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  • 1. Agostoni, C
    et al.
    Buonocore, G
    Carnielli, VP
    De Curtis, M
    Darmaun, D
    Decsi, T
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, ND
    Fusch, C
    Genzel-Boroviczeny, O
    Goulet, O
    Kalhan, SC
    Kolacek, S
    Koletzko, B
    Lapillonne, A
    Mihatsch, W
    Moreno, L
    Neu, J
    Poindexter, B
    Puntis, J
    Putet, G
    Rigo, J
    Riskin, A
    Salle, B
    Sauer, P
    Shamir, R
    Szajewska, H
    Thureen, P
    Turck, D
    van Goudoever, JB
    Ziegler, EE
    Enteral nutrient supply for preterm infants: commentary from the European society of paediatric gastroenterology, hepatology and nutrition committee on nutrition2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

  • 2. Arslanoglu, Sertac
    et al.
    Corpeleijn, Willemijn
    Moro, Guido
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Donor Human Milk for Preterm Infants: Current Evidence and Research Directions2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 4, p. 535-542Article in journal (Other academic)
    Abstract [en]

    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.

  • 3.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 390-395Article in journal (Refereed)
    Abstract [en]

    Objectives: Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. Methods: In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg . kg(-1).day(-1) of iron supplements from 6 weeks to 6 months of age: At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. Results: At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.00 6). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Conclusions: Iron supplements with 2 mg . kg(-1) . day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

  • 4.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, B
    Persson, L A
    Sex differences in iron stores of adolescents: what is normal?1995In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 20, no 2, p. 215-24Article in journal (Refereed)
    Abstract [en]

    We evaluated iron status and its determinants in healthy adolescents. Fasting morning blood samples from a school-based cross-sectional study were analyzed for serum ferritin (SF), serum iron, total iron-binding capacity, and circulating transferrin receptors. Physical development, chronic disease, medication, dietary intake, and physical activity were assessed using clinical examination, questionnaires, and 7-day records. The risk of having low serum ferritin values was estimated using bivariate and multivariate regression. Subjects were 867 healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF values increased with pubertal stage in boys but not in girls. Five percent of the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old boys, 7% compared to 1% of the 17-year-old girls had SF values > 100 micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had serum iron values < 15 microM, and 22% had transferrin saturation values < 16%. Mean total iron intakes of the boys were high [1.6 times recommended daily allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in girls but not in boys. Total iron intake or other dietary factors, physical development, or level of physical activity did not influence the risk of low SF. The findings of this study suggest that the differences in iron status between boys and girls in adolescence results primarily from biological differences other than menstrual bleeding or insufficient iron intake. Furthermore, the results question the role of SF as an indicator of iron deficiency in adolescence, in particular if age and sex are not taken into consideration. We suggest that different reference values for SF, including the cut-off limit for low SF, adjusted for age and sex, should be considered. The high iron intakes and corresponding high SF values found in the older boys are noticeable in light of the possible negative health consequences of iron overload.

  • 5. Braegger, Christian
    et al.
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Vitamin D in the Healthy European Paediatric Population2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 6, p. 692-701Article in journal (Refereed)
    Abstract [en]

    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.

  • 6. Bronsky, Jiri
    et al.
    Campoy, Cristina
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Nataša Fidler
    Gerasimidis, Konstantinos
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Moltu, Sissel Jennifer
    Verduci, Elvira
    Vora, Rakesh
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition2019In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 68, no 5, p. 742-760Article in journal (Refereed)
    Abstract [en]

    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.

  • 7. Bruck, Wolfram M
    et al.
    Redgrave, Michele
    Tuohy, Kieran M
    Lönnerdal, Bo
    Graverholt, Gitte
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gibson, Glenn R
    Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants2006In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 43, no 5, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Objective: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived healthpromoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, a-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study.

    Patients and Methods: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-Jac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation.

    Results: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a. predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora.

    Conclusions: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed).

  • 8. Casper, Charlotte
    et al.
    Carnielli, Virgilio P.
    Hascoet, Jean-Michel
    Lapillonne, Alexandre
    Maggio, Luca
    Timdahl, Kristina
    Olsson, Birgitta
    Vagero, Marten
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 59, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    Objectives: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt-stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. Methods: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. Results: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g.kg(-1).day(-1) (P<0.001) compared with placebo (mean 16.86 vs 13.93 g.kg(-1).day(-1)) and significantly decreased the risk of suboptimal growth (<15 g.kg(-1).day(-1)) (30% vs 52%, P = 0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P = 0.013) and 8.55% (P = 0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo. Conclusions: In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.

  • 9.
    Connolly, Eamonn
    et al.
    Dept of Research, BioGaia, Stockholm.
    Abrahamsson, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Björkstén, Bengt
    Centrum för Allergiforskning KI, Stockholm.
    Safety of D(-)-lactic acid producing bacteria in the human infant2005In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 41, no 4, p. 489-492Article in journal (Refereed)
  • 10.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Korponay-Szabó, Ilma R
    Kovács, Judit B
    Szalai, Zsuzsanna
    Mäki, Markku
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Prediction of clinical and mucosal severity of celiac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 2, p. 140-146Article in journal (Refereed)
    Abstract [en]

    Objectives: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity. Patients and Methods: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group 1), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included. Serum levels of antibodies against recombinant tissue transglutaminase were determined with ELISA using standard curves for quantification of antibodies. Results: Immunoglobulin (Ig)A antibodies against tissue transglutaminase (IgA-TGA) were detected in all of the patients with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%)were higher than in group II (81%), group III (73%), and the DH group (67%). Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between groups I and II. Conclusions: High levels of IgA-TGA and IgG-TGA antibodies were associated with the grade of mucosal villous atrophy and a more severe clinical presentation. The combined measurement of IgA-TGA and IgG-TGA enables a noninvasive prediction of small intestinal villous atrophy with high accuracy, and may reduce the need for a biopsy in patients with suspected CD.

  • 11. Degraeuwe, Pieter L J
    et al.
    Beld, Monique P A
    Ashorn, Merja
    Canani, Roberto Berni
    Day, Andrew S
    Diamanti, Antonella
    Fagerberg, Ulrika L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henderson, Paul
    Kolho, Kaija-Leena
    Van de Vijver, Els
    van Rheenen, Patrick F
    Wilson, David C
    Kessels, Alfons G H
    Faecal calprotectin in suspected paediatric inflammatory bowel disease.2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 339-346Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an individual risk prediction rule using individual patient data.

    METHODS: MEDLINE, EMBASE, DARE, and MEDION databases were searched to identify cohort studies evaluating the diagnostic performance of FC in paediatric patients suspected of having IBD. A standard study-level meta-analysis was performed. In an individual patient data meta-analysis, we reanalysed the diagnostic accuracy on a merged patient dataset. Using logistic regression analysis we investigated whether and how the FC value and patient characteristics influence the diagnostic precision. A prediction rule was derived for use in clinical practice and implemented in a spreadsheet calculator.

    RESULTS: According to the study-level meta-analysis (9 studies, describing 853 patients), FC has a high overall sensitivity of 0.97 (95% confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8 diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 μg/g there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative results. The final logistic regression model was based on individual data of 545 patients and included both FC level and age. The area under the receiver operating characteristic curve of this derived prediction model was 0.92 (95% CI 0.89-0.94).

    CONCLUSIONS: In high-prevalence circumstances, FC can be used as a noninvasive biomarker of paediatric IBD with only a small risk of missing cases. To quantify the individual patients' risk, we developed a simple prediction model based on FC concentration and age. Although the derived prediction rule cannot substitute the clinical diagnostic process, it can help in selecting patients for endoscopic evaluation.

  • 12.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Iron Requirements of Infants and Toddlers2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 58, no 1, p. 119-129Article in journal (Refereed)
    Abstract [en]

    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 <bold></bold> kg(-1) <bold></bold> day(-1)). Marginally low-birth-weight infants (2000-2500 g) should receive iron supplements of 1-2 mg <bold></bold> kg(-1) <bold></bold> 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.

  • 13.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Enteral Iron Supplementation in Preterm Infants: Response to Letter to the Editor2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 64, no 1, p. e26-Article in journal (Refereed)
  • 14.
    Earp, Justin C.
    et al.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Mehrotra, Nitin
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Peters, Kristina E.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Fiorentino, Robert P.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Griebel, Donna
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Lee, Sue C.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Mulberg, Andrew
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Rohss, Kerstin
    Former Employee AstraZeneca R&D Molndal, Molndal, Sweden..
    Sandstrom, Marie
    Former Employee AstraZeneca R&D Molndal, Molndal, Sweden..
    Taylor, Amy
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Tornoe, Christoffer W.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA.;Novo Nordisc, Aalborg, Denmark..
    Wynn, Erica L.
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    van der Walt, Jan-Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Astellas Pharma Europe BV, Global Clin Pharmacol & Exploratory Dev, Leiden, Netherlands..
    Garnett, Christine
    US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3154, Silver Spring, MD 20993 USA..
    Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure-Response2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 65, no 3, p. 272-277Article in journal (Refereed)
    Abstract [en]

    Objectives: Food and Drug Administration approval of proton-pump inhibitors for infantile gastroesophageal reflux disease has been limited by intrapatient variability in the clinical assessment of gastroesophageal reflux disease. For children 1 to 17 years old, extrapolating efficacy from adults for IV esomeprazole was accepted. The oral formulation was previously approved in children. Exposure-response and exposure matching analyses were sought to identify approvable pediatric doses. Methods: Intragastric pH biomarker comparisons between children and adults were conducted. Pediatric doses were selected to match exposures in adults and were based on population pharmacokinetic (PK) modeling and simulations with pediatric esomeprazole data. Observed IV or oral esomeprazole PK data were available from 50 and 117 children, between birth and 17 years, respectively, and from 65 adults, between 20 and 48 years. A population PK model developed using these data was used to simulate steady-state esomeprazole exposures for children at different doses to match the observed exposures in adults. Results: Exposure-response relationships of intragastric pH measures were similar between children and adults. The PK simulations identified a dosing regimen for children that results in comparable steady-state area under the curve to that observed after 20 mg in adults. For IV esomeprazole, increasing the infusion duration to 10 to 30 minutes in children achieves matching C-max values with adults. Conclusions: The exposure-matching analysis permitted approval of an esomeprazole regimen not studied directly in clinical trials. Exposureresponse for intragastric pH-permitted approval for the treatment of gastroesophageal reflux disease in children in whom it was not possible to evaluate the adult primary endpoint, mucosal healing assessed by endoscopy.

  • 15.
    Einberg, Afrodite Psaros
    et al.
    Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Filipovich, Olga
    North-Western State Medical University of I.I.Mechnikov, Saint Petersburg, Russia.
    Nyström, Jessica
    Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
    Zhirkov, Anton
    Science Research Institute of Children's Infections, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia.
    Brenndörfer, Erwin Daniel
    Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
    Frelin, Lars
    Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
    Rukoiatkina, Elena
    Maternity Hospital No. 16, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia; Department of Pediatrics, Gynecology and Female Reproductology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia.
    Lobzin, Yuriy
    Science Research Institute of Children's Infections, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia.
    Sällberg, Matti
    Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
    Fischler, Björn
    Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
    Lutckii, Anton
    Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden; Science Research Institute of Children's Infections.
    Lack of association between interleukin 28B polymorphism and vertical transmission of hepatitis C2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 65, no 6, p. 608-612Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Single genetic nucleotide polymorphism (rs12979860) near the gene for Interleukin 28B (IL28B), is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon based therapies in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate if IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT).

    METHODS: Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T and T/T) as well as by viral genotype.

    RESULTS: The proportion of children with genotype C/C was the same in the vertically infected (36%, 17/47) and the exposed uninfected children (38%, 29/76). No difference was seen when stratifying for viral genotype. There was no association between mothers' IL28B genotype and the risk of vertical transmission.

    CONCLUSION: Regardless of viral genotype we found no association between IL28B genotype and the risk of HCV-VT. The IL28B genotype CC, which has been shown to be favourable in other settings, was not protective of HCV-VT. Thus, other factors possibly associated with the risk of HCV-VT need to be explored.

  • 16. Fewtrell, Maly
    et al.
    Bronsky, Jiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Mis, Natasa Fidler
    Hojsak, Iva
    Hulst, Jessie M.
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 64, no 1, p. 119-132Article in journal (Refereed)
    Abstract [en]

    This position paper considers different aspects of complementary feeding (CF), focussing on healthy term infants in Europe. After reviewing current knowledge and practices, we have formulated these recommendations: Timing: Exclusive or full breast-feeding should be promoted for at least 4 months (17 weeks, beginning of the 5th month of life) and exclusive or predominant breast-feeding for approximately 6 months (26 weeks, beginning of the 7th month) is a desirable goal. Complementary foods (solids and liquids other than breast milk or infant formula) should not be introduced before 4 months but should not be delayed beyond 6 months. Content: Infants should be offered foods with a variety of flavours and textures including bitter tasting green vegetables. Continued breast-feeding is recommended alongside CF. Whole cows' milk should not be used as the main drink before 12 months of age. Allergenic foods may be introduced when CF is commenced any time after 4 months. Infants at high risk of peanut allergy (those with severe eczema, egg allergy, or both) should have peanut introduced between 4 and 11 months, following evaluation by an appropriately trained specialist. Gluten may be introduced between 4 and 12 months, but consumption of large quantities should be avoided during the first weeks after gluten introduction and later during infancy. All infants should receive iron-rich CF including meat products and/or iron-fortified foods. No sugar or salt should be added to CF and fruit juices or sugar sweetened beverages should be avoided. Vegan diets should only be used under appropriate medical or dietetic supervision and parents should understand the serious consequences of failing to follow advice regarding supplementation of the diet. Method: Parents should be encouraged to respond to their infant's hunger and satiety queues and to avoid feeding to comfort or as a reward.

  • 17. Fewtrell, Mary S.
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hojsak, Iva
    Hulst, Jessie M.
    Kennedy, Kathy
    Koletzko, Berthold
    Mihatsh, Walter
    Stijnen, Theo
    Attrition in Long-Term Nutrition Research Studies: A Commentary by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Early Nutrition Research Working Group2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 1, p. 180-182Article in journal (Refereed)
    Abstract [en]

    Long-term follow-up of randomised trials and observational studies provide the best evidence presently available to assess long-term effects of nutrition, and such studies are an important component in determining optimal infant feeding practices. Attrition is, however, an almost inevitable occurrence with increasing age at follow-up. There is a common assumption that studies with <80% follow-up rates are invalid or flawed, and this criticism seems to be more frequently applied to follow-up studies involving randomised trials than observational studies. In this article, we explore the basis and evidence for this 80% rule and discuss the need for greater consensus and clear guidelines for analysing and reporting results in this specific situation.

  • 18. Fidler Mis, Nataša
    et al.
    Braegger, Christian
    Bronsky, Zjiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas D.
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Mihatsch, Walter
    Molgaard, Christian
    Vora, Rakesh
    Fewtrell, Mary
    Response to Letter: How Much Free Sugars Intake Should Be Recommended for Children Younger Than 2 Years Old?2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 66, no 3, p. E87-E88Article in journal (Refereed)
  • 19.
    Grodzinsky, Ewa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Andersson, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Comparative evaluation of serological tests for celiac disease: A European initiative toward standardization.2000In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 31, p. 513-519Article in journal (Refereed)
  • 20.
    Hernell, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Aggett, Peter
    Fewtrell, Mary
    Koletzko, Berthold
    Rey, Jean
    Chapter 7. The Contributions of the ESPGHAN Committees on Nutrition to Paediatric Nutrition2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 66, p. S144-S153Article in journal (Refereed)
    Abstract [en]

    The first Committee on Nutrition (CoN) was founded in 1974. Two years later nutrition (N) was added to the society's name, which then became ESPGAN. The Committee systematised compositional and quality criteria for breast milk substitutes and food for special medical purposes, the first of many examples on how recommendations and comments published by the Committees on Nutrition (CsoN) were adopted by the European Economic Community, later the European Union and also influenced the World Health Organization/Food and Agriculture Organization of the United Nations Codex standards. A second CoN focusing on preterm infants was established in 1979 and its recommendations on nutrition of these infants were widely implemented. The third and standing CoN, established 1986, started to organise high-quality symposia at the annual meetings appreciating the need to enhance the expertise in nutritional research. From 1991 the CoN has organised Summer Schools in paediatric nutrition for young colleagues further emphasising its educational interest and more recently an annual, more specialised Nutrition Masterclass. Successively the interest of the CoN has expanded to other areas, such as highlighting dilemmas and uncertainties in the field of nutrition including the design, choice of outcomes and statistical analysis of trials in infant nutrition. The work of the CsoN have had great impact on paediatric nutrition and the committee will continue its important role by writing commentaries and systematic reviews and revising guidelines when required to inform and stimulate discussion among colleagues as well as stimulate training in paediatric nutrition by organising workshops and scientific meetings, training courses, and other approaches, and by interaction with other expert groups.

  • 21.
    Hernell, Olle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bläckberg, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Chen, Q
    Sternby, B
    Nilsson, A
    Does the bile salt-stimulated lipase of human milk have a role in the use of the milk long-chain polyunsaturated fatty acids?1993In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 16, no 4, p. 426-431Article in journal (Refereed)
    Abstract [en]

    Long-chain polyunsaturated (LCP) fatty acids derived from linoleic (18:2 n-6) and alpha-linolenic (18:3 n-3) acids are considered essential nutrients in preterm infants. The efficiency by which such fatty acids are released as absorbable products from triacylglycerol was explored in vitro using rat chylomicron triacylglycerol as substrate. When incubated with purified human pancreatic colipase-dependent lipase and colipase, arachidonic acid (20:4 n-6) was released less efficiently than linoleic acid from such triacylglycerol. This difference was not seen when purified human milk bile salt-stimulated lipase (BSSL) was incubated with the triacylglycerol substrate, and it was almost abolished when colipase-dependent lipase (with colipase) and BSSL acted simultaneously, as they do in breast-fed infants. There was no difference in arachidonic acid and eicosapentaenoic acid (20:5 n-3) release rates with either colipase-dependent lipase or BSSL, albeit the release was more rapid with the milk enzyme than with colipase-dependent lipase. Again, the most efficient release as absorbable free fatty acids was achieved when the two lipases operated together. The relative resistance to hydrolysis of arachidonic acid and eicosapentaenoic acid by colipase-dependent lipase was best explained by the localization of the first double bond to the delta-5 position of the respective fatty acid. The results obtained suggest that BSSL is of importance for the efficient use of human milk LCP fatty acids.

  • 22. Hojsak, Iva
    et al.
    Braegger, Christian
    Bronsky, Jiri
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Mis, Nataša Fidler
    Mihatsch, Walter
    Molgaard, Christian
    van Goudoever, Johannes
    Arsenic in rice: a cause for concern2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 1, p. 142-145Article in journal (Refereed)
    Abstract [en]

    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.

  • 23. Hojsak, Iva
    et al.
    Bronsky, Jiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Mis, Natasa Fidler
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Vora, Rakesh
    Fewtrell, Mary
    Young Child Formula: A Position Paper by the ESPGHAN Committee on Nutrition2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 66, no 1, p. 177-185Article in journal (Refereed)
    Abstract [en]

    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.

  • 24. Hojsak, Iva
    et al.
    Colomb, Virginie
    Braegger, Christian
    Bronsky, Jiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Mis, Natasa Fidler
    Hulst, Jessie M.
    Indrio, Flavia
    Lapillonne, Alexandre
    Mihatsch, Walter
    Molgaard, Christian
    van Goudoever, Johannes
    Fewtrell, Mary
    ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children: a Systematic Review and Meta-analysis2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 5, p. 776-792Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 25.
    Holgerson, Pernilla L
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Vestman, Nelly R
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Tanner, Anne CR
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oral microbial profile discriminates breast-fed from formula-fed infants2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 2, p. 127-136Article in journal (Refereed)
    Abstract [en]

    Objectives: Little is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli.

    Methods: A total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri.

    Results: Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis.

    Conclusions: The microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk.

  • 26. Hossain, Md Iqbal
    et al.
    Nahar, Baitun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Hamadani, Jena D.
    Ahmed, Tahmeed
    Brown, Kenneth H.
    Effects of Community-based Follow-up Care in Managing Severely Underweight Children2011In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 53, no 3, p. 310-319Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the present study was to assess the effects of community-based follow-up care, food supplementation, and/or psychosocial stimulation on the recovery of severely underweight children.

    Patients and Methods: A total of 507 severely underweight children (weight-for-age z score <-3) ages 6 to 24 months hospitalized at the International Center for Diarrheal Disease Research, Bangladesh, were randomly assigned to 1 of the following regimens for 3 months once they recovered from diarrhea: fortnightly follow-up care at the International Center for Diarrheal Disease Research, Bangladesh Hospital, including growth monitoring, health education, and micronutrient supplementation (group H-C, n = 102); fortnightly follow-up at community clinics, using the same treatment regimen as group H-C (group C-C, n = 99); community-based follow-up as per group C-C plus cereal-based supplementary food (SF) (group C-SF, n = 101); follow-up as per group C-C plus psychosocial stimulation (PS) (group C-PS, n - 102); or follow-up as per group C-C plus both SF and PS (group C-SF + PS, n = 103).

    Results: There were no significant differences in baseline characteristics by treatment group. Attendance at scheduled follow-up visits was greater in groups C-SF, C-SF + PS, and C-PS than in C-C and H-C; P<0.05. Rates of weight gain were greater in groups C-SF + PS, C-SF, and C-PS (0.88-1.01 kg) compared with groups C-C and H-C (0.63-0.76 kg), P<0.05. Three-factor analysis of covariance of the effects of treatment components indicated that weight gain and change in weight-for-age z score and weightfor- length z score were greater in groups that received SF (P< 0.05) and linear growth was greater among children managed in the community (P = 0.002).

    Conclusions: Positioning follow-up services in the community increases follow-up visits and promotes greater linear growth; providing SF, with or without PS, increases clinic attendance and enhances nutritional recovery. Community-based service delivery, especially including SF, permits better rehabilitation of greater numbers of severely underweight children.

  • 27. Hossain, Md Iqbal
    et al.
    Nahar, Baitun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hamadani, Jena D.
    Ahmed, Tahmeed
    Roy, Anjan Kumar
    Brown, Kenneth H.
    Intestinal Mucosal Permeability of Severely Underweight and Nonmalnourished Bangladeshi Children and Effects of Nutritional Rehabilitation2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 51, no 5, p. 638-644Article in journal (Refereed)
    Abstract [en]

    Objective: Lactulose/mannitol (L/M) intestinal permeability tests were completed to compare the intestinal function of severely underweight children recovering from diarrhea and other illnesses and of nonmalnourished children from the same communities, and to evaluate the effects of food supplementation, with or without psychosocial stimulation, on the changes in intestinal function among the underweight children. Patients and Methods: Seventy-seven malnourished children completed intestinal permeability studies at baseline and 3 months after receiving 1 of the following randomly assigned treatment regimens: group-C-fortnightly follow-up at community-based follow-up units, including growth monitoring and promotion, health education, and micronutrient supplementation, n = 17; group-SF-same as group-C plus supplementary food (SF) to provide 150 to 300 kcal/day, n = 23; group-PS-same as group-C plus psychosocial stimulation (PS), n = 17; or group-SF+PS-same as group-C plus SF and PS, n = 20. Seventeen nonmalnourished children were included as comparison subjects. Results: The malnourished children's mean +/- SD initial age was 13.1 +/- 4.0 months, their mean weight-for-age z score was -3.82 +/- 0.61, and their median (interquartile range) urinary L/M recovery ratio was 0.16 (0.10-0.28). Eighty-four percent of the children had L/M >= 0.07, suggestive of impaired intestinal function. The median L/M of the malnourished children was significantly greater than that of 17 relatively well-nourished children (median 0.09; interquartile range 0.05-0.12; P = 0.001). There were no significant differences in baseline characteristics of the severely malnourished children by treatment group. Following treatment, the L/M ratio improved in all of the groups (P < 0.001), but there were no significant differences in these changes by treatment group. There was a significant positive association between weight gain and the magnitude of improvement in L/M ratio (r = 0.30, P = 0.012). Conclusions: Intestinal mucosal function, as measured by sugar permeability, is impaired among severely underweight children. Intestinal permeability improves in relation to weight gain, but intestinal mucosal recovery is not specifically related to the types or amount of food supplementation or PS provided in this trial.

  • 28.
    Högberg, L
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Is spelt wheat toxic to those with celiac disease.2000In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 31, p. 321-321Article in journal (Refereed)
  • 29.
    Högberg, Lotta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Björkengren-Johansson, Lars
    Barnkliniken Borås.
    Jansson, Gunnar
    Barnkliniken Motala.
    Can braces provoke oral lesions in Crohn Disease?2002In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 35, p. 708-709Article in journal (Refereed)
  • 30.
    Johansson, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Nordyke, Katrina
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Myléus, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Celiac Dietary Adherence Test simplifies Determining Adherence to a Gluten-Free Diet in Swedish Adolescents2019In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801Article in journal (Refereed)
    Abstract [en]

    Objectives: The aims of the study were to ascertain whether the Celiac Dietary Adherence Test (CDAT) could contribute in determining adherence to a gluten-free diet in celiac disease patients and to evaluate the diet adherence and well-being of a study population five years after a celiac disease screening known as “Exploring the Iceberg of Celiacs in Sweden”.

    Methods: Through the screening, 90 adolescents (born 1997) were diagnosed with biopsy-proven celiac disease at twelve-years of age. Of them, 70 (78%) came to a five-year follow-up where anti–tissue transglutaminase antibodies 2 (TG2-IgA) was tested and a questionnaire was filled in, including CDAT, which consists of seven questions related to adherence. Non-parametrical tests were utilized to determine associations between adherence measures.

    Results: Among the adolescents, 86% were adherent to a gluten-free diet five years after screening, 38% reported their general well-being as excellent, 50% very well, and 12% well. Statistically significant associations were seen between TG2-IgA and the CDAT score (p=0.033), and the self-reported adherence question and the CDAT score (p < 0.001).

    Conclusions: The screening-detected adolescents reported a high level of well-being and adherence to a gluten-free diet five years after screening. We conclude that the CDAT can be used in clinical practice as an estimation of adherence to a gluten-free diet. It would be most suitable to use in conjunction with currently used adherence measures, but can also be used as a stand-alone method when others are not accessible.

  • 31. Karlsland Åkeson, Pia
    et al.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Serum Vitamin D Depends Less on Latitude Than on Skin Color and Dietary Intake During Early Winter in Northern Europe2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 4, p. 643-649Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate if dietary vitamin D intake is adequate for sufficient vitamin D status during early winter in children living in Sweden, irrespective of latitude or skin color.

    METHODS: As part of a prospective, comparative, two-center intervention study in northern (63°N) and southern (55°N) Sweden, dietary intake, serum 25-hydroxyvitamin D (S-25(OH) D), associated laboratory variables, and socio-demographic data were studied in 5 to 7-year-old children with fair and dark skin in November and December.

    RESULTS: 206 children with fair/dark skin were included, 44/41 and 64/57 children in northern and southern Sweden, respectively. Dietary vitamin D intake was higher in northern than southern Sweden (p=0.001), irrespective of skin color, partly due to higher consumption of fortified foods, but only met 50-70% of national recommendations (10 μg/day). S-25(OH) D was higher in northern than southern Sweden, in children with fair (67 vs. 59 nmol/L; p < 0.05) and dark skin (56 vs. 42 nmol/L; p < 0.001). S-25(OH) D was lower in dark than fair skinned children at both sites (p < 0.01), and below 50 nmol/L in 40 and 75% of dark-skinned children in northern and southern Sweden, respectively.

    CONCLUSIONS: Insufficient vitamin D status was common during early winter in children living in Sweden, particularly in those with dark skin. Although, higher dietary vitamin D intake in northern than southern Sweden attenuated the effects of latitude, a northern country of living combined with darker skin and vitamin D intake below recommendations are important risk factors for vitamin D insufficiency.

  • 32. Keen, Christina
    et al.
    Olin, Anna-Carin
    Eriksson, Susanne
    Ekman, Anna
    Lindblad, Anders
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Beermann, Christopher
    Strandvik, Birgitta
    Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 5, p. 537-544Article in journal (Refereed)
    Abstract [en]

    Objectives: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. Patients and Methods: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. Results: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. Conclusions: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.

  • 33.
    Korponay-Szabó, Ilma R.
    et al.
    Dept. of Pediatrics, Celiac Disease Center, Heim Pál Children´s Hospital, Budapest.
    Vecsei, Zsófia
    Király, Róbert
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Chirdo, Fernando
    Nemes, Eva
    Fésüs, László
    Mäki, Markku
    Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize2008In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 46, no 3, p. 253-261Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Deamidated gliadin peptides are efficient antigens in diagnostic tests for celiac disease, and results correlate better with transglutaminase 2-based assays than those with native gliadin. We investigated whether deamidated gliadin antigens are structurally similar to transglutaminase 2 or could mimic transglutaminase epitopes. PATIENTS AND METHODS: Serum samples from 74 celiac and 65 control patients, and 13 different transglutaminase 2-specific monoclonal mouse antibodies were investigated for their binding to commercially available deamidated gliadin peptides using enzyme-linked immunosorbent assay, competition studies, and molecular modelling. RESULTS: The enzyme-linked immunosorbent assay with deamidated gliadin peptides had 100% sensitivity and 98.5% specificity in patients. Deamidated gliadin epitopes also were recognized by 3 transglutaminase-specific monoclonal antibodies, and antibodies affinity-purified with deamidated gliadin peptides from celiac patient sera reacted with transglutaminase but did not show endomysial binding. The binding of the monoclonal antibodies to deamidated gliadin was inhibited dose dependently by full-length recombinant human transglutaminase, its fragments containing the binding sites of these monoclonal antibodies, or by celiac patient antibodies. Deamidated gliadin peptides decreased the binding of transglutaminase-specific monoclonal antibodies to transglutaminase. Three different cross-reacting transglutaminase epitopes were found, of which 2 are located in the C-terminal domain and 1 is conformational. The binding of celiac serum samples to deamidated gliadin peptides could not be abolished by transglutaminase or by any of the transglutaminase-specific monoclonals, indicating that celiac sera also contain additional antibodies to gliadin epitopes different from transglutaminase. CONCLUSIONS: Certain deamidated gliadin-derived peptides and transglutaminase 2 epitopes have similar 3-dimensional appearance. This homology may contribute to the induction of transglutaminase autoantibodies by molecular mimicry.

  • 34.
    Lagerqvist, Carina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jidell, Erik
    Juto, Per
    Olcén, Per
    Stenlund, Hans
    Hernell, Olle
    Ivarsson, Anneli
    Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age2008In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 47, no 4, p. 428-35Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS: Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.

  • 35.
    Laurin, Pia
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wolving, Mats
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Even small amounts of gluten cause relapse in children with celiac disease2002In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 34, no 1, p. 26-30Article in journal (Refereed)
    Abstract [en]

    Background: Previously, a gluten challenge was customary to establish the diagnosis of celiac disease in children. There are no clear recommendations on how to perform this challenge or what markers to rely on for timing the biopsy after the challenge. The authors' aim was to monitor gluten intake, clinical symptoms, and antibody kinetics to evaluate the influence of gluten exposure during the challenge.

    Methods: Twenty-five children under investigation for suspected celiac disease were challenged. One child was excluded because blood samples, food records, or biopsy was lacking. Median age at the postchallenge biopsy was 3.8 (2.7-8.8) years. The families kept daily records of the children's gluten intake and of symptoms that occurred. Blood samples were taken monthly for analysis of antigliadin and endomysium antibodies and total immunoglobulin A (IgA). A third biopsy was performed when clinical symptoms suggested a relapse.

    Results: All 24 children showed deterioration of the mucosa or elevated antibodies during gluten challenge. Median duration of the challenge was 13 (5-51) weeks, and mean gluten intake was 1.7 (0.2-4.3) g/d and 0.1 (0.02-0.26) g/kg daily.

    Conclusions: Gluten intake during the challenge varied widely, and the parents were unable to give their children the recommended amount. Despite the small amounts given, all children showed signs of relapse at a clinical, laboratory, or histologic level. Much smaller amounts of gluten than previously suggested seem sufficient to cause relapse during gluten challenge in children.

  • 36.
    Lindberg, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Early onset of ulcerative colitis: long-term follow-up with special reference to colorectal cancer and primary sclerosing cholangitis.2008In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 46, no 5, p. 534-538Article in journal (Refereed)
  • 37. Lindberg, Tor
    et al.
    Engberg, Staffan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jakobsson, I
    Lönnerdal, Bo
    Digestion of proteins in human milk, human milk fortifier, and preterm formula in infant rhesus monkeys.1997In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 24, no 5, p. 537-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is limited information in the literature on the capacity of the preterm infant to digest human and bovine milk proteins. We therefore studied in vivo the luminal phase of the hydrolysis of proteins in human milk, human milk fortifier, and preterm formula in preterm rhesus monkeys and in infant rhesus monkeys at 6 weeks and 7 months of age.

    METHODS: Protein hydrolysis was followed by polyacrylamide gradient gel electrophoresis and electroimmunoassay. The serum level of absorbed unhydrolyzed human alpha-lactalbumin was measured by a radioimmunoassay method. Trypsin and elastase activities in duodenal contents were measured before and after the meal.

    RESULTS: In 6-week-old monkeys, the enzyme activities decreased by 50% postprandially, whereas they increased in 7-month-old monkeys. In preterm and in 6-week-old monkeys, hydrolysis of human and bovine whey proteins was slow, and in 6-week-old monkeys, 30-50% of the proteins could still be detected immunochemically in duodenal contents after 60 min. At these ages, serum level of absorbed alpha-lactalbumin were high. At 7 months of age, no or small (lactoferrin and bovine serum albumin) amounts of the proteins could be detected in duodenal contents after 15 min. At this age alpha-lactalbumin was not measurable in serum.

    CONCLUSIONS: The low capacity to digest whey proteins in suckling monkeys may depend upon an immaturity of the exocrine pancreas to respond to secretogogues.

  • 38. Lindberg, Tor
    et al.
    Engberg, Staffan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöberg, L B
    Lönnerdal, Bo
    In vitro digestion of proteins in human milk fortifiers and in preterm formula.1998In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 27, no 1, p. 30-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Knowledge about the digestibility of the proteins in new products designed for feeding preterm infants is limited. The purpose of this study was to observe in vitro the hydrolysis of the bovine and human whey proteins in such products.

    METHODS: Proteins in human milk, in human milk fortifiers (Presemp [Semper AB, Stockholm, Sweden] and Enfamil [Mead Johnson, Evansville, IN, U.S.A.] human milk fortifiers), in preterm formulas (Similac Special Care [Ross, Columbus, OH, U.S.A.] and Enfalac [Mead Johnson]), and whey protein concentrates with varying degrees of denaturation were digested by duodenal juice from healthy preterm infants, from a 3-year-old child, and from adults. Digestion was studied in vitro using polyacrylamide gradient gel electrophoresis, electroimmunoassay, and nonprotein nitrogen analysis.

    RESULTS: Casein was the protein most rapidly degraded in all products. Human and bovine whey proteins were more slowly digested; as much as 68% of human lactoferrin was still immunoreactive after 40 minutes of digestion. The corresponding figure for bovine serum albumin was 24-69%; for B-lactoglobulin, 20-40%; for bovine alpha-lactalbumin, 20-51%; and for human alpha-lactalbumin, 41%. Contrary to common belief, digestibility of bovine whey proteins decreased with a high degree of denaturation of the proteins.

    CONCLUSIONS: Bovine whey proteins in human milk fortifiers and in preterm formulas are relatively slowly digested in vitro by normal duodenal juice. The results may have implications for the design of products for feeding preterm infants.

  • 39. Logan, BK
    et al.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    Endogenous ethanol production in a child with short-gut syndrome2003In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 36, p. 419-420Article in journal (Refereed)
  • 40.
    Lorentzon Fagerberg, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Lindholm, Johan
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Finkel, Yigael
    Fecal calprotectin: a quantitative marker of colonic inflammation in children with inflammatory bowel disease2007In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 45, no 4, p. 414-420Article in journal (Refereed)
    Abstract [en]

    Objectives: The protein calprotectin (S100 A8/A9) is present in neutrophils, monocytes, and macrophages. Colorectal inflammation can be detected by increased excretion of fecal calprotectin (FC). The aim of this study was to evaluate FC as a quantitative marker of inflammatory activity in children with inflammatory bowel disease (IBD). Patients and Methods: Thirty-nine children with IBD delivered a fecal spot sample and underwent colonoscopy. The samples were examined with an enzyme-linked immunosorbent assay for FC (Calprest, Eurospital, Trieste, Italy). The concentrations were correlated to macroscopic and microscopic assessments of extent and severity of inflammation in 8 colonic segments for each patient. Results: FC correlated significantly to the macroscopic extent (Spearman p=0.61) and the severity (Spearman p=0.52) of colonic inflammation and to a macroscopic, combined extent and severity score (Spearman p = 0.65). Significant correlations also were found to the microscopic extent (Spearman p=0.71) and severity (Spearman p = 0.72) of colonic inflammation and to a microscopic, combined extent and severity score (Spearman p=0.75). The median FC was 392 μg/g (95% confidence interval [CI], 278-440) in children with clinical IBD symptoms (n=23) and 32.9 μg/g (95% CI, 9.4-237) in asymptomatic IBD patients (n= 16). Of the asymptomatic children, 56% had a complete microscopic mucosal healing, and their median FC was 9.9 μg/g (95% CI, 5.9-41.9). Conclusions: FC can be used as a surrogate marker for estimation of colonic inflammation in pediatric IBD. Normalized FC concentration seems to indicate complete mucosal healing. FC is simple to obtain and analyze; this should facilitate objective assessment and monitoring of IBD activity.

  • 41. Ludvigsson, JF
    Book review: SPSS 10.0 for use in Windows 95,98,2000; Windows ME; Mac OS 9.04 or later (Power Macintosh G3, including iMacs, 233 MHz, 64 MB ram)2001In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 33, p. 355-356Article in journal (Other (popular science, discussion, etc.))
  • 42.
    Ludvigsson, JF
    Linköping University, Department of Clinical and Experimental Medicine.
    Book Review: Studying a Study and Testing a Test by RK Riegelman, Lippincott Williams & Wilkins 2000.2001In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 33, p. 226-227Article in journal (Other (popular science, discussion, etc.))
  • 43.
    Ludvigsson, Jonas
    et al.
    Barnkliniken Örebro.
    Ansved, Pär
    Barnkliniken, Kalmar .
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hammersjö, Jan-Åke
    Barnkliniken, Västervik .
    Johansson, Calle
    Barnkliniken, Jönköping .
    Edvardsson, Stig
    Barnkliniken, Växjö .
    Ljungkrantz, Magnus
    Barnkliniken, Karlskrona .
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Symptoms and signs have changed in Swedish children with coeliac disease.2004In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 38, p. 181-186Article in journal (Refereed)
  • 44. Lönnerdal, Bo
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    An Opinion on "Staging'' of Infant Formula: A Developmental Perspective on Infant Feeding2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 1, p. 9-21Article, review/survey (Refereed)
    Abstract [en]

    Breast milk is a dynamic fluid with compositional changes occurring throughout the period of lactation. Some of these changes in nutrient concentrations reflect the successively slowing growth rate and developmental changes in metabolic requirements that infants undergo during the first year of life. Infant formula, in contrast, has a static composition, intended to meet the nutritional requirements of infants from birth to 6 or 12 months of age. To better fit the metabolic needs of infants and to avoid nutrient limitations or excesses, we suggest that infant formulas should change in composition with the age of the infant, that is, different formulas are created/used for different ages during the first year of life. We propose that specific formulas for 0 to 3 months (stage 1), 3 to 6 months (stage 2), and 6 to 12 months (stage 3) of age may be nutritionally and physiologically advantageous to infants. Although this initially may impose some difficult practical/conceptual issues, we believe that this staging concept would improve nutrition of formula-fed infants and, ultimately, improve outcomes and make their performance more similar to that of breast-fed infants.

  • 45.
    Malmborg, Petter
    et al.
    Dept Womens & Childrens Hlth, Astrid Lindgren Childrens Hosp, Karolinska Institute, Stockholm, Sweden.
    Grahnquist, Lena
    Dept Womens & Childrens Hlth, Astrid Lindgren Childrens Hosp, Karolinska Institute, Stockholm, Sweden.
    Lindholm, Johan
    Department of Oncology-Pathology, Karolinska Univ Hosp, Karolinska Institute, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hildebrand, Hans
    Dept Womens & Childrens Hlth, Astrid Lindgren Childrens Hosp, Karolinska Institute, Stockholm, Sweden.
    Increasing incidence of paediatric inflammatory bowel disease in northern stockholm county, 2002-20072013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 1, p. 29-34Article in journal (Refereed)
  • 46. Mihatsch, Walter A.
    et al.
    Braegger, Christian
    Bronsky, Jiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Mis, Nataša F.
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Mølgaard, Christian
    Embleton, Nicholas
    van Goudoever, Johannes
    Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 63, no 1, p. 123-129Article in journal (Refereed)
    Abstract [en]

    Vitamin K deficiency bleeding (VKDB) due to physiologically low vitamin K plasma concentrations is a serious risk for newborn and young infants and can be largely prevented by adequate vitamin K supplementation. The aim of this position paper is to define the condition, describe the prevalence, discuss current prophylaxis practices and outcomes, and to provide recommendations for the prevention of VKDB in healthy term newborns and infants. All newborn infants should receive vitamin K prophylaxis and the date, dose, and mode of administration should be documented. Parental refusal of vitamin K prophylaxis after adequate information is provided should be recorded especially because of the risk of late VKDB. Healthy newborn infants should either receive 1 mg of vitamin K-1 by intramuscular injection at birth; or 3 x 2 mg vitamin K-1 orally at birth, at 4 to 6 days and at 4 to 6 weeks; or 2 mg vitamin K-1 orally at birth, and a weekly dose of 1 mg orally for 3 months. Intramuscular application is the preferred route for efficiency and reliability of administration. The success of an oral policy depends on compliance with the protocol and this may vary between populations and healthcare settings. If the infant vomits or regurgitates the formulation within 1 hour of administration, repeating the oral dose may be appropriate. The oral route is not appropriate for preterm infants and for newborns who have cholestasis or impaired intestinal absorption or are too unwell to take oral vitamin K-1, or those whose mothers have taken medications that interfere with vitamin K metabolism. Parents who receive prenatal education about the importance of vitamin K prophylaxis may be more likely to comply with local procedures.

  • 47. Mis, Natasa Fidler
    et al.
    Braegger, Christian
    Bronsky, Jiri
    Campoy, Cristina
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas D.
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Mihatsch, Walter
    Molgaard, Christian
    Vora, Rakesh
    Fewtrell, Mary
    Sugar in Infants, Children and Adolescents: A Position Paper of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition2017In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 65, no 6, p. 681-696Article in journal (Refereed)
    Abstract [en]

    The consumption of sugars, particularly sugar-sweetened beverages (SSBs; beverages or drinks that contain added caloric sweeteners (ie, sucrose, high-fructose corn syrup, fruit juice concentrates), in European children and adolescents exceeds current recommendations. This is of concern because there is no nutritional requirement for free sugars, and infants have an innate preference for sweet taste, which may be modified and reinforced by pre- and postnatal exposures. Sugar-containing beverages/free sugars increase the risk for overweight/obesity and dental caries, can result in poor nutrient supply and reduced dietary diversity, and may be associated with increased risk of type 2 diabetes mellitus, cardiovascular risk, and other health effects. The term "free sugars,'' includes all monosaccharides/disaccharides added to foods/beverages by the manufacturer/cook/consumer, plus sugars naturally present in honey/syrups/unsweetened fruit juices and fruit juice concentrates. Sugar naturally present in intact fruits and lactose in amounts naturally present in human milk or infant formula, cow/goatmilk, and unsweetened milk products is not free sugar. Intake of free sugars should be reduced and minimised with a desirable goal of <5% energy intake in children and adolescents aged >= 2 to 18 years. Intake should probably be even lower in infants and toddlers <2 years. Healthy approaches to beverage and dietary consumption should be established in infancy, with the aim of preventing negative health effects in later childhood and adulthood. Sugar should preferably be consumed as part of a main meal and in a natural form as human milk, milk, unsweetened dairy products, and fresh fruits, rather than as SSBs, fruit juices, smoothies, and/or sweetened milk products. Free sugars in liquid form should be replaced by water or unsweetened milk drinks. National Authorities should adopt policies aimed at reducing the intake of free sugars in infants, children and adolescents. This may include education, improved labelling, restriction of advertising, introducing standards for kindergarten and school meals, and fiscal measures, depending on local circumstances.

  • 48.
    Myléus, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Webb, Charlotta
    Danielsson, Lars
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Högberg, Lotta
    Karlsson, Eva
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenhammar, Lars
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Wall, Stig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Carlsson, Annelie
    Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic2009In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 49, no 2, p. 170-176Article in journal (Refereed)
    Abstract [en]

    Objetive: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases.

    Patients and methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.

    Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33).

    Conclusions: The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.

  • 49.
    Mårtensson, Thomas
    et al.
    Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.
    Szakos, Attila
    Karolinska University Hospital, Department of Clinical Pathology and Cytology, Stockholm, Sweden.
    Mellgren, Karin
    University of Gothenburg, Department of Pediatrics, Institute of Clinical Sciences Sahlgrenska Academy, Sweden.
    Toporski, Jacek
    Skåne University Hospital, Department of Pediatrics, Lund, Sweden.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Casswall, Thomas H
    Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.
    Gustafsson, Britt
    Karolinska Institutet, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm, Sweden.
    Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft-Versus-Host Disease.2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 66, no 5, p. 744-750Article in journal (Refereed)
    Abstract [en]

    Objectives: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially life-threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI-GVHD and relevant differential diagnoses.

    Methods: Retrospective multicenter study based on histopathological re-evaluation of biopsies and hospital record data, collected from children with suspected GI-GVHD.

    Results: Forty-four children with 51 endoscopic occasions (81 procedures) were included. Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI-GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies collected from rectosigmoid-ileocolonic-, rectosigmoid-, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI-GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (P = 0.03).

    Conclusions: Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI-GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI-GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.

  • 50.
    Norstrom, Fredrik
    et al.
    Umea Univ, Sweden.
    van der Pals, Maria
    Lund Univ, Sweden.
    Myleus, Anna
    Umea Univ, Sweden.
    Hammarroth, Solveig
    Praktikertjanst, Sweden.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Isaksson, Anders
    Lund Univ, Sweden.
    Ivarsson, Anneli
    Umea Univ, Sweden.
    Carlsson, Annelie
    Lund Univ, Sweden.
    Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 67, no 1, p. 64-68Article in journal (Refereed)
    Abstract [en]

    Objectives: Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. Data are, however, lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. Methods: A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid-stimulating hormone and free thyroxine. Results: TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). Conclusions: The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicates that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

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