(-1) · day(-1). Follow-on formulas should be iron-fortified; however, there is not enough evidence to determine the optimal iron concentration in follow-on formula. From the age of 6 months, all infants and toddlers should receive iron-rich (complementary) foods, including meat products and/or iron-fortified foods. Unmodified cow's milk should not be fed as the main milk drink to infants before the age of 12 months and intake should be limited to <500 mL/day in toddlers. It is important to ensure that this dietary advice reaches high-risk groups such as socioeconomically disadvantaged families and immigrant families.

MYO5B and bile salt export pump contribute to cholestatic liver disorder in microvillous inclusion disease.

UNLABELLED: Microvillous inclusion disease (MVID) is a congenital disorder of the enterocyte related to mutations in the MYO5B gene, leading to intractable diarrhea often necessitating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver disease akin to progressive familial intrahepatic cholestasis (PFIC). Our aim was to investigate the mechanisms by which MYO5B mutations affect hepatic biliary function and lead to cholestasis in MVID patients. Clinical and biological features and outcome were reviewed. Pretransplant liver biopsies were analyzed by immunostaining and electron microscopy. Cholestasis occurred before (n = 5) or after (n = 3) ITx and was characterized by intermittent jaundice, intractable pruritus, increased serum bile acid (BA) levels, and normal gamma-glutamyl transpeptidase activity. Liver histology showed canalicular cholestasis, mild-to-moderate fibrosis, and ultrastructural abnormalities of bile canaliculi. Portal fibrosis progressed in 5 patients. No mutation in ABCB11/BSEP or ATP8B1/FIC1 genes were identified. Immunohistochemical studies demonstrated abnormal cytoplasmic distribution of MYO5B, RAB11A, and BSEP in hepatocytes. Interruption of enterohepatic BA cycling after partial external biliary diversion or graft removal proved the most effective to ensure long-term remission. CONCLUSION: MVID patients are at risk of developing a PFIC-like liver disease that may hamper outcome after ITx. Our results suggest that cholestasis in MVID patients results from (1) impairment of the MYO5B/RAB11A apical recycling endosome pathway in hepatocytes, (2) altered targeting of BSEP to the canalicular membrane, and (3) increased ileal BA absorption. Because cholestasis worsens after ITx, indication of a combined liver ITx should be discussed in MVID patients with severe cholestasis. Future studies will need to address more specifically the effect of MYO5B dysfunction in BA homeostasis.

Donor human milk for preterm infants: current evidence and research directions.

The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

Commercially premixed 3-chamber bags for pediatric parenteral nutrition are available for hospitalized children.

Hospitalized children are vulnerable to malnutrition during serious illness or recovery from injury and are at subsequent risk of increased morbidity and growth retardation. In cases in which enteral nutrition is not possible, parenteral nutrition (PN) can be used to ensure that patients at nutritional risk receive appropriate amounts of macro- and micronutrients. Nutritional needs cannot be met by 1 standard PN formulation in pediatric patients (term to 18 y) because of the wide range of needs according to age, weight, degree of maturity, and disease state. Preparation of individualized PN is associated with several limitations, including prescribing errors, stability issues, and risk of infection. These risks may be avoided by the availability of a range of pediatric PN formulations provided as commercial premixed 3-chamber bags (3-CBs). These 3-CBs were developed in conjunction with experienced neonatologists and pediatricians in accordance with international guidelines. A prospective study has previously shown the practical handling and ease of use of 2 formulations of these 3-CBs, 1 designed for term infants and toddlers up to 2 y of age and 1 for children and adolescents aged 2-18 y. The majority of pharmacists and nurses described the 3-CB as easy to use and favored it over individual bottles, bags compounded on the ward, ready-to-use compounded bags, and premixes prepared by the pharmacy and tailored to patient needs. These formulations offer a means of improving the quality of care in hospital pediatric units, particularly in the absence of a nutrition support team.

World Health Organization 2006 child growth standards and 2007 growth reference charts: A discussion paper by the committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Growth charts are essential for evaluating children's health including their nutrition; however, the evaluation of child growth trajectories and consequently the decision to intervene are highly dependent on the growth charts used. The aim of this discussion paper of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition is to provide information on the background and rationale of the World Health Organization (WHO) 2006 child growth standards and WHO 2007 growth reference charts, describe their development, outline their main innovative aspects, discuss potential limitations, and make recommendations. WHO 2006 child growth standards (0-5 years) are based on prospectively collected data describing the growth of healthy infants who were breast-fed according to WHO recommendations, showing a pattern of linear growth, which is remarkably consistent between different countries and ethnic groups. WHO 2007 growth reference charts (5-19 years) are based mainly on a re-analysis of National Centre for Health Statistics data from 1977, without information on feeding. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recommends that WHO child growth standards should be used to monitor growth in all children in the age range 0 to 2 years in Europe, whether breast- or formula-fed, and that they should be considered to be used in the age range 2 to 5 years. Implementation of the WHO child growth standards should be preceded by evaluation of the implication of their use on national healthcare policies. Health professionals should be guided on their use and interpretation and an adequate communication strategy should be available locally to ensure that parents receive clear and consistent advice. The decision on whether to implement the WHO growth references (5-19 years) should be made by national bodies because the growth pattern during the 5- to 19-year period differs between populations.

Vitamin D in the healthy European paediatric population.

In recent years, reports suggesting a resurgence of vitamin D deficiency in the Western world, combined with various proposed health benefits for vitamin D supplementation, have resulted in increased interest from health care professionals, the media, and the public. The aim of this position paper is to summarise the published data on vitamin D intake and prevalence of vitamin D deficiency in the healthy European paediatric population, to discuss the health benefits of vitamin D and to provide recommendations for the prevention of vitamin D deficiency in this population. Vitamin D plays a key role in calcium and phosphate metabolism and is essential for bone health. There is insufficient evidence from interventional studies to support vitamin D supplementation for other health benefits in infants, children, and adolescents. The pragmatic use of a serum concentration >50 nmol/L to indicate sufficiency and a serum concentration <25 nmol/L to indicate severe deficiency is recommended. Vitamin D deficiency occurs commonly among healthy European infants, children, and adolescents, especially in certain risk groups, including breast-fed infants, not adhering to the present recommendation for vitamin D supplementation, children and adolescents with dark skin living in northern countries, children and adolescents without adequate sun exposure, and obese children. Infants should receive an oral supplementation of 400 IU/day of vitamin D. The implementation should be promoted and supervised by paediatricians and other health care professionals. Healthy children and adolescents should be encouraged to follow a healthy lifestyle associated with a normal body mass index, including a varied diet with vitamin D-containing foods (fish, eggs, dairy products) and adequate outdoor activities with associated sun exposure. For children in risk groups identified above, an oral supplementation of vitamin D must be considered beyond 1 year of age. National authorities should adopt policies aimed at improving vitamin D status using measures such as dietary recommendations, food fortification, vitamin D supplementation, and judicious sun exposure, depending on local circumstances.

Documentation of functional and clinical effects of infant nutrition: setting the scene for COMMENT.

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.

SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome.

Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-complex cofactors, this lead was not investigated in initial studies. The Ski complex is a multiprotein complex required for exosome-mediated RNA surveillance, including the regulation of normal mRNA and the decay of nonfunctional mRNA. Considering the fact that TTC37 is homologous to Ski3p, we explored a gene encoding another Ski-complex cofactor, SKIV2L, in six individuals presenting with typical syndromic diarrhea without variation in TTC37. We identified mutations in all six individuals. Our results show that mutations in genes encoding cofactors of the human Ski complex cause syndromic diarrhea, establishing a link between defects of the human exosome complex and a Mendelian disease.

Benefits of a new pediatric triple-chamber bag for parenteral nutrition in preterm infants.

OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, flexibility, and ease of handling and use of the Ped3CB-A 300  mL, the first ready-to-use multichamber parenteral nutrition (PN) system, with optional lipid bag activation, specially designed for administration to preterm infants. MATERIALS AND METHODS: In this prospective, open-label, multicenter, noncomparative, phase III clinical trial, preterm infants were treated with Ped3CB-A for 5 to 10 consecutive days. RESULTS: A total of 113 preterm infants were enrolled in the study and 97 (birth weight 1382 ±â€Š520 g; gestational age 31.2 ±â€Š2.5 weeks; postnatal age administration 5.6 ±â€Š6.1 days) were included in the per protocol analysis accounting for 854 perfusion days. Double-chamber bag activation was used for 32 perfusion days. Macronutrient, electrolyte, and mineral supplements were primarily administered through a Y-line or directly in the activated bag. In all, 199 additions (mainly sodium, 95%) were made to the Ped3CB-A bags on 197 infusion days (23.1%) in 43 infants (44.3%). More than 1 of these nutrients was added to the bag on only 1 perfusion day. Mean and maximum parenteral nutrient intakes were 2.8 ±â€Š0.7 and 3.6 ±â€Š0.8  g amino acids per kilogram per day, and 80 ±â€Š20 and 104 ±â€Š22  kcal · kg(-1) · day(-1). Mean weight gain represented 10.0, 21.5, and 22. 6 g · kg(-1) · day(-1) according to age at inclusion (0-3, 4-7, or >7 days of life). A visual analog scale was completed and produced positive results. No adverse events were attributable to the design of the Ped3CB-A system. CONCLUSIONS: Ped3CB-A provides easy-to-use, well-balanced, and safe nutritional support. Nutritional intakes and weight gain were within the recent PN recommendations in preterm infants.