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  • 1.
    Abrahamsson, Jonas
    et al.
    Queen Silvia Children’s Hospital, Gothenburg.
    Forestier, Erik
    Heldrup, Jesper
    Jahnukainen, Kirsi
    Jónsson, Olafur G.
    Lausen, Birgitte
    Palle, Josefine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Zeller, Bernward
    Hasle, Henrik
    Aarhus University Hospital Skejby, Aarhus.
    Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 3, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Purpose

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.

    Patients and Methods

    All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (>= 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation.

    Results

    Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%).

    Conclusion

    The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.

  • 2. Af Sandeberg, Margareta
    et al.
    Wettergren, Lena
    Bjork, Olle
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Johansson, Eva
    Is school attendance during initial childhood cancer treatment associated with infection?2012In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 59, no 6, p. 1112-1112Article in journal (Other academic)
  • 3.
    Agrasada, Grace V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kylberg, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Exclusive breastfeeding of low birth weight infants for the first six months: infant morbidity and maternal and infant anthropometry2011In: Asia Pacific Journal of Clinical Nutrition, ISSN 0964-7058, E-ISSN 1440-6047, Vol. 20, no 1, p. 62-68Article in journal (Refereed)
    Abstract [en]

    Background: to report anthropometry and morbidity among term low birth weight infants and anthropometry of their first time mothers during the first six months in relation to breastfeeding practice. Methods: we examined data from a randomized controlled trial in Manila, the Philippines. Of the 204 mothers randomized, 68 mothers received eight postpartum breastfeeding counseling sessions, the rest did not. Maternal and infant anthropometric data at birth, 2, 4 and 6 months were taken. During seven follow-up hospital visits, an independent interviewer recorded feeding data. Results: the 24 infants exclusively breastfed from birth to six months did not have diarrhea compared to 134 partially breastfed (mean 2.3 days) and 21 non-breastfed infants (mean 2.5 days). Partially breastfed and non-breastfed infants compared to exclusively breastfed infants had more frequent, as well as more severe episodes of respiratory infections. At six months, neither overall gain in infant weight, length and head circumferences nor mean maternal weight and body mass index differed significantly between the feeding groups. Conclusions: exclusive breastfeeding for 6 months can be recommended in term low birth weight infants, who were protected from diarrhea, had fewer respiratory infections, required no hospitalization and had catch up growth. Exclusively breastfeeding mothers did not differ from mothers who breastfed partially or those who did not breastfeed with regard to weight changes at six months.

  • 4.
    Agren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Zelenin, Sergey
    Department of Woman and Child Health, Karolinska Institute, Sweden.
    Svensson, Lill-Britt
    Department of Woman and Child Health, Karolinska Institute, Sweden.
    Nejsum, Lene N
    The Water and Salt Research Center, Aarhus University, Denmark.
    Nielsen, Soren
    The Water and Salt Research Center, Aarhus University, Denmark.
    Aperia, Anita
    Department of Woman and Child Health, Karolinska Institute, Sweden.
    Sedin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Antenatal Corticosteroids and Postnatal Fluid Restriction Produce Differential Effects on AQP3 Expression, Water Handling, and Barrier Function in Perinatal Rat Epidermis2010In: Dermatology research and practice, ISSN 1687-6113Article in journal (Refereed)
    Abstract [en]

    Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3) is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18) rat pups were studied after antenatal corticosteroid exposure (ANS), and neonatal (P1) rat pups after an 18 h fast. Transepidermal water loss (TEWL) and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration), while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin.

  • 5.
    Ahlgren, Kerstin M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moretti, Silvia
    Lundgren, Brita Ardesjö
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Iulia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åhlin, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Norling, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Perheentupa, Jaakko
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Crewther, Pauline E.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bensing, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Scott, Hamish S.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Romani, Luigina
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model2011In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 41, no 1, p. 235-245Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.

  • 6. Ahlgrim, C.
    et al.
    Gutermuth, J.
    Onell, A.
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Schaeffner, I
    Darsow, U.
    Pfab, F.
    Brockow, K.
    Ring, J.
    Behrendt, H.
    Jakob, T.
    Huss-Marp, J.
    Comparison of Molecular Multiplex and Singleplex Analysis of IgE to Grass Pollen Allergens in Untreated German Grass Pollen-Allergic Patients2015In: Journal of investigational allergology & clinical immunology, ISSN 1018-9068, E-ISSN 1698-0808, Vol. 25, no 3, p. 190-195Article in journal (Refereed)
    Abstract [en]

    Background: The ImmunoCAP ISAC 112 platform is the only commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with the molecular singleplex ImmunoCAP IgE platform are lacking. Objective:To compare the multiplex ISAC 112 platform and the singleplex ImmunoCAP platform in regard to IgE to grass pollen allergens in untreated grass pollen allergic patients in Germany. Methods: Serum samples from 101 adults with grass pollen allergy were analyzed for specific IgE (sIgE) to 8 allergenic molecules from timothy grass pollen and to the 112 allergenic molecules included in the ISAC panel. The results for the multiplex and singleplex tests were subsequently analyzed statistically. Results: Comparison of sIgE to grass pollen allergens detected by ISAC 112 and the singleplex ImmunoCAP assay revealed the following correlation coefficients: 0.88 (rPhl p1), 0.96 (rPhl p2), 0.70 (nPhl p4), 0.94 (rPhl p5b), 0.92 (rPhl p6), 0.85 (rPhl p11), and 0.78 (rPhl p12). Conclusion: Molecular testing with ISAC 112 correlates well with the ImmunoCAP platform for respective molecular timothy grass pollen allergens.

  • 7.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Univ Groningen, Dept Behav Physiol, Groningen, Netherlands.;Karolinska Inst, Ctr Gender Med, Stockholm, Sweden..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Gene Expression in Placentas From Nondiabetic Women Giving Birth to Large for Gestational Age Infants2015In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 22, no 10, p. 1281-1288Article in journal (Refereed)
    Abstract [en]

    Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.

  • 8.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Forslund, Anders H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size2013In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 168, no 1, p. 26-29Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

    STUDY DESIGN:

    Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

    RESULTS:

    Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

    CONCLUSION:

    The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.

  • 9.
    Albertsson-Wikland, Kerstin
    et al.
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Kriström, Berit
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Lundberg, Elena
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Aronson, A Stefan
    Department of Pediatrics, Halmstad Hospital, Sweden.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hagenäs, Lars
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Ivarsson, Sten-A
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ritzén, Martin
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Westgren, Ulf
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Westphal, Otto
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Aman, Jan
    School of Health and Medical Sciences, Örebro University, Sweden.
    Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion2014In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no 3, p. 158-170Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency.

    METHODS: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH(67)) given as one (GH(67×1); n = 35) or two daily injections (GH(33×2); n = 36), or to remain on a single 33 µg/kg/day dose (GH(33×1); n = 40). Growth was assessed as heightSDSgain for prepubertal, pubertal and total periods, as well as AHSDS versus the population and the midparental height.

    RESULTS: Pubertal heightSDSgain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33×1), 0.41, p < 0.05). AHSDS was greater on GH(67) (GH(67×1), -0.84; GH(33×2), -0.83) than GH(33) (-1.25, p < 0.05), and heightSDSgain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target heightSDS.

    CONCLUSION: Pubertal heightSDSgain and AHSDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once- and twice-daily GH(67) regimens.

  • 10.
    Albertsson-Wikland, Kerstin
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Medicinargatan 11, SE-40530 Gothenburg, Sweden..
    Martensson, Anton
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Medicinargatan 11, SE-40530 Gothenburg, Sweden.;Stat Konsultgrp, SE-41319 Gothenburg, Sweden..
    Savendahl, Lars
    Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden..
    Niklasson, Aimon
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg Pediat Growth Res Ctr,Dept Pediat, SE-41685 Gothenburg, Sweden..
    Bang, Peter
    Linkoping Univ, Dept Clin & Expt Med, Div Pediat, SE-58185 Linkoping, Sweden..
    Dahlgren, Jovanna
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg Pediat Growth Res Ctr,Dept Pediat, SE-41685 Gothenburg, Sweden..
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kristrom, Berit
    Umea Univ, Dept Clin Sci, Pediat, SE-90185 Umea, Sweden..
    Norgren, Svante
    Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden..
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, SE-41319 Gothenburg, Sweden..
    Oden, Anders
    Stat Konsultgrp, SE-41319 Gothenburg, Sweden.;Chalmers, Dept Math Sci, SE-41296 Gothenburg, Sweden..
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 5, p. 2149-2159Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 11. Albin, Anna-Karin
    et al.
    Ankarberg-Lindgren, Carina
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Albertsson-Wikland, Kerstin
    Ritzen, E. Martin
    Does Growth Hormone Treatment Influence Pubertal Development in Short Children?2011In: Hormone Research in Paediatrics, ISSN 1663-2818, Vol. 76, no 4, p. 262-272Article in journal (Refereed)
    Abstract [en]

    Aim: To study the influence of growth hormone (GH) treatment on the initiation and progression of puberty in short children.

    Methods: This prospective, randomized, controlled study included 124 short children (33 girls) who received GH treatment (Genotropin (R); Pfizer Inc.) from a mean age of 11 years until near adult height [intent-to-treat (ITT) population]. Children were randomized into three groups: controls (n = 33), GH 33 mu g/kg/day (n = 34) or GH 67 mu g/kg/day (n = 57). Prepubertal children at study start constituted the per-protocol (PP) population (n = 101). Auxological measurements were made and puberty was staged every 3 months. Serum sex-steroid concentrations were assessed every 6 months.

    Results: No significant differences were found between the groups, of both PP and ITT populations, in time elapsed from start of treatment until either onset of puberty, age at start of puberty or age at final pubertal maturation in either sex. In the ITT population, pubertal duration was significantly longer in GH-treated girls, and maximum mean testicular volume was significantly greater in GH-treated boys than controls, but there were no differences in testosterone levels between the groups.

    Conclusion: GH treatment did not influence age at onset of puberty and did not accelerate pubertal development. In boys, GH treatment appeared to increase testicular volume.

  • 12. Aldrimer, Mattias
    et al.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Niklasson, Frank
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 4, p. 326-332Article in journal (Refereed)
    Abstract [en]

    Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

  • 13.
    Almblad, Ann-Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Caring for the Acutely, Severely Ill Child-A Multifaceted Situation with Paradoxical Elements: Swedish Healthcare Professionals' Experiences2016In: Journal of Pediatric Nursing: Nursing Care of Children and Families, ISSN 0882-5963, E-ISSN 1532-8449, Vol. 31, no 5, p. E293-E300Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to describe healthcare professionals' experience of caring for acutely, severely ill children in hospital in Sweden.

    Design and Methods: Five focus group interviews were conducted with nurses, nurse assistants and physicians comprising a total of 20 participants. Data were analyzed using qualitative content analysis.

    Results: An overall theme emerged that describes healthcare professionals' experiences as: "being in a multifaceted area of tension with paradoxical elements". The theme is based on three categories: proficiency of the individuals and the team is the fundamental base; interactions are crucial in an area of tension; and wellbeing of the individual is a balance of contradictory emotions. With maintained focus on the ill child, proficiency is the fundamental base, interactions are crucial, and moreover contradictory emotions are described.

    Conclusions: The interplay based on proficiency may influence the assessments and treatments of acutely, severely ill children.

    Practice Implications: Recognizing the multifaceted area of tension with paradoxical elements, practical teamwork exercises, a structured approach, and assessment tools could be a possible way to develop interprofessional team collaboration to improve the care of acutely, severely ill children in order to increase patient safety.

  • 14.
    Al-Shamkhi, Nasrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlen, S. E.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Hedlin, G.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Middelveld, R.
    Karolinska Inst, Inst Environm Med, Expt Asthma & Allergy Res Unit, Stockholm, Sweden..
    Bjerg, A.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Ekerljung, L.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Olin, A. C.
    Univ Gothenburg, Sect Occupat & Environm Med, Dept Publ Hlth & Community Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Sommar, J.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Forsberg, B.
    Umea Univ, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 9, p. 1185-1193Article in journal (Refereed)
    Abstract [en]

    Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

  • 15.
    Alving, Kjell
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Basic aspects of exhaled nitric oxide2010In: European Respiratory Monograph, ISSN 1025-448X, E-ISSN 2075-6674, Vol. 49, p. 1-31Article, review/survey (Refereed)
    Abstract [en]

    Nitric oxide (NO) in orally exhaled air mainly originates fromthe respiratory epithelium. NO is produced by inducible NOsynthase (iNOS), which is regulated by signal transducer andactivator of transcription (STAT)-1 under the influence ofhomeostatic interferon-c. In patients with asthma, iNOSexpression is upregulated by interleukin (IL)-4 and IL-13 viathe activation of STAT-6 in the bronchial epithelium. Thus,exhaled NO primarily signals local T-helper cell type 2-driveninflammation in the bronchial mucosa. With these character-istics, exhaled NO will be a suitable marker for predicting theresponse to inhaled corticosteroids, and to monitor the anti-inflammatory effect.The methodology for measuring exhaled NO has beenstandardised based on international consensus. The determi-nants of exhaled NO levels are fairly well characterised, withthe most important being cigarette smoking, nitrate intake, airpollution, allergen sensitisation and exposure, along withheight, sex and age. A future development may be the estima-tion of peripheral airway inflammation by measuring exhaledNO at multiple exhalation flow rates.

  • 16.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Grönqvist, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Cernvall, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hedström, Mariann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lyhagen, Johan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Mattsson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence: a 10-year follow-up study2016In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 25, no 5, p. 582-589Article in journal (Refereed)
    Abstract [en]

    Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.

    Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.

    Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.

    Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer

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  • 17.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thorsell Cederberg, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lindahl Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Losing your context - Exploration of emotional suffering after cancer during adolescence2016Conference paper (Refereed)
  • 18.
    Ander, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Mattsson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Toft, Teolinda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Norberg, Annika Lindahl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    U-CARE: YoungCan-Development of an Internet-Based Self-Help Program of Psychosocial Support and Psychological Treatment2013Conference paper (Refereed)
  • 19.
    Andersson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effects of Delayed versus Early Cord Clamping on Healthy Term Infants2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to study maternal and infant effects of delayed cord clamping (≥180 seconds, DCC) compared to early (≤10 seconds, ECC) in a randomised controlled trial. Practice and guidelines regarding when to clamp the cord vary globally, and different meta-analyses have shown contradictory conclusions on benefits and disadvantages of DCC and ECC.

    The study population consisted of 382 term infants born after normal pregnancies and randomised to DCC or ECC after birth. The primary objective was iron stores and iron deficiency at 4 months of age, but the thesis was designed to investigate a wide range of suggested effects associated with cord clamping.

    Paper I showed that DCC was associated with improved iron stores at 4 months (45% higher ferritin) and that the incidence of iron deficiency was reduced from 5.7% to 0.6%. Neonatal anaemia at 2-3 days was less frequent in the DCC group, 1.2% vs. 6.3%. There were no differences between the groups in respiratory symptoms, polycythaemia, or hyperbilirubinaemia.

    In paper II we demonstrated that DCC versus ECC was not associated with higher risk for maternal post partum haemorrhage and rendered a comparable ratio of valid umbilical artery blood gas samples.

    In paper III, the Ages and Stages Questionnaire was used to assess neurodevelopment at 4 months. The total scores did not differ, but the DCC group had a higher score in the problem-solving domain and a lower score in the personal-social domain. Immunoglobulin G level was 0.7 g/L higher in the DCC group at 2–3 days, but did not differ at 4 months. Symptoms of infection up to 4 months were comparable between groups.

    Finally, in paper IV, iron stores and neurodevelopment were similar between groups at 12 months. Gender specific outcome on neurodevelopment at 12 months was discovered, implying positive effects from DCC on boys and negative on girls.

    We conclude that delaying umbilical cord clamping for 180 seconds is safe and associated with a significantly reduced risk for iron deficiency at 4 months, which may have neurodevelopmental effects at a later age.

    List of papers
    1. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial
    Open this publication in new window or tab >>Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial
    2011 (English)In: The BMJ, E-ISSN 1756-1833, Vol. 343, p. d7157-Article in journal (Refereed) Published
    Abstract [en]

    Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

    Design: Randomised controlled trial.

    Setting: Swedish county hospital.

    Participants: 400 full term infants born after a low risk pregnancy.

    Intervention: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery).

    Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

    Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 mu g/L v 81 mu g/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

    Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-168430 (URN)10.1136/bmj.d7157 (DOI)000299016400004 ()
    Available from: 2012-02-10 Created: 2012-02-10 Last updated: 2023-08-28Bibliographically approved
    2. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial
    Open this publication in new window or tab >>Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial
    Show others...
    2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 567-574Article in journal (Refereed) Published
    Abstract [en]

    Objective

    To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling.

    Design

    Secondary analysis of a parallel-group, single-center, randomized controlled trial.

    Setting

    Swedish county hospital.

    Population

    382 term deliveries after a low-risk pregnancy.

    Methods

    Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2.

    Main outcome measures

    PPH and proportion of valid blood gas samples.

    Results

    The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC.

    Conclusions

    Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

    National Category
    Medical and Health Sciences
    Research subject
    Medical Science; Obstetrics and Gynaecology; Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-196866 (URN)10.1111/j.1600-0412.2012.01530.x (DOI)000319060200011 ()22913332 (PubMedID)
    Available from: 2013-03-14 Created: 2013-03-14 Last updated: 2017-12-06Bibliographically approved
    3. Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial
    Open this publication in new window or tab >>Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial
    2013 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, p. 525-531Article in journal (Refereed) Published
    Abstract [en]

    AIM:

    To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4 months of life.

    METHODS:

    Full-term infants (n = 382) were randomised to delayed (≥180 sec) or early cord clamping (≤10 sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4 months. Immunoglobulin G was measured at birth, 2-3 days and 4 months. Parents recorded any symptoms indicating infection during the first 4 months of life.

    RESULTS:

    The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p = 0.03] at 4 months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p = 0.01]. The IgG level was higher in the DCC group at 2-3 days (11.7 vs. 11.0 g/L, p = 0.004), but did not differ between the groups at 4 months. Symptoms of infection were comparable between the groups.

    CONCLUSION:

    Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4 months of age, but may have an impact on specific neurodevelopmental domains.

    National Category
    Medical and Health Sciences
    Research subject
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-196867 (URN)10.1111/apa.12168 (DOI)000317361400029 ()23336628 (PubMedID)
    Available from: 2013-03-14 Created: 2013-03-14 Last updated: 2017-12-06Bibliographically approved
    4. A randomized trial of delayed versus early cord clamping: iron status and neurodevelopment at 12 months of age
    Open this publication in new window or tab >>A randomized trial of delayed versus early cord clamping: iron status and neurodevelopment at 12 months of age
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To investigate effects of delayed umbilical cord clamping, as compared to early, on iron status and infant development at 12 months of age.

    Study design: Term infants (n = 382) were randomly assigned to delayed (≥180 sec) or early (≤10 sec) umbilical cord clamping. Follow up at 12 months of age included evaluation of iron status (ferritin, transferrin saturation, transferrin receptor, reticulocyte hemoglobin equivalent and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire.

    Results: At 12 months 347 infants were assessed. The two randomization groups did not differ in iron status or in neurodevelopment; 13 had iron deficiency and only one infant had iron deficiency anemia. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ were infant sex and breastfeeding within one hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that delayed cord clamping was associated with a 5 points higher ASQ score among boys, but a 12 points lower score in girls, out of a maximum of 300 points.

    Conclusions: Delayed cord clamping increases neonatal hemoglobin levels and improves iron status at four months of age, but does not affect ferritin levels or neurodevelopment assessed by ASQ in a selected population of healthy term born infants. However, minor effects on neurodevelopment may not be possible to demonstrate with the size of the study population and the chosen method for assessment. The current data indicate that effects of delayed cord clamping may differ according to infant sex and that boys may benefit more from delayed cord clamping than girls.

    National Category
    Medical and Health Sciences
    Research subject
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-198166 (URN)
    Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2013-08-30
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    fulltext
  • 20.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellof, Magnus
    Andersson, Dan
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effect of Delayed vs Early Umbilical Cord Clamping on Iron Status and Neurodevelopment at Age 12 Months A Randomized Clinical Trial2014In: JAMA PEDIATR, ISSN 2168-6203, Vol. 168, no 6, p. 547-554Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping. OBJECTIVE To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ). INTERVENTIONS Infants were randomized to DCC (>= 180 seconds after delivery) or ECC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was iron status at age 12 months; the secondary outcome was ASQ score. RESULTS In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P =.40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P =.42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P =.04 for the interaction term). CONCLUSIONS AND RELEVANCE Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated.

  • 21.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Andersson, Dan
    Department of Pediatrics, Hospital of Halland, Halmstad, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    A randomized trial of delayed versus early cord clamping: iron status and neurodevelopment at 12 months of ageManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To investigate effects of delayed umbilical cord clamping, as compared to early, on iron status and infant development at 12 months of age.

    Study design: Term infants (n = 382) were randomly assigned to delayed (≥180 sec) or early (≤10 sec) umbilical cord clamping. Follow up at 12 months of age included evaluation of iron status (ferritin, transferrin saturation, transferrin receptor, reticulocyte hemoglobin equivalent and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire.

    Results: At 12 months 347 infants were assessed. The two randomization groups did not differ in iron status or in neurodevelopment; 13 had iron deficiency and only one infant had iron deficiency anemia. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ were infant sex and breastfeeding within one hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that delayed cord clamping was associated with a 5 points higher ASQ score among boys, but a 12 points lower score in girls, out of a maximum of 300 points.

    Conclusions: Delayed cord clamping increases neonatal hemoglobin levels and improves iron status at four months of age, but does not affect ferritin levels or neurodevelopment assessed by ASQ in a selected population of healthy term born infants. However, minor effects on neurodevelopment may not be possible to demonstrate with the size of the study population and the chosen method for assessment. The current data indicate that effects of delayed cord clamping may differ according to infant sex and that boys may benefit more from delayed cord clamping than girls.

  • 22.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Andersson, Dan
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, p. 525-531Article in journal (Refereed)
    Abstract [en]

    AIM:

    To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4 months of life.

    METHODS:

    Full-term infants (n = 382) were randomised to delayed (≥180 sec) or early cord clamping (≤10 sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4 months. Immunoglobulin G was measured at birth, 2-3 days and 4 months. Parents recorded any symptoms indicating infection during the first 4 months of life.

    RESULTS:

    The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p = 0.03] at 4 months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p = 0.01]. The IgG level was higher in the DCC group at 2-3 days (11.7 vs. 11.0 g/L, p = 0.004), but did not differ between the groups at 4 months. Symptoms of infection were comparable between the groups.

    CONCLUSION:

    Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4 months of age, but may have an impact on specific neurodevelopmental domains.

  • 23.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andersson, Dan
    Clausen, Jesper
    Domellöf, Magnus
    Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 567-574Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling.

    Design

    Secondary analysis of a parallel-group, single-center, randomized controlled trial.

    Setting

    Swedish county hospital.

    Population

    382 term deliveries after a low-risk pregnancy.

    Methods

    Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2.

    Main outcome measures

    PPH and proportion of valid blood gas samples.

    Results

    The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC.

    Conclusions

    Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

  • 24.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Andersson, Dan
    Domellöf, Magnus
    Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial2011In: The BMJ, E-ISSN 1756-1833, Vol. 343, p. d7157-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

    Design: Randomised controlled trial.

    Setting: Swedish county hospital.

    Participants: 400 full term infants born after a low risk pregnancy.

    Intervention: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery).

    Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

    Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 mu g/L v 81 mu g/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

    Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia.

  • 25.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Department of Research and Development, Region Halland, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
    Elective caesarean: does delay in cord clamping for 30 s ensure sufficient iron stores at 4 months of age? A historical cohort control study2016In: BMJ Open, E-ISSN 2044-6055, Vol. 6, no 11, article id e012995Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare iron stores in infants born after elective caesarean section (CS) and a 30 s delay of umbilical cord clamping with those born vaginally after early (≤10 s) or delayed (≥180 s) cord clamping.

    DESIGN: Prospective observational study with historical control.

    SETTING: Swedish county hospital.

    POPULATION: 64 infants born after elective CS were compared with a historical control of 166 early clamped and 168 delayed clamped after vaginal birth.

    METHODS: Blood and iron status were measured in blood samples collected at birth, 48-96 hours after birth, 4 and 12 months of age.

    PRIMARY AND SECONDARY OUTCOME MEASURES: Ferritin at 4 months of age was the primary outcome, second outcome measures were other indicators of iron status, and haemoglobin, at 4 and 12 months of age, as well as respiratory distress at 1 and 6 hours after birth.

    RESULTS: At 4 months infants born by elective CS had better iron status than those born vaginally subjected to early cord clamping, shown by higher adjusted mean difference of ferritin concentration (39 µg/L (95% CI 10 to 60)) and mean cell volume (1.8 fL (95% CI 0.6 to 3.0)); and lower levels of transferrin receptors (-0.39 mg/L (95% CI -0.69 to -0.08)). No differences were seen between infants born after elective CS and delayed clamped vaginally born infants at 4 months. No differences were found between groups at 12 months of age.

    CONCLUSIONS: Waiting to clamp the umbilical cord for 30 s after elective CS results in higher iron stores at 4 months of age compared with early cord clamping after vaginal birth, and seems to ensure iron status comparable with those achieved after 180 s delayed cord clamping after vaginal birth.

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  • 26.
    Andersson, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lindquist, Barbro
    Hosp Halland, Habilitat Ctr, Halmstad, Sweden..
    Lindgren, Magnus
    Lund Univ, Dept Psychol, Lund, Sweden..
    Stjernqvist, Karin
    Lund Univ, Dept Psychol, Lund, Sweden..
    Domellof, Magnus
    Umea Univ, Dept Clin Sci, Pediat Unit, Umea, Sweden..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Effect of Delayed Cord Clamping on Neurodevelopment at 4 Years of Age A Randomized Clinical Trial2015In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 169, no 7, p. 631-638Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayuci umbilical cord clamping (CC) prevents iron deficiency at 4 to 6 months of age, but long-term effects after 12 months of age have not been reported. OBJECTIVE To investigate the effects of delayed CC compared with early CC on neurodevelopment at 4 years of age. DESIGN, SETTING, AND PARTICIPANTS Follow-up of a randomized clinical trial conducted from April 16, 2008, through May 21, 2010, at a Swedish county hospital. Children who were included in the original study (n = 382) as full-term infants born after a low-risk pregnancy were invited to return for follow-up at 4 years of age. Wechsler Preschool and Primary Scale of Intelligence (WPPSI-111) and Movement Assessment Battery for Children (Movement ABC) scores (collected between April 18, 2012, and July 5, 2013) were assessed by a blinded psychologist. Between April 11, 2012, and August 13, 2013, parents recorded their child's development using the Ages and Stages Questionnaire, Third Edition (ASQ) and behavior using the Strengths and Difficulties Questionnaire. All data were analyzed by intention to treat. INTERVENTIONS Randomization to delayed CC (>= 180 seconds after delivery) or early CC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was full-scale IQ as assessed by the were development as assessed by the scales from the WPPSI-III and Movement ABC, development as recorded using the ASQ, and behavior using the Strengths and Difficulties Questionnaire. RESULTS We assessed 263 children (68.8%). No differences were found in WPPSI-III scores between groups. Delayed CC improved the adjusted mean differences (AMDs) in the ASQ personal-social (AMD, 2.8; 95% Cl, 0.8-4.7) and fine-motor (AMD, 2.1; 95% Cl, 0.2-4.0) domains and the Strengths and Difficulties Questionnaire prosocial subscale (AMD, 0.5; 95% Cl, >0.0-0.9). Fewer children in the delayed-CC group had results below the cutoff in the ASQ fine-motor domain (11.0% vs 3.7%; P =.02) and the Movement ABC bicycle-trail task (12.9% vs 3.8%; P =.02). Boys who received delayed CC had significantly higher AMDs in the WPPSI-III processing-speed quotient (AMD, 4.2; 95% Cl, 0.8-7.6; P =.02), Movement ABC bicycle-trail task (AMD, 0.8; 95% Cl, 0.1-1.5; P =.03), and fine-motor (AMD, 4.7; 95% Cl, 1.0-8.4; P =.01) and personal-social (AMD, 4.9; 95% Cl, 1.6-8.3; P =.004) domains of the ASQ. CONCLUSIONS AND RELEVANCE Delayed CC compared with early CC improved scores in the fine-motor at 4 years of age, especially in boys, indicating that optimizing the time to CC may affect neurodevelopment in a low-risk population of children born in a high-income country.

  • 27.
    Angsten, Gertrud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Finkel, Yigael
    Lucas, Steven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kassa, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Paulsson, Mattias
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination With ω-6/9 Lipid Emulsions2012In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 36, no 5, p. 587-595Article in journal (Refereed)
    Abstract [en]

    Background:

    Newborn infants with short bowel syndrome (SBS) represent a high risk group of developing intestinal failure-associated liver disease (IFALD) which may be fatal. However, infants have a great capacity for intestinal growth and adaptation if IFALD can be prevented or reversed. A major contributing factor to IFALD may be the soybean oil-based intravenous lipid emulsions used since the introduction of parenteral nutrition (PN) 40 years ago.

    Methods:

    This retrospective study compares the outcome in 20 neonates with SBS treated with parenteral fish oil (Omegaven) in combination with omega-6/9 lipid emulsions (ClinOleic) with the outcome in a historical cohort of 18 patients with SBS who received a soybean oil-based intravenous lipid emulsion (Intralipid).

    Results:

    Median gestational age was 26 weeks in the treatment group and 35.5 weeks in the historical group. All patients were started on PN containing Intralipid that was switched to ClinOleic/Omegaven in the treatment group at a median age of 39 gestational weeks. In the treatment group, direct bilirubin levels were reversed in all 14 survivors with cholestasis (direct bilirubin >50 umol/). Median time to reversal was 2.9 months. Only 2 patients died of liver failure (10%).  In the historical cohort, 6 patients (33%) died of liver failure and only 2 patients showed normalization of bilirubin levels.

    Conclusions:

    Parenteral fish oil in combination with omega-6/9 lipid emulsions was associated with improved outcome in premature neonates with SBS. When used instead of traditional soybean-based emulsions, this mixed lipid emulsion may facilitate intestinal adaptation by increasing the IFALD-free period.

  • 28.
    Arvidsson, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Eeg-OLofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Läkare inom neuropediatriken : Aktuell situation2004Report (Other (popular science, discussion, etc.))
  • 29.
    Arvonen, Miika
    et al.
    Kuopio Univ Hosp, Dept Pediat, Kuopio, Finland.;Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland..
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Pokka, Tytti
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Karttunen, Tuomo J.
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, Canc & Translat Med Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Pathol, Oulu, Finland..
    Vahasalo, Paula
    Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.;Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland..
    Stoll, Matthew L.
    Univ Alabama Birmingham, Dept Pediat, CPP N 210 M,1600 7th Ave South, Birmingham, AL 35233 USA..
    Gut microbiota-host interactions and juvenile idiopathic arthritis2016In: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 14, article id 44Article, review/survey (Refereed)
    Abstract [en]

    Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

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  • 30.
    Austeng, Dordi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Blennow, Mats
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Fritz, Thomas
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellström, Ann
    Holmgren, Per Ake
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Jakobsson, Peter
    Jeppsson, Annika
    Johansson, Kent
    Kallen, Karin
    Lagercrantz, Hugo
    Laurini, Ricardo
    Lindberg, Eva
    Lundqvist, Anita
    Marsal, Karel
    Nilstun, Tore
    Nordén Lindeberg, Solveig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Norman, Mikael
    Olhager, Elisabeth
    Oestlund, Ingrid
    Serenius, Fredrik
    Simic, Marija
    Sjörs, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stigson, Lennart
    Stjernqvist, Karin
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tornqvist, Kristina
    Wennergren, Margareta
    Wallin, Agneta
    Westgren, Magnus
    Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)2010In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 7, p. 978-992Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

  • 31.
    Bandara, Sandya
    et al.
    Hospital Peradeniya, Sri Lanka.
    Nyqvist, Kerstin Hedberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Musmar, Samar M J
    Faculty of Medicine and Health Sciences, An-Najah National University, Palestine.
    Procaccini, Diane B
    Lactation Services, Capital Health Hospital, New Jersey, USA.
    Wang, Shu-Fang
    Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.
    RoundTable discussion: Use of alternative feeding methods in the hospital2012In: Journal of Human Lactation, ISSN 0890-3344, E-ISSN 1552-5732, Vol. 28, no 2, p. 122-124Article in journal (Refereed)
  • 32. Bang, P.
    et al.
    Bjerknes, R.
    Dahlgren, J.
    Dunkel, L.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Juul, A.
    Kriström, B.
    Tapanainen, P.
    Åberg, V.
    A Comparison of Different Definitions of Growth Response in Short Prepubertal Children Treated with Growth Hormone2011In: Hormone Research in Paediatrics, ISSN 1663-2818, Vol. 75, no 5, p. 335-345Article in journal (Refereed)
    Abstract [en]

    Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial. Aim: Assess various criteria of poor response. Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) <=-2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS -3.2. Results: Median [25-75 percentile] first-year gain in Ht SDS was 0.65 (0.40-0.90) and height velocity (HtV) 8.67 (7.51-9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 mu g/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5. Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

  • 33.
    Baylis, Rebecca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gradin, Maria
    Hedberg Nyqvist, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rubertsson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    First-time events between parents and preterm infants are affected by the designs and routines of neonatal intensive care units2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, p. 1045-1052Article in journal (Refereed)
    Abstract [en]

    AIM:

    Early parental bonding with preterm babies is particularly important, and the aim of our study was to explore when parents experienced what they regarded as important events for the first time while their infant was in the neonatal intensive care unit (NICU).

    METHODS:

    The study was part of a longitudinal project on Kangaroo Mother Care at two Swedish university hospitals. The parents of 81 infants completed questionnaires during their infants' hospital stay.

    RESULTS:

    Most parents saw and touched their infants immediately after birth, but only a few could hold them skin to skin or swaddle them. Other important events identified by parents included the first time they performed care giving activities and did so independently, interaction and closeness with the infant, signs of the infant's recovery and integration into the family. The timing of the events depended on the physical design of the NICU, whether parents' could stay with their infant round-the-clock and when they were allowed to provide care under supervision and on their own.

    CONCLUSION:

    The design and routines of the NICU dictated when parents first interacted with their infants. Clinical guidelines that facilitate early contact with preterm babies can help parents to make the transition to their parental role.

  • 34.
    Beckman, Linda
    et al.
    Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden..
    Janson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden..
    von Kobyletzki, Laura
    Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden.;Lund Univ, Dept Dermatol, Skane Univ Hosp, Malmo, Sweden..
    Associations between neurodevelopmental disorders and factors related to school, health, and social interaction in schoolchildren: Results from a Swedish population-based survey2016In: Disability and Health Journal, ISSN 1936-6574, E-ISSN 1876-7583, Vol. 9, no 4, p. 663-672Article in journal (Refereed)
    Abstract [en]

    Background: Children and adolescents with autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) are more likely to be surrounded by different risk factors. In order to work preventively with decreasing ADHD and ASD symptoms, there is a need of more knowledge concerning risk factors. Objective: This study aimed to investigate school, health, lifestyle and social interactions association with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) among schoolchildren aged 6-17 years. Methods: Data for 18,416 children and adolescents aged 6-17 years in the county of Varmland, Sweden, from the school year 2012/2013 and 2013/2014 were obtained from the Student Health Database, which includes information on health examinations by school nurses and self-reported information of mental and physical health, social relations, physical activity, and school conditions. Results: Of all participants, 2.4% reported only ADHD and 1.6% reported only ASD. The results confirmed that ADHD or ASD was significantly associated with worse school experiences, lower socioeconomic status, less physical activity, more substance use, weaker social network and more impairments than those without ADHD or ASD. Conclusions: Knowledge of risk or protective factors during school years is needed to develop interventions to reduce symptoms of neurodevelopmental disorders in children and adolescents.

  • 35. Benyi, Emelie
    et al.
    Kieler, Helle
    Linder, Marie
    Ritzen, Martin
    Carlstedt-Duke, Jan
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Westphal, Otto
    Savendahl, Lars
    Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence2014In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no 2, p. 89-96Article in journal (Refereed)
    Abstract [en]

    Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or nonmalignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-infinity) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort. (C) 2014 S. Karger AG, Basel

  • 36.
    Bergström, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Tomlinson, M.
    Squires, J.
    Duong, Duc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hoa, D. P.
    Källestål, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Pervin, J.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Nga, Nguyen Thu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rahman, A.
    Waiswa, P.
    Zelaya, E.
    Estabrooks, C.
    Wallin, L.
    The context assessment for community health tool: investigating why what works where2013In: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 18, no SI, p. 203-204Article in journal (Other academic)
  • 37. Bergström, Sten-Erik
    et al.
    Boman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Eriksson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Formgren, Hans
    Foucard, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hörte, Lars-Gunnar
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Spetz-Nyström, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hedlin, Gunilla
    Asthma mortality among Swedish children and young adults, a 10-year study2008In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 102, no 9, p. 1335-1341Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous reports indicate that morbidity and mortality from asthma have increased during the past decades. Here, the mortality rate associated with asthma and possible risk factors in children and young adults in Sweden during the period 1994-2003 were evaluated. METHODS: The medical profession was asked to report suspected cases of death from asthma in individuals 1-34 years of age. All death certificates containing relevant ICD codes were reviewed. Medical records and autopsy reports were assessed and telephone interviews with next-of-kin performed. RESULTS: During the 10-year period 37 deaths due to asthma were identified. The median age at the time of death was 27 years and 6 of the deceased were younger than 15. The overall incidence of death from asthma decreased from 1.54 deaths per million in 1994 to 0.53 per million in 2003. Common risk factors were under-treatment (23/37), poor adherence to prescribed treatment (17/37) and adverse psychosocial situation (19/37). An alarming finding was that 11 of the 37 deaths were probably caused by food allergy and for 8 subjects death was associated with exposure to pet dander. The death certificates were found to contain inaccuracies with 30% of those for whom asthma was reported as the underlying cause having died from other causes. CONCLUSION: Asthma mortality in children and young adults in Sweden decreased between 1994 and 2003. Food allergy and inadequate treatment were the major risk factors for such a death. Recognition and special care of patients with asthma who have shown signs of non-compliance, denial or severe food allergy must be encouraged.

  • 38.
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Anti-inflammatory effect by exclusive enteral nutrition (EEN) in a patient with juvenile idiopathic arthritis (JIA): brief report2014In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 33, no 8, p. 1173-1175Article in journal (Refereed)
    Abstract [en]

    There is extensive evidence for influence of gut microbiota on health. Exclusive enteral nutrition (EEN) possibly changes gut microbiota, but the exact pathophysiological role is unknown. EEN has been shown to have an anti-inflammatory effect in children with Mb Crohn, an inflammatory bowel disease. The intestinal tract is very scarcely studied in children with juvenile idiopathic arthritis (JIA), but data points to an immunologically important role. The aim of this study was to explore if EEN had any anti-inflammatory effect in children with JIA. The first patient enrolled in the study was followed for 1 year. She had onset of severe polyarticular disease at 3.2 years of age, negative in RF, anti-CCP, ANA, and HLA-B27. She was included in the study at 7.4 years of age. Exclusive enteral nutrition was given in two periods of almost 7 weeks each, several months apart, during the year of the study. Clinical and laboratory status were assessed before, during, and after treatment periods. In this patient, EEN had remarkable anti-inflammatory effect that was sustained for months after each of two separate treatment periods. Exclusive enteral nutrition is a possible anti-inflammatory treatment in patients with JIA, but to what extent EEN is effective in other children with JIA needs to be explored, as well as the possible pathophysiological role of EEN in those children.

  • 39.
    Berntson, Lillemor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Univ Uppsala Hosp, Dept Pediat, Unit Pediat Rheumatol, S-75185 Uppsala, Sweden..
    Agback, Peter
    Swedish Univ Agr Sci, Dept Chem & Biotechnol, Uppsala, Sweden..
    Dicksved, Johan
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, Uppsala, Sweden..
    Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN)2016In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 35, no 6, p. 1501-1506Article in journal (Refereed)
    Abstract [en]

    The microbiome and immune system of the digestive tract are highly important in both health and disease. Exclusive enteral nutrition (EEN) is a common anti-inflammatory treatment in children with Crohn's disease in the European countries, and the mechanism is most likely linked to changes in the intestinal microbiome. In the present study, EEN was given in two treatment periods several months apart to a patient with very severe, disabling juvenile idiopathic arthritis (JIA), with a remarkable clinical response as the result. The aim of the present study was to study how the EEN treatment influenced the microbiome and metabolome of this patient. Fecal samples from before, during, and between treatments with EEN were studied. The microbiome was analyzed by sequencing of 16S rRNA amplicons using Illumina MiSeq, and the metabolome was analyzed using nuclear magnetic resonance. The microbiome changed markedly from treatment with EEN, with a strong reduction of the Bacteroidetes phylum. Metabolic profiles showed clear differences before, during, and between treatment with EEN, where butyrate, propionate, and acetate followed a cyclic pattern with the lowest levels at the end of each treatment period. This patient with JIA showed remarkable clinical improvement after EEN treatment, and we found corresponding changes in both the fecal microbiome and the metabolome. Further studies are needed to explore the pathophysiological role of the intestinal canal in children with JIA.

  • 40.
    Berntson, Lillemor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hedlund-Treutiger, I.
    Karolinska Inst Sodersjukhuset, Sachs Childrens Hosp, Stockholm, Sweden..
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis2016In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 34, no 5, p. 941-945Article in journal (Refereed)
    Abstract [en]

    Objective There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). Methods Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). Results EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). Conclusion Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients.

  • 41.
    Berntson, Lillemor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordal, Ellen
    Fasth, Anders
    Aalto, Kristiina
    Herlin, Troels
    Nielsen, Susan
    Rygg, Marite
    Zak, Marek
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)2014In: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 12, p. 22-Article in journal (Refereed)
    Abstract [en]

    Background: Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods: The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results: Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions: Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.

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  • 42.
    Berthold, Malin
    et al.
    Thermo Fisher Sci, Uppsala, Sweden..
    Bjerg, Anders
    Univ Gothenburg, Krefting Res Ctr, Gothenburg, Sweden.;Obstruct Lung Dis Nothern Sweden OLIN Studies, Norrbotten Cty Council, Lulea, Sweden..
    Winberg, Anna
    Obstruct Lung Dis Nothern Sweden OLIN Studies, Norrbotten Cty Council, Lulea, Sweden.;Umea Univ Hosp, S-90185 Umea, Sweden..
    Mattsson, Lars
    Thermo Fisher Sci, Uppsala, Sweden..
    Borres, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Thermo Fisher Sci, Uppsala, Sweden..
    Ronmark, Eva
    Obstruct Lung Dis Nothern Sweden OLIN Studies, Norrbotten Cty Council, Lulea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, OLIN Unit, Umea, Sweden..
    Association of Sensitization to Specific Pet Allergen Components with Asthma Symptoms in School Children2015In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 135, no 2, p. AB22-AB22Article in journal (Other academic)
  • 43.
    Beukelman, Timothy
    et al.
    Univ Alabama Birmingham, 1600 7th Ave South,CPP 210, Birmingham, AL 35233 USA.;Univ Alabama Birmingham, Div Pediat Rheumatol, 1600 7th Ave South,CPP 210, Birmingham, AL 35233 USA..
    Anink, Janneke
    Erasmus MC, Rotterdam, Netherlands..
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala Univ Hosp, Uppsala, Sweden..
    Duffy, Ciaran
    Childrens Hosp Eastern Ontario, Ottawa, ON, Canada..
    Ellis, Justine A.
    Murdoch Childrens Res Inst, Genes Environm & Complex Dis, Parkville, Vic, Australia..
    Glerup, Mia
    Aarhus Univ Hosp, Aarhus, Denmark..
    Guzman, Jaime
    Univ British Columbia, Vancouver, BC, Canada..
    Horneff, Gerd
    Asklepios Klin Sankt Augsutin, St Augustin, Germany..
    Kearsley-Fleet, Lianne
    Univ Manchester, Manchester, Lancs, England..
    Klein, Ariane
    Asklepios Klin Sankt Augsutin, St Augustin, Germany..
    Klotsche, Jens
    German Rheumatism Res Ctr, Berlin, Germany..
    Magnusson, Bo
    Karolinska Univ Hosp, Stockholm, Sweden..
    Minden, Kirsten
    German Rheumatism Res Ctr, Berlin, Germany..
    Munro, Jane E.
    Royal Childrens Hosp, Melbourne, Vic, Australia..
    Niewerth, Martina
    German Rheumatism Res Ctr, Berlin, Germany..
    Nordal, Ellen
    Univ Hosp North Norway, Tromso, Norway..
    Ruperto, Nicolino
    Ist Giannina Gaslini, Genoa, Italy..
    Santos, Maria Jose
    Hosp Garcia de Orta, Almada, Portugal..
    Schanberg, Laura E.
    Duke Univ, Durham, NC 27706 USA..
    Thomson, Wendy
    Univ Manchester, Manchester, Lancs, England..
    van Suijlekom-Smit, Lisette
    Erasmus MC, Rotterdam, Netherlands..
    Wulffraat, Nico
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Hyrich, Kimme
    Univ Manchester, Manchester, Lancs, England.;Cent Manchester Fdn Trust, Manchester, Lancs, England..
    A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities2017In: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 15, article id 31Article in journal (Refereed)
    Abstract [en]

    Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration.

    Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods.

    Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events.

    Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

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  • 44.
    Bjerg, A.
    et al.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Ekerljung, L.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Eriksson, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Naslund, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Sjölander, S.
    ThermoFisher Sci, ImmunoDiagnost, Uppsala, Sweden..
    Rönmark, E.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;OLIN Unit, Dept Publ Hlth & Clin Med Occupat & Environm Med, Umea, Sweden..
    Dahl, Å.
    Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Holmberg, K.
    Sahlgrens Univ Hosp, Dept Otorhinolaryngol, Gothenburg, Sweden..
    Wennergren, G.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden.;Gothenburg Univ, Dept Pediat, Gothenburg, Sweden..
    Torén, K.
    Gothenburg Univ, Sahlgrenska Acad, Dept Publ Hlth & Community Med, Gothenburg, Sweden..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Lötvall, J.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Lundbäck, B.
    Gothenburg Univ, Dept Internal Med & Clin Nutr, Krefting Res Ctr, Gothenburg, Sweden..
    Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 10, p. 1328-1336Article in journal (Refereed)
    Abstract [en]

    Background To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. Objective To study allergic sensitization, its risk factors and time trends in prevalence. Methods Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. Results Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. Conclusion Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.

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  • 45.
    Bjerg, Anders
    et al.
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, SE-40530 Gothenburg, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, OLIN Unit, Occupat & Environm,Med, Umea, Sweden..
    Winberg, Anna
    Umea Univ, Dept Clin Sci, OLIN Unit, Pediat, Umea, Sweden..
    Berthold, Malin
    ThermoFisher Sci, Uppsala, Sweden..
    Mattsson, Lars
    ThermoFisher Sci, Uppsala, Sweden..
    Borres, Magnus P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. ThermoFisher Sci, Uppsala, Sweden..
    Ronmark, Eva
    Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, SE-40530 Gothenburg, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, OLIN Unit, Occupat & Environm,Med, Umea, Sweden..
    A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren2015In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 6, p. 557-563Article in journal (Refereed)
    Abstract [en]

    BackgroundAnimal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. MethodsA random sample of 696 children (11-12years) from a Swedish population-based cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. ResultsOf 259 animal-sensitized children (0.1 kU(A)/l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1-15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and co-sensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. ConclusionsAmong schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.

  • 46. Bjermer, Leif
    et al.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Diamant, Zuzana
    Magnussen, Helgo
    Pavord, Ian
    Piacentini, Giorgio
    Price, David
    Roche, Nicolas
    Sastre, Joaquin
    Thomas, Mike
    Usmani, Omar
    Current evidence and future research needs for FeNO measurement in respiratory diseases2014In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 108, no 6, p. 830-841Article, review/survey (Refereed)
    Abstract [en]

    Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.

  • 47. Bjursell, Magnus K.
    et al.
    Blom, Henk J.
    Cayuela, Jordi Asin
    Engvall, Martin L.
    Lesko, Nicole
    Balasubramaniam, Shanti
    Brandberg, Goran
    Halldin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Falkenberg, Maria
    Jakobs, Cornelis
    Smith, Desiree
    Struys, Eduard
    von Dobeln, Ulrika
    Gustafsson, Claes M.
    Lundeberg, Joakim
    Wedell, Anna
    Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function2011In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 89, no 4, p. 507-515Article in journal (Refereed)
    Abstract [en]

    Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.

  • 48.
    Björk, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Svendsen, P
    Moström, U
    Pellettieri, L
    Endovascular treatment of a spinal arteriovenous malformation in a 21-month-old boy1994In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 83, no 12, p. 1326-1331Article in journal (Other academic)
    Abstract [en]

    Reports of spinal arteriovenous malformations in children are rare. This case report describes a 21-month-old boy whose first symptom was attacks of abdominal pain, followed gradually by neurological symptoms. The diagnosis was made using magnetic resonance imaging and spinal angiography, and the patient was successfully treated with embolization.

  • 49. Björkenstam, Charlotte
    et al.
    Weitoft, Gunilla Ringbäck
    Hjern, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nordström, Peter
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ljung, Rickard
    School grades, parental education and suicide: a national register-based cohort study2011In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 65, no 11, p. 993-998Article in journal (Refereed)
    Abstract [en]

    Background

    To investigate whether school performance is a risk factor for suicide death later in life and, if so, to what extent this is explained by intergenerational effects of parental education.

    Methods

    This population-based cohort study comprises national birth cohorts between 1972 and 1981 in Sweden. We followed 898 342 students, graduating between 1988 and 1997 from the 9 years of compulsory school, equivalent to junior high school, until 31 December 2006, generating 11 148 758 person-years and 1490 suicides. Final school grades, in six categories, and risk of suicide were analysed with Poisson regression.

    Results

    The incidence rate ratio (RR) for suicide death for students with the lowest grades was 4.57 (95% CI 2.82 to 7.40) for men and 2.67 (1.42 to 5.01) for women compared to those with highest grades after adjustment for a number of sociodemographic and parental morbidity variables, such as year of graduation, parental education, lone parenthood, household receiving social welfare or disability pension, place of schooling, adoption, maternal age and parent's mental illness. Students with grades in the middle categories had RRs in between. These relationships were not modified by parental education.

    Conclusions

    The strong association between low school grades and suicide in youth and young adulthood emphasises the importance of both primary and secondary prevention in schools.

  • 50. Bland, Richard D.
    et al.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gunnar Sedin Obituary2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 8, p. 893-893Article in journal (Refereed)
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