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  • 51. Ankarberg-Lindgren, Carina
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norjavaara, Ensio
    Physiological Estrogen Replacement Therapy for Puberty Induction in Girls: A Clinical Observational Study2014Ingår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 81, nr 4, s. 239-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E-2) patches in a large outpatient setting. Methods: In a retrospective study, serum E-2 levels from 18 clinics were analyzed at the Goteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism. Exclusion criteria were pubertas tarda and pubertal arrest. Eighty-eight observations (50 with Turner syndrome, TS) were included. Serum E-2 levels were determined by extraction + radioimmunoassay (detection limit 4 pmol/l) and analyzed in relation to the dose of Evorel (R) (25 mu g/24 h, containing 1.60 mg estradiol hemihydrate; Janssen-Cilag Pharmaceutica N.V., Beerse, Belgium). Results: There was a linear relationship between serum E-2 and the weight-based dose, with r = 0.56, p < 0.0001 for all observations and r = 0.59, p < 0.0001 for the TS study group. Linear regression analysis for doses of 0.05-0.07 mu g/kg resulted in serum levels of 17-23 pmol/l (TS 17-24 pmol/l) and doses of 0.08-0.12 mu g/kg in 26-39 pmol/l (TS 27-39 pmol/l). Conclusions: For the initiation of ERT with nocturnally administered E-2 patches, we recommend reduced starting doses of 0.05-0.07 mu g/kg, with the goal of mimicking E-2 levels during gonadarche. In older girls, when breast development is of high priority, the starting dose can still be 0.08-0.12 mu g/kg. (C) 2014 S. Karger AG, Basel

  • 52. Annus, T
    et al.
    Björkstén, B
    Mai, X M
    Nilsson, L
    Riikjärv, M A
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Bråbäck, L
    Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren.2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 12, s. 1846-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors.

    OBJECTIVE: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries.

    METHODS: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Linköping (n = 911) and Ostersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol.

    RESULTS: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in Ostersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Linköping and 58% in Ostersund) bronchial hyper-responsiveness (BHR) (48% in Linköping and Ostersund) and anti-asthmatic treatment (63% in Linköping and 81% in Ostersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (Ostersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children.

    CONCLUSIONS: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

  • 53. Arslanoglu, Sertac
    et al.
    Corpeleijn, Willemijn
    Moro, Guido
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Donor Human Milk for Preterm Infants: Current Evidence and Research Directions2013Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, nr 4, s. 535-542Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

  • 54. Ascher, H
    et al.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ivarsson, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Kristiansson, B
    Lindberg, T
    Stenhammar, L
    [Infant food and celiac disease. Risk of increase when changing the diet]1994Ingår i: Lakartidningen, ISSN 0023-7205, Vol. 91, nr 49, s. 4641-3Artikel i tidskrift (Övrigt vetenskapligt)
  • 55. Askelöf, Ulrica
    et al.
    Andersson, Ola
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fasth, Anders
    Hallberg, Boubou
    Hellström-Westas, Lena
    Pettersson, Karin
    Westgren, Magnus
    Wiklund, Ingela E.
    Götherström, Cecilia
    Wait a minute?: An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60-and 180-second umbilical cord clamping2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 12, artikel-id e017215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping.

    Design: Prospective observational study with two historical controls.

    Setting: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden.

    Methods: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at <= 10 s (n= 200) or >= 180 s (n= 200) after delivery.

    Results: After adjustment for age differences at the time of follow- up, serum ferritin concentrations were 77, 103 and 114 mu g/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29).

    Conclusion: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency.

  • 56. Aspberg, Sara
    et al.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kahan, Thomas
    Källén, Bengt
    Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma2010Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, nr 4 Pt 2, s. e733-e739Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously demonstrated an association between neonatal phototherapy and/or neonatal icterus and risk of hospitalization for childhood asthma. This study included children who were prescribed anti-asthmatic medication on a population basis to study exposures during the foetal and neonatal period and risk of childhood asthma. The Swedish Medical Birth Register was linked to the Swedish Prescribed Drug Register. Perinatal data for singleton children who were prescribed anti-asthmatic medication (n = 61,256) were compared with corresponding data for all singleton children born in Sweden from 1 January 1990 to 30 June 2003 and surviving to 1 July 2005 (n = 1,338,319). Mantel-Haenszel's odds ratios were calculated after adjustment for various known confounders. Being the first-born child, maternal age above 44 yr, involuntary childlessness for more than 1 yr, maternal smoking during pregnancy, maternal diabetes mellitus of any kind, pre-eclampsia, caesarean section, and instrumental vaginal delivery were all associated with an increased prescription of anti-asthmatic medication during childhood. Preterm birth, low birth weight, being small for gestational age, respiratory problems, mechanical ventilation, and sepsis and/or pneumonia were also associated with increased drug prescriptions. Neonatal phototherapy and/or icterus were risk determinants for children who developed asthma before the age of 12. After controlling for confounders, the odds ratio for phototherapy and/or icterus remained at 1.30 (95% confidence interval 1.16-1.47). In conclusion, this large population-based study confirms an association between some maternal and perinatal factors and childhood asthma, including neonatal phototherapy and/or icterus.

  • 57. Aspberg, Sara
    et al.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kahan, Thomas
    Källén, Bengt
    Fetal and perinatal risk factors for inflammatory bowel disease.2006Ingår i: Acta paediatrica, ISSN 0803-5253, Vol. 95, nr 8, s. 1001-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To study the influence of specific factors and events during pregnancy and the perinatal period on the risk of children developing inflammatory bowel disease. METHODS: Population-based national register study. Linkage between the Swedish Medical Birth Register and the Swedish Hospital Discharge Register during the period 1987 to 2000 identified 455 singleton infants who later developed inflammatory bowel disease. Data for these children were compared with data for all children born in Sweden during the same period. RESULTS: Smoking during early pregnancy reduced the risk of inflammatory bowel disease (odds ratio (OR) 0.71, 95% CI 0.55-0.91). For ulcerative colitis the odds ratio was 0.70 (95% CI 0.56-0.86), and for Crohn's disease 0.73 (95% CI 0.58-0.94). Infections during the neonatal period seemed to increase the risk of inflammatory bowel disease (OR 17.6, 95% CI 3.6-51.6), but the number of observed events was small. The other factors examined did not influence the risk of inflammatory bowel disease. CONCLUSION: Maternal smoking during early pregnancy reduces the risk for the child to be hospitalized with a diagnosis of inflammatory bowel disease. Severe neonatal infections may increase the risk. Thus, some exposures during the fetal and neonatal period seem to affect the risk of inflammatory bowel disease later in life.

  • 58. Aspberg, Sara
    et al.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kahan, Thomas
    Källén, Bengt
    Is neonatal phototherapy associated with an increased risk for hospitalized childhood bronchial asthma?2007Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 18, nr 4, s. 313-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This population-based register study examined if factors during the fetal and neonatal period influence the risk for the child to develop bronchial asthma (asthma). From the Swedish Hospital Discharge Register we identified children, born between 1987 and 1999, who had been hospitalized for asthma up to 2001. Thus, the outcome measure contains only hospitalized cases, not all children with asthma. Children younger than 2 yr at admission were excluded because of the uncertainty about the diagnosis of asthma in younger children. The remaining 14,803 children were compared with all children born the same years, recorded in the Swedish Medical Birth Registry, for information on pre- and perinatal characteristics. Odds ratios (ORs) were calculated with Mantel-Haenszel technique and 95% confidence intervals (CIs) with Miettinen's test-based method. The presence of various maternal and neonatal confounders were identified and adjusted for in the analyses. The association between some known factors and childhood asthma were confirmed: young maternal age, maternal smoking, period of unwanted childlessness, low maternal level of education, maternal diabetes, preterm birth, low birth weight, small-for-gestational age, caesarean section, and instrumental vaginal delivery. A number of neonatal characteristics were shown to be independent risk factors: sepsis or pneumonia, neonatal respiratory problems and treatments, neonatal icterus, and/or neonatal phototherapy. The association with icterus and phototherapy remained after exclusion of cases showing other neonatal risk factors and after adjustment for maternal factors (OR 1.27, 95% CI: 1.08-1.50), and increased to 1.5 if the children had been hospitalized for asthma more than once. In conclusion, our results suggest an association between neonatal icterus and/or treatment with neonatal phototherapy and hospitalized childhood asthma. This association needs further exploration.

  • 59. Austeng, Dordi
    et al.
    Blennow, Mats
    Ewald, Uwe
    Fellman, Vineta
    Fritz, Thomas
    Hellström-Westas, Lena
    Hellström, Ann
    Holmgren, Per Åke
    Holmström, Gerd
    Jakobsson, Peter
    Jeppsson, Annika
    Johansson, Kent
    Källén, Karin
    Lagercrantz, Hugo
    Laurini, Ricardo
    Lindberg, Eva
    Lundqvist, Anita
    Marsál, Karel
    Nilstun, Tore
    Nordén-Lindeberg, Solveig
    Norman, Mikael
    Olhager, Elisabeth
    Östlund, Ingrid
    Serenius, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Simic, Marija
    Sjörs, Gunnar
    Stigson, Lennart
    Stjernqvist, Karin
    Strömberg, Bo
    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)2010Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, nr 7, s. 978-992Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 60. Axelsson, Inge
    et al.
    Naumburg, Estelle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Prietsch, Silvio O. M.
    Zhang, Linjie
    Effects of inhaled corticosteroids on growth in children with persistent asthma: Impact of drug molecules and delivery devices - An overview of Cochrane reviews2019Ingår i: Paediatric Respiratory Reviews, ISSN 1526-0542, E-ISSN 1526-0550, Vol. 32, s. 28-29Artikel i tidskrift (Refereegranskat)
  • 61. Axelsson, Inge
    et al.
    Naumburg, Estelle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Prietsch, Silvio O. M.
    Zhang, Linjie
    Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth2019Ingår i: Cochrane Database of Systematic Reviews, ISSN 1469-493X, E-ISSN 1469-493X, nr 6, artikel-id CD010126Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.

    Objectives: To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.

    Search methods: We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.

    Selection criteria: We selected parallel‐group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.

    Data collection and analysis: At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta‐analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random‐effects model for meta‐analyses. We did not perform planned subgroup analyses due to there being too few included trials.

    Main results: We included six randomized trials involving 1199 children aged from 4 to 12 years (per‐protocol population: 1008), with mild‐to‐moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.

    One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI ‐0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).

    Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane‐metered dose inhaler (HFA‐MDI) and beclomethasone administered via chlorofluorocarbon‐metered dose inhaler (CFC‐MDI) at an equivalent dose (MD ‐0.44 cm/year, 95% CI ‐1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).

    Authors' conclusions: This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head‐to‐head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real‐life observational studies seem more attractive and feasible.

  • 62. Axelsson, Inge
    et al.
    Silfverdal, Sven Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Pneumonia mortality among children in Brazil: a success story2011Ingår i: Jornal de pediatria, ISSN 1678-4782, Vol. 87, nr 2, s. 85-87Artikel i tidskrift (Övrigt vetenskapligt)
  • 63. Axelsson, Irene
    et al.
    Finkel, Yigael
    Michaelsen, Kim Fleischer
    Gebre-Medhin, Mehari
    Hernell, Olle
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Jakobsson, Iréne
    Perlhagen, John
    Jansson, Martina
    [Complementary food to breastfed infants. Introduction can wait until the age of six months but not longer]2004Ingår i: Lakartidningen, ISSN 0023-7205, Vol. 101, nr 3, s. 195-7Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    [Article in Swedish]

  • 64.
    Back, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Drug treatment in children with cardiac diseases -     support for chosen drug.2019Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 65. Balgobind, Brian V
    et al.
    Raimondi, Susana C
    Harbott, Jochen
    Zimmermann, Martin
    Alonzo, Todd A
    Auvrignon, Anne
    Beverloo, H Berna
    Chang, Myron
    Creutzig, Ursula
    Dworzak, Michael N
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Gibson, Brenda
    Hasle, Henrik
    Harrison, Christine J
    Heerema, Nyla A
    Kaspers, Gertjan J L
    Leszl, Anna
    Litvinko, Nathalia
    Nigro, Luca Lo
    Morimoto, Akira
    Perot, Christine
    Pieters, Rob
    Reinhardt, Dirk
    Rubnitz, Jeffrey E
    Smith, Franklin O
    Stary, Jan
    Stasevich, Irina
    Strehl, Sabine
    Taga, Takashi
    Tomizawa, Daisuke
    Webb, David
    Zemanova, Zuzana
    Zwaan, C Michel
    van den Heuvel-Eibrink, Marry M
    Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.2009Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 114, nr 12, s. 2489-2496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.

  • 66.
    Bang, P
    et al.
    Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
    Bjerknes, R
    Department of Clinical Medicine, Section for Pediatrics, University of Bergen, Norway.
    Dahlgren, J
    Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Dunkel, L
    Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
    Gustafsson, J
    Department of Women’s and Children’s Health, University of Uppsala, Sweden.
    Juul, A
    Department of Growth and Reproduction, University of Copenhagen, Denmark.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Tapanainen, P
    Department of Pediatrics and Adolescence, University of Oulu, Finland.
    Åberg, V
    Institut Produits Synthèse (IPSEN) AB, Kista, Sweden.
    A comparison of different definitions of growth response in short prepubertal children treated with growth hormone2011Ingår i: Hormone research in paediatrics, ISSN 1663-2826, Vol. 75, nr 5, s. 335-345Artikel i tidskrift (Refereegranskat)
    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 μg/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.

  • 67. Barbany, Gisela
    et al.
    Andersen, Mette K
    Autio, Kirsti
    Borgström, Georg
    Franco, Lucia Cavalier
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Heim, Sverre
    Heinonen, Kristina
    Hovland, Randi
    Johansson, Bertil
    Johannsson, Johann H
    Kjeldsen, Eigil
    Nordgren, Ann
    Palmqvist, Lars
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Additional aberrations of the ETV6 and RUNX1 genes have no prognostic impact in 229 t(12;21)(p13;q22)-positive B-cell precursor acute lymphoblastic leukaemias treated according to the NOPHO-ALL-2000 protocol2012Ingår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 36, nr 7, s. 936-938Artikel i tidskrift (Refereegranskat)
  • 68. Barman, Malin
    et al.
    Johansson, Sara
    Hesselmar, Bill
    Wold, Agnes E.
    Sandberg, Ann-Sofie
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 7, s. e67920-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods: From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results: The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P < 0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p < 0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (P-trend < 0.001), n-6 LCPUFA (P-trend = 0.001), and total LCPUFA (P-trend < 0.001) and decreased linearly with the proportions of total MUFA (P-trend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion: A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.

  • 69. Barman, Malin
    et al.
    Jonsson, Karin
    Hesselmar, Bill
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sandberg, Ann-Sofie
    Wold, Agnes E.
    No association between allergy and current 25-hydroxy vitamin D in serum or vitamin D intake2015Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, nr 4, s. 405-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim Vitamin D may be involved in allergy development, but there is conflicting evidence. We investigated if dietary intake of vitamin D and levels of 25OHD in serum differed between allergic and nonallergic adolescents and if serum 25OHD correlated with dietary intake of vitamin D or season of blood sampling.

    Methods Serum 25-hydroxy vitamin D (25OHD) levels were analysed in 13-year-old subjects with atopic eczema (n=55), respiratory allergy (n=55) or no allergy (n=55). Intake of fat-containing foods was assessed by food-frequency questionnaires, and total daily vitamin D intake was calculated. Logistic regression was used to adjust for gender, parental allergy and time of blood sampling.

    Results Subjects with atopic eczema or respiratory allergy did not differ from nonallergic controls regarding serum 25OHD levels or calculated vitamin D intake. Subjects sampled in the autumn had significantly higher levels of serum 25OHD than subjects sampled in the winter or spring. Serum 25OHD levels correlated to consumption of vitamin D-fortified lean milk (p=0.001).

    Conclusion The findings suggest no association between allergy and 25OHD levels in serum or vitamin D intake in adolescents. Serum 25OHD levels correlated to intake of vitamin D-fortified lean milk.

  • 70.
    Barman, Malin
    et al.
    Göteborg, Sweden.
    Jonsson, Karin
    Göteborg, Sweden.
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wold, Agnes E.
    Göteborg, Sweden.
    Sandberg, Ann-Sofie
    Göteborg, Sweden.
    Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema2014Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, nr 9, s. 968-976Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: Long-chain polyunsaturated fatty acids (LCPUFAs) are immunomodulatory, but their role in allergy development is controversial. We investigated whether proportions of LCPUFAs in serum phospholipids were related to allergic diagnosis, seafood intake and LCPUFA proportions in cord blood.

    Methods: Serum was obtained from 148 birth cohort children at 13 years of age. Forty had atopic eczema, 53 had respiratory allergy, and 55 were nonallergic. Proportions of LCPUFAs were determined in serum phospholipids; cord blood from 128 of the individuals was previously analysed. Seafood intake was estimated using questionnaires.

    Results: Allergic and nonallergic individuals did not differ significantly regarding individual LCPUFAs. However, arachidonic acid over docosahexaenoic acid (DHA) ratio was higher in allergic, compared with nonallergic, adolescents. In nonallergic individuals, LCPUFA proportions in cord serum and adolescent serum correlated weakly. In individuals with atopic eczema and respiratory allergy, these correlations were weak or absent. A moderate correlation between seafood intake and serum DHA was seen in nonallergic individuals and those with respiratory allergy, but not in those with atopic eczema.

    Conclusion: Serum LCPUFA pattern was similar in allergic and nonallergic adolescents. Fatty acid metabolism may be altered in atopic eczema subjects, suggested by poor correlations between fatty acid intake and serum levels.

  • 71. Barman, Malin
    et al.
    Murray, Fiona
    Bernardi, Angelina I.
    Broberg, Karin
    Bölte, Sven
    Hesselmar, Bill
    Jacobsson, Bo
    Jonsson, Karin
    Kippler, Maria
    Rabe, Hardis
    Ross, Alastair B.
    Sjöberg, Fei
    Strömberg, Nicklas
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Vahter, Marie
    Wold, Agnes E.
    Sandberg, Ann-Sofie
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Sunderby Research Unit, Region Norrbotten, Luleå, Sweden.
    Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden2018Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, nr 10, artikel-id e022013Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health. Methods and analysis The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health. Ethics and dissemination The NICE cohort has been approved by the Regional Ethical Review Board in Umea, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.

  • 72. Barman, Malin
    et al.
    Nilsson, Staffan
    Torinsson Naluai, Åsa
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wold, Agnes E
    Sandberg, Ann-Sofie
    Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort)2015Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 7, nr 12, s. 10100-10115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.

  • 73.
    Bas, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Forsberg, G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sjöberg, Veronika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?2009Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, nr 2, s. 189-195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Coeliac disease is a small intestine enteropathy caused by permanent intolerance to wheat gluten. Gluten intake by patients with coeliac disease provokes a strong reaction by intestinal intraepithelial lymphocytes (IELs), which normalises on a gluten-free diet. AIM: To investigate whether impaired extrathymic T cell maturation and/or secondary T cell receptor (TCR) gene recombination in IELs are features of coeliac disease which could contribute to the failure of establishing tolerance to gluten.

    METHODS: Expression levels of the four splice-forms of recombination activating gene-1 (RAG1) mRNA and preT alpha-chain (preTalpha) mRNA were determined in IEL-subsets of children with coeliac disease and controls. Frequencies of RAG1 expressing IELs were determined by immunomorphometry.

    RESULTS: In controls, the RAG1-1A/2 splice-form selectively expressed outside the thymus, was dominant and expressed in both mature (TCR(+)) and immature (CD2(+)CD7(+)TCR(-)) IELs ( approximately 8 mRNA copies/18S rRNA U). PreTalpha was expressed almost exclusively in CD2(+)CD7(+)TCR(-) IELs ( approximately 40 mRNA copies/18S rRNA U). By contrast, RAG1 and preTalpha mRNA levels were low in patients with coeliac disease compared to controls, both with active disease and with inactive, symptom-free disease on a gluten-free diet (p values <0.01 for mature and <0.05 for immature IELs). Similarly, the frequencies of RAG1+ IELs were significantly lower in patients with coeliac disease compared to controls (p<0.001).

    CONCLUSIONS: Patients with coeliac disease appear to have an impaired capacity for extrathymic TCR gene rearrangement. This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten.

  • 74.
    Bas, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Forsberg, Göte
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Utility of the housekeeping genes 18S rRNA, β-actin, and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) for normalisation in real-time quantitative RT-PCR analysis of gene expression in human T lymphocytes2004Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 59, nr 6, s. 566-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The accuracy of 18S rRNA, β-actin mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as indicators of cell number when used for normalization in gene expression analysis of T lymphocytes at different activation stages was investigated. Quantitative real-time reverse transcriptase-polymerase chain reaction was used to determine the expression level of 18S rRNA, β-actin mRNA, GAPDH mRNA and mRNA for six cytokines in carefully counted samples of resting human peripheral blood mononuclear cells (PBMCs), intestinal lymphocytes and PBMCs subjected to polyclonal T-cell activation. The 18S rRNA level in activated and resting PBMCs and intestinal lymphocytes was essentially the same, while the levels of β-actin and GAPDH mRNAs fluctuated markedly upon activation. When isolated γδTCR+, CD4+ and CD8+ subpopulations were studied, 18S rRNA levels remained unchanged after 21 h of activation but increased slightly after 96 h. In contrast, there was a 30–70-fold increase of GAPDH mRNA/cell in these cell populations upon activation. Cytokine analysis revealed that only normalization to 18S rRNA gave a result that satisfactorily reflected their mRNA expression levels per cell. In conclusion, 18S rRNA was the most stable housekeeping gene and hence superior for normalization in comparative analyses of mRNA expression levels in human T lymphocytes.

  • 75.
    Bazan, Aleksander
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Are permanent disabilities missed in children with severe infections? – A long term follow-up study after bacterial meningitis2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 76.
    Bazan, Aleksander
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Are permanent disabilities missed in children with severe infections?: A long term followup study after bacterial meningitis2017Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    AIM: Acute bacterial meningitis is associated with high risk of neurological disabilities, however less is known about other long-term sequalae. We aimed to analyse this risk and evaluated current follow-up recommendations.

    METHODS: We used medical records from children aged one month to 17 years treated for acute bacterial meningitis in Västerbotten County, Sweden, during 1986-2015. From these, we extracted data to estimate the prevalence of the sequalae and assess the efficiency of current guidelines.

    RESULTS We reviewed medical records of 80 patients from discharge until present time, an average period of 19 years. Current guidelines were effective in detecting permanent neurological sequalae and hearing impairment, present in 32% and 18% of all patients respectively. However, psychiatric sequalae, noted in 28% of all patients, including neuropsychological symptoms noted in 13% of all patients, were discovered in average 15 years after routine follow-up ended.

    CONCLUSION: Current follow-up guidelines is sufficient for detection of neurological and hearing sequelae. However, neurodevelopmental disorders are often discovered several years after routine follow-up. Therefore, current guidelines should be modified with stricter follow-up routines and extended follow-up period to enable detection of these disabilities, thereby preventing unnecessary suffering for the affected child.

  • 77. Belshe, Robert B
    et al.
    Edwards, Kathryn M
    Vesikari, Timo
    Black, Steven V
    Walker, Robert E
    Hultquist, Micki
    Kemble, George
    Connor, Edward M
    Gothefors, Leif
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Live attenuated versus inactivated influenza vaccine in infants and young children.2007Ingår i: N Engl J Med, ISSN 1533-4406, Vol. 356, nr 7, s. 685-96Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    BACKGROUND: Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children. METHODS: Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004-2005 influenza season. RESULTS: Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002). CONCLUSIONS: Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. (ClinicalTrials.gov number, NCT00128167 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

  • 78. Beltempo, Marc
    et al.
    Isayama, Tetsuya
    Vento, Máximo
    Lui, Kei
    Kusuda, Satoshi
    Lehtonen, Liisa
    Sjörs, Gunnar
    Håkansson, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. hSwedish Neonatal Quality Register, Department of Pediatrics/Neonatal Services, Umeå University Hospital, Umeå, Sweden.
    Adams, Mark
    Noguchi, Akihiko
    Reichman, Brian
    Darlow, Brian A
    Morisaki, Naho
    Bassler, Dirk
    Pratesi, Simone
    Lee, Shoo K
    Lodha, Abhay
    Modi, Neena
    Helenius, Kjell
    Shah, Prakesh S
    Respiratory Management of Extremely Preterm Infants: An International Survey2018Ingår i: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 114, nr 1, s. 28-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies.

    OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration.

    METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015.

    RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%).

    CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.

  • 79. Bentsen, Beint
    et al.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Finkel, Yigael
    Fläring, Urban
    Torp Hansen, Kari
    Kok, Karin
    Moltu, Sissel
    Petrini, Pia
    Thomassen, Rut Anne
    Pediatrisk parenteral nutrition.: Nordisk handbok.2010Ingår i: Pediatrisk parenteral nutrition.: Nordisk handbok. / [ed] Yigael Finkel, Uppsala: Fresenius Kabi , 2010Kapitel i bok, del av antologi (Refereegranskat)
  • 80.
    Berg, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Early childhood neurological development in association to socioeconomic factors  a study in the county of Västerbotten2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 81. Berg, S
    et al.
    Trollfors, B
    Claesson, B A
    Alestig, K
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hugosson, S
    Lindquist, L
    Olcén, P
    Romanus, V
    Strangert, K
    Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden.1996Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 28, nr 3, s. 247-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

  • 82. Berghammer, Malin C
    et al.
    Brink, Eva
    Rydberg, Annika M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dellborg, Mikael
    Ekman, Inger
    Committed to Life: Adolescents' and Young Adults' Experiences of Living with Fontan Circulation2015Ingår i: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 10, nr 5, s. 403-412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Single ventricle defects are among the most complex congenital heart defects and the development of advanced surgical procedures in recent decades has created the first generation of adolescents and young adults living with this condition. Yet little is known about how these individuals experience life and what impact the heart defect has on their life in general. Objective: The aim was to illuminate and gain a deeper understanding of adolescents' and young adults' experiences of living with a surgically palliated univentricular heart. Design: Seven open-ended in-depth interviews were conducted, transcribed, and analyzed according to the henomenological hermeneutical method. All adolescents and young adults operated before 1995 according to the Fontan procedure or the total cavo-pulmonary connection procedure at one pediatric cardiology unit were included in the study. They were 17-32 years of age (median age 22 years). Results: The interpretation of the interview transcripts showed that the participants experienced living with a surgically palliated univentricular heart in terms of feeling exceptional, strong, and healthy. This was supported by two structural analyses, where three themes emerged: happiness over being me, focusing on possibilities, and being committed to life. Conclusion: Living with a Fontan circulation included negative experiences but the analyses clearly demonstrated a feeling of being strong and healthy. An appreciation of having survived and being committed to life was found to be an integral part of the development of the interviewees' existential growth. This probably strengthens them further in their ability to balance expectations and hurdles in life. This study provides valuable insights into the experience of patients after the Fontan procedure and the importance of a positive health care environment throughout their lives.

  • 83. Berglund, L
    et al.
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Tärnvik, A
    [Treatment of tularemia in children].1998Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 95, nr 36, s. 3758-Artikel i tidskrift (Refereegranskat)
  • 84.
    Berglund, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Att födas för liten2011Ingår i: BarnBladet, ISSN 0349-1994, Vol. 36, nr 4, s. 6-9Artikel i tidskrift (Övrigt vetenskapligt)
  • 85.
    Berglund, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation on iron status, health and neurological development in marginally low birth weight infants.2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation.

    Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight.

    Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age.

    Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.

  • 86.
    Berglund, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Järnbrist - ett problem bland svenska barn?2012Ingår i: Barnläkaren, ISSN 1651-0534, nr 5, s. 13-14Artikel i tidskrift (Övrigt vetenskapligt)
  • 87.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Barns järnbehov och hur vi bäst kan skydda barnhjärnan2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 11, s. 460-463Artikel i tidskrift (Refereegranskat)
  • 88.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Meeting iron needs for infants and children2014Ingår i: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 17, nr 3, s. 267-272Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Purpose of reviewIron deficiency early in life is associated with impaired neurological development. This study reviews the latest research on how to best meet iron requirements in infants and children.Recent findingsThere is concurrent evidence that delayed cord clamping is well tolerated and improves infant iron stores. Iron supplements or enriched complementary foods starting before 6 months of life do not reduce iron deficiency prevalence in low-risk populations. However, for low birth weight infants, iron supplements before 6 months of life have long-term benefits. Iron deficiency anaemia (IDA) during the second half year of life is rare in countries with high compliance to iron-rich complementary foods, but remains a major problem globally. In high-risk populations, iron supplementation reduces IDA and possibly improves growth. However, increased risk of infections is a concern and optimal preventive strategies have not yet been determined. Finally, there is concurrent evidence that iron supplementation of anaemic school-aged children reduces IDA and possibly improves neuropsychological outcomes.SummaryInterventions for prevention of iron deficiency should be prioritized in risk groups. However, the unclear long-term benefits and possible risk of adverse effects, particularly increased infections in developing countries, prompt further large-scale, double-blinded trials.

  • 89.
    Berglund, Staffan K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Chmielewska, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Starnberg, Josefine
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Norman, Mikael
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, s. 111-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Low-birth-weight infants (LBW) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age.

    Methods We randomized 285 marginally LBW (2,000-2,500 g) infants to receive 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 7 years of age, 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using the parental questionnaires Child Behavior Checklist (CBCL) and Five to Fifteen (FTF).

    Results There were no significant differences between the intervention groups in WISC-IV or FTF. However, the CBCL scores for externalizing problems were significantly different, in favor of supplemented children (P=0.045). When combining the supplemented groups, they had significantly lower scores for externalizing behavior compared with placebo (median (interquartile range): 44 [34;51] vs. 48.5 [41;56] P=0.013), and their risk ratio (95% confidence interval) for a total behavioral score above the cutoff for clinical problems was 0.31 (0.09-1.0), P=0.054.

    Conclusion Lower scores of externalizing behavior in supplemented children support our previous findings at 3 years, and suggest that iron supplementation may have long-lasting effects on behavioral functions.

  • 90.
    Berglund, Staffan K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Centre of Excellence for Paediatric Research EURISTIKOS, Department of Paediatrics, School of Medicine, University of Granada, Avda. De Madrid 11, 18012 Granada, Spain.
    García-Valdes, Luz
    Torres-Espinola, Francisco J.
    Segura, Maria Teresa
    Martínez-Zaldivar, Cristina
    Aguilar, Maria J.
    Agil, Ahmad
    Lorente, Jose A.
    Florido, Jesús
    Padilla, Carmen
    Altmäe, Signe
    Marcos, Acensión
    Carmen López-Sabater, M.
    Campoy, Cristina
    Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE)2016Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 16, artikel-id 207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted.

    Methods: In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers.

    Results: Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood.

    Conclusions: We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children.

  • 91.
    Berglund, Staffan K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Björn, Matias
    Lindberg, Josefine
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Norman, Mikael
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Marginally low birth weight increases the risk of underweight and short stature at three and a half years of age2016Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, nr 6, s. 610-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Little is known about the long-term health of marginally low birth weight (LBW) children. This study characterised growth among infants weighing 2,000g-2,500g and explored the prevalence and predictors of sustained growth restriction.

    METHOD: This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below -2 were considered underweight and short respectively.

    RESULTS: The mean SDS for weight and height showed a rapid increase before 12-19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature.

    CONCLUSION: Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch-up growth during the first five months after birth identified those at highest risk.

  • 92.
    Berglund, Staffan K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lindberg, Josefine
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Bjorn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants2014Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, nr 5, s. 477-482Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF. METHODS: We randomized 285 low-birth-weight infants (2,000-2,500g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth.

  • 93.
    Berglund, Staffan K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. EURISTIKOS Excellence Centre for Paediatric Research, University of Granada, Granada, Spain.
    Torres-Espinola, Francisco J.
    Garcia-Valdes, Luz
    Teresa Segura, Ma
    Martinez-Zaldivar, Cristina
    Padilla, Carmen
    Rueda, Ricardo
    Petez Garcia, Miguel
    McArdle, Harry J.
    Campoy, Cristina
    The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring2017Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 118, nr 7, s. 533-540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI >= 25 kg/m(2)) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113.3 (SD 9.9) v. 117.1 (SD 9.2), P=0.039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114.0 (SD 9.7) v. 121.5 (SD 10.9), P = 0.039) and lower receptive, expressive and composite (99.5 (SD 8.6) v. 107.6 (SD 8.3), P= 0.004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12.3 (SD 2.0) v. 13.0 (SD 2.1), P = 0.037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.

  • 94.
    Berglund, Staffan K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life2015Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, nr 3, s. 390-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 95.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lönnerdal, Bo
    The Department of Nutrition, University of California, Davis, CA, USA.
    Westrup, Björn
    The Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants2011Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, nr 6, s. 1553-1561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. OBJECTIVE: The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). DESIGN: We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. RESULTS: Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (±SD) concentration of 19.2 ± 2.5 ng/mL in the 2-mg/kg group compared with 13.0 ± 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. CONCLUSIONS: Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454.

  • 96.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Bjorn
    Department of Women and Child Health, Karolinska Institute, SE-182 88 Stockholm, Sweden.
    Haraldsson, Elisabet
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Engstrom, Berit
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Domellof, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation on auditory brainstem response in marginally LBW infants2011Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, nr 6, s. 601-606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    LBW infants are at risk of iron deficiency (ID), which is associated with impaired nervous system development and may lead to prolonged auditory brainstem response (ABR) latencies. We hypothesized that iron supplementation shortens ABR latencies in marginally LBW (MLBW, 2000-2500 g) infants. In a randomized, controlled trial, 285 healthy MLBW infants received 0, 1, or 2 mg iron/kg/d of iron supplements from 6 wk to 6 mo of age. ABR absolute wave V latencies and central conduction time (CCT) were measured at the endpoint. There were no significant differences between groups in ABR wave V latencies (n = 218). Furthermore, there were no significantly prolonged ABR latencies in infants with ID (n = 32). CCT was significantly higher in the 2 mg group than in the placebo group (n = 126). However, there were no significant correlations between CCT and iron intake or any iron status variable, suggesting that differences in CCT were not caused by iron. We conclude that iron supplements did not improve ABR latencies, and iron-deficient MLBW infants did not have impaired ABR latencies at 6 mo, suggesting that ABR is not a sensitive measure of impaired neurological development or that mild/moderate ID causes no such impairment in MLBW infants.

  • 97.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Iron supplements reduce the risk of iron deficiency anemia in marginally low birth weight infants2010Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 126, nr 4, s. e874-e883Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Low birth weight infants are at risk for iron deficiency (ID). Most LBW infants have marginally low birth weight (MLBW, 2000–2500 g) and it is not known whether they benefit from iron supplements. The objective of this trial was to study the effects of iron supplementation in MLBW infants.

    METHOD: In a randomized controlled trial, we assigned 285 healthy, MLBW infants to receive iron supplements at a dose of 0 (placebo), 1, or 2 mg/kg per day between 6 weeks and 6 months of age. Hemoglobin levels, ferritin levels, transferrin saturation, mean cell volume, and transferrin receptor levels were analyzed at 6 months. Growth and morbidity were monitored.

    RESULTS: Iron supplementation resulted in significant dose-dependent effects on hemoglobin and all iron status indicators at 6 months. The prevalence of ID at 6 months was 36% in the placebo group, 8.2% in the 1 mg/kg per day group, and 3.8% in the 2 mg/kg per day group (P < .001). The prevalence rates of ID anemia (IDA) were 9.9%, 2.7%, and 0%, respectively (P = .004). Among infants who were exclusively breastfed at 6 weeks, the prevalence of IDA was 18% in the placebo group. There were no significant differences between groups in growth or morbidity.

    CONCLUSIONS: MLBW infants have relatively high risks of ID and IDA, especially if they are breastfed. Iron supplementation at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively, with no short-term adverse effects on morbidity or growth.

  • 98.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Division of Neonatology, Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation of LBW infants on cognition and behavior at 3 years2013Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 131, s. 47-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. METHODS: In a randomized controlled trial, 285 marginally LBW (2000-2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4-14.2). CONCLUSIONS: Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.

  • 99. Bergman, Annika
    et al.
    Young, Cecilia
    Miadi-Fargier, Houda
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sjukvård och samhälle får betala högt pris för rotavirusinfektioner hos barn: Svensk deskriptiv kostnadsstudieger prisuppgifter2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 16, s. 1186-1191Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Rotavirus gastroenterit is the most frequent cause of severe diarrhoea in children <5 years of age. Morbidity and resource use due to rotavirus are substantial, though comprehensive data on the economic impact of the disease in Sweden are lacking. The objective of this study was to estimate the average cost per episode of confirmed rotavirus gastroenteritis in primary care, emergency department and hospital settings in Sweden. The total societal cost (including direct medical, direct nonmedical and indirect cost) per episode was estimated to SEK4307 in the primary care setting, SEK5837 in the emergency department setting and to SEK19 456 in the hospital setting. Loss of productivity due to work absenteeism among parents was one of the major costs from a societal perspective. The result shows that rotavirus incurs considerable resource utilisation in all health care settings and substantial costs for the health care sector and the society.

  • 100.
    Bergström, E
    et al.
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Hernell, O
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Obesity and insulin resistance in childhood and adolescence.2005Ingår i: From Preventive Nutrition: The Comprehensive Guide for Health Professionals, third ed, Humana Press Inc. Totowa, NJ , 2005, s. 293-316Kapitel i bok, del av antologi (Övrigt vetenskapligt)
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