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  • 101. 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.

  • 102.
    Karlsson Videhult, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age2015In: International Journal of Food Sciences and Nutrition, ISSN 0963-7486, E-ISSN 1465-3478, Vol. 66, no 6, p. 686-691Article in journal (Refereed)
    Abstract [en]

    We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10 8 CFU from 4 to 13 months of age. At age 8-9 years, 120 children were reassessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.

  • 103.
    Karlsson Videhult, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age2015In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 54, no 3, p. 355-363Article in journal (Refereed)
    Abstract [en]

    PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers.

    METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting.

    RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05).

    CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.

  • 104. Koletzko, Berthold
    et al.
    Baker, Susan
    Cleghorn, Geoff
    Neto, Ulysses Fagundes
    Gopalan, Sarath
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Hock, Quak Seng
    Jirapinyo, Pipop
    Lonnerdal, Bo
    Pencharz, Paul
    Pzyrembel, Hildegard
    Ramirez-Mayans, Jaime
    Shamir, Raanan
    Turck, Dominique
    Yamashiro, Yuichiro
    Zong-Yi, Ding
    Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group.2005In: J Pediatr Gastroenterol Nutr, ISSN 0277-2116, Vol. 41, no 5, p. 584-99Article in journal (Refereed)
    Abstract [en]

    The Codex Alimentarius Commission of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) develops food standards, guidelines and related texts for protecting consumer health and ensuring fair trade practices globally. The major part of the world's population lives in more than 160 countries that are members of the Codex Alimentarius. The Codex Standard on Infant Formula was adopted in 1981 based on scientific knowledge available in the 1970s and is currently being revised. As part of this process, the Codex Committee on Nutrition and Foods for Special Dietary Uses asked the ESPGHAN Committee on Nutrition to initiate a consultation process with the international scientific community to provide a proposal on nutrient levels in infant formulae, based on scientific analysis and taking into account existing scientific reports on the subject. ESPGHAN accepted the request and, in collaboration with its sister societies in the Federation of International Societies on Pediatric Gastroenterology, Hepatology and Nutrition, invited highly qualified experts in the area of infant nutrition to form an International Expert Group (IEG) to review the issues raised. The group arrived at recommendations on the compositional requirements for a global infant formula standard which are reported here.

  • 105. Koletzko, Berthold
    et al.
    Fewtrell, Mary
    Gibson, Robert
    van Goudoever, Johannes B.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Szajewska, Hania
    Shamir, Raanan
    Core Data Necessary for Reporting Clinical Trials on Nutrition in Infancy2015In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 66, no 1, p. 31-35Article in journal (Refereed)
    Abstract [en]

    This paper presents an updated and revised summary of the 'core data set' that has been proposed to be recorded and reported in all clinical trials on infant nutrition by the recently formed Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). This core data set was developed based on a previous proposal by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition in 2003. It comprises confidential data to identify subjects and facilitate contact for further follow-up, data to characterize the cohort studied and data on withdrawals from the study, and some additional core data for all nutrition studies on preterm infants. We recommend that all studies on nutrition in infancy should collect and report this core data set to facilitate interpretation and comparison of results from clinical studies, and of systematic data evaluation and meta-analyses. Editors of journals publishing such reports are encouraged to require the reporting of the minimum data set described here either in the main body of the publication or as supplementary online material.

  • 106.
    K:son Blomquist, Hans
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Frängsmyr, Agneta
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Dermatology and Venerology.
    Bäck, Ove
    Dietary intake of vitamin D during the second half of infancy in Swedish infants2004In: Scandinavian Journal of Food & Nutrition, ISSN 1748-2976, Vol. 48, no 4, p. 173-177Article in journal (Refereed)
  • 107.
    Lagerqvist, C
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Juto, P
    Persson, L A
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Screening for adult coeliac disease - which serological marker(s) to use?2001In: J Intern Med, ISSN 0954-6820, Vol. 250, no 3, p. 241-8Article in journal (Refereed)
  • 108.
    Lagerqvist, Carina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlbom, Ingrid
    Hansson, Tony
    Jidell, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olcén, Per
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age.2008In: J Pediatr Gastroenterol Nutr, ISSN 1536-4801, Vol. 47, no 5, p. 428-35Article in journal (Other academic)
  • 109.
    Larsson, Christel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Moderately elevated body mass index is associated with metabolic variables and cardiovascular risk factors in Swedish children2011In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, no 1, p. 102-108Article in journal (Refereed)
    Abstract [en]

    Aim: To evaluate associations between anthropometrics and metabolic variables as well as cardiovascular risk factors among children.

    Methods: Subjects were recruited from a cohort of 274 healthy children in Umeå, Sweden. Anthropometric measures, blood pressure and venous blood samples were collected at age 10 years and simultaneously from parents.

    Results: Altogether 144 children (53%), 142 mothers and 123 fathers participated. The prevalence of overweight and obesity among the children was 18 and 2%, respectively. Overweight children (above age- and sex-specific cut offs corresponding adult BMI ≥ 25 kg/m2), compared to normal weight children, had significantly higher BMI already during infancy and higher S-insulin and Homeostatic Model Assessment (HOMA) index at 10 years. The children’s BMI was positively associated with waist (boys’ r = 0.67, girls’ r = 0.81), hip (r = 0.68), waist/hip ratio (girls’ r = 0.37), waist/height ratio (boys’ r = 0.59, girls’ r = 0.80), sagittal abdominal diameter (r = 0.75), S-insulin (r = 0.45), HOMA index (r = 0.49), systolic blood pressure (r = 0.24), mothers’ BMI (girls’ r = 0.42) and mothers’ waist (girls’ r = 0.42).

    Conclusion: Children at 10 years of age with moderately elevated BMI had higher levels of some metabolic variables and cardiovascular risk factors than did normal weight children, and there was a correlation between BMI and some metabolic variables as well as cardiovascular risk factors.

  • 110.
    Larsson, Christel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Lind, T
    Hernell, O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Anthropometric data and metabolic risk factors in Swedish children2008In: The 9th Nordic Nutrition Conference, Copenhagen, Denmark, 2008Conference paper (Other academic)
  • 111. Lee, Hanna
    et al.
    Padhi, Emily
    Hasegawa, Yu
    Larke, Jules
    Parenti, Mariana
    Wang, Aidong
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Slupsky, Carolyn
    Compositional dynamics of the milk fat globule and its role in infant development2018In: Frontiers in Pediatrics, ISSN 2296-2360, Vol. 6, article id 313Article, review/survey (Refereed)
    Abstract [en]

    Human milk is uniquely optimized for the needs of the developing infant. Its composition is complex and dynamic, driven primarily by maternal genetics, and to a lesser extent by diet and environment. One important component that is gaining attention is the milk fat globule (MFG). The MFG is composed of a triglyceride-rich core surrounded by a tri-layer membrane, also known as the milk fat globule membrane (MFGM) that originates from mammary gland epithelia. The MFGM is enriched with glycerophospholipids, sphingolipids, cholesterol, and proteins, some of which are glycosylated, and are known to exert numerous biological roles. Mounting evidence suggests that the structure of the MFG and bioactive components of the MFGM may benefit the infant by aiding in the structural and functional maturation of the gut through the provision of essential nutrients and/or regulating various cellular events during infant growth and immune education. Further, antimicrobial peptides and surface carbohydrate moieties surrounding the MFG might have a pivotal role in shaping gut microbial populations, which in turn may promote protection against immune and inflammatory diseases early in life. This review seeks to: (1) understand the components of the MFG, as well as maternal factors including genetic and lifestyle factors that influence its characteristics; (2) examine the potential role of this milk component on the intestinal immune system; and (3) delineate the mechanistic roles of the MFG in infant intestinal maturation and establishment of the microbiota in the alimentary canal.

  • 112.
    Li, X
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Chen, R
    Lindquist, S
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Expression of cellular inhibitor of apoptosis protein-2 in human subcutaneous and omental adipose tissue2004In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 28, no 3, p. 352-356Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In the current study, we addressed the question if there is depot-specific expression of cellular inhibitor of apoptosis protein-2 (cIAP2) already in childhood and if the relative expression changes with age in parallel with increasing risk of developing visceral adiposity. SUBJECTS: Paired samples of human omental (OM) and subcutaneous (SC) adipose tissue were obtained from 23 patients (12 children and 11 adults). METHOD: mRNA level of cIAP2 was determined using reverse transcription-polymerase chain reaction (RT-PCR) and protein expression confirmed by Western blotting. Apoptosis indices were determined by terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL). RESULTS: cIAP2 mRNA was 1.51-fold higher in OM compared with SC adipose tissue (OM>SC in 20 of 23 subjects; P<0.001). Western blots were in agreement with mRNA expression (OM>SC in nine of 10 subjects, P<0.01). Subgroup analyses showed depot difference in both children (P<0.01) and adults (P<0.05). Contrary to the hypothesis, depot-specific difference in mRNA expression of cIAP2 was significantly higher in children compared with adults (P<0.05). We were unable to demonstrate any difference in the basal apoptosis rate between adipocytes from the two depots. There was no significant association between cIAP2 mRNA expression and BMI or sex. CONCLUSIONS: The results demonstrated for the first time that depot-specific difference in cIAP2 expression is consistent in children and adults. This suggests that the higher expression of cIAP2 in OM than in SC adipose tissue may be due to inherent properties of cells from the two depots. The more pronounced depot-specific difference in children than in adults may reflect a net gain in visceral adipose tissue during growth.

  • 113.
    Li, X.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Chen, R.
    Children's Research Institute of Nanjing Medical University, Nanjing, China.
    Myrnäs, Torbjörn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Angsten, G.
    Department of Pediatric Surgery, University Children's Hospital, Uppsala, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Depot-specific messenger RNA expression of 11 beta-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 5, p. 820-828Article in journal (Refereed)
    Abstract [en]

    Objective: To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11-hydroxysteroid dehydrogenase type 1 (11-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children.

    Design: Paired biopsies (SC and OM) were obtained from 54 children (age 0.17–16 years, body mass index (BMI) 12.5–28.3 kg/m2, BMI standard deviation score (SDS) -2.5–4.5) and 16 adults (age 27–79 years, BMI 19–46 kg/m2) undergoing open abdominal surgery. mRNA levels of 11-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR).

    Results: 11-HSD1 mRNA level was higher in OM than in SC (P<0.05), whereas leptin mRNA was higher in SC than in OM (P<0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11-HSD1 mRNA in SC was positively associated with BMI SDS (P<0.05), whereas in OM it was positively associated with age (P<0.05). The association between 11-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC:P<0.001, OM: P<0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11-HSD1 (P<0.05) and leptin (P<0.001) in SC. When normal weight and overweight children were analyzed separately, 11-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P<0.05).

    Conclusion: There are depot-specific differences in mRNA levels of 11-HSD1 and leptin in children and adults. The positive association of 11-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.

  • 114.
    Li, Xiaonan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Angsten, Gertrud
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Yi, Jun
    Olsson, Tommy
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Adiponectin and peroxisome proliferator-activated receptor gamma expression in subcutaneous and omental adipose tissue in children.2008In: Acta Paediatr, ISSN 0803-5253, Vol. 97, no 5, p. 630-5Article in journal (Other academic)
  • 115.
    Li, Xiaonan
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Lowe, Mark
    Noppa, Laila
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Bile Salt-Stimulated Lipase and Pancreatic Lipase-Related Protein 2 Are the Dominating Lipases in Neonatal Fat Digestion in Mice and Rats.2007In: Pediatr Res, ISSN 0031-3998Article in journal (Refereed)
    Abstract [en]

    During infancy, the basic conditions for digestion of dietary fat differ from later in life. The bile salt-stimulated lipase (BSSL) is an enzyme expressed in the exocrine pancreas and in some species (including human) also in the lactating mammary gland and secreted with the milk. The aim of this study was to compare the ontogeny of four pancreatic lipases [BSSL, pancreatic triglyceride lipase (PL), pancreatic lipase-related protein 2 (PLRP2), and phospholipase A2 (PLA2)] in one species that supplies BSSL with milk (the mouse) and one that does not (the rat). We followed expression of the four pancreatic lipases from postnatal d 1 until after weaning in both species. We found that BSSL and PLRP2, two lipases with broad substrate specificity, dominated. It was not until weaning that significant expression of PL and PLA2 were induced. Thus, BSSL and PLRP2 seem to be responsible for fat digestion as long as milk is the main food. Moreover, the early temporal pattern of BSSL expression differed between species. We speculate that the milk-borne BSSL is able to compensate for a slower ontogeny of pancreatic BSSL expression in the mouse.

    PMID: 17805199 [PubMed - as supplied by publisher]

  • 116. Li, Xiaonan
    et al.
    Peng, Yongmei
    Li, Zailing
    Christensen, Britt
    Heckmanns, Anne B.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Feeding Infants Formula With Probiotics or Milk Fat Globule Membrane: A Double-Blind, Randomized Controlled Trial2019In: Frontiers in Pediatrics, ISSN 2296-2360, Vol. 7, article id 347Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM).

    Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year.

    Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048).

    Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.

  • 117.
    Lif Holgerson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Harnevik, L
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Tanner, ACR
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Mode of birth delivery affects oral microbiota in infants2011In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 90, no 10, p. 1183-1188Article in journal (Refereed)
    Abstract [en]

    Establishment of the microbiota of the gut has been shown to differ between infants delivered by Caesarian section (C-section) and those delivered vaginally. The aim of the present study was to compare the oral microbiota in infants delivered by these different routes. The oral biofilm was assayed by the Human Oral Microbe Identification Microarray (HOMIM) in healthy three-month-old infants, 38 infants born by C-section, and 25 infants delivered vaginally. Among over 300 bacterial taxa targeted by the HOMIM microarray, Slackia exigua was detected only in infants delivered by C-section. Further, significantly more bacterial taxa were detected in the infants delivered vaginally (79 species/species clusters) compared with infants delivered by C-section (54 species/species clusters). Multivariate modeling revealed a strong model that separated the microbiota of C-section and vaginally delivered infants into two distinct colonization patterns. In conclusion, our study indicated differences in the oral microbiota in infants due to mode of delivery, with vaginally delivered infants having a higher number of taxa detected by the HOMIM microarray.

  • 118.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Stenlund, Hans
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, Lars-Åke
    Dietary iron intake is positively associated with hemoglobin concentration during infancy but not during the second year of life.2004In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 134, no 5, p. 1064-1070Article in journal (Refereed)
    Abstract [en]

    Iron status during infancy and early childhood reflects highly dynamic processes, which are affected by both internal and external factors. The regulation of iron metabolism seems to be subjected to developmental changes during infancy, although the exact nature of these changes and their implications are not fully understood. We wanted to explore the association between dietary iron intake and indicators of iron status, and to assess temporal changes in these variables. This was done by secondary analysis of data from a recently conducted dietary intervention trial in which healthy, term, well-nourished infants were randomly assigned to consume iron-fortified infant cereals with regular or low phytate content, or iron-fortified infant formula. Dietary iron intake from 6 to 8 mo and from 9 to 11 mo was associated with hemoglobin (Hb) concentration at 9 mo (r = 0.27, P < 0.001) and 12 mo (r = 0.21, P = 0.001), respectively, but iron intake from 12 to 18 mo was not associated with Hb at 18 mo. In contrast, iron intake from 6 to 11 mo was not associated with serum ferritin (S-Ft) at 9 or 12 mo, whereas iron intake from 12 to 17 mo was positively associated with S-Ft at 18 mo (r = 0.14, P = 0.032). These shifts in associations between dietary iron intake, and Hb and S-Ft, respectively, may be due to developmental changes in the channeling of dietary iron to erythropoiesis relative to storage, in the absence of iron deficiency anemia. These observations should be taken into consideration when evaluating iron nutritional status during infancy and early childhood.

  • 119.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ulrica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindberg, Lene
    Lonnerdal, Bo
    Tennefors, Catharina
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Study protocol: optimized complementary feeding study (OTIS): a randomized controlled trial of the impact of a protein-reduced complementary diet based on Nordic foods2019In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, article id 134Article in journal (Refereed)
    Abstract [en]

    Background: What we eat as infants and children carries long-term consequences. Apart from breastfeeding, the composition of the complementary diet, i.e. the foods given to the infant during the transition from breast milk/infant formula to regular family foods affects the child's future health. A high intake of protein, a low intake of fruits, vegetables and fish and an unfavorable distribution between polyunsaturated and saturated fats are considered to be associate with health risks, e.g. obesity, type 2 diabetes and dyslipidemia later in life.

    Methods: In a randomized, controlled study from 6 to 18months of age we will compare the currently recommended, Swedish complementary diet to one based on Nordic foods, i.e. an increased intake of fruits, berries, vegetables, tubers, whole-grain and game, and a lower intake of sweets, dairy, meat and poultry, with lower protein content (30% decrease), a higher intake of vegetable fats and fish and a systematic introduction of fruits and greens. The main outcomes are body composition (fat and fat-free mass measured with deuterium), metabolic and inflammatory biomarkers (associated with the amount of body fat) in blood and urine, gut microbiota (thought to be the link between early diet, metabolism and diseases such as obesity and insulin resistance) and blood pressure.We will also measure the participants' energy and nutrient intake, eating behavior and temperament through validated questionnaires, acceptance of new and unfamiliar foods through video-taped test meals and assessment of cognitive development, which we believe can be influenced through an increased intake of fish and milk fats, notably milk fat globule membranes (MFGM).

    Discussion: If the results are what we expect, i.e. improved body composition and a less obesogenic, diabetogenic and inflammatory metabolism and gut microbiota composition, a more sustainable nutrient intake for future health and an increased acceptance of healthy foods, they will have a profound impact on the dietary recommendations to infants in Sweden and elsewhere, their eating habits later in life and subsequently their long-term health.

    Trial registration: NCT02634749. Registration date 18 December 2015.

  • 120.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lönnerdal, Bo
    Persson, Lars-Åke
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Tennefors, Catharina
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Effects of weaning cereals with different phytate contents on hemoglobin, iron stores, and serum zinc: a randomized intervention in infants from 6 to 12 mo of age2003In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 78, no 1, p. 168-175Article in journal (Refereed)
    Abstract [en]

    Background: Weaning foods frequently contain phytate, an inhibitor of iron and zinc absorption, which may contribute to the high prevalence of iron and zinc deficiency seen in infancy.

    Objective: The objective was to investigate whether either an extensive reduction in the phytate content of infant cereals or the use of milk-based, iron-fortified infant formula would improve iron and zinc status in infants.

    Design: In a double-blind design, infants (n = 300) were randomly assigned to 3 cereal groups from 6 to 12 mo of age: commercial milk-based cereal drink (MCD) and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milk-based infant formula and porridge with the usual phytate content (IF group). Venous blood samples were collected at 6 and 12 mo. Dietary intake was recorded monthly. After the intervention, 267 infants remained in the analysis.

    Results: Hemoglobin concentrations of < 110 g/L, serum ferritin concentrations of < 12 µg/L, and serum zinc concentrations of < 10.7 µmol/L had overall prevalences at baseline and 12 mo of 28% and 15%, 9% and 18%, and 22% and 27%, respectively. After the intervention, there were no significant differences in any measure of iron or zinc status between the CC and the PR groups. However, hemoglobin was significantly higher (120 g/L compared with 117 g/L; P = 0.012) and the prevalence of anemia was lower (13% compared with 23%; P = 0.06) in the PR group than in the IF group, which could be explained by differences in daily iron intake between the 2 groups.

    Conclusion: Extensive reduction in the phytate content of weaning cereals had little long-term effect on the iron and zinc status of Swedish infants.

  • 121.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Persson, L- A
    Lönnerdal, B
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of weaning cereals with different phytate content on growth, development and morbidity: a randomized intervention trial in infants from 6 to 12 months of age.2004In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 12, p. 1575-1582Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Phytate decreases iron and zinc bioavailability and contributes to deficiencies of iron and zinc, potentially causing anaemia, poor psychomotor development, impaired growth and increased risk of diarrhoea and respiratory infections. AIM: To investigate whether a reduced dietary intake of phytate, either via extensively phytate-reduced infant cereals [milk cereal drinks (MCDs) and porridge] or a milk-based infant formula, would improve growth and development and reduce morbidity in infants. DESIGN: Infants (n = 300) were, in a double-blind design, randomized to three diet intervention groups from 6 to 12 mo of age-commercial MCD and porridge (CC group), phytate-reduced MCD and phytate-reduced porridge (PR group), or milkbased infant formula and porridge with regular phytate content (IF group)-then followed until 18 mo. Dietary intake, anthropometry, development (Bayley Scales of Infant Development) and episodes of infectious diseases were registered. Results: There were no significant differences between study groups in growth, development or morbidity until 12 mo of age. The IF group had a 77% higher risk (95% CI: 1.05-2.97) of diarrhoea compared to the PR group during the 12-17-mo period. Infants with haemoglobin concentration (Hb) < 110 g/l at 12 mo had lower attained weight at 18 mo (11.14 kg vs 11.73 kg, p = 0.012). Infants with serum zinc (S-Zn) <10.7 pmol/l at 12 mo had higher risk of respiratory infections (RR = 1.74, 95% CI: 1.19-2.56) compared to controls. CONCLUSION: Phytate reduction had no effect on growth, development or incidence of diarrhoeal or respiratory infections. Infants with low Hb or low S-Zn may be at higher risk of poor growth and respiratory infections, even in this high-income population.

  • 122.
    Lindquist, Susanne
    et al.
    Umeå University. Lipum AB, Umeå, Sweden.
    Alenius, Gerd-Marie
    Umeå University.
    Berntson, Lillemor
    Umeå University.
    Rantapää-Dahlqvist, Solbritt
    Umeå University.
    Lundberg, Lennart
    Wang, Yuhang
    Umeå University.
    Hernell, Olle
    Umeå University. Lipum AB, Umeå, Sweden.
    A novel target for treatment of inflammatory joint diseases2019In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 1525-1526Article in journal (Other academic)
    Abstract [en]

    Background: The bile salt-stimulated lipase (BSSL) is a hitherto unrecognized player in inflammation. Animals devoid of BSSL (knockout mice) are protected from developing collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA), and antibodies directed towards BSSL has been proven to prevent or mitigate arthritis in mouse and rat arthritis models1. In humans, BSSL is present in blood2 and accumulate at sites of inflammation. Patients with acute pancreatitis have significantly increased plasma BSSL levels compared to healthy controls. Whether BSSL in blood originates from pancreas, inflammatory cells, or both remains to be elucidated.

    Objectives: To determine BSSL concentration in blood samples from patients with inflammatory joint disorders and to evaluate possible relationships between circulating BSSL levels and disease-activity variables.

    Methods: BSSL concentrations in plasma or serum were determined in patients with rheumatoid arthritis (RA), psoriasis arthritis (PsA), and juvenile idiopathic arthritis (JIA) by a sandwich enzyme-linked immunosorbent assay (ELISA). Correlations between BSSL concentrations and disease activity score, erythrocyte sedimentation rate (ESR), blood levels of C-reactive protein (CRP), S100A8/9, leukocyte- and neutrophil counts, proinflammatory cytokines and chemokines were analyzed using Spearman rank-order correlation.

    Results: Significant correlations between BSSL concentration in plasma and disease activity score (DAS28, rS=0.31, p=0.007), ESR (rS=0.58, p<0.000), CRP (rS=0.42, p=0.012), leukocytes (rS=0.66, p<0.000), and neutrophils (rS=0.71, p<0.000) were found in RA. The BSSL plasma concentration decreased with duration of treatment with the TNFα inhibitor infliximab, in parallel with decreasing DAS28 score.

    BSSL concentration was significantly higher in sera from PsA patients with both oligo- and polyarthritis compared with healthy controls. Moreover, BSSL concentration in serum correlated significantly with S100A8/A9 and CRP concentrations (rS=0.54, p<0.001 and rS=0.49, p<0.001, respectively). No correlation between levels of BSSL and cytokines or chemokines were found in RA or PsA plasma or serum, respectively.

    In JIA, levels of BSSL in serum correlated significantly with JIA disease activity score (JADAS27) (rS=0.26, p=0.007), ESR (rS=0.47, p<0.000), and leukocytes (rS=0.32, p<0.000).

    Conclusion: BSSL concentration in serum and plasma correlated with disease activity in patients with inflammatory joint disorders, i.e. RA, PsA and JIA. These data in humans support the relevance of our previous studies in rodents and therefore also our hypothesis 1 that BSSL is a novel target for treatment of inflammatory diseases.

  • 123.
    Lindquist, Susanne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lundberg, Lennart
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, p. e47006-Article in journal (Refereed)
    Abstract [en]

    Objective: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL), in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. Methods: Collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT) mice with BSSL-deficient 'knock-out' (BSSL-KO) and BSSL-heterozygous (BSSL-HET) littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. Results: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. Conclusion: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

  • 124.
    Lindquist, Susanne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lipid digestion and absorption in early life: an update.2010In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 13, no 3, p. 314-20Article in journal (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: To highlight our understanding of digestion and absorption of dietary lipids in newborn infants, and specifically how these processes differ from those in children and adults. RECENT FINDINGS: The intestinal concentration of pancreatic triglyceride lipase (PTL) and bile salts is lower in newborns compared to later in life. Instead the PTL-related protein 2 and bile salt-stimulated lipase (BSSL) are the key enzymes secreted from pancreas, which in concerted action with gastric lipase operate to achieve efficient fat absorption during infancy. BSSL is also present in human milk which affects fat absorption and growth in breast-fed preterm infants. Under conditions of low luminal bile salt concentrations fat absorption is likely to occur from liquid crystalline product phases, which may result in absorption from an extended part of the small intestinal mucosal surfaces compared to adults. Chylomicron assembly and secretion also seem to adapt to the specific situation of the newborn. SUMMARY: Both fat digestion and product absorption are different in newborn infants compared to adults; other lipases are used for digestion and different physical-chemical phases may be used for product absorption. Why these differences occur is still an unsolved question of considerable importance to neonatal nutrition.

  • 125. Lönnerdal, Bo
    et al.
    Bergström, S
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hjalmarsson, K
    Sundqvist, A K
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cloning and sequencing of a cDNA encoding human milk beta-casein.1990In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 269, no 1, p. 153-6Article in journal (Refereed)
    Abstract [en]

    A cDNA of 1065 bp encoding the human milk beta-casein was cloned and sequenced using a synthetic oligodeoxyribonucleotide probe and a human mammary gland library. The nucleotide (nt) sequence contained an open reading frame sufficient to encode the entire amino-acid (aa) sequence of a beta-casein precursor protein consisting of 210 aa and a signal peptide of 15 aa. The nt sequence shows 45-62% homology to those of bovine, ovine, rat, and mouse beta-caseins. The highly phosphorylated site, which is responsible for the calcium-binding capacity of beta-casein, the signal peptide, and a sequence encoding for an inhibitor to the angiotensin-converting enzyme seem highly conserved among the beta-caseins with known sequences.

  • 126.
    Lönnerdal, Bo
    et al.
    Department of Nutrition, University of California, Davis, CA.
    Georgieff, Michael K.
    University of Minnesota Masonic Children's Hospital, Division of Neonatology, University of Minnesota School of Medicine, Minneapolis, MN.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant2015In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 167, no 4, Supplement, p. S8-S14Article in journal (Refereed)
  • 127. 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.

  • 128.
    Lönnerdal, Bo
    et al.
    Department of Nutrition, University of California, Davis, Calif., USA.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Homeostatic regulation of iron and its role in normal and abnormal iron status in infancy and childhood2011In: Annales Nestlé, ISSN 1661-4011, Vol. 68, no 3, p. 96-104Article in journal (Refereed)
    Abstract [en]

    Iron is important in neurodevelopment and cognitive function, and globally preventing iron deficiency and iron deficiency anemia remains a high priority. Term breast-fed infants and infants fed an iron-fortified formula usually have a satisfactory iron status during the first 6 months of life, but there are still ambiguities in assessing iron status in infants and how to properly meet their iron requirements. This is particularly evident for preterm infants, who are born with low iron stores, and for whom recommendations for iron provision vary considerably. In part, this may be due to immaturity in the regulation of iron homeostasis in young infants. Whereas 9-month-old infants appear to be able to downregulate iron absorption when being iron replete, 6-month-old infants cannot do this. Iron may be provided as drops or in iron-fortified products, but the forms provided may be metabolized differently, and excess iron in drops may cause adverse effects, possibly due to a limited ability to regulate iron absorption in young infants. Adverse effects are manifested by decreased growth: in well-nourished infants by reduced gain in length, in poorly nourished populations by lower gain in weight. The mechanism behind the decreased growth is not known, but it may involve free radical-mediated effects of iron or an interaction with zinc absorption/homeostasis. It therefore seems that iron drops should not be given to iron-replete infants.

  • 129. Lönnerdal, Bo
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Under- and overnutrition of iron in infancy and early childhood2014In: The Nest, ISSN 1270–9743, Vol. 35, p. 6-7Article in journal (Other academic)
  • 130.
    Myleus, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Persson, Lars-åke
    Women's and Children's Health, International Maternal and Child Health, Uppsala University, Uppsala, Sweden.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Early vaccinations are not risk factors for Celiac Disease2012In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 130, no 1, p. E63-E70Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk.

    METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guerin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis.

    RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years.

    CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies. Pediatrics 2012;130:e63-e70

  • 131.
    Myléus, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Persson, Lars-Åke
    International Maternal and Child Health, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Early infections are associated with increased risk for celiac disease: an incident case-referent study2012In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 12, no 1, p. 194-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Celiac disease is defined as a 'chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Sweden has experienced an "epidemic" of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic.

    METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child's general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents.

    RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001).

    CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

  • 132.
    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.

  • 133. Naarding, Marloes A
    et al.
    Dirac, Annette M
    Ludwig, Irene S
    Speijer, Dave
    Lindquist, Susanne
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Vestman, Eva-Lotta
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Stax, Martijn J
    Geijtenbeek, Teunis B H
    Pollakis, Georgios
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Paxton, William A
    Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells.2006In: Antimicrob Agents Chemother, ISSN 0066-4804, Vol. 50, no 10, p. 3367-74Article in journal (Refereed)
    Abstract [en]

    A wide range of pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, Mycobacterium, Leishmania, and Helicobacter pylori, can interact with dendritic cell (DC)-specific ICAM3-grabbing nonintegrin (DC-SIGN), expressed on DCs and a subset of B cells. More specifically, the interaction of the gp120 envelope protein of HIV-1 with DC-SIGN can facilitate the transfer of virus to CD4+ T lymphocytes in trans and enhance infection. We have previously demonstrated that a multimeric LeX component in human milk binds to DC-SIGN, preventing HIV-1 from interacting with this receptor. Biochemical analysis reveals that the compound is heat resistant, trypsin sensitive, and larger than 100 kDa, indicating a specific glycoprotein as the inhibitory compound. By testing human milk from three different mothers, we found the levels of DC-SIGN binding and viral inhibition to vary between samples. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and matrix-assisted laser desorption ionization analysis, we identified bile salt-stimulated lipase (BSSL), a Lewis X (LeX)-containing glycoprotein found in human milk, to be the major variant protein between the samples. BSSL isolated from human milk bound to DC-SIGN and inhibited the transfer of HIV-1 to CD4+ T lymphocytes. Two BSSL isoforms isolated from the same human milk sample showed differences in DC-SIGN binding, illustrating that alterations in the BSSL forms explain the differences observed. These results indicate that variations in BSSL lead to alterations in LeX expression by the protein, which subsequently alters the DC-SIGN binding capacity and the inhibitory effect on HIV-1 transfer. Identifying the specific molecular interaction between the different forms may aid in the future design of antimicrobial agents.

  • 134.
    Nordyke, Katrina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Olsson, Cecilia
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Epidemiological research drives a paradigm shift in complementary feeding: the celiac disease story and lessons learnt2010In: Drivers of Innovation in Pediatric Nutrition / [ed] Koletzko B,Koletzko S,Ruemmele F, S. Karger, 2010, p. 65-79Conference paper (Other academic)
    Abstract [en]

    Breast milk is the initial natural food for infants, but already during the second half year complementary feeding is essential. Epidemiological research, first on celiac disease and later on atopic diseases, has driven a paradigm shift with respect to most favorable age to introduce complementary feeding. Simplified, this implies a shift from later to earlier introduction, which is now taken into account in recommendations on infant feeding. Complementary feeding, including all foods, should not be initiated for any infant before 4 months of age, and not later than around 6 months, including infants with elevated disease risk (e.g. for celiac disease or atopic diseases). Motivating reasons could be that ongoing breastfeeding provides an 'immunological umbrella' and/ or a different age interval gives a 'window of opportunity' for developing oral tolerance towards gluten and other food antigens. This will for some infants be in conflict with recent WHO recommendations on exclusive breastfeeding for 6 months. Epidemiology has evolved over time and could, if increasingly used, contribute even more to innovations in pediatric nutrition and other phenomena related to population health.

  • 135.
    Olivecrona, Gunilla
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Ehrenborg, Ewa
    Semb, Henrik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Makoveichuk, Elena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lindberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hayden, Michael R
    Gin, Peter
    Davies, Brandon S J
    Weinstein, Michael M
    Fong, Loren G
    Beigneux, Anne P
    Young, Stephen G
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia2010In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 51, no 6, p. 1535-1545Article in journal (Refereed)
    Abstract [en]

    We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. Lipoprotein lipase (LPL) activity and mass in pre- and post-heparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [35S]Methionine incorporation studies on adipose tissue showed that newly synthesized LPL was normal in size and normally glycosylated. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids being derived from de novo lipogenesis, rather than from the plasma lipoproteins. Given the delayed release of LPL into the plasma after heparin, we suspected that the chylomicronemia might be caused by mutations in GPIHBP1. Indeed, all three affected siblings were compound heterozygotes for missense mutations involving highly conserved cysteines in the Ly6 domain of GPIHBP1 (C65S and C68G). The mutant GPIHBP1 proteins reached the surface of transfected CHO cells but were defective in their ability to bind LPL (as judged by both cell-based and cell-free LPL binding assays). Thus, the conserved cysteines in the Ly6 domain are crucial for GPIHBP1 function.

  • 136.
    Olsson, Cecilia
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Lönnberg, Göran
    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.
    Difference in celiac disease risk between Swedish birth cohorts suggests an opportunity for primary prevention2008In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 122, no 3, p. 528-34Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Sweden experienced a unique epidemic of celiac disease in children <2 years of age. The epidemic was partly explained by changes in infant feeding over time and indicated a multifactorial pathogenesis. The main aim of this study was to analyze celiac disease risk in epidemic and postepidemic birth cohorts up to preschool age, to explore further the opportunity for primary prevention. METHODS: A population-based incidence register of celiac disease in children covering the entire nation from 1998 to 2003 and part of the country back to 1973 was analyzed. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria for celiac disease were used. The annual incidence rate for each age group and the cumulative incidence according to age for each birth cohort were calculated. RESULTS: A considerable difference in cumulative incidences of celiac disease at comparable ages was demonstrated between birth cohorts from the epidemic and postepidemic periods. The difference persisted during the preschool years, although it decreased somewhat with age. During the last years of the follow-up period, there was again a successive increase in incidence rate among children <2 years of age. CONCLUSIONS: The difference in celiac disease risk between birth cohorts at comparable ages suggests an opportunity for primary prevention. This highlights the importance of further exploring the role of infant feeding and exogenous factors besides dietary gluten that might initiate or prevent disease development. Moreover, on the basis of postepidemic incidence trends, we speculate that the Swedish epidemic might not have been as unique as thought previously, although its magnitude was striking.

  • 137.
    Olsson, Cecilia
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Lönnberg, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    The Swedish epidemic of celiac disease: a follow up2006In: The XIIth International Celiac Disease Symposium, 2006Conference paper (Other (popular science, discussion, etc.))
  • 138.
    Olsson, Cecilia
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Regional variation in celiac disease risk within Sweden revealed by the nationwide prospective incidence register.2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 2, p. 337-342Article in journal (Refereed)
    Abstract [en]

    AIM: To determine if there is any regional celiac disease (CD) risk variation in the Swedish childhood population. METHODS: Prospective nationwide Swedish incidence register of CD in children 0-15 years of age, with the present analysis covering the period from 1998 to 2003. ESPGHAN diagnostic criteria for CD were used. Regions were classified according to the Nomenclature of Territorial Units for Statistics. The incidence rate for each region, gender, age group and year of diagnosis was calculated. RESULTS: A regional variation in CD risk was demonstrated. The childhood populations in 'West Sweden' and 'Småland and the islands', situated in the southern part of the country, had a significantly higher incidence rate compared to in 'North Middle Sweden' and 'Stockholm', situated in the central part. This regional variation was not explained by variations in risk by gender, age at diagnosis or year of diagnosis. CONCLUSION: The Swedish regional variation in CD risk supports multifactorial disease aetiology. Continued efforts are warranted to define factors, besides gluten exposure, that modulate CD risk.

  • 139.
    Ou, Gangwei
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hörstedt, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Forsberg, Göte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Drobni, Mirva
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease2009In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 12, p. 3058-3067Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. METHODS: Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. RESULTS: The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.

  • 140. Perlhagen, John
    et al.
    Flodmark, Carl-Erik
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    [Obesity in children--prevention is the only realistic solution of the problem]2007In: Lakartidningen, ISSN 0023-7205, Vol. 104, no 3, p. 138-41Article in journal (Other academic)
    Abstract [sv]

    [Article in Swedish]

  • 141. Persson, L A
    et al.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Breast-feeding protects against celiac disease in childhood--epidemiological evidence.2002In: Adv Exp Med Biol, ISSN 0065-2598, Vol. 503, p. 115-23Article in journal (Refereed)
  • 142.
    Pietz, Grzegorz
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    De, Rituparna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sjöberg, Veronika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Immunopathology of childhood celiac disease: Key role of intestinal epithelial cells2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, article id e0185025Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria.

    METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells.

    RESULTS: More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells.

    CONCLUSION: A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

  • 143.
    Pietz, Grzegorz
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Israelsson, Anne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nyunt Wai, Sun
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Influences of celiac disease associated bacteria on functions of intestinal epithelium: an in vitro studyManuscript (preprint) (Other academic)
  • 144.
    Pietz, Grzegorz
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sjöberg, Veronika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Gene expression profile of the epithelial reaction in childhood Celiac diseaseManuscript (preprint) (Other academic)
  • 145. Przyrembel, Hildegard
    et al.
    Antoine, Jean Michel
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Turck, D
    Underwood, E
    Secretin, M C
    From innovation to implementation.2005In: Adv Exp Med Biol, ISSN 0065-2598, Vol. 569, p. 49-53Article in journal (Other academic)
    Abstract [en]

    Requirements for the safety and nutritional adequacy of infant formula are set by legislation and aim for the best possible substitute for human milk with regard to growth, development and biological effects. This is, however, a continuous process and has to be supported by science-driven innovative activities of manufacturers and be confirmed by adequate clinical studies performed according to agreed standards.

  • 146. Rioux, France M
    et al.
    Lindmark, Gunilla
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Does inadequate maternal iron or DHA status have a negative impact on an infant's functional outcomes?2006In: Acta Paediatr, ISSN 0803-5253, Vol. 95, no 2, p. 137-44Article in journal (Other academic)
    Abstract [en]

    Marginal intake of iron and omega-3 long-chain fatty acids (DHA) is prevalent among pregnant women. It is not clear to what extent poor iron or DHA status during pregnancy impacts on an infant's functional outcomes. A few studies suggest that inadequate maternal iron or DHA status may be associated with suboptimal functional outcomes in infants. In addition, there is a lack of prospective studies using randomized, double-blind design or experimental studies with appropriate animal models. Although both nutrients are involved in early brain development and their metabolism is interrelated, no study has examined the interaction between iron and omega-3 fatty acids during pregnancy. CONCLUSION: Long-term studies on large cohorts of pregnant women and their infants are needed to determine whether inadequate iron or DHA status during pregnancy is detrimental to infant neurodevelopment.

  • 147.
    Sandström, Olof
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Graverholt, Gitte
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of alpha-lactalbumin-enriched formula containing different concentrations of glycomacropeptide on infant nutrition.2008In: Am J Clin Nutr, ISSN 0002-9165, Vol. 87, no 4, p. 921-8Article in journal (Other academic)
  • 148.
    Sandström, Olof
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Depertment of Clinical Sciences, Pediatrics, Lunds university.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Högberg, Lotta
    Department of Clinical and Experimental Medicine, Linköping University.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in a sequential testing2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 4, p. 472-476Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening.

    Methods: Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted.

    Results: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies.

    Conclusions: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.

  • 149. Shamir, Raanan
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Leshno, Moshe
    Cost-effectiveness analysis of screening for celiac disease in the adult population.2006In: Med Decis Making, ISSN 0272-989X, Vol. 26, no 3, p. 282-93Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Celiac disease (CD) is common and, when undiagnosed, may result in increased mortality, suggesting that mass screening could be justified. The authors examined the cost-effectiveness (CE) of such an approach, assuming a higher mortality rate in undiagnosed CD and that adhering to a gluten-free diet (GFD) reduces the mortality rate. METHODS: The authors developed a state transition Markov model, evaluating the CE of screening an entire population at the age of 18. Screening strategies included no screening v. screening by IgA antiendomysial antibodies (EMA), IgA human antitissue transglutaminase antibodies (TTG), and TTG verified by EMA. All strategies were examined with and without evaluation for IgA deficiency, and they all included an intestinal biopsy. Effects of variables were examined using sensitivity analysis. Effectiveness was assessed by life expectancy for each strategy and the incremental average CE ratio for each. RESULTS: Base-case analysis revealed US$49,491 and US$572,616 per life year gained for screening compared to no screening using EMA or TTG, respectively. The CE of screening with EMA was most influenced by the prevalence of CD and the standardized mortality ratio (SMR) for untreated CD patients. Screening was cost-effective in populations with a relatively high prevalence of CD or when the SMR for untreated CD patients was higher than 1.5. The model was insensitive to changes in the cost of serological markers and diagnostic endoscopy. CONCLUSION: Assuming an SMR of 1.5 or higher for untreated CD patients, mass screening for CD is cost-effective in populations with a relatively high prevalence of CD over a wide range of ages at screening. From a CE perspective, EMA is the preferred serological marker for mass screening. Screening for CD would be justified only if the uncertainties regarding the validity of our assumptions are substantiated.

  • 150.
    Silfverdal, Sven Arne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Livsmedelstillsatser kan ökahyperaktivitet hos barn: Resultat från brittisk studie stärker sambandet2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 6, p. 354-355Article in journal (Other academic)
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