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  • 451.
    Samuelsson, Stefan
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Behavioural Sciences, Teaching and Learning in School, Teacher Education and other Educational Settings.
    Finnström, Orvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Flodmark, Olof
    Dept of Neuroradiology, KS, Stockholm .
    Gäddlin, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Leijon, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Wadsby, Marie
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Child and Adolescent Psychiatry.
    A longitudinal study of reading skills among very-low-birthweight children: Is there a catch-up?2006In: Journal of Pediatric Psychology, ISSN 0146-8693, E-ISSN 1465-735X, Vol. 31, no 9, p. 967-977Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the development of reading skills among very-low-birthweight (VLBW) children and to what extent reading difficulties at 9 years of age persist unchanged, are attenuated, or are enhanced at 15 years of age. Methods: Fifty-six VLBW and 52 normal birthweight (NBW) children were assessed on word decoding, word recognition, and reading comprehension at 9 and 15 years of age. Results: VLBW children showed deficits in reading skill at 9 years of age, while most differences obtained at 15 years of age did not reach significance. VLBW children improved their reading comprehension between 9 and 15 years of age more than NBW children, and when controlling for individual differences in IQ, VLBW children improved both their reading comprehension and word-recognition skill. Conclusion: The results suggest that VLBW children display positive changes over time in reading skills. © The Author 2006. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved.

  • 452.
    Samuelsson, Stefan
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Behavioural Sciences, Teaching and Learning in School, Teacher Education and other Educational Settings.
    Finnström, Orvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Leijon, Ingemar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Mård, Selina
    Linköping University, Department of Behavioural Sciences.
    Phonological and surface profiles of reading difficulties among very low birth weight children: Comverging evidence for the developmental lag hypothesis2000In: Scientific studies of reading : the official journal of the Society for the Scientific Study of Reading, ISSN 1088-8438, Vol. 4, p. 197-217Article in journal (Refereed)
  • 453.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Space-time clustering at birth and at diagnosis of type 1 diabetes mellitus in relation to early clinical manifestation2003In: Journal of Pediatric Endocrinology & Metabolism (JPEM), ISSN 0334-018X, E-ISSN 2191-0251, Vol. 16, no 6, p. 859-867Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether space-time clustering at diagnosis of type 1 diabetes mellitus (DM1) is related to clinical manifestations and to see whether there is a time-space clustering at birth of children who later develop DM1. Patients: Using the method by Knox, clustering was analysed in all 1,144 children diagnosed between 1977 and 1994 in south-east Sweden. Results: The strongest significance was obtained for the cut-off value of 5 kin and 7 months (p <0.01). Using this cut-off, children with a short duration of symptoms before diagnosis had the same degree of clustering as children with a longer duration. Children diagnosed during autumn and winter tended to have a higher degree of clustering than children diagnosed during spring and summer. We found no significant clustering regarding birthplace and birth month. Conclusion: This study is consistent with the existence of space-time clustering at diagnosis. The most plausible explanation is that infections elicit several cases of DM1 in children in whom the disease process has already begun.

  • 454.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hanås, Ragnar
    Barnkliniken NÄL, Uddevalla.
    Whiss, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children2008In: World Journal of Pediatrics, ISSN 1708-8569, Vol. 4, no 3, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Background: HbA1c levels are infl uenced by the glycemic control of previous 2-3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is diffi cult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profi les to evaluate their relationship with HbA1c. Methods: Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period. Results: There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profi les during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations. Conclusions: Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations. © Springer 2008.

  • 455.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, B
    Queen Silvia Children's Hospital, Sweden.
    Carlsson, A
    Lund University Hospital, Sweden.
    Forsander, G
    Queen Silvia Children's Hospital, Sweden.
    Ivarsson, S
    University Hospital MAS, Sweden.
    Kockum, I
    Karolinska Institute, Sweden.
    Lernmark, A
    Lund University, Sweden.
    Marcus, C
    Karolinska University Hospital, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Residual beta cell function at diagnosis of type 1 diabetes in children and adolescents varies with gender and season2013In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 29, no 1, p. 85-89Article in journal (Refereed)
    Abstract [en]

    Background

    There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease.

    We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D.

    Methods

    In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D.

    Results

    C-peptide was lower in younger children, 0–10 years of age (0.23 ± 0.20 nmol/L) than in older children, 11–18 years of age (0.34 ± 0.28 nmol/L) (p  < 0.000 ). There was a seasonal variation in non-fasting serum C-peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C-peptide was highest, whereas fewer patients were diagnosed in April and May when serum C-peptide was significantly lower (p < 0.01). The seasonal variation of C-peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C-peptide than boys (p < 0.05), especially in early puberty.

    Conclusions

    Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials.

  • 456.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed Type 1 diabetes and control children and their family members2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 1, p. 64-67Article in journal (Refereed)
    Abstract [en]

    Aims: The gut flora is quantitatively the most important source of microbial stimulation and may provide a primary signal in the maturation of the immune system. We compared the microflora-associated characteristics (MACs) in 22 children with newly diagnosed diabetes, 27 healthy controls, and their family members to see if there were differences between the children and if there was a familial pattern. Methods: The MACs were assessed by determining the concentrations of eight short-chain fatty acids (SCFA), mucin, urobilin, b-aspartylglycine, coprastanol and faecal tryptic activity (FTA). Results: There were no statistically significant differences between the concentrations of SCFA in the diabetes and control children. Members of families with a diabetic child had a higher concentration of acetic acid (P < 0.02) and lower concentrations of several other SCFAs than control families (P < 0.05-0.02). The other MACs showed no differences between the children or between the two family groups. Conclusion: In this pilot study we saw no differences in the MACs between children with diabetes and their controls. There were, however, some differences between the family members of diabetic children and controls that may indicate a familial pattern regarding the production of SCFAs by the gut flora. The role of the gut flora in relation to the risk of developing Type 1 diabetes needs to be analysed in larger and/or prospective studies.

  • 457.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Löfman, Owe
    Norwegian University of Life Science, Norway.
    Geochemical Correlates to Type 1 Diabetes Incidence in Southeast Sweden: An Environmental Impact?2014In: Journal of environmental health, ISSN 0022-0892, Vol. 76, no 6, p. 146-154Article in journal (Refereed)
    Abstract [en]

    The authors aim was to explore whether geological factors contribute to geographical variation in the incidence of type 1 diabetes. All children diagnosed with type 1 diabetes in southeastern Sweden during 1977-2006 were defined geographically by their place of residence and were allocated x and y coordinates in the national grid. The population at risk, all children 0-16 years of age, was geocoded in a similar manner. Three of the analyzed minerals in moraine and one of the analyzed minerals in brook water plants were significantly associated with type 1 diabetes at the time of diagnosis. Additionally, the birthplace of the children who subsequently developed diabetes differed in relation to some of the minerals. In communities with high incidence and in communities with low incidence, children were diagnosed with type 1 diabetes in areas with the same high or low level of elements. The authors findings in their pilot study indicate a possible geographical covariation of incidence and some geological factors.

  • 458.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Oikarinen, Sami
    University of Tampere.
    Hyoty, Heikki
    University of Tampere.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Low zinc in drinking water is associated with the risk of type 1 diabetes in children2011In: PEDIATRIC DIABETES, ISSN 1399-543X, Vol. 12, no 3, p. 156-164Article in journal (Refereed)
    Abstract [en]

    Aim: To explore if drinking water may influence the development of type 1 diabetes in children, either via enterovirus spread via drinking water or quality of drinking water related to acidity or concentration of certain minerals. Methods: One hundred and forty-two families with a child with diabetes and who lived either in seven municipalities with a high annual diabetes incidence during 1977-2001 and in six municipalities with the lowest incidence during those 25 yr were asked to participate. Three hundred and seventy-three families in these communities were used as controls. The families filled a 200-mL plastic bottle with their tap drinking water and returned it by mail. The water samples were analyzed for pH, zinc, iron, nitrate, nitrite, nitrate-nitrogen and nitrite-nitrogen, and occurrence of enterovirus RNA. Results: Enterovirus RNA was not found in the tap water samples. The concentration of zinc, nitrate, and nitrate-nitrogen was lower in the municipalities with high incidence of type 1 diabetes. The water samples from families with a child with diabetes had lower concentration of zinc than water samples from control families. Conclusion: Low zinc in drinking water is associated with the risk of developing type 1 diabetes during childhood. Enterovirus does not seem to be spread via drinking water in a country with modern water works.

  • 459.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Steineck, Isabelle
    Herning Hospital, Denmark .
    Gubbjornsdottir, Soffia
    University of Gothenburg, Sweden .
    A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in childhood is related to metabolic control, macroalbuminuria, and retinopathy in early adulthood - a pilot study using two nation-wide population based quality registries2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, no 3, p. 229-235Article in journal (Refereed)
    Abstract [en]

    BackgroundIntensive treatment of patients with type 1 diabetes delays the onset of long-term complications. ObjectivesOn the basis of the information from two nation-wide quality registers, we investigated to which extent HbA1c values 3-15months after diagnosis in childhood are related to metabolic control, albuminuria, and retinopathy in early adulthood. MethodsIn Sweden, physicians register all children and adolescents with type 1 diabetes mellitus in the Swedish Pediatric Quality Registry. After 18yr of age, people with diabetes are followed by the Swedish National Diabetes Register. We identified 1543 children and adolescents with a mean age of 13.9yr at diagnosis and a mean duration of type 1 diabetes mellitus of 7.1yr. ResultsChildren and adolescents with poor metabolic control (mean HbA1c 70mmol/mol (8.6 %)) adjacent to diagnosis had a significantly higher mean HbA1c value years later as adults than did patients with a good metabolic control [less than50mmol/mol (6.7%) (pless than0.001)]. The patients in the high group were also less physically active and smoked more as adults. The proportion of females was higher in the poor metabolic group. Patients with a high mean HbA1c 3-15months after diagnosis had significantly more often macroalbuminuria and retinopathy in early adulthood. ConclusionsMetabolic control adjacent to the diagnosis of type 1 diabetes in childhood or adolescence can predict metabolic control in early adulthood. It is therefore very important that pediatric diabetes teams identify key factors for successful early metabolic control. Actively using quality registries may be one such factor.

  • 460.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Clinical characteristics at onset of Type 1 diabetes in children diagnosed between 1977 and 2001 in the south-east region of Sweden2005In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 68, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    To survey clinical characteristics at diagnosis for children diagnosed with Type 1 diabetes during 25 years in the south-east part of Sweden we included all 1903 children <16 years of age and who had been diagnosed between 1977 and 2001 in the south-east region of Sweden. A nurse or doctor in the diabetes team obtained information from medical records. Over the 25 years the mean duration of symptoms prior to diagnosis was 17.8 ± 26.4 days and the mean glucose level at diagnosis was 23.6 ± 9.7 mmol/l. Three percent of the children (n = 50) had a pH value ≤ 7.1. The youngest children (0-5 years) had shorter duration of symptoms, lower blood-glucose levels and less often had ketonuria than the oldest children (11-15 years) but more often suffered from infections prior to diagnosis. The proportion of children diagnosed in the group 0-5 years of age increased over the study-period, apart from the last 5 years, while children with pH value ≤ 7.3 decreased significantly as did the proportion of children with ketonuria or infection. The clinical characteristics at diagnosis of diabetes are heterogeneous, especially in the oldest age group. Some characteristics varied with time. © 2004 Elsevier Ireland Ltd. All rights reserved.

  • 461.
    Sandin, Anna
    et al.
    Barnkliniken, Umeå lasarett.
    Annus, T
    Tartu University Childrens Hospital, Tartu, Estonia.
    Björkstén, Bengt
    Institute of Environment, Karolinska Institute, Stockholm.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Riikjärv, M-A
    Tallin Childrens Hospital, Tallin, Estonia.
    van Hage-Hamsten, M
    Medicinkliniken, Klinisk immunologi och allergi, Karolinska institutet, Stockholm.
    Bråbäck, Lennart
    Dept of Public Health and Research, Sundsvall.
    Prevalence of self-reported food allergy and IgE antibodies to food allergens in Swedish and Estonian schoolchildren2005In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 59, no 3, p. 399-403Article in journal (Refereed)
    Abstract [en]

    Objective: To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries. Design and setting: As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Östersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children. Subjects: Children aged 10-11 y. Results: The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Östersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5). Conclusion: Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries. © 2005 Nature Publishing Group. All rights reserved.

  • 462.
    Savilahti, Erkki
    et al.
    Hospital for Children and Adolescents Helsinki, Finland.
    Siltanen, Mirjami
    Hospital for Children and Adolescents Helsinki, Finland.
    Kajosaari, Merja
    Hospital for Children and Adolescents Helsinki, Finland.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Saarinen, Kristiina
    Hospital for Children and Adolescents Helsinki, Finland.
    IgA antibodies, TGF-β1 and -β2, and Soluble CD14 in the colostrum and development of atopy by age 42005In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 58, no 6, p. 1300-1305Article in journal (Refereed)
    Abstract [en]

    Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-β in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (>3.5 or <0.5 mo), these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-β1 and -β2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4. Copyright © 2005 International Pediatric Research Foundation, Inc.

  • 463.
    Schleiermacher, Gudrun
    et al.
    Institute National Sante and Rech Medical U830, France; Institute Curie, France.
    Javanmardi, Niloufar
    University of Gothenburg, Sweden.
    Bernard, Virginie
    Institute Curie, France.
    Leroy, Quentin
    Institute Curie, France.
    Cappo, Julie
    Institute National Sante and Rech Medical U830, France.
    Rio Frio, Thomas
    Institute Curie, France.
    Pierron, Gaelle
    Institute Curie, France.
    Lapouble, Eve
    Institute Curie, France.
    Combaret, Valerie
    Centre Leon Berard, France.
    Speleman, Frank
    Ghent University Hospital, Belgium.
    de Wilde, Bram
    Ghent University Hospital, Belgium.
    Djos, Anna
    University of Gothenburg, Sweden.
    Ora, Ingrid
    Lund University, Sweden.
    Hedborg, Fredrik
    Uppsala University, Sweden; Uppsala University, Sweden.
    Traeger, Catarina
    Astrid Lindgren Childrens Hospital, Sweden.
    Holmqvist, Britt-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Abrahamsson, Jonas
    University of Gothenburg, Sweden.
    Peuchmaur, Michel
    Hop University of Robert Debre, France; University of Paris 07, France.
    Michon, Jean
    Institute Curie, France.
    Janoueix-Lerosey, Isabelle
    Institute National Sante and Rech Medical U830, France.
    Kogner, Per
    Astrid Lindgren Childrens Hospital, Sweden.
    Delattre, Olivier
    Institute National Sante and Rech Medical U830, France.
    Martinsson, Tommy
    University of Gothenburg, Sweden.
    Emergence of New ALK Mutations at Relapse of Neuroblastoma2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 25, p. 2727-+Article in journal (Refereed)
    Abstract [en]

    Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. Methods We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). Conclusion In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.

  • 464.
    Schmiegelow, Kjeld
    et al.
    Rigshospital.
    Al-Modhwahi, Ibrahim
    Rigshospital.
    Behrendtz, Mikael
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forestier, Erik
    Umeå University Hospital.
    Hasle, Henrik
    Aarhus University Hospital.
    Heyman, Mats
    Astrid Lindgrens Barnsjukhus.
    Kristinsson, Jon
    University Hospital, Reykjavik.
    Nersting, Jacob
    University Hospital, Trondheim.
    Svendsen, Anne Louise
    University of Copenhagen.
    Vettenranta, Kim
    University Hospital, Helsinki.
    Weinshilboum, Richard
    Mayo Clinic.
    Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study2009In: BLOOD, ISSN 0006-4971, Vol. 113, no 24, p. 6077-6084Article in journal (Refereed)
    Abstract [en]

    Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m(2); P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.

  • 465.
    Schoenrock, Andrew
    et al.
    Carleton University, Ottawa, Canada.
    Samanfar, Bahram
    Carleton University, Ottawa, Canada.
    Pitre, Sylvain
    Carleton University, Ottawa, Canada.
    Hooshyar, Mohsen
    Carleton University, Ottawa, Canada.
    Jin, Ke
    University of Toronto, Toronto, Canada.
    Phillips, Charles A
    University of Tennessee, Knoxville, Tennessee, USA.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gothenburg University, Gothenburg, Sweden.
    Phanse, Sadhna
    University of Toronto, Toronto, Canada.
    Omidi, Katayoun
    University of Toronto, Toronto, Canada.
    Gui, Yuan
    University of Toronto, Toronto, Canada.
    Alamgir, Md
    University of Toronto, Toronto, Canada.
    Wong, Alex
    University of Toronto, Toronto, Canada.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Gothenburg University, Gothenburg, Sweden.
    Babu, Mohan
    University of Regina, Regina, Saskatchewan, Canada.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Gothenburg University, Gothenburg, Sweden.
    Langston, Michael A
    Carleton University, Ottawa, Canada.
    Green, James R
    Carleton University, Ottawa, Canada.
    Dehne, Frank
    Carleton University, Ottawa, Canada.
    Golshani, Ashkan
    Carleton University, Ottawa, Canada.
    Efficient prediction of human protein-protein interactions at a global scale2014In: BMC bioinformatics, ISSN 1471-2105, Vol. 15, no 1, p. 383-Article in journal (Refereed)
    Abstract [en]

    BackgroundOur knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods.ResultsOn the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments.ConclusionsThe speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.

  • 466.
    Sedimbi, S K
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Luo, X R
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sanjeevi, C B
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lernmark, Ake
    Landin-Olsson, Mona
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Björck, Elizabeth
    Nyström, Lennarth
    Ohlson, Lars Olof
    Scherstén, Bengt
    Ostman, Jan
    Aili, M
    Bååth, L E
    Carlsson, E
    Edenwall, H
    Forsander, G
    Granström, B W
    Gustavsson, I
    Hanås, R
    Hellenberg, L
    Hellgren, H
    Holmberg, E
    Hörnell, H
    Ivarsson, Sten-A
    Johansson, C
    Jonsell, G
    Kockum, K
    Lindblad, B
    Lindh, A
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Myrdal, U
    Neiderud, J
    Segnestam, K
    Sjöblad, S
    Skogsberg, L
    Strömberg, L
    Ståhle, U
    Thalme, B
    Tullus, K
    Tuvemo, T
    Wallensteen, M
    Westphal, O
    Dahlquist, Gisela
    Aman, J
    SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.2007In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 6, p. 518-21Article in journal (Refereed)
    Abstract [en]

    SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

  • 467.
    Selbing, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Anghagen, O
    Bylund, B
    Nelson, Nina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nylander, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Engvall, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Velocity vector imaging to assess fetal myocardial function2007In: Ultrasound Obstet Gynecol.,2007, 2007Conference paper (Other academic)
    Abstract [en]

         

  • 468.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Could parenting stress and lack of support/confidence function as mediating mechanisms between certain environmental factors and the development of autoimmunity in children? – A study within ABIS2002In: Annals of the New York Academy of Science, ISSN 0077-8923, Vol. 958, p. 431-435Article in journal (Refereed)
    Abstract [en]

    Despite extensive research, the etiology of type 1 diabetes is still to a large extent unknown. We would like to propose psychoimmunology as one possible pathway. Psychological mechanisms are directly linked to hormonal and nervous signals, which increase the need for insulin and affect the immune system. Disparate factors of social, environmental, and medical character have been associated with the onset of type 1 diabetes or with the autoimmune process leading to the disease—for instance, parental age, maternal infections, delivery mood, need for neonatal intensive care, and low socioeconomic status. Our results, based on the analyses of 4337 nonselected newborn children and their mothers, show that all these risk factors were also associated with psychological mechanisms (defined as lack of social support/confidence and high parenting stress). These results support the hypothesis of psychological mechanisms as mediating variables between a number of disparate risk factors and the development of type 1 diabetes.

  • 469.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Mothers’ attachment insecurity and diabetes-related autoantibodies in their infants2004In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1037, p. 110-113Article in journal (Refereed)
    Abstract [en]

    Psychological stress may, via hormonal levels, increase insulin resistance. The aim of this study was to investigate whether mothers' attachment insecurity is associated with the induction or progression of diabetes-related autoimmunity in early childhood. Adult attachment interviews were conducted with 18 mothers of infants who were positive, and 32 mothers of infants who were negative, for glutamic acid decarboxylase, selected from ABIS, a large prospective population-based project. The proportion of children with insecure mothers was larger, but not significantly so, in the autoantibody-positive group than in the negative group. If an association exists between maternal attachment insecurity and diabetes-related autoimmunity during infancy, it does not appear to be strong.

  • 470.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Psychosocial correlates of parenting stress, lack of support and lack of confidence/security2004In: Scandinavian Journal of Psychology, ISSN 0036-5564, Vol. 45, no 2, p. 169-179Article in journal (Refereed)
    Abstract [en]

    The purpose of the current study was to identify important correlates of parenting stress, frequently conceptualized as a mediator of suboptimal family function, and of social support and confidence/security, often regarded as buffers. Potential correlates of these concepts were assessed in questionnaires at delivery and at one year, in a sample of 16,000 families in Sweden. Predictors (1) of parenting stress were parental dissatisfaction and poor child sleeping patterns; (2) of lack of support included lack of confidence/security, parents born abroad, single motherhood, and maternal health problems; and (3) of lack of confidence/security were lack of support and serious life events. Mothers lacking social support or confidence/security exhibited significantly higher stress. Although parenting stress is a complex phenomenon certain risk factors can be emphasized, such as sleep problems which appear more important than child health problems. These risk factors can be used both in efforts to prevent stress and in studies of stress effects.

  • 471.
    Sepa, Anneli
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Psychological stress and the risk of diabetes-related autoimmunity: A review article2006In: Neuroimmunomodulation, ISSN 1021-7401, E-ISSN 1423-0216, Vol. 13, no 5-6, p. 301-308Article in journal (Refereed)
    Abstract [en]

    The β cell stress hypothesis suggests that any phenomenon that induces insulin resistance, and thereby extra pressure on the β cells, should be regarded as a risk factor for type 1 diabetes (T1D). Psychological stress decreases insulin sensitivity and increases insulin resistance and may hence be important in the development/onset of T1D. The aim of the current review article was to evaluate existing empirical evidence concerning an association between psychological stress and development/onset of T1D as well as diabetes-related autoimmunity. Ten retrospective case-control studies were found. Nine studies showed a positive association between stress and development/onset of T1D in children, adolescents or adults. One study did not find an association between stress and development/onset of T1D. An association between stress and diabetes-related autoimmunity was found at 1 and 2- 3 years of age in a large epidemiological study of the general population. The hypothesis that psychological stress (via β cell stress or direct influence on the immune system) may contribute to the induction or progression of diabetes-related autoimmunity has gained some strong initial support, but is in need of further empirical verification. It seems much clearer that stress can precipitate manifest T1D, although the biological mechanisms are still not known. Copyright © 2006 S. Karger AG.

  • 472.
    Serenius, Fredrik
    et al.
    Uppsala University, Sweden and Umeå University, Sweden .
    Kallen, Karin
    Lund University, Sweden .
    Blennow, Mats
    Karolinska Institute, Sweden .
    Ewald, Uwe
    Uppsala University, Sweden .
    Fellman, Vineta
    Lund University, Sweden .
    Holmström, Gerd
    Uppsala University, Sweden .
    Lindberg, Eva
    Örebro University, Sweden .
    Lundqvist, Pia
    Lund University, Sweden .
    Marsal, Karel
    Lund University, Sweden .
    Norman, Mikael
    Karolinska Institute, Sweden .
    Olhager, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Stigson, Lennart
    Gothenburg University, Sweden .
    Stjernqvist, Karin
    Lund University, Sweden .
    Vollmer, Brigitte
    Karolinska Institute, Sweden .
    Strömberg, Bo
    Uppsala University, Sweden .
    Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden2013In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 68, no 12, p. 781-783Article in journal (Other academic)
    Abstract [en]

     A proactive approach to the care of extremely preterm infants has increased survival and lowered the gestational age of viability, but these improvements may be associated with later neurodevelopmental disability. EXPRESS is a national population-based prospective study of all infants born alive or stillborn at less than 27 weeks’ gestation between 2004 and 2007 in Sweden. This prospective follow-up study was undertaken to assess neurologic and developmental outcome of the EXPRESS cohort at 2.5 years corrected age compared with a matched control group born at term.

    Of 707 live-born infants, 497 (70%) survived to corrected age 2.5 years; the final cohort included 491 children. Each preterm child was matched with 2 control subjects at 2.5 years chronological age. Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development (Bayley III). Cerebral palsy (CP), visual and hearing disability, and a composite outcome of overall disabilities were assessed. The overall outcome was characterized as no, mild, moderate, and severe disability.

    Of 415 infants assessed with clinical examinations, 399, 393, and 382, respectively, completed the Bayley III cognitive, language, and motor scales; 366 control children were assessed with Bayley III. The mean composite cognitive, language, and motor scores for children in the preterm and control groups were 94 ± 12 and 104 ± 11, respectively (P < 0.001), 98 ± 17 and 109 ± 12 (P < 0.001), respectively, and 94 ± 16 and 107 ± 14 (P < 0.001), respectively. Normal cognitive development or mild cognitive disability was found in 354 preterm children (88.8%) and 364 control children (99.5%). Moderate or severe cognitive disability was present in 20 preterm children (5.0%) and 1 control child (0.3%) (P < 0.001) and in 25 (6.3%) and 1 (0.3%), respectively (P < 0.001). Normal language development or mild language disability was found in 330 children (83.9%) in the preterm group and with 351 (97.5%) in the control group (all group comparisons, P < 0.001). Normal motor development or mild motor disability occurred in 324 (84.8%) and 348 (98.6%) of children in the preterm and control groups, respectively. Moderate or severe mental developmental delay was seen in 88 and 10 children (20% and 2.8%), respectively (P < 0.001).

    In the preterm group, Bayley III cognitive, language, and motor scores increased with advancing gestational age at birth by 2.5 points (99% confidence interval [CI], 1.0–4.0) per week (P < 0.001), by 3.6 points (99% CI, 1.6–5.6) per week (P < 0.001), and by 2.5 points (99% CI, 0.5–4.5) per week scores (P = 0.001), respectively. Cerebral palsy was present in 32 preterm children (7.0%; 99% CI, 3.9–10.1%). Of 456 preterm children, 42.1% were classified as normal, 30.7% as having mild disabilities, and 27.2% as having moderate or severe disabilities (vs 78.1%, 18.6%, 3.3% of control subjects, respectively; P < 0.001 for all comparisons). The proportion of children with mild or no disabilities increased from 40% at 22 weeks to 83% at 26 weeks (P < 0.001 for trend). Moderate or severe disabilities decreased from 60% at 22 weeks to 17% at 26 weeks (P < 0.001 for trend).

    The impact of prematurity on neurodevelopmental outcome indicates that further improvements in neonatal care are necessary. Although preterm children had poorer neurodevelopmental outcomes than those born at term, 73% had no or mild disability, and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling couples facing extremely preterm birth of their infant

  • 473.
    Serenius, Fredrik
    et al.
    Uppsala University, Sweden Umeå University, Sweden .
    Källén, Karin
    Lund University, Sweden .
    Blennow, Mats
    Karolinska Institute, Stockholm, Sweden.
    Ewald, Uwe
    Uppsala University, Sweden .
    Fellman, Vineta
    Lund University, Sweden .
    Holmström, Gerd
    Uppsala University, Sweden .
    Lindberg, Eva
    Örebro University, Sweden .
    Lundqvist, Pia
    Lund University, Sweden .
    Marsal, Karel
    Lund University, Sweden .
    Norman, Mikael
    Karolinska Institute, Stockholm, Sweden.
    Olhager, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Stigson, Lennart
    University of Gothenburg, Sweden .
    Stjernqvist, Karin
    Lund University, Sweden .
    Vollmer, Brigitte
    Karolinska Institute, Stockholm, Sweden .
    Strömberg, Bo
    Uppsala University, Sweden .
    Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden2013In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 309, no 17, p. 1810-1820Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE:

    Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors.

    OBJECTIVE:

    To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age).

    DESIGN, SETTING, AND PARTICIPANTS:

    Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences.

    MAIN OUTCOMES AND MEASURES:

    Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age.

    RESULTS:

    At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001).

    CONCLUSIONS AND RELEVANCE:

    Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

  • 474.
    Serenius, Fredrik
    et al.
    Uppsala University, Sweden Umeå University, Sweden .
    Sjors, Gunnar
    Uppsala University, Sweden .
    Blennow, Mats
    Karolinska University Hospital, Sweden .
    Fellman, Vineta
    Lund University, Sweden .
    Holmstrom, Gerd
    Uppsala University, Sweden .
    Marsal, Karel
    Lund University, Sweden .
    Lindberg, Eva
    University of Örebro, Sweden .
    Olhager, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Stigson, Lennart
    Sahlgrens University Hospital, Sweden .
    Westgren, Magnus
    Karolinska University Hospital, Sweden .
    Kallen, Karin
    Lund University, Sweden .
    EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 1, p. 27-37Article in journal (Refereed)
    Abstract [en]

    AimThe aim of this study was to investigate differences in mortality up to 1year of age in extremely preterm infants (before 27weeks) born in seven Swedish healthcare regions. MethodsNational prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. ResultsAmong 844 foetuses alive at mothers admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24weeks. Among 707 infants born alive, regional differences were found both in mortality before 12h and in the 365-day mortality rate for the subgroup (22-24weeks) and for the total group (22-26weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12h or for infants born at 25weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. ConclusionMortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

  • 475.
    Sherry, Nicole
    et al.
    Massachusetts General Hospital.
    Hagopian, William
    NW Diabetes Research Institute.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Jain, Sunil M
    TOTALL Diabetes Hormone Research Institute.
    Wahlen, Jack
    Endocrine Research Specialists.
    Ferry, Robert J
    Atlanta Diabet Associates,.
    Bode, Bruce
    Atlanta Diabet Associates.
    Aronoff, Stephen
    Research Institute Dallas.
    Holland, Christopher
    MacroGenics.
    Carlin, David
    MacroGenics.
    King, Karen L
    MacroGenics.
    Wilder, Ronald L
    PAREXEL Int.
    Pillemer, Stanley
    Amer Biopharma Corp.
    Bonvini, Ezio
    MacroGenics.
    Johnson, Syd
    MacroGenics.
    Stein, Kathryn E
    MacroGenics.
    Koenig, Scott
    MacroGenics.
    Herold, Kevan C
    Yale University.
    Daifotis, Anastasia G
    MacroGenics.
    Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial2011In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 378, no 9790, p. 487-497Article in journal (Refereed)
    Abstract [en]

    Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve beta-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. less thanbrgreater than less thanbrgreater thanMethods In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protege study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0.5 U/kg per day and glycated haemoglobin A(1c) (HbA(1c)) of less than 6-5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. less thanbrgreater than less thanbrgreater thanFindings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19.8% (41/207) in the 14-day full-dose group; 13.7% (14/102) in the 14-day low-dose group; 20.8% (22/106) in the 6-day full-dose group; and 20.4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0.03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). less thanbrgreater than less thanbrgreater thanInterpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in beta-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.

  • 476.
    Shields, Beverley M
    et al.
    University of Exeter, England .
    Henley, William
    University of Exeter, England .
    Besser, Rachel E J
    University of Exeter, England .
    Hattersley, Andrew T
    University of Exeter, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Letter: Response to Comment on: Besser et al. Lessons From the Mixed-Meal Tolerance Test: Use of 90-Minute and Fasting C-Peptide in Pediatric Diabetes.2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 12, p. E222-E222Article in journal (Other academic)
    Abstract [en]

    n/a

  • 477.
    Shin, J-H
    et al.
    Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.
    Janer, M
    Institute for Systems Biology, Seattle, WA, USA.
    McNeney, B
    Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.
    Blay, S
    Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.
    Deutsch, K
    Institute for Systems Biology, Seattle, WA, USA.
    Sanjeevi, C B
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kockum, I
    Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
    Lernmark, A
    Department of Medicine, Robert H. Williams Laboratory, University of Washington, Seattle, WA, USA.
    Graham, J
    Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Björck, Elizabeth
    Eriksson, Jan
    Nyström, Lennarth
    Ohlson, Lars Olof
    Scherstén, Bengt
    Ostman, Jan
    Aili, M
    Bååth, L E
    Carlsson, E
    Edenwall, H
    Forsander, G
    Granström, B W
    Gustavsson, I
    Hanås, R
    Hellenberg, L
    Hellgren, H
    Holmberg, E
    Hörnell, H
    Ivarsson, Sten-A
    Johansson, C
    Jonsell, G
    Kockum, K
    Lindblad, B
    Lindh, A
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Myrdal, U
    Neiderud, J
    Segnestam, K
    Sjöblad, S
    Skogsberg, L
    Strömberg, L
    Ståhle, U
    Thalme, B
    Tullus, K
    Tuvemo, T
    Wallensteen, M
    Westphal, O
    Aman, J
    IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.2007In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 6, p. 503-12Article in journal (Refereed)
    Abstract [en]

    In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

  • 478.
    Silfvernagel, Kristin
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Gren Landell, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Emanuelsson, Marie
    Linköping University, Department of Behavioural Sciences and Learning.
    Carlbring, Per
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Individually tailored internet-based cognitive behavior therapy for adolescents with anxiety disorders: A pilot effectiveness study2015In: Internet Interventions, ISSN 2214-7829, Vol. 2, no 3, p. 297-302Article in journal (Refereed)
    Abstract [en]

    This is the first study of adolescents suffering from anxiety disorder in Sweden to receive individually tailored internet-based treatment within a child and adolescent psychiatric clinic. The primary aim of this effectiveness study was to examine the effects of tailored internet-based cognitive behaviour therapy for adolescents.

    11 adolescents, aged 15-19 years, were allocated to treatment after assessment. Screening consisted of online questionnaires followed by a diagnostic face-to-face interview at the clinic. Treatment consisted of individually prescribed cognitive behaviour therapy (CBT) text modules adapted for the age group. Therapist guidance was via an online platform along with telephone support and face-to-face sessions if needed.

    Statistically significant improvements were found on all dependent measures immediately following treatment for the 8 adolescents who completed treatment. The within-group effect size on the Beck Anxiety Inventory, the primary outcome measure, was d = 2.51 at post-treatment and 80 percent (4/5) adolescents no longer met DSM-IV criteria for their primary anxiety disorder as measured by the Anxiety Disorders Interview Schedule for DSM- IV: Child and Parent Versions.

    Based on the results from this pilot study the tentative conclusion might be that tailored internet delivered CBT could be useful for adolescents with anxiety disorders along with standard treatment delivered in child and adolescent psychiatric clinics.

  • 479.
    Simonen-Tikka, Marja-Leena
    et al.
    National Institute Health and Welf, Finland .
    Hiekka, Anna-Kaisa
    National Institute Health and Welf, Finland .
    Klemola, Paivi
    National Institute Health and Welf, Finland .
    Poussa, Tuija
    StatConsulting TuijaPoussa, Finland .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Korpela, Riitta
    University of Helsinki, Finland .
    Vaarala, Outi
    National Institute Health and Welf, Finland .
    Roivainen, Merja
    National Institute Health and Welf, Finland .
    Early human enterovirus infections in healthy Swedish children participating in the PRODIA pilot study2012In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 84, no 6, p. 923-930Article in journal (Refereed)
    Abstract [en]

    Human enteroviruses (HEV) are common, especially in childhood and during the enterovirus season, causing mainly asymptomatic infections but also mild and severe illnesses. Numerous studies have shown the association between HEV infections and type 1 diabetes. Here, the prevalence of HEV infections was studied in healthy Swedish children with increased HLA-associated risk for type 1 diabetes participating in the PRODIA pilot study in which children were randomized to receive probiotics or placebo during the first 6 months of life. Stool specimens collected from 197 children in every 3 months from the age of 3 to 24 months were screened for HEV using traditional viral culturing method and identified with reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing of the partial VP1 coding part of the viral genome. Altogether 4.8% (52/1,094) of the specimens were HEV-positive and 22.3% (44/197) of the children excreted HEV during the follow-up. HEV-A and HEV-B were present in 2.1 and 2.7% of the specimens, respectively. HEV-C and HEV-D viruses were not detected. In total, 17 different HEV serotypes were detected and the most common findings were CV-A9 (13.5%), CV-A16 (11.5%), and CV-A2 (9.6%). The majority of the infections (92.3%) were during the enterovirus season extending from July to December. Probiotic treatment did not affect significantly the risk of HEV infections during the 2-year follow-up although a trend for transient decrease for HEV positivity (HEV-A and/or HEV-B) by the age of 12 months was observed in children who received probiotics [OR 0.40; 95% confidence interval 0.15 to 1.08; P-value 0.071, generalized estimating (GEE) analysis]. According to the results, HEV-A findings were nearly as common as HEV-B findings among the healthy children participating in this study. Also it was shown that serotypes belonging to HEV-A species can be detected by means of viral culturing.

  • 480.
    Sjöberg, Veronika
    et al.
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Pietz, Grzegorz
    ology, Immunology, Umeå University, Umeå, Sweden.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sundström, Mia
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Olof
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Hernell, Olle
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Hammarström, Sten
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Hammarström, Marie-Louise
    Department of Clinical Microbiology, Immunology, Umeå University, Umeå, Sweden.
    Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease.2014In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 5, no e58Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.

    METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.

    RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).

    CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.

  • 481.
    Sjögren, YM
    et al.
    Dept of Immunology Wennergren Inst, Stockholm.
    Duchén, Karel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindh, F
    Isosep AB Tullinge, Sweden.
    Björkstén, Bengt
    Inst of Environmental Medicine KI, Stockholm.
    Sverremark-Ekström, E
    Dept of Immunology Wennergren Inst, Stockholm.
    Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age2007In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 18, no 1, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Several recent studies have demonstrated a relationship between the composition of the gut microbiota in infancy and subsequent development of allergic disease. Human milk is the major food in infancy and may thus profoundly influence the composition of the gut flora. Oligosaccharides in breast milk survive the passage through the stomach and are utilized by the gut microbiota. As the relationship between breast feeding and childhood allergy is controversial we hypothesized that the composition of oligosaccharides in breast milk might explain the controversy. Nine of the most abundant neutral oligosaccharides in human milk were analysed in colostrum samples from allergic and non-allergic women and related to subsequent development of allergy in their children. The carbohydrate fraction of the colostrum was separated by gel permeation chromatography and neutral oligosaccharides, tri- to hexasaccharides were collected. Neutral oligosaccharides were analysed with high-performance liquid chromatography. There was a large variation in the concentration of neutral oligosaccharides in colostrum, which could not be explained by the allergic status of the women. Allergic children consumed higher amounts of neutral oligosaccharides in total, although not significantly (p = 0.12). When different oligosaccharides were analysed separately, there was no significant difference in consumption between the infants who developed atopic allergy later (n = 9) and infants who did not (n = 11). Thus, the amount of neutral oligosaccharides in colostrum does not directly correlate with maternal allergy, nor with allergy development in children up to 18 months of age. © 2007 The Authors.

  • 482.
    Skoglund, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hampe, Christiane S
    Department of Medicine, University of Washington, Seattle, WA, USA.
    GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes2012In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 13, no 3, p. 244-250Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. Previously we have shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by an increase in GAD autoantibody (GADA) titers. The aim of the present study was to investigate whether GAD-alum treatment affected the GADA epitope pattern.

    Methods. Serum samples of patients treated with GAD-alum (n=33) or placebo (n=27), at baseline and 1, 3, 9, and 15 months after initiation of treatment, were tested for their binding capacity to specific GADA epitopes in an epitope specific radioligand-binding assay with six GAD65-specific recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78 and N-GAD65 mAb).

    Results. For the period included in this study (baseline to 15 months) no difference in variability of binding to any of the tested rFab were observed. However, a higher median response to the b96.11-defined epitope in the first 3 months after the initial injection was observed in GAD-alum treated patients (-8.1%, min -72.4%, max 39.6%) compared to patients receiving placebo (1.5%, min -28.3%, max 28.6%) (p=0.02). This effect was especially evident in GAD-alum treated patients who experienced an increase of more than 100% in their GADA titer from baseline to 3 months (n=27), where we observed an 10.8% (-10.8%, min -72.4%, max 30.5%) increase in binding to the b96.11 epitope over the  first 3 months post initial injection (p=0.04). Subsequently the recognition of the b96.11-defined epitope in the GAD-alum group decreased between 3 and 15 months (8.3%, min -17.1%, max 36.7%) compared to the placebo group (-2.4%, min -32.8%, max 30.1%) (p<0.05) and returned to levels similar to that observed at baseline. Correlations between GADA titer and epitope binding for b96.11 and DPD were observed in the placebo group, but not in the GADalum group, at 3 and 15 months after initial treatment.

    Conclusions/interpretation. We conclude that administration of GAD-alum temporarily induced increased binding to one epitope specificity of GADA.

  • 483.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Seroprevalence of Borrelia IgG antibodies among young Swedish children in relation to reported tick bites, symptoms and previous treatment for Lyme borreliosis: a population-based survey2010In: ARCHIVES OF DISEASE IN CHILDHOOD, ISSN 0003-9888, Vol. 95, no 12, p. 1013-1016Article in journal (Refereed)
    Abstract [en]

    Background Lyme borreliosis (LB) is the most common tickborne infection in Sweden and the seroprevalence of Borrelia immunoglobulin G (IgG) antibodies varies between 2% and 26%. The seroprevalence in young Swedish children is unknown and the relation to clinical data has not been previously studied. Objective To determine the seroprevalence of Borrelia IgG antibodies in serum of young Swedish children and to relate it to gender, geographical location, reported tick bites, symptoms and previous treatment for LB. Methods 2000 healthy 5-year-old children (n=2000) were randomly selected from among participants of a larger prospective population-based study, the ABIS (All Babies in Southeast Sweden) study. Serum samples were collected and a Borrelia specific ELISA test (Dako) were performed for IgG antibody detection. Clinical data were collected from questionnaires completed by the parents. Results The seroprevalence of Borrelia IgG antibodies was 3.2% (64/2000). Previous tick bite had been noted in 66% of these seropositive children but the majority (94%) had not previously been treated for LB. In addition, another 55 children reported a history of LB but were negative to Borrelia IgG antibodies in serum. Many of these seronegative children had received treatment for erythema migrans (n=24), which is a clinical diagnosis. Whether children were correctly treated or overtreated for LB is however unknown. No differences in gender, geographical location or reported tick bites were found when comparing Borrelia-seropositive children (n=64) and seronegative children with previous LB (n=55). Conclusion This population-based study demonstrates a Borrelia IgG antibody seroprevalence of 3.2% in young Swedish children. Very few of these seropositive children report previous symptoms or treatment for LB. Thus the findings suggest that exposure to the Borrelia spirochaete (with subsequent antibody response in serum) does occur in young children, mostly without giving rise to clinical LB. Future studies on cell-mediated immune responses are needed to investigate explanatory immunological mechanisms.

  • 484.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Bergström, Sven
    Umeå University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis2012In: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2012, no 294587Article in journal (Refereed)
    Abstract [en]

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-gamma, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1 beta, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown.

  • 485.
    Skrodeniene, Erika
    et al.
    Institute of Endocrinology, Kaunas.
    Jasinskiene, Edita
    Kaunas University Hospital.
    Padaiga, Zilvinas
    Kaunas University of Medicine.
    Sadauskaite-Kuehne, Vaiva
    Institute of Endocrinology, Kaunas.
    Marciulionyte, Dalia
    Institute of Endocrinology, Kaunas.
    Verkauskiene, Rasa
    Kaunas University Hospital.
    Sanjeevi, Carani
    Karolinska Institute.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Frequency of HLA DR-DQ haplotypes in Lithuanian children with type 1 diabetes and controls2008In: HORMONE RESEARCH, ISSN 0301-0163, vol 70, 2008, Vol. 70, p. 253-254Conference paper (Refereed)
  • 486.
    Skrodeniene, Erika
    et al.
    Kaunas University of Medicine.
    Marciulionyte, Dalia
    Kaunas University of Medicine.
    Jasinskiene, Edita
    Kaunas University of Medicine.
    Sadauskaite-Kuehne, Vaiva
    Karolinska Institutet.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    HLA class II alleles and haplotypes in Lithuanian children with type 1 diabetes and healthy children (HLA and type 1 diabetes)2010In: MEDICINA-LITHUANIA, ISSN 1010-660X, Vol. 46, no 8, p. 505-510Article in journal (Refereed)
    Abstract [en]

    Objective. Type 1 diabetes mellitus is a slowly progressive autoimmune disease. The genetic background of type 1 diabetes mellitus is polygenic with the major disease locus located in the human leukocytes antigen (HLA) region. High risk and protective alleles, haplotypes, and genotypes have been determined in Lithuanian children with type 1 diabetes mellitus and healthy children. Material and methods. In this case-control study, 124 children with diabetes (55 males and 69 females; mean age, 9.2 +/- 3.9 years) were tested for HLA class II and compared with 78 healthy controls (43 males and 35 females; mean age, 10.8 +/- 3.4 years; range, 0-15 years). HLA DRB1, DQA1, and DQB1 alleles were genotyped using a polymerase chain reaction. Results. TID risk-associated haplotypes (DR4)-DQA1*0301-DQB1*0302, (DR3)-DQAI*0501-DQB1*0201, and (DR1)-DQA1*0101-04-DQB1*0501 were more prevalent among children with diabetes than controls (50.0%, 41.1%, and 37.9% vs. 10.3%, 5.1%, and 24.4%, Pandlt;0.001). The haplotypes (DR4)-DQA1*0301-DQB1*0302 and ( DR3)-DQA1*0501-DQB1*0201 increased T1D risk by 8.75 and 12.93 times, respectively (Pandlt;0.001). Protective haplotypes (DR2)-DQA1*0102-B1*0602, (DR11/12/13)-DQAI*05-DQB1*0301, and (DR13)-DQA1*0103-DQB1*0603 were significantly more prevalent among controls than children with diabetes (25.6%, 33.3%, 19.2% vs. 0%, 3.2%, 0%; Pandlt;0.001). These frequencies are quite similar to those from neighbor countries with varying incidence of type 1 diabetes mellitus. Conclusions. HLA class II haplotypes associated with type 1 diabetes mellitus positively or negatively were the same in Lithuanian children as in other European Caucasian populations. Differences in incidence and clinical manifestations of type 1 diabetes might be due to different environmental factors and/or lifestyle.

  • 487.
    Skrodeniene, Erika
    et al.
    Laboratory of General Endocrinology, Institute of Endocrinology, Kaunas University of Medicine, Lithuania.
    Marciulionyte, Dalia
    Laboratory of General Endocrinology, Institute of Endocrinology, Kaunas University of Medicine, Lithuania.
    Padaiga, Zilvinas
    Department of Preventive Medicine, Kaunas University of Medicine, Lithuania.
    Jasinskiene, Edita
    Department of Pediatric Endocrinology, Kaunas University of Medicine, Lithuania.
    Sadauskaite-Kuehne, Vaiva
    Laboratory of General Endocrinology, Institute of Endocrinology, Kaunas University of Medicine, Lithuania.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Environmental risk factors in prediction of childhood prediabetes2008In: Medicina (Kaunas), ISSN 1010-660X, E-ISSN 1648-9144, Vol. 44, no 1, p. 56-63Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The damage of beta cells occurs during the asymptomatic prodromal period called prediabetes before onset of diabetes mellitus. It is characterized by the presence of islet cell autoantibodies (ICAs). The aim of this study was to find out what environmental factors predict ICA seroconversion in healthy schoolchildren in Lithuania.

    MATERIAL AND METHODS: Sera from 3053 nondiabetic schoolchildren living in Lithuania were investigated for ICAs. ICAs were measured in undiluted sera by indirect immunofluorescence method. All ICA-positive and randomly selected ICA-negative children were invited to participate in the study. Response rate in the families of ICA-positive children was 100% and in ICA-negative-76.5%. Data from 13 ICA-positive and 199 ICA-negative schoolchildren were included in the analysis. Information on the environmental factors was collected via questionnaires.

    RESULTS: Proportions of breastfed children were similar in ICA-positive and ICA-negative schoolchildren. Full cow's milk was introduced at one month of age or earlier more often in ICA-positive than ICA-negative schoolchildren (8.3% and 1.1%, respectively; P=0.05). Cereal before 3 months of age was introduced more often in ICA-positive than ICA-negative schoolchildren (7.7% and 0.5%, respectively; P=0.01). The mothers of cases took medicine during pregnancy more often than mothers of controls did (61.5% and 14.1%, respectively; P<0.001). More than half (53.8%) of ICA-positive children lived in homes where family members were smoking indoors, while this was recorded only for 26.6% of controls (P=0.04).

    CONCLUSIONS: Early introduction of cow's milk and cereal, the intake of medicine during pregnancy, and indoor smoking of family members are risk factors that predict the development of prediabetes among Lithuanian children.

  • 488.
    Skrodeniene, Erika
    et al.
    Kaunas University of Medicine, Lithuania.
    Marciulionyte, Dalia
    Kaunas University of Medicine, Lithuania.
    Padaiga, Žilvinas
    Kaunas University of Medicine, Lithuania.
    Jasinskiene, Edita
    Hospital of Kaunas University of Medicine, Lithuania.
    Sadauskaite-Kuehne, Vaiva
    Parkwayhealth Medical Center, China.
    Sanjeevi, Carani B.
    Department of Molecular Medicine and Surgery, Karolinska Institute, Sweden.
    Vitkauskiene, Astra
    Kaunas University of Medicine, Lithuania.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Associations between HLA class II haplotypes, environmental factors and type 1 diabetes mellitus in Lithuanian children with type 1 diabetes and controls2010In: Polish Annals of Medicine, ISSN 1230-8013, Vol. 17, no 1, p. 7-15Article in journal (Refereed)
    Abstract [en]

    Introduction. The onset of type 1 diabetes (T1D) is determined by genetic predisposition and environmental factors. Aim. The aim of our work was to identify associations between human leukocytes antigen (HLA) class II alleles, environmental factors and T1D in Lithuania. Materials and methods. Our case-control study included 124 diabetic children (mean age 9.19±3.94 years) and 78 controls (mean age 10.77±3.36 years). The age ranged from 0 to 15 years. HLA-DRB1, DQA1 and DQB1 alleles were genotyped using polymerase chain reaction. Information concerning the environmental factors was collected via questionnaires. Results. Logistic regression model indicated that three haplotypes: (DR3)-DQA1*0501-DQB1*0201, (DR4)-DQA1*0301-DQB1*0302 and (DR1)-DQA1 *010-04-DQB1*0501, increased the T1D risk statistically significantly 18.1, 12.3 and 3.4 times, respectively, while (DR11/12/13)-DQA1*05-DQB1*0301 haplotype decreased the risk of T1D 9.1 times. Several different regression models included environmental factors and different sets of risk and protective haplotypes. The results suggest that living in a remote area with lower population density during pregnancy increased the risk of T1D, as well as short breastfeeding, introduction of eggs before 5th month of age and infections during the last 6 months before diagnosis. Smoking during pregnancy as well as rubella and varicella virus infections seemed to decrease the risk of T1D. These associations were revealed while evaluating only environmental factors and when different HLA haplotypes together with environmental factors were included in the regression model. Discussion. The HLA typing shows that the differences in the incidence of T1D between Lithuania and neighboring countries cannot be explained only by genetics, but lifestyle and/or environmental factors should be considered. A number of studies presented here, have shown conflicting results regarding environmental factors and their associations with T1D. Conclusions. Both genetic and environmental factors play a major role in diabetes development and protection. However, even quite rapidly ongoing changes of environmental factors and lifestyle in Lithuania have not helped us to reveal any clear picture.

  • 489.
    Soderstrom, U.
    et al.
    University of Örebro, Sweden; Uppsala University, Sweden; Malarsjukhuset Hospital, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sahlqvist, L.
    Uppsala University, Sweden.
    Aman, J.
    University of Örebro, Sweden; Örebro University Hospital, Sweden.
    Impaired metabolic control and socio-demographic status in immigrant children at onset of Type 1 diabetes2014In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 31, no 11, p. 1418-1423Article in journal (Refereed)
    Abstract [en]

    AimThe aim of the present study was to compare clinical and socio-demographic conditions at the onset of Type1 diabetes in children born to immigrant families and children born to Swedish families, and to assess whether those conditions had an impact on metabolic status. Methods and designThis was an observational nationwide population-based matched cohort study on prospectively recorded registry data of all children with diabetes in Sweden and their families during 2000-2010. Out of a total of 13415 children from the Swedish Childhood Diabetes Registry (SWEDIABKIDS), 879 children born to immigrant parents were collected. To these we added 2627 children with Swedish-born parents, matched for gender, age and year of onset of Type1 diabetes. ResultsThe proportion of low capillary pH (less than7.30) at onset was higher in the immigrant cohort [25.8% vs. 16.4% in the Swedish cohort (Pless than0.001)]. HbA(1c) was also higher [95mmol/mol (10.8%) vs. 88mmol/mol (10.2%), respectively (Pless than0.001)]. In a logistic regression model with low pH as the dependent variable, we were unable to reveal any significant association to socio-demographic factors, but the odds ratio for HbA(1c) was 0.983 (95%CI 0.976-0.991) and for plasma glucose was 0.953 (95%CI 0.933-0.973). ConclusionChildren born to immigrant parents have lower capillary pH and higher HbA(1c) at diabetes onset. Immigrant families harbour lower socio-demographic living conditions, but this fact does not seem to influence the inferior metabolic condition at diabetes onset.

  • 490.
    Sonnenschein-van der Voort, Agnes M. M
    et al.
    Erasmus MC, Netherlands Erasmus MC, Netherlands Erasmus MC, Netherlands .
    Arends, Lidia R.
    Erasmus MC, Netherlands Erasmus University, Netherlands Erasmus University, Netherlands .
    de Jongste, Johan C.
    Erasmus Medical Center, Rotterdam, The Netherlands.
    Annesi-Maesano, Isabella
    Erasmus MC, Netherlands INSERM, France University of Paris 06, France .
    Arshad, S. Hasan
    St Marys Hospital, England .
    Barros, Henrique
    University of Porto, Portugal .
    Basterrechea, Mikel
    Public Health Div Gipuzkoa, Spain Spanish Consortium Research Epidemiol and Public Health CIBE, Spain .
    Bisgaard, Hans
    University of Copenhagen, Denmark Copenhagen University Hospital, Denmark .
    Chatzi, Leda
    University of Crete, Greece .
    Corpeleijn, Eva
    University of Groningen, Netherlands .
    Correia, Sofia
    University of Porto, Portugal .
    Craig, Leone C.
    University of Aberdeen, Scotland .
    Devereux, Graham
    University of Aberdeen, Scotland .
    Dogaru, Cristian
    University of Bern, Switzerland .
    Dostal, Miroslav
    Academic Science Czech Republic, Czech Republic .
    Duchén, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Eggesbo, Merete
    Norwegian Institute Public Heatlh, Norway .
    Kors van der Ent, C.
    University of Medical Centre Utrecht, Netherlands .
    Fantini, Maria P.
    University of Bologna, Bologna, Italy.
    Forastiere, Francesco
    Lazio Regional Health Serv, Italy .
    Frey, Urs
    University of Basel, Switzerland .
    Gehring, Ulrike
    University of Utrecht, Netherlands .
    Gori, Davide
    University of Bologna, Bologna, Italy.
    van der Gugten, AnneC.
    University of Medical Centre Utrecht, Netherlands .
    Hanke, Wojciech
    Nofer Institute Occupat Med, Poland .
    Henderson, A. John
    University of Bristol, England .
    Heude, Barbara
    INSERM, France University of Paris 11, France .
    Iniguez, Carmen
    Spanish Consortium Research Epidemiol and Public Health CIBE, Spain University of Valencia, Spain University of Valencia, Spain .
    Inskip, Hazel M.
    University of Southampton, England .
    Keil, Thomas
    Charite, Germany University of Wurzburg, Germany .
    Kelleher, CecilyC.
    University of Coll Dublin, Ireland .
    Kogevinas, Manolis
    National School Public Heatlh, Greece .
    Kreiner-Moller, Eskil
    University of Copenhagen, Denmark Copenhagen University Hospital, Denmark .
    Kuehni, Claudia E.
    University of Bern, Switzerland .
    Kuepers, LeanneK.
    University of Groningen, Netherlands .
    Lancz, Kinga
    Slovak Medical University, Slovakia .
    Larsen, PernilleS.
    University of Copenhagen, Denmark .
    Lau, Susanne
    Charite, Germany .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Mommers, Monique
    Maastricht University, Netherlands .
    Nybo Andersen, Anne-Marie
    University of Copenhagen, Denmark .
    Palkovicova, Lubica
    Slovak Medical University, Slovakia .
    Pike, Katharine C.
    University of Southampton, England .
    Pizzi, Costanza
    University of Turin, Italy .
    Polanska, Kinga
    Nofer Institute Occupat Med, Poland .
    Porta, Daniela
    Lazio Regional Health Serv, Italy .
    Richiardi, Lorenzo
    University of Turin, Italy .
    Roberts, Graham
    St Marys Hospital, England .
    Schmidt, Anne
    University of Bern, Switzerland .
    Sram, RadimJ.
    Academic Science Czech Republic, Czech Republic .
    Sunyer, Jordi
    St Marys Hospital, England Spanish Consortium Research Epidemiol and Public Health CIBE, Spain Centre Research Environm Epidemiol CREAL, Spain Pompeu Fabra University, Spain Hospital del Mar, Spain .
    Thijs, Carel
    Maastricht University, Netherlands .
    Torrent, Maties
    University of Bologna, Italy .
    Viljoen, Karien
    University of Coll Dublin, Ireland .
    Wijga, Alet H.
    National Institute Public Health and Environm RIVM, Netherlands .
    Vrijheid, Martine
    St Marys Hospital, England Spanish Consortium Research Epidemiol and Public Health CIBE, Spain Centre Research Environm Epidemiol CREAL, Spain Pompeu Fabra University, Spain .
    Jaddoe, VincentW . V.
    Erasmus MC, Netherlands Erasmus MC, Netherlands Erasmus MC, Netherlands .
    Duijts, Liesbeth
    Erasmus MC, Netherlands Erasmus MC, Netherlands Erasmus MC, Netherlands .
    Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children2014In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 133, no 5, p. 1317-1329Article in journal (Refereed)
    Abstract [en]

    Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age less than 37 weeks) and low birth weight (less than 2500 g) with childhood asthma outcomes. Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P less than. 05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

  • 491.
    Sorkio, Susa
    et al.
    National Institute for Health and Welfare Finland.
    Cuthbertson, David
    University of South Florida.
    Barlund, Sonja
    National Institute for Health and Welfare Finland.
    Reunanen, Antti
    Georgia State University.
    Berseth, Carol L
    Bristol Myers Squibb Co.
    Koski, Katriina
    University of Helsinki.
    Ormisson, Anne
    University of Tartu.
    Savilahti, Erkki
    University of Helsinki.
    Uusitalo, Ulla
    University South Florida.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Becker, Dorothy J
    Childrens Hospital Pittsburgh.
    Dupre, John
    Robarts Research Institute.
    P Krischer, Jeffrey
    University South Florida.
    Knip, Mikael
    University of Helsinki.
    Akerblom, Hans K
    University of Helsinki.
    Virtanen, Suvi M
    National Institute for Health and Welfare Finland.
    Breastfeeding patterns of mothers with type 1 diabetes: results from an infant feeding trial2010In: DIABETES-METABOLISM RESEARCH AND REVIEWS, ISSN 1520-7552, Vol. 26, no 3, p. 206-211Article in journal (Refereed)
    Abstract [en]

    Background Both the initiation and maintenance of breastfeeding have been reported to be negatively affected by maternal type 1 diabetes (T1D). The aim of this study was to prospectively examine the breastfeeding patterns among mothers with and without T1D participating in a large international randomized infant feeding trial (TRIGR). Methods Families with a member affected by T1D and with a newborn infant were invited into the study. Those who had HLA-conferred genetic susceptibility for T1D tested at birth with gestation andgt;35 weeks and were healthy were eligible to continue in the trial. Among the 2160 participating children, 1096 were born to women with T1D and 1064 to unaffected women. Information on infant feeding was acquired from the family by frequent prospective dietary interviews. Results Most (andgt;90%) of the infants of mothers with and without T1D were initially breastfed. Breastfeeding rates declined more steeply among mothers with than without T1D being 50 and 72% at 6 months, respectively. Mothers with T1D were younger, less educated and delivered earlier and more often by caesarean section than other mothers (p andlt; 0.01). After adjusting for all these factors associated with the termination of breastfeeding, there was no difference in the duration of breastfeeding among mothers with and without T1D. Conclusions Maternal diabetes status per se was not associated with shorter breastfeeding. The lower duration of breastfeeding in mothers with T1D is largely explained by their more frequent caesarean sections, earlier delivery and lower age and education.

  • 492.
    Stemann Larsen, Pernille
    et al.
    University of Copenhagen, Denmark .
    Kamper-Jorgensen, Mads
    University of Copenhagen, Denmark .
    Adamson, Ashley
    University of Newcastle, Australia .
    Barros, Henrique
    University of Porto, Portugal .
    Bonde, Jens Peter
    Bispebjerg Hospital, Denmark .
    Brescianini, Sonia
    Ist Super Sanita, Italy .
    Brophy, Sinead
    Swansea University, Wales .
    Casas, Maribel
    Centre Research Environm Epidemiol CREAL, Spain Hospital del Mar, Spain Spanish Consortium Research Epidemiol and Public Health CIBE, Spain .
    Devereux, Graham
    Royal Aberdeen Childrens Hospital, Scotland .
    Eggesbo, Merete
    Norwegian Institute Public Heatlh, Norway .
    Fantini, Maria Pia
    University of Bologna, Italy .
    Frey, Urs
    University of Childrens Hospital UKBB, Switzerland University of Childrens Hospital Bern, Switzerland .
    Gehring, Ulrike
    University of Utrecht, Netherlands .
    Grazuleviciene, Regina
    Vytautas Magnus University, Lithuania .
    Brink Henriksen, Tine
    Aarhus University Hospital, Denmark .
    Hertz-Picciotto, Irva
    University of Calif Davis, CA USA .
    Heude, Barbara
    University of Paris Sud, France .
    Hryhorczuk, Daniel O.
    University of Illinois, IL USA .
    Inskip, Hazel
    University of Southampton, England .
    Jaddoe, Vincent W. V.
    Erasmus MC, Netherlands .
    Lawlor, Debbie A.
    University of Bristol, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kelleher, Cecily
    University of Coll Dublin, Ireland .
    Kiess, Wieland
    Hospital Children and Adolescents, Germany Leipzig Research Centre Civilizat Disease, Germany .
    Koletzko, Berthold
    Ludwig Maximilians University of Munich Med, Germany .
    Kuehni, Claudia Elisabeth
    University of Bern, Switzerland .
    Kull, Inger
    Karolinska Institute, Sweden Karolinska Institute, Sweden Sachs Childrens Hospital, Sweden .
    Boye Kyhl, Henriette
    Odense University Hospital, Denmark .
    Magnus, Per
    Norwegian Institute Public Heatlh, Norway .
    Momas, Isabelle
    Paris Descartes University, France .
    Murray, Dierdre
    National University of Ireland University of Coll Cork, Ireland .
    Pekkanen, Juha
    University of Eastern Finland, Finland .
    Polanska, Kinga
    Nofer Institute Occupat Med, Poland .
    Porta, Daniela
    Lazio Regional Health Serv, Italy .
    Poulsen, Gry
    University of Copenhagen, Denmark .
    Richiardi, Lorenzo
    University of Turin, Italy .
    Roeleveld, Nel
    Radboud University of Nijmegen, Netherlands .
    Skovgaard, Anne Mette
    University of Copenhagen, Denmark .
    Sram, Radim J.
    Institute Expt Medical AS CR, Czech Republic .
    Strandberg-Larsen, Katrine
    University of Copenhagen, Denmark .
    Thijs, Carel
    Maastricht University, Netherlands .
    Van Eijsden, Manon
    University of Amsterdam, Netherlands University of Amsterdam, Netherlands .
    Wright, John
    Bradford Royal Infirm, England .
    Vrijheid, Martine
    Centre Research Environm Epidemiol CREAL, Spain .
    Nybo Andersen, Anne-Marie
    University of Copenhagen, Denmark .
    Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research2013In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 27, no 4, p. 393-414Article, review/survey (Refereed)
    Abstract [en]

    Background During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. Methods European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. Results In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. Conclusion This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

  • 493.
    Stenhammar, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Fälth-Magnusson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Hallert, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Welfare and Care (IVV), Self-Care and Learning. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Högberg, Lotta
    Barn och ungdomsmed kliniken Vrinnevisjukhuset, Norrköping.
    Magnusson, Karl-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Från ax till limpa - några svenska bidrag till forskningen om celiaki2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 48, p. 3932-3937Article in journal (Other academic)
  • 494.
    Stenhammar, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Ascher, Henry
    Avd för Pediatrik, Sahlgrenska sjukhuset Göteborg.
    Danneus, Anders
    Avd för Pediatrik, Universitetssjukhuset, Uppsala .
    Hernell, Olle
    Avd för Pediatrik, Universitetssjukhuset, Umeå .
    Ivarsson, Anneli
    Avd för Pediatrick, Universitetssjukhuset, Umeå .
    Lindberg, Eva
    Avd för Pediatrik, Universitetssjukhuset, Örebro .
    Lindquist, Bo
    Barnmottagningen, Odenplan, Stockholm .
    Nivenius, Kerstin
    Avd för Pediatrik, Universitetssjukhuset, Lund .
    How do Swedish paediatric clinics diagnose coeliac disease? Results of a nationwide questionnaire study2006In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 95, no 11, p. 1495-1497Article in journal (Refereed)
    Abstract [en]

    Background and aim: Diagnosis of coeliac disease is based on the demonstration of enteropathy in a small bowel biopsy. Correct diagnosis is of utmost importance, since the need for dietary management is life long, and inadequate treatment may lead to potentially serious complications. The Swedish Working Group for Paediatric Coeliac Disease has published guidelines for the diagnosis of childhood coeliac disease. The present questionnaire was designed in order to create the basis for revision of those guidelines. Methods: In 2004, a nationwide questionnaire concerning current diagnostic routines was sent to all 45 paediatric clinics performing small bowel biopsy. All clinics responded. Results: All clinics base their diagnosis on small bowel biopsy findings at presentation. Furthermore, in 24 (53%) of the clinics, children with suspected coeliac disease are investigated by small bowel biopsy both at presentation and follow-up while on a gluten-free diet. Eighteen (40%) of the clinics employ a different diagnostic routine for children under 2 y of age than for those older than 2 y. All clinics use coeliac serological testing at various stages of the diagnostic procedure. Conclusion: All Swedish paediatric clinics perform a small bowel biopsy at presentation in children with suspected coeliac disease, and the majority of clinics perform a second biopsy when the child is on a gluten-free diet. Serological testing is frequently used as a diagnostic aid and in the monitoring of the disease while on a gluten-free diet. © 2006 Taylor & Francis.

  • 495.
    Stenhammar, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Hallert, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Social and Welfare Studies. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Genmodifierade sädesslag - alternativ för patienter med celiaki2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 10, p. 740-740Article in journal (Other academic)
  • 496.
    Stenhammar, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Högberg, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Ivarsson, Anneli
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
    Laurin, Pia
    Myléus, Anna
    Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Letter: Coeliac disease and socio-economic status2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 8, p. e328-Article in journal (Refereed)
  • 497.
    Stenhammar, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Nordwall, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Strömberg, Leif
    Barnkliniken, Vrinnevisjukhuset, Norrköping.
    Moderate dose inhaled budesonide disguising symptoms of Addison's disease in an asthmatic boy with silent celiac disease2005In: Journal of pediatric pharmacology and therapeutics, ISSN 1551-6776, Vol. 10, no 3, p. 108-111Article in journal (Refereed)
  • 498.
    Stenhammar, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Högberg, Lotta
    Barn och ungdomsmed kliniken Vrinnevisjukhuset, Norrköping.
    Saalman, Robert
    Drottning Silvias barn och ungdomssjukhus Göteborg.
    Havre kan ingå i den glutenfria kosten2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, p. 1610-1611Article in journal (Other academic)
  • 499.
    Stensson, M.
    et al.
    Center of Oral Health, School of Health Sciences, Jönköping.
    Koch, G.
    Department of Pediatric Dentistry, Institute for Postgraduate Dental Education, Jönköping.
    Coric, S.
    Department of Pediatric Dentistry, Institute for Postgraduate Dental Education, Jönköping.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Birkhed, D.
    Department of Cariology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wendt, L.-W.
    Center of Oral Health, School of Health Sciences, Jönköping.
    Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age2014In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 48, no 2, p. 111-117Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and carious lesions, plaque and gingivitis were recorded. Saliva and plaque were sampled for determination of mutans streptococci (MS) and lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA). Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo group were caries-free (p < 0.01). The prevalence of approximal caries lesions was lower in the probiotic group (0.67 ± 1.61 vs. 1.53 ± 2.64; p < 0.05) and there were fewer sites with gingivitis compared to the placebo group (p < 0.05). There were no significant differences between the groups with respect to frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride supplements (p < 0.05). There were no intergroup differences with respect to L. reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems that daily supplementation with L. reuteri from birth and during the first year of life is associated with reduced caries prevalence and gingivitis score in the primary dentition at 9 years of age.

  • 500.
    Stoltz Sjostrom, Elisabeth
    et al.
    Umeå University, Sweden .
    Ohlund, Inger
    Umeå University, Sweden .
    Ahlsson, Fredrik
    Uppsala University, Sweden .
    Engstrom, Eva
    University of Gothenburg, Sweden .
    Fellman, Vineta
    Lund University, Sweden .
    Hellstrom, Ann
    University of Gothenburg, Sweden .
    Kallen, Karin
    Lund University, Sweden .
    Norman, Mikael
    Karolinska Institute, Sweden .
    Olhager, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Serenius, Fredrik
    Umeå University, Sweden .
    Domellof, Magnus
    Umeå University, Sweden .
    Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 11, p. 1067-1074Article in journal (Refereed)
    Abstract [en]

    AimTo explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants. less thanbrgreater than less thanbrgreater thanMethodsRetrospective population-based study of all ELGA infants (andlt;27weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70days of postnatal age were retrieved from hospital records. less thanbrgreater than less thanbrgreater thanResultsStudy infants (n=531) had a meanSD gestational age of 25.3 +/- 1.1weeks and a birth weight of 765 +/- 170g. Between 0 and 70days, average daily energy and protein intakes were 120 +/- 11kcal/kg and 3.2 +/- 0.4g/kg, respectively. During this period, standard deviation scores for weight, length and head circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational age, baseline anthropometrics and severity of illness into account, lower energy intake correlated with lower gain in weight (r=+0.315, pandlt;0.001), length (r=+0.215, pandlt;0.001) and head circumference (r=+0.218, pandlt;0.001). Protein intake predicted growth in all anthropometric outcomes, and fat intake was positively associated with head circumference growth. less thanbrgreater than less thanbrgreater thanConclusionExtremely low gestational age infants received considerably less energy and protein than recommended and showed postnatal growth failure. Nutrient intakes were independent predictors of growth even after adjusting for severity of illness. These findings suggest that optimized energy and macronutrient intakes may prevent early growth failure in these infants.

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