Intestinal microbiota development and gestational age in preterm neonates

The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weight <1500 g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the first weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary effects and birth mode had little influence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and finally Bifidobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.Peer reviewe

Enhanced nutrient supply and intestinal microbiota development in very low birth weight infants

BACKGROUND: Promoting a healthy intestinal microbiota may have positive effects on short- and long-term outcomes in very low birth weight (VLBW; BW = 28 weeks) infants and a steeper decrease in relative Staphylococcus abundance in extremely preterm (EP, gestational age <28 weeks) infants as compared to controls. Relative Bifidobacterium abundance tended to increase more in MVP controls compared to the intervention group. Abundance of pathogens was not increased in the intervention group. Higher relative Bifidobacterium abundance was associated with improved weight gain. CONCLUSION: Nutrition may affect richness, diversity, and microbiota composition. There was no increase in relative abundance of pathogens among infants receiving enhanced nutrient supply. Favorable microbiota development was associated with improved weight gain.Peer reviewe

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

Microbiota development in preterm and term infants

Microbiota development in (pre)term infants receiving various durations of postpartum antibiotic treatment. Determined through 16S rRNA gene amplicon sequencing (MiSeq, Illumina

Microbiota development in preterm and term infants

Microbiota development in (pre)term infants receiving various durations of postpartum antibiotic treatment. Determined through 16S rRNA gene amplicon sequencing (MiSeq, Illumina

Microbiota development in preterm and term infants

Microbiota development in (pre)term infants receiving various durations of postpartum antibiotic treatment. Determined through 16S rRNA gene amplicon sequencing (MiSeq, Illumina

Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants

Background: Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. Objective: To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. Design: Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. Results: Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after discharge. At 5 months CA, adiponectin concentrations were higher in the intervention group and correlated with weight gain before term (r=0.35) and nutrient supply (0.35≤r≤0.45). Leptin concentrations correlated with weight gain after term and IGF-1 concentrations with length growth before and after term and head growth after term (0.36≤r≤0.53). Conclusion: Enhanced nutrient supply improved early postnatal growth and may have prevented rapid catch-up growth later in infancy. Adiponectin concentration at 5 months CA was higher in the intervention group and correlated positively with early weight gain and nutrient supply. Early nutrition and growth may affect metabolic markers in infancy.Clinical Trial Registration (ClinicalTrials.gov) no.: NCT0110321

Effects of nutrition therapy on growth, inflammation and metabolism in immature infants : a study protocol of a double-blind randomized controlled trial (ImNuT)

BACKGROUND: Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain maturation and inflammation mediated neonatal morbidities are unknown. The aim of this study is to determine whether early supply of ARA and DHA improves brain maturation and neonatal outcomes in infants born before 29 weeks of gestation. METHODS: Infants born at Oslo University Hospital are eligible to participate in this double-blind randomized controlled trial. Study participants are randomized to receive an enteral FA supplement of either 0.4 ml/kg MCT-oil™ (medium chain triglycerides) or 0.4 ml/kg Formulaid™ (100 mg/kg of ARA and 50 mg/kg of DHA). The FA supplement is given from the second day of life to 36 weeks' postmenstrual age (PMA). The primary outcome is brain maturation assessed by Magnetic Resonance Imaging (MRI) at term equivalent age. Secondary outcomes include quality of growth, incidence of neonatal morbidities, cardiovascular health and neuro-development. Target sample size is 120 infants (60 per group), this will provide 80% power to detect a 0.04 difference in mean diffusivity (MD, mm2/sec) in major white matter tracts on MRI. DISCUSSION: Supplementation of ARA and DHA has the potential to improve brain maturation and reduce inflammation related diseases. This study is expected to provide valuable information for future nutritional guidelines for preterm infants. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03555019 . Registered 4 October 2018- Retrospectively registered

Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight &lt; 1500 g) randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR) was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate). The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight &lt; 10th percentile for gestational age) as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype

Nutrition and intestinal rehabilitation of children with short bowel syndrome: a position paper of the ESPGHAN Committee on Nutrition. Part 1: from intestinal resection to home discharge

: Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-centre experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached > 90% agreement. The first the part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN