Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition

Background: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. / Methods: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. / Results: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. / Conclusions: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential

Probiotics and Preterm Infants: A Position Paper by the ESPGHAN Committee on Nutrition and the ESPGHAN Working Group for Probiotics and Prebiotics

More than 10,000 preterm infants have participated in randomised controlled trials on probiotics worldwide, suggesting that probiotics in general could reduce rates of necrotising enterocolitis (NEC), sepsis, and mortality. However, answers to relevant clinical questions as to which strain to use, at what dosage, and how long to supplement, are not available. On the other hand, an increasing number of commercial products containing probiotics are available from sometimes suboptimal quality. Also, a large number of units around the world are routinely offering probiotic supplementation as the standard of care despite lacking solid evidence. Our recent network meta-analysis identified probiotic strains with greatest efficacy regarding relevant clinical outcomes for preterm neonates. Efficacy in reducing mortality and morbidity was found for only a minority of the studied strains or combinations. In the present position paper, we aim to provide advice which specific strains might potentially be used and which strains should not be used. Besides, we aim to address safety issues of probiotic supplementation to preterm infants, who have reduced immunological capacities and occasional indwelling catheters. For example, quality reassurance of the probiotic product is essential, probiotic strains should be devoid of transferable antibiotic resistance genes, and local microbiologists should be able to routinely detect probiotic sepsis. Provided all safety issues are met, there is currently a conditional recommendation (with low certainty of evidence) to provide either L. rhamnosus GG ATCC53103 or the combination of B. infantis Bb-02, B. lactis Bb-12, and Str. thermophilus TH-4 in order to reduce NEC rates

Predicting outcomes in pediatric ulcerative colitis for management optimization: systematic review and consensus statements from the pediatric inflammatory bowel disease–ahead program

Background & Aims: A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms. Methods: Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements. Results: Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, cancer and mortality. At diagnosis, disease extent (6 studies, N = 627; P =.035), Pediatric Ulcerative Colitis Activity Index score (4 studies, n = 318; P <.001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (2 studies, n = 557; P =.0004), extraintestinal manifestations (4 studies, n = 526; P =.048), and disease extension over time may predict colectomy, whereas primary sclerosing cholangitis (PSC) may be protective. Acute severe colitis may be predicted by disease severity at onset and hypoalbuminemia. Higher Pediatric Ulcerative Colitis Activity Index score and C-reactive protein on days 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of primary sclerosing cholangitis, longstanding colitis (>10 years), male sex, and younger age at diagnosis. Conclusions: These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC

Predicting outcomes in pediatric Crohn's disease for management optimization: systematic review and consensus statements from the pediatric inflammatory bowel disease–ahead program

Background & Aims: A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. Methods: A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. Results: Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. Conclusions: These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN

We acknowledge all the authors of the ESPGHAN/ESPR/ESPEN/CSPEN pediatric parenteral nutrition guidelines for their contributions and vote (Christian Braegger, University Children’s Hospital, Zurich, Switzerland; Jiri Bronsky, University Hospital Motol, Prague, Czech Republic; Cristina Campoy, Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain; Magnus Domellof, Department of Clinical Sciences, Pediatrics, Umeå University, Sweden; Nicholas Embleton, Newcastle University, Newcastle upon Tyne, UK; Mary Fewtrell, UCL Great Ormond Street Institute of Child Health, London, UK; Natasa Fidler, University Medical Centre Ljubljana, Ljubljana, Slovenia; Axel Franz, University Children’s Hospital, Tuebingen, Germany; Oliver Goulet, University Sordonne-Paris-Cite; Paris-Descartes Medical School, Paris, France; Corina Hartmann, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel and Carmel Medical Center, Israel; Susan Hill, Great Ormond Street Hospital for Children, NHS Foundation Trust and UCL Institute of Child Health, London, UK; Iva Hojsak, Children’s Hospital Zagreb, University of Zagreb School of Medicine, University of J. J. Strossmayer School of Medicine Osijek, Croatia; Sylvia Iacobelli, CHU La Reunion, Saint Pierre, France; Frank Jochum, Ev. Waldkrankenhaus Spandau, Berlin, Germany; Koen Joosten, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands; Sanja Kolacek, Children’s Hospital, University of Zagreb School of Medicine, Zagreb, Croatia; Alexandre Lapillone, Paris-Descartes University, Paris, France; Szimonetta Lohner, Department of Pediatrics, University of Pecs, Pecs, Hungary; Dieter Mesotten, KU Leuven, Leuven, Belgium; Walter Mihatsch, Ulm University, Ulm, and Helios Hospital, Pforzheim, Germany; Francis Mimouni, Department of Pediatrics, Division of Neonatology, The Wilf Children’s Hospital, the Shaare Zedek Medical Center, Jerusalem, and the Tel Aviv University, Tel Aviv, Israel; Christian Molgaard, Department of Nutrition, Exercise and Sports, University of Copenhagen, and Paediatric Nutrition Unit, Rigshospitalet, Copenhagen, Denmark; Sissel Moltu, Oslo University Hospital, Oslo, Norway; Antonia Nomayo, Ev. Waldkrankenhaus Spandau, Berlin, Germany; John Puntis, The General Infirmary at Leeds, Leeds, UK; Arieh Riskin, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel; Miguel Saenz de Pipaon, Department of Neonatology, La Paz University Hospital, Red de Salud Materno Infantil y Desarrollo e SAMID, Universidad Autonoma de Madrid, Madrid, Spain; Raanan Shamir, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel; Tel Aviv University, Tel Aviv, Israel; Peter Szitanyi, General University Hospital, First Faculty of Medicine, Charles University in Prague, Czech Republic; Merit Tabbers, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Chris van den Akker, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Hans van Goudoever, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Sacha Verbruggen, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands; Cai Wei, Shanghai Jiao Tong University, Shanghai, China; Weihui Yan, Department of Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China) and the members of the ESPR Section on Nutrition, Gastroenterology and Metabolism (Fredrik Ahlsson, Uppsala University Children’s Hospital and Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; Sertac Arslanoglu, Division of Neonatology, Department of Pediatrics, Istanbul Medeniyet University, Istanbul, Turkey; Wolfgang Bernhard, Department of Neonatology, Children’s Hospital, Faculty of Medicine, Eberhard-Karls- University, Tübingen, Germany; Janet Berrington, Newcastle Neonatal Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Signe Bruun, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark; Christoph Fusch, Department of Pediatrics, Paracelsus Medical School, General Hospital of Nuremberg, Nuremberg, Germany; Shalabh Garg, South Tees Hospitals, Middlesborough, UK; Maria Gianni, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Ann Hellstrom, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Claus Klingenberg, Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway; Helen Mactier, Neonatal Unit, Princess Royal Maternity Hospital, Glasgow, UK; Neena Modi, Section of Neonatal Medicine, Department of Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK; Niels Rochow, Division of Neonatology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Paola Rogerro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Umberto Simeoni, Division of Pediatrics, CHUV & University of Lausanne, Lausanne, Switzerland; Atul Singhal, Paediatric Nutrition, UCL Great Ormond Street Institute of Child Health, London, UK.; Ulrich Thome, Department of Neonatology, Universitatsklinikum Leipzig, Leipzig, Germany; Anne Twomey, Department of Neonatology, The National Maternity Hospital, Dublin, Ireland; Mireille Vanpee, Karolinska University Hospital, Stockholm, Sweden; Gitte Zachariassen, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark) for their vote.Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this

Parenteral provision of micronutrients to pediatric patients: an international expert consensus paper

© 2020 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1002/jpen.1990INTRODUCTION:Micronutrients (vitamins and trace elements) are essential to all nutrition. For children and neonates who are dependent upon nutrition support therapies for growth and development, the prescribed regimen must supply all essential components. This paper aims to facilitate interpretation of existing clinical guidelines into practical approaches for the provision of micronutrients in pediatric parenteral nutrition. METHODS:An international, interdisciplinary expert panel was convened to review recent evidence-based guidelines and published literature to develop consensus- based recommendation on practical micronutrient provision in pediatric parenteral nutrition. RESULTS:The guidelines and evidence have been interpreted as answers to 10 commonly asked questions around the practical principles for provision and monitoring of micronutrients in pediatric patients CONCLUSION: Micronutrients are an essential part of all parenteral nutrition and should be included in the pediatric nutrition therapy care plan.Published versio

Infliximab in young paediatric IBD patients : it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients = 10 years). Median age was 8.3 years (IQR 6.9-8.9) in YP compared with 14.3 years (IQR 12.8-15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 mu g/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0-12.9) vs. OP; 5.5 mg/kg (IQR 5.0-9.3);p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI - 1.2 to - 1.01);p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP;p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known

Young Child Formula: A Position Paper by the ESPGHAN Committee on Nutrition

Young child formulae (YCF) are milk-based drinks or plant protein-based formulae intended to partially satisfy the nutritional requirements of young children ages 1 to 3 years. Although widely available on the market, their composition is, however, not strictly regulated and health effects have not been systematically studied. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition (CoN) performed a systematic review of the literature to review the composition of YCF and consider their role in the diet of young children. The review revealed limited data but identified that YCF have a highly variable composition, which is in some cases inappropriate with very high protein and carbohydrate content and even high amounts of added sugars. Based on the evidence, ESPGHAN CoN suggests that the nutrient composition of YCF should be similar to that of follow-on formulae with regards to energy and nutrients that may be deficient in the diets of European young children such as iron, vitamin D, and polyunsaturated fatty acids (n-3 PUFAs), whereas the protein content should aim toward the lower end of the permitted range of follow-on formulae if animal protein is used. There are data to show that YCF increase intakes of vitamin D, iron, and n-3 PUFAs. However, these nutrients can also be provided via regular and/or fortified foods or supplements. Therefore, ESPGHAN CoN suggests that based on available evidence there is no necessity for the routine use of YCF in children from 1 to 3 years of life, but they can be used as part of a strategy to increase the intake of iron, vitamin D, and n-3 PUFA and decrease the intake of protein compared with unfortified cow's milk. Follow-on formulae can be used for the same purpose. Other strategies for optimizing nutritional intake include promotion of a healthy varied diet, use of fortified foods, and use of supplements

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. Impact: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice.However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion