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  • 301. Ljungman, Gustaf
    et al.
    Jakobson, Åke
    Behrendtz, Mikael
    Ek, Torben
    Friberg, Lars-Göran
    Hjalmars, Ulf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hjorth, Lars
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pal, Niklas
    Sandstedt, Bengt
    Österlundh, Gustaf
    Gustafsson, Göran
    Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 20072011In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, no 5, p. 750-757Article in journal (Refereed)
    Abstract [en]

    Aim:  Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival.

    Methods:  We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population.

    Results:  Two thousand four hundred and eighty-seven children (<15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01).

    Conclusions:  The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.

  • 302. Lui, Kei
    et al.
    Lee, Shoo K
    Kusuda, Satoshi
    Adams, Mark
    Vento, Maximo
    Reichman, Brian
    Darlow, Brian A
    Lehtonen, Liisa
    Modi, Neena
    Norman, Mikael
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bassler, Dirk
    Rusconi, Franca
    Lodha, Abhay
    Yang, Junmin
    Shah, Prakesh S
    Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries2019In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 215, p. 32-40.e14Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates.

    STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed.

    RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany.

    CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm.

  • 303.
    Lundberg, Elena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Growth hormone responsiveness in children: results from Swedish multicenter clinical trials of growth hormone treatment2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The general aims of the thesis were to study GH responsiveness by estimation of pharmacokinetics and bioavailability of injected recombinant human GH (rhGH), of growth response as gain in heightSDS during childhood and puberty, and IGF-I response as change in circulating IGF-ISDS and IGFBP3SDS. Methods Short children were recruited during 1988–1999 into two national randomized multicentre clinical trials on growth until adult height. A group of 117 GHD patients who had been treated from prepuberty with a single GH dose of 33μg/kg/day for at least 1 year were randomized at onset of puberty either to remain on this dose regimen or to an increased dose, GH67μg/kg/day, administered once daily or divided into two doses, GH33x2μg/kg/day. Data on IGF-ISDS and IGF binding protein 3 (IGFBP3)SDS were available from 111 patients and analysed as stated below. The 151 short prepubertal non-GHD patients were randomized into three groups: untreated controls, GH33 or GH67μg/kg/day. A subpopulation from both trials, 128 patients examined annually in Gothenburg, formed the study sample on GH uptake. They received sc GH injections to obtain 16–24 hour GH curves and the GH pharmacokinetics and bioavailability was calculated. Results: A dose-dependent effect on Cmax was found with great intra- and inter-individual variability. Of the Cmax variability, 43% was explained by the rhGH dose and proxies for injection depth. Median bioavailability of the injected dose was 71%, with great variation, mainly dependent on injection depth. In the IGHD group a dose-dependent difference in pubertal gain in heightSDS was found, with mean of 0.8 for the GH67 group and 0.4 for GH33, p<0.01. The mean total gain in heightSDS during treatment was 1.9 for GH67 and 1.4 for GH33, p<0.01. A dose-dependent pubertal ΔIGF-ISDS was 0.5 vs −0.1, p=0.007, correlating to pubertal gain in heightSDS, p=0.003; and was the most important variable to explain the variation in pubertal gain in heightSDS. In the non-GHD group the ΔIGF-ISDS from baseline to mean study level was dose-dependent 2.07 vs 1.20, p=0.001; and correlated negatively with baseline values of IGF-ISDS, rho= -0.56 for GH67, p=0.001, vs rho= -0.82 for GH33, p=0.0001, and correlated positively with gain in heightSDS in both GH-treated groups, rho= 0.42, p<0.001. In multivariable regression analyses, ΔIGF-ISDS was always an important explanatory variable for long-term growth response from the prepubertal period until adult height, while the IGF-ISDS study level per se was not. Conclusion: Growth response to GH treatment was dose dependent with great variability between patients. More pubertal growth was attained by an increased rhGH dose, mimicking the physiology of healthy children, in whom GH secretion rate increases during puberty. This resulted in a gain in IGF-ISDS closely correlating to pubertal gain in heightSDS in both IGHD and non-GHD patients. A broad range in GH responsiveness was found for both growth and IGF response in both diagnostic groups, but lower in the non-GHD group. Higher uptake of a given GH dose was observed after a deep injection and a higher GH concentration. These results are clinically applicable for individuals who remain short close to onset of puberty; by identifying and deeply injecting a rhGH dose that accounts for individual responsiveness, we can stimulate an increment in IGF-ISDS that correlates to gain in heightSDS during puberty.

  • 304.
    Lundberg, Elena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosberg, Sten
    Albertsson-Wikland, Kerstin
    Are the GH Treatment Doses in Use within Secretion Rates of Healthy Children?2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, p. 378-378Article in journal (Other academic)
  • 305.
    Lundberg, Elena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosberg, Sten
    Albertsson-Wikland, Kerstin
    Broad variability in pharmacokinetics of GH following rhGH injecetions in children2018In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 40, p. 61-68Article in journal (Other academic)
    Abstract [en]

    Objective: Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking.

    Design: Children with/without GH-deficiency participating in clinical trials were followed prospectively (≤8 times). Blood was sampled pre-GH-injection (dose GH33/GH67 μg/kg) and either every 30 min thereafter for 24 h (Experimental-setting; 59 GH-curves/15 children); or every 2 h thereafter for 16 h (Clinical-setting; 429 GH-curves/117 children). Pharmacokinetics were estimated by time Tmax (h) of maximal GH-concentration (Cmax, mU/L) and area under the curve for 16 h (AUC, mU/L ∗ h).

    Results: In the Clinical-setting, median Cmax was 71 mU/L and AUC was 534 mU/L ∗ h, with coefficients of variation for intra-individual variation of 39% and 36%, respectively, and inter-individual variation of 44% and 42%, respectively. 43% of Cmax and AUC variability was explained by GH-dose and proxies for injection depth (baseline GH-level, GHpeakwidth, BMISDS). In the Experimental- versus Clinical-setting, 85% and 40% of GH-curves, respectively, reached zero-levels within 24 h. A longer duration was found following a more superficial GH-injection. Spontaneous GH-peaks were identified already 6 h after the GH-injection in about half of the curves of both GHD and non-GHD patients.

    Conclusion: Very broad intra-individual and inter-individual variability was found. A high GH-peak will optimize growth effects; the highest Cmax was found after a deep injection of GH at the higher dose and concentration. In as many as 60% of the children, GH remained detectable in serum after 24 h; a constant GH-level will promote IGF-I and metabolic effects.

  • 306.
    Lundberg, Elena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosberg, Sten
    Albertsson-Wikland, Kerstin
    GH-Pattern with High Trophs are Often Found after Daily sc rhGH-Injection in Children2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, p. 377-377Article in journal (Other academic)
  • 307.
    Lundberg, Elena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Albertsson-Wikland, Kerstin
    Normalized pubertal tempo of masculinisation and pubertal height gain in boys with MPHD, using a physiological treatment approach with low dose testosterone and adequate dose rhGH2019In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 91, p. 467-468Article in journal (Other academic)
  • 308.
    Lundberg, Elena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Holmlund, Mariell
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Albertsson-Wikland, Kerstin
    Normalized pubertal tempo of maturation and pubertal height gain in girls with MPHD, using a physiological treatment approach with natural estrogens & rhGH2019In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 91, p. 462-463Article in journal (Other academic)
  • 309.
    Lundberg, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hellström, Sten
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Development and Validation of a New Grading Scale for Otitis Media2013In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 32, no 4, p. 341-345Article in journal (Refereed)
    Abstract [en]

    Background: Grading of acute otitis media (AOM) is important in clinical situations as well as in research. Current grading scales for AOM have used a 6 to 9 point scoring system primarily based on variation of redness and bulging of the tympanic membrane (TM). This study aimed to develop and validate a new scale for grading AOM. Method: The scale was developed in 3 stages based on 32 patients with images taken of the TM when a child attended healthcare centre with othalgia and at follow-up visits. Content validity was used as the method for the first 2 stages. An expert panel reviewed the scale and repeated the process on a revised scale. Reliability was tested with a different expert panel that used the final scale on a sample of TM images in a test-retest and inter-rater and intra-rater agreements were calculated. Results: The scale was developed in 3 steps using expert committees. During the process the description of vascularization was judged to be of insufficient importance for our scale. Inter-rater agreement was moderate (kappa = 0.52) and intra-rater agreement was good (kappa = 0.66 to 0.89) in the test-retest of the final scale. Conclusions: The developed AOM image-based grading scale demonstrates substantial inter- and intra-rater reliability with potential use in clinical research and telemedicine applications. Furthermore, the parameter "redness of TM" is of less importance in our scale as compared with other available grading systems.

  • 310.
    Lundberg, Veronica
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Health-related quality of life among Swedish children with Juvenile Idiopathic Arthritis: parent-child discrepancies, gender differences and comparison with a European cohort2017In: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 15, article id 26Article in journal (Refereed)
    Abstract [en]

    Background: This study investigates gender differences in self-reports and between parent and child reports in Healthrelated Quality of Life (HRQOL), measured with disease-specific and generic instruments for chronic disease. Comparison of HRQOL results in this Juvenile Idiopathic Arthritis (JIA) sample to a European cohort of children with JIA and one of children with other health conditions are also made. Methods: Fifty-three children with juvenile idiopathic arthritis (JIA), aged 8-18 years, and their parents completed the condition-specific DISABKIDS for JIA, and the DISABKIDS generic instrument for chronic conditions (DCGM-37) in a cross-sectional study. European reference data were used for comparison of child and parental reports. Results: Child self-reports in DCGM-37 and DISABKIDS for JIA showed no gender differences. Parental and child reports of the child's HRQOL differed only in DCGM-37; this was among girls who scored their independence (p = 0.03), physical limitation (p = 0.01), social exclusion (p = 0.03), emotions (p < 0.01), and general transformed score (p < 0.01) higher than did their parents. Our sample of children with JIA reported more physical limitation compared to samples of European children with JIA (p = 0.01), European children with chronic conditions (p < 0.01), and their parents (p = 0. 01 and p < 0.01). The Swedish children reported more problem with understanding compared to the European JIA sample (p = 0.03). Swedish parents perceived their children's independence significantly lower than did the European parents of JIA children (p < 0.01), as well as European parents of children with chronic conditions (p = 0.03). The Swedish parents also perceived their children to have significantly lower social inclusion (p < 0.05) and general transformed score (p = 0.04), in comparison to European parents of children with chronic conditions. Conclusions: Parent-child differences in assessment of quality of life depend on the HRQOL instrument used, especially among girls. In comparison to European cohorts, our sample of children with JIA experienced more physical limitations and less understanding.

  • 311.
    Lundberg, Veronica
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Petersen, Solveig
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Eurenius, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Health-related quality of life in girls and boys with juvenile idiopathic arthritis: self- and parental reports in a cross-sectional study.2012In: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 10, p. 33-Article in journal (Refereed)
    Abstract [en]

    ABSTRACT: BACKGROUND: Juvenile Idiopathic Arthritis (JIA) affects children and adolescents with both short-term and long-term disability. These children also report lower health-related quality of life (HRQOL) compared to their healthy peers. However, there seems to be some discrepancies between self- and parent-reports, and gender differences need to be further studied. This study aims to describe HRQOL in girls and boys with JIA, and to explore gender differences in self-reports compared to parent-reports of HRQOL in children with JIA. METHODS: Fifty-three children and adolescents with JIA (70% girls and 30% boys) with a median age of 14 years (8--18 years), and their parents, participated in this cross-sectional study in Sweden. Data was systematically collected prior to ordinary visits at a Pediatric outpatient clinic, during a period of 16 months (2009--2010). Disability was assessed with the Childhood Health Assessment Questionnaire (CHAQ), and disease activity by physicians' assessments and Erythrocyte Sedimentation Rate (ESR). The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) was used to assess self- and parent-reports of HRQOL in the child. RESULTS: In this sample of children with generally low disease activity and mild to moderate disability, more than half of the children experienced suboptimal HRQOL, equally in girls and boys. Significant differences between self- and parent-reports of child HRQOL were most evident among girls, with lower parent-reports regarding the girl's physical- and psychosocial health as well as in the total HRQOL score. Except for the social functioning subscale, where parents' reports were higher compared to their sons, there were no significant differences between boys- and parent-reports. CONCLUSIONS: More than half of the girls and boys experienced suboptimal HRQOL in this sample, with no gender differences. However, there were differences between self- and parent-reports of child HRQOL, with most significant differences found among the girls. Thus, differences between self- and parent-reports of child HRQOL must be taken into account in clinical settings, especially among girls with JIA.

  • 312.
    Lundgren, Katrine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Does breastfeeding, compared to formula-feeding, give health benefits with regard to early neurological development and infections? - A study of infants in Västerbotten, Sweden2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 313. Lundgren, Pia
    et al.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Källen, Karin
    Holmström, Gerd
    Hård, Anna-Lena
    Smith, Lois E.
    Löfqvist, Chatarina
    Hellström, Ann
    WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, article id e73256Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the ability of a postnatal weight-gain algorithm (WINROP) to identify sight-threatening retinopathy of prematurity (ROP type 1) in a nation-based extremely preterm infant cohort.

    METHODS: This study enrolled all 707 live-born extremely preterm (gestational age [GA] <27 weeks) infants, born 2004-2007 in Sweden; the Extremely preterm Infants in Sweden Study (EXPRESS). WINROP analysis was performed retrospectively in 407 of the infants using weekly weight gain to assess the preterm infant's risk of developing ROP type 1 requiring treatment. GA, birthweight (BW), and weekly postnatal weight measurements were entered into WINROP. WINROP signals with an alarm to indicate if the preterm infant is at risk for ROP type 1.

    RESULTS: In this extremely preterm population, WINROP correctly identified 96% (45/47) of the infants who required treatment for ROP type 1. The median time from alarm to treatment was 9 weeks (range, 4-20 weeks).

    CONCLUSIONS: WINROP, an online surveillance system using weekly weight gain, identified extremely preterm infants at risk for ROP type 1 requiring treatment at an early stage and with high sensitivity in a Swedish nation-based cohort.

  • 314. Lundgren, Pia
    et al.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Smith, Lois
    Wu, Carolyn
    VanderVeen, Deborah
    Hellström, Ann
    Löfqvist, Chatarina
    The specificity of the WINROP algorithm can be significantly increased by reassessment of the WINROP alarm2015In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 108, no 2, p. 152-156Article in journal (Refereed)
    Abstract [en]

    Background: Retinopathy of prematurity (ROP) is a sight-threatening disease affecting extremely preterm infants. The introduction of new ROP screening surveillance systems, with higher sensitivity and specificity than established ROP screening guidelines, has the potential to reduce the number of stressful eye examinations in these infants.

    Objectives: To improve the specificity of the WINROP (Weight, Insulin-like growth factor-I, Neonatal, ROP) surveillance system, identifying extremely preterm infants requiring treatment for ROP.

    Methods: Two cohorts that had previously been subjected to WINROP analyses were included and reevaluated in this study. The weight at WINROP alarm for extremely preterm infants, born at gestational age <27 weeks, was reevaluated and by establishing 'safe' WINROP alarm weight limits, an intersample reassessment of WINROP alarm was performed. The two cohorts were as follows: (1) the Extremely Preterm Infants in Sweden Study (EXPRESS) cohort, infants born in Sweden during 2004-2007 (n = 407), and (2) extremely preterm infants in a North American co-hort, born during 2006-2009 (n = 566).

    Results: In the EXPRESS cohort, 12.5% (40/319) of the infants who previously received a WINROP alarm were now reassessed as having no alarm; the specificity of WINROP in EXPRESS increased from 23.9% (86/360) to 35.0% (126/360). In the North American cohort, 15.4% (81/526) were reassessed as having no alarm; the specificity increased from 8.5% (38/447) to 26.6% (119/447). The sensitivity persisted as 97.5% in EXPRESS (45/47) and 98.3% (117/119) in the North American cohort.

    Conclusions: The specificity of the WINROP surveillance system for extremely preterm infants can be significantly improved by reassessment using the weight at WINROP alarm.

  • 315. Lundmark, Elisabet
    et al.
    Stenberg, Arne
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Nevéus, Tryggve
    Reboxetine in therapy-resistant enuresis: a randomized placebo-controlled study2016In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 12, no 6, p. 397.e1-397.e5Article in journal (Refereed)
    Abstract [en]

    Introduction: A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. Aim: The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart. Patients and methods: The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period. Results: Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data. Discussion: The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown. Conclusion: Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.

  • 316. Lundqvist, P.
    et al.
    Jonsson, L.
    Selander, B.
    Wihlborg, J.
    van Den Berg, Johannes
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jakobsson, U.
    SWEDISH MOTHERS EXPEREINCES OF KANGAROO MOTHER CARE DURING GROUND AMBULANCE NEONATAL TRANSPORTS2016In: EUROPEAN JOURNAL OF PEDIATRICS, ISSN 0340-6199, Vol. 175, no 11, p. 1457-1457Article in journal (Refereed)
  • 317. Lupo, P.
    et al.
    Luna-Gierke, R.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Scheurer, M.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Papworth, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Perinatal and Familial Risk Factors for Soft-Tissue Sarcomas in Children, Adolescents, and Young Adults: A Population-Based Birth Cohort Study, Sweden, 1973-20122017In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 64, p. S4-S5Article in journal (Other academic)
    Abstract [en]

    Background/Objectives: Perinatal factors have been associated with soft-tissue sarcomas (STS) in case-control studies. However, (1) the specific contributions of factors including fetal growth remain unknown, (2) these factors have not been examined in large cohort studies, and (3) few assessments have evaluated risk in specific STS subtypes. Therefore, we sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. Design/Methods: We identified 5,063,499 individuals in the Swedish Birth Registry born during 1973-2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including: fetal growth, gestational age, presence of a congenital anomaly, and parental age. Poisson regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations between selected factors and STS overall, as well as by common subtypes. Results: There were 673 children, adolescents, and young adults diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital anomaly was associated with STS risk (IRR=1.70, 95% CI: 1.23-2.35). This association was stronger (IRR=2.89, 95% CI: 1.25-6.70) in more recent years (2000-2012). High fetal growth was also associated with STS during the same time period (IRR=1.87, 95% CI: 1.06-3.30). Being born preterm (35 years) was inversely associated with the risk of developing synovial sarcoma (IRR=0.50, 95% CI: 0.26-0.94). Conclusions: In this cohort study, those with congenital anomalies and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways influencing the risk of STS. Our findings could implicate novel mechanisms underlying susceptibility to STS and may inform future surveillance, prevention, and treatment efforts.

  • 318. Lynøe, Niels
    et al.
    Elinder, Göran
    Hallberg, Boubou
    Rosén, Måns
    Sundgren, Pia
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Is accepting circular reasoning in shaken baby studies bad science or misconduct?2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 9, p. 1445-1446Article in journal (Other academic)
  • 319. Lynøe, Niels
    et al.
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Consensus should be adapted to the evidence and not vice-versa2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 8, p. 1476-1476Article in journal (Refereed)
  • 320. Lynøe, Niels
    et al.
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    No similarities between the Wakefield report on measles, mumps and rubella vaccine and the Swedish report on traumatic shaking2020In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Article in journal (Refereed)
  • 321. Löfving, Anders
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hellström-Westas, Lena
    Andersson, Ola
    Reference intervals for reticulocyte hemoglobin content in healthy infants2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, no 5, p. 657-661Article in journal (Refereed)
    Abstract [en]

    Objectives: Iron deficiency anemia in childhood is a serious public health problem worldwide. Reticulocyte hemoglobin content (Ret-He) is a novel biomarker of iron deficiency adopted for adults but there is a lack of reference intervals for Ret-He in infants. The aim of this study was to provide data from healthy infants.

    Methods: Swedish infants (n = 456), born at term after normal pregnancies were included. Ret-He was measured at birth (umbilical cord sample), 48–72 h, 4 months, and 12 months. Reference intervals were calculated as ±2 standard deviations from the mean of Ret-He.

    Results: Reference intervals for newborn Ret-He were 27.4 to 36.0 pg/L (N = 376) in the cord sample, 28.1–37.7 pg/L (N = 253) at 48–72 h, 25.6–33.4 pg/L (N = 341) at four months and 24.9–34.1 pg/L (N = 288) at 12 months. Ret-He was significantly lower among iron-deficient infants, at 4 months mean difference (95% CI) −4.2 pg/L (−6.1 to −2.4) and at 12 months mean difference (95% CI) −3.4 pg/L (−5.0 to −1.8).

    Conclusions: This longitudinal study presents Ret-He reference intervals based on non-anemic and non-iron-deficient infants and constitutes a step towards standardizing Ret-He as a pre-anemia biomarker of iron deficiency in children.

  • 322.
    Lönnerdal, Bo
    et al.
    Department of Nutrition, University of California, Davis, CA.
    Georgieff, Michael K.
    University of Minnesota Masonic Children's Hospital, Division of Neonatology, University of Minnesota School of Medicine, Minneapolis, MN.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant2015In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 167, no 4, Supplement, p. S8-S14Article in journal (Refereed)
  • 323. Lönnerdal, Bo
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    An Opinion on "Staging'' of Infant Formula: A Developmental Perspective on Infant Feeding2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 1, p. 9-21Article, review/survey (Refereed)
    Abstract [en]

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

  • 324. Lönnerdal, Bo
    et al.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Under- and overnutrition of iron in infancy and early childhood2014In: The Nest, ISSN 1270–9743, Vol. 35, p. 6-7Article in journal (Other academic)
  • 325. Manousou, Sofia
    et al.
    Johansson, Birgitta
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
    Eriksson, Janna
    Gutefeldt, Kerstin
    Tornhage, Carl-Johan
    Eggertsen, Robert
    Malmgren, Helge
    Hulthen, Lena
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nyström Filipsson, Helena
    Role of iodine-containing multivitamins during pregnancy for children’s brain function: protocol of an ongoing randomised controlled trial: the SWIDDICH study2018In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 4, article id e019945Article in journal (Refereed)
    Abstract [en]

    Introduction: Iodine is essential for normal brain development. Moderate and severe fetal iodine deficiency results in substantial to serious developmental delay in children. Mild iodine deficiency in pregnancy is associated with neurodevelopmental deficits in the offspring, but evidence from randomised trials is lacking. The aim of the Swedish Iodine in Pregnancy and Development in Children study is to determine the effect of daily supplementation with 150 µg iodine during pregnancy on the offspring’s neuropsychological development up to 14 years of age.

    Methods and analysis: Thyroid healthy pregnant women (n=1275: age range 18–40 years) at ≤12 weeks gestation will be randomly assigned to receive multivitamin supplements containing 150 µg iodine or non-iodine-containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children-V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years. Iodine status (urinary iodine concentration) will be measured during pregnancy and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones, thyroglobulin), and deiodinase type 2 polymorphisms will be measured during pregnancy and in the offspring at 7 and 14 years. Structural MRI or other relevant structural or functional brain imaging procedures will be performed in a subgroup of children at 7 and 14 years. Background and socioeconomic information will be collected at all follow-up times.

    Ethics and dissemination: This study is approved by the Ethics Committee in Göteborg, Sweden (Diary numbers: 431-12 approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017 (children follow-up)). According to Swedish regulations, dietary supplements are governed by the National Food Agency and not by the Medical Product Agency. Therefore, there is no requirement for a monitoring committee and the National Food Agency does not perform any audits of trial conduct. The trial will be conducted in accordance with the Declaration of Helsinki. The participating sites will be contacted regarding important protocol changes, both orally and in writing, and the trial registry database will be updated accordingly. Study results will be presented at relevant conferences, and submitted to peer-reviewed journals with open access in the fields of endocrinology, paediatrics and nutrition. After the appropriate embargo period, the results will be communicated to participants, healthcare professionals at the maternal healthcare centres, the public and other relevant groups, such as the national guideline group for thyroid and pregnancy and the National Food Agency.

  • 326. Martin, Lisa J
    et al.
    Sjörs, Gunnar
    Reichman, Brian
    Darlow, Brian A
    Morisaki, Naho
    Modi, Neena
    Bassler, Dirk
    Mirea, Lucia
    Adams, Mark
    Kusuda, Satoshi
    Lui, Kei
    Feliciano, Laura San
    Håkansson, Stellan
    Swedish Neonatal Quality Register, Department of Pediatrics/Neonatal Services, Umeå University Hospital, Umeå, Sweden.
    Isayama, Tetsuya
    Mori, Rintaro
    Vento, Max
    Lee, Shoo K
    Shah, Prakesh S
    Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: an International Study2016In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 30, no 5, p. 450-461Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates.

    METHODS: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated.

    RESULTS: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively].

    CONCLUSION: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable.

  • 327.
    Mattsson, Hanna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Tools and infrastructure for drug development in new-borns, children of all ages and adolescents2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 328. Mejàre, Ingegerd A.
    et al.
    Klingberg, Gunilla
    Mowafi, Frida K.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Twetman, Svante H. A.
    Tranaeus, Sofia H.
    A Systematic Map of Systematic Reviews in Pediatric Dentistry: What Do We Really Know?2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0117537Article in journal (Refereed)
    Abstract [en]

    Objectives To identify, appraise and summarize existing knowledge and knowledge gaps in practice-relevant questions in pediatric dentistry. Methods A systematic mapping of systematic reviews was undertaken for domains considered important in daily clinical practice. The literature search covered questions in the following domains: behavior management problems/dental anxiety; caries risk assessment and caries detection including radiographic technologies; prevention and non-operative treatment of caries in primary and young permanent teeth; operative treatment of caries in primary and young permanent teeth; prevention and treatment of periodontal disease; management of tooth developmental and mineralization disturbances; prevention and treatment of oral conditions in children with chronic diseases/developmental disturbances/obesity; diagnosis, prevention and treatment of dental erosion and tooth wear; treatment of traumatic injuries in primary and young permanent teeth and cost-effectiveness of these interventions. Abstracts and full text reviews were assessed independently by two reviewers and any differences were solved by consensus. AMSTAR was used to assess the risk of bias of each included systematic review. Reviews judged as having a low or moderate risk of bias were used to formulate existing knowledge and knowledge gaps. Results Out of 81 systematic reviews meeting the inclusion criteria, 38 were judged to have a low or moderate risk of bias. Half of them concerned caries prevention. The quality of evidence was high for a caries-preventive effect of daily use of fluoride toothpaste and moderate for fissure sealing with resin-based materials. For the rest the quality of evidence for the effects of interventions was low or very low. Conclusion There is an urgent need for primary clinical research of good quality in most clinically-relevant domains in pediatric dentistry.

  • 329. Mesotten, D.
    et al.
    Joosten, K.
    van Kempen, A.
    Verbruggen, S.
    Braegger, Christian
    Bronsky, Jiri
    Cai, Wei
    Campoy, Cristina
    Carnielli, Virgilio
    Darmaun, Dominique
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Fewtrell, Mary
    Fidler Mis, Natasa
    Franz, Axel
    Goulet, Olivier
    Hartman, Corina
    Hill, Susan
    Hojsak, Iva
    Iacobelli, Silvia
    Jochum, Frank
    Joosten, Koen
    Kolacek, Sanja
    Koletzko, Berthold
    Ksiazyk, Janusz
    Lapillonne, Alexandre
    Lohner, Szimonetta
    Mesotten, Dieter
    Mihalyi, Krisztina
    Mihatsch, Walter A.
    Mimouni, Francis
    Molgaard, Christian
    Moltu, Sissel J.
    Nomayo, Antonia
    Picaud, Jean Charles
    Prell, Christine
    Puntis, John
    Riskin, Arieh
    Saenz De Pipaon, Miguel
    Senterre, Thibault
    Shamir, Raanan
    Simchowitz, Venetia
    Szitanyi, Peter
    Tabbers, Merit M.
    Van Den Akker, Chris H. B.
    Van Goudoever, Johannes B.
    Van Kempen, Anne
    Verbruggen, Sascha
    Wu, Jiang
    Weihui, Yan
    ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Carbohydrates2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 6, p. 2337-2343Article in journal (Refereed)
  • 330. Metcalfe, J. R.
    et al.
    D'Vaz, N.
    Makrides, M.
    Gold, M. S.
    Quinn, P.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. School of Paediatrics and Child Health, The University of Western Australia, Perth.
    Loh, R.
    Prescott, S. L.
    Palmer, D. J.
    Elevated IL-5 and IL-13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 2, p. 308-316Article in journal (Refereed)
    Abstract [en]

    Background

    Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure.

    Objective

    To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy.

    Methods

    Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive ‘early egg’ or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge.

    Results

    In 4–month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by ‘early’ introduction of egg.

    Conclusions & Clinical Relevance

    Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.

  • 331. Mihatsch, W.
    et al.
    Shamir, R.
    van Goudoever, J. B.
    Fewtrell, M.
    Lapillonne, A.
    Lohner, S.
    Mihalyi, K.
    Decsi, T.
    Braegger, Christian
    Bronsky, Jiri
    Cai, Wei
    Campoy, Cristina
    Carnielli, Virgilio
    Darmaun, Dominique
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Fewtrell, Mary
    Fidler Mis, Natasa
    Franz, Axel
    Goulet, Olivier
    Hartman, Corina
    Hill, Susan
    Hojsak, Iva
    Iacobelli, Silvia
    Jochum, Frank
    Joosten, Koen
    Kolacek, Sanja
    Koletzko, Berthold
    Ksiazyk, Janusz
    Lapillonne, Alexandre
    Lohner, Szimonetta
    Mesotten, Dieter
    Mihalyi, Krisztina
    Mihatsch, Walter A.
    Mimouni, Francis
    Molgaard, Christian
    Moltu, Sissel J.
    Nomayo, Antonia
    Picaud, Jean Charles
    Prell, Christine
    Puntis, John
    Riskin, Arieh
    Saenz De Pipaon, Miguel
    Senterre, Thibault
    Shamir, Raanan
    Simchowitz, Venetia
    Szitanyi, Peter
    Tabbers, Merit M.
    Vlasselaers, Dirk
    Van Den Akker, Chris H. B.
    Van Goudoever, Johannes B.
    Van Kempen, Anne
    Verbruggen, Sascha
    Wu, Jiang
    Yan, Weihui
    ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Guideline development process for the updated guidelines2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 6, p. 2306-2308Article in journal (Refereed)
  • 332. Mihatsch, Walter A.
    et al.
    Braegger, Christian
    Bronsky, Jiri
    Cai, Wei
    Campoy, Cristina
    Carnielli, Virgilio
    Darmaun, Dominique
    Desci, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Natasa Fidler
    Franz, Axel
    Goulet, Olivier
    Hartman, Corina
    Susan, Hill
    Hojsak, Iva
    Lacobelli, Silvia
    Jochum, Frank
    Joosten, Koen
    Kolacek, Sanja
    Koletzko, Berthold
    Ksiazyk, Janusz
    Lapillonne, Alexandre
    Lohner, Szimonetta
    Mesotten, Dieter
    Mihalyi, Krisztina
    Mimouni, Francis
    Molgaard, Christian
    Moltu, Sissel J.
    Nomayo, Antonia
    Picaud, Jean Charles
    Prell, Christine
    Puntis, John
    Riskin, Arieh
    Saenz de Pipaon, Miguel
    Senterre, Thibault
    Shamir, Ranaan
    Simchowitz, Venetia
    Szitanyi, Peter
    Tabbers, Merit M.
    van den Akker, Chris H. B.
    van Goudoever, Johannes B.
    van Kempen, Anne
    Verbruggen, Sascha
    Wu, Jiang
    Yan, Weihui
    ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 6, p. 2303-2305Article in journal (Refereed)
  • 333. Mihatsch, Walter A.
    et al.
    Braegger, Christian
    Bronsky, Jiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Mis, Nataša F.
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Mølgaard, Christian
    Embleton, Nicholas
    van Goudoever, Johannes
    Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 63, no 1, p. 123-129Article in journal (Refereed)
    Abstract [en]

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

  • 334. Milani, Lili
    et al.
    Lundmark, Anders
    Kiialainen, Anna
    Nordlund, Jessica
    Flaegstad, Trond
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Heyman, Mats
    Jonmundsson, Gudmundur
    Kanerva, Jukka
    Schmiegelow, Kjeld
    Söderhäll, Stefan
    Gustafsson, Mats G
    Lönnerholm, Gudmar
    Syvänen, Ann-Christine
    DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia.2010In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, no 6, p. 1214-25Article in journal (Refereed)
    Abstract [en]

    Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.

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

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

  • 336. Modvig, S.
    et al.
    Madsen, H. O.
    Siitonen, S. M.
    Rosthoj, S.
    Tierens, A.
    Juvonen, V
    Osnes, L. T. N.
    Valerhaugen, H.
    Hultdin, M.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thorn, I
    Matuzeviciene, R.
    Stoskus, M.
    Marincevic, M.
    Fogelstrand, L.
    Lilleorg, A.
    Toft, N.
    Jonsson, O. G.
    Pruunsild, K.
    Vaitkeviciene, G.
    Vettenranta, K.
    Lund, B.
    Abrahamsson, J.
    Schmiegelow, K.
    Marquart, H. , V
    Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia2019In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 33, no 6, p. 1324-1336Article in journal (Refereed)
    Abstract [en]

    Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10−3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4–9.0, p = 0.008) for day 29 FCM-MRD ≥ 10−3and 5.6 (95% CI 2.0–16, p = 0.001) for PCR-MRD ≥ 10−3 compared with MRD < 10−3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10−4–<10−3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10−4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10−4 had a cumulative incidence of relapse of 2.3% (95% CI 0–6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.

  • 337. Mohlkert, Lilly -Ann
    et al.
    Hallberg, Jenny
    Broberg, Olof
    Hellström, Monica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Halvorsen, Cecilia Pegelow
    Sjoberg, Gunnar
    Bonamy, Anna -Karin Edstedt
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Preterm arteries in childhood: dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm2017In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, no 2, p. 299-306Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-y-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term. METHODS: Children born extremely preterm (EXP, n = 176, birthweights: 348-1,161 g) and at term (CTRL, n = 174, birth weights: 2,430-4,315 g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (CIMT), and the stiffness index of the CCA and aorta. RESULTS: Arteries were 5-10% narrower in EXP than in CTRL (P < 0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD = 0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL. CONCLUSION: In 6-y-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.

  • 338. Msimang, Veerle M. Y.
    et al.
    Page, Nicola
    Groome, Michelle J.
    Moyes, Jocelyn
    Cortese, Margaret M.
    Seheri, Mapaseka
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Chagan, Meera
    Madhi, Shabir A.
    Cohen, Cheryl
    Impact of Rotavirus Vaccine on Childhood Diarrheal Hospitalization After Introduction Into the South African Public Immunization Program2013In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 32, no 12, p. 1359-1364Article in journal (Refereed)
    Abstract [en]

    Background: Oral rotavirus vaccine was introduced into the South African routine immunization program in August 2009 administered at 6 and 14 weeks with no catch-up. We described the change in rotavirus-associated diarrheal hospitalizations among children <5 years at 3 sentinel sites from 2009 through 2011. Methods: During 2009 through 2011, we compared the proportion of enrolled children aged <5 years hospitalized with acute gastroenteritis and testing rotavirus positive. We used hospital data to determine the change in diarrhea hospitalizations and estimated total numbers of rotavirus hospitalizations by adjusting for nonenrolled patients. Stool samples were tested for rotavirus using enzyme immunoassay. Results: In 2009 (May-December), 46% (404/883) of samples among children <5 years tested rotavirus positive, decreasing to 33% (192/580) (P < 0.001) in 2010 and 29% (113/396) (P < 0.001) in 2011. Compared with May-December 2009, total diarrhea hospitalizations among children aged <5 years was one-third lower in May-December of 2010 and 2011. Among infants, adjusted rotavirus hospitalizations were 61% (n = 267) and 69% (n = 214) lower, respectively, in 2010 and 2011 when compared with 2009 (n = 689), and 45 and 50 percentage points greater than the reduction in rotavirus-negative cases. Among children <5 years, rotavirus hospitalizations were 54% and 58% lower in 2010 and 2011, compared with 2009 (40 and 44 percentage points greater than reduction in rotavirus-negative cases). Rotavirus reductions occurred in rural and urban settings. Conclusion: Using published estimates of rotavirus hospitalization burden, we estimate that at least 13,000 to 20,000 hospitalizations in children <2 years were prevented in the 2 years after rotavirus vaccine introduction.

  • 339. Myburgh, Hermanus C.
    et al.
    van Zijl, Willemien H.
    Swanepoel, DeWet
    Hellstrom, Sten
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Speech-Language Pathology and Audiology, University of Pretoria, Pretoria, South Africa.
    Otitis Media Diagnosis for Developing Countries Using Tympanic Membrane Image-Analysis2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 5, p. 156-160Article in journal (Refereed)
    Abstract [en]

    Background: Otitis media is one of the most common childhood diseases worldwide, but because of lack of doctors and health personnel in developing countries it is often misdiagnosed or not diagnosed at all. This may lead to serious, and life-threatening complications. There is, thus a need for an automated computer based image-analyzing system that could assist in making accurate otitis media diagnoses anywhere. Methods: A method for automated diagnosis of otitis media is proposed. The method uses image-processing techniques to classify otitis media. The system is trained using high quality pre-assessed images of tympanic membranes, captured by digital video-otoscopes, and classifies undiagnosed images into five otitis media categories based on predefined signs. Several verification tests analyzed the classification capability of the method. Findings: An accuracy of 80.6% was achieved for images taken with commercial video-otoscopes, while an accuracy of 78.7% was achieved for images captured on-site with a low cost custom-made video-otoscope. Interpretation: The high accuracy of the proposed otitis media classification system compares well with the classification accuracy of general practitioners and pediatricians (similar to 64% to 80%) using traditional otoscopes, and therefore holds promise for the future in making automated diagnosis of otitis media in medically underserved populations. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 340.
    Myléus, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Persson, Lars-Åke
    International Maternal and Child Health, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Early infections are associated with increased risk for celiac disease: an incident case-referent study2012In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 12, no 1, p. 194-Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 341.
    Myléus, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Reilly, Norelle R.
    Green, Peter H.R.
    Rate, Risk Factors and Outcomes of Non-adherence in Pediatric Patients with Celiac Disease: a Systematic Review2019In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, article id 31173891Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: The only treatment for celiac disease is strict adherence to a gluten-free diet (GFD). We performed a systematic review to investigate the rate of adherence to a GFD in children with celiac disease, risk factors that affect adherence, and outcomes of non-adherence.

    METHODS: We searched PubMed, Cochrane Library, EBSCO, and Scopus for studies through January 2019. We included observational studies of ≥50 children diagnosed with celiac disease and recommended for placement on a GFD. We collected data on adherence assessment (self-report, serology tests, structured dietary interview, biopsies, or assays for gluten immunogenic peptides), risk factors, and outcomes related to adherence. Findings were presented with medians, range, and a narrative synthesis.

    RESULTS: We identified 703 studies; of these, 167 were eligible for full-text assessment and 49 were included in the final analysis, comprising 7850 children. Rates of adherence to a GFD ranged from 23% to 98%. Comparable rates (median rates of adherence, 75%-87%) were found irrespective of how assessments were performed. Adolescents were at risk of non-adherence and children whose parents had good knowledge about celiac disease adhered more strictly. Non-adherence associated with patient growth, symptoms, and quality of life.

    CONCLUSION: In a systematic review of 49 studies of children with celiac disease, we found substantial variation in adherence to a GFD among patients. Rate of adherence was not associated with method of adherence measurement, so all methods appear to be useful, with lack of consensus on the ideal metric. Studies are needed to determine the best method to ensure adherence and effects on long-term health.

  • 342. Månsson, Johanna
    et al.
    Stjernqvist, Karin
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Uppsala University, Sweden.
    Ådén, Ulrika
    Källén, Karin
    Agreement Between Bayley-III Measurements and WISC-IV Measurements in Typically Developing Children2019In: Journal of Psychoeducational Assessment, ISSN 0734-2829, E-ISSN 1557-5144, Vol. 37, no 5, p. 603-616Article in journal (Refereed)
    Abstract [en]

    The study aim was to explore the relationship between a developmental assessment at preschool age and an intelligence quotient (IQ) assessment at school age. One hundred sixty-two children were assessed at 2.5 years with the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) and then at 6.5 years with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The Bayley-III Cognitive Index score was the Bayley entity that showed the highest correlation with WISC-IV Full-Scale IQ (FSIQ; r = .41). There was a significant difference between the individual WISC-IV FSIQ and the Bayley-III Cognitive Index scores. Analyses showed an average difference of -4 units and 95% limits of agreement of -18.5 to 26.4 units. A multivariate model identified the Bayley-III Cognitive Index score as the most important predictor for FSIQ and General Ability Index (GAI), respectively, in comparison with demographic factors. The model explained 24% of the total FSIQ variation and 26% of the GAI variation. It was concluded that the Bayley-III measurement was an insufficient predictor of later IQ.

  • 343.
    Naumburg, Estelle
    Sektionen för pediatrik, institutionen för kvinnors och barns hälsa, Akademiska barnsjukhuset, Uppsala.
    Nya forskningsresultat om perinatala riskfaktorer: återupplivning med syrgas ökar risk for barnleukemi2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, no 24, p. 2745-2747Article in journal (Refereed)
    Abstract [en]

    The five studies presented in this thesis were all conducted in Sweden as population based case-control studies. Children with Down's syndrome were excluded. A total of 652 cases were encompassed in the studies. Exposure data were blindly extracted from standardized medical records. There was no association between prenatal exposure to ultrasound or diagnostic x-rays and childhood leukemia. A history of maternal lower genital tract infection significantly increased the risk of childhood leukemia. This association was especially evident in children diagnosed at four years or older or in infancy. Resuscitation with 100% oxygen with a facemask and bag directly postpartum was associated with increased risk of childhood lymphatic leukemia. Previously described exposure risks related to childhood leukemia could not be confirmed by these studies. However, this thesis indicates that events during pregnancy or the neonatal period are associated with increased risks of lymphatic and infant leukemia.

  • 344.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women's and Children's Health, Section for Pediatrics, Uppsala University, Uppsala, Sweden.
    Bellocco, Rino
    Cnattingius, Sven
    Hall, Per
    Boice, John D
    Ekbom, Anders
    Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes2001In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 156, no 6, p. 718-723Article in journal (Refereed)
    Abstract [en]

    The relationship between childhood leukemia and prenatal exposure to low-dose ionizing radiation remains debatable. This population-based case-control study investigated the association between prenatal exposure to diagnostic X-ray examinations (for different types of examinations and at different stages of pregnancy) and the risk of childhood lymphatic and myeloid leukemia. All children born and diagnosed with leukemia between 1973-1989 in Sweden (578 lymphatic and 74 myeloid) were selected as cases, and each was matched (by sex and year of birth) to a healthy control child (excluding Down's syndrome). Exposure data were abstracted blindly from all available medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. It was found that prenatal X-ray examinations resulting in direct fetal exposure were not associated with a significant overall increased risk for childhood leukemia (OR = 1.11, 95% CI 0.83-1.47), for lymphatic leukemia (OR = 1.04, 95% CI 0.77-1.40), or for myeloid leukemia (OR = 1.49, 95% CI 0.48-4.72). There was little evidence of a dose response or variation in risk by trimester of exposure or age at diagnosis. Thus X-ray examinations performed during pregnancy in the 1970s and 1980s in Sweden did not affect the risk of childhood leukemia discernibly.

  • 345.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Section for Paediatrics, Uppsala University, Uppsala, Sweden.
    Bellocco, Rino
    Cnattingius, Sven
    Hall, Per
    Ekbom, Anders
    Prenatal ultrasound examinations and risk of childhood leukaemia: case-control study2000In: BMJ (Clinical Research Edition), ISSN 0959-8138, Vol. 320, no 7230, p. 282-283Article in journal (Refereed)
  • 346.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Section for Pediatrics, Uppsala University, Akademiska Barnsjukhuset, Uppsala, Sweden.
    Bellocco, Rino
    Cnattingius, Sven
    Jonzon, Anders
    Ekbom, Anders
    Perinatal exposure to infection and risk of childhood leukemia2002In: Medical and Pediatric Oncology, ISSN 0098-1532, E-ISSN 1096-911X, Vol. 38, no 6, p. 391-397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A population-based case-control study was conducted to investigate the association between childhood leukemia and infectious exposures during pregnancy and early neonatal period.

    PROCEDURE: Children born and diagnosed with leukemia between 1973 and 1989 in Sweden (578 lymphatic, 74 myeloid) were selected as cases. One control was randomly selected for each case and individually matched by sex, month, and year of birth. Children with Down's syndrome were excluded. Exposure data were blindly abstracted from antenatal, obstetric, and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression.

    RESULTS: A history of maternal infection was not significantly associated with childhood leukemia, OR = 1.25 (95% CI 0.95-1.65). Maternal lower genital tract infection significantly increased the risk of childhood leukemia, OR = 1.78 (95% CI 1.17-2.72), and especially for children over 4 years of age at diagnosis, OR = 2.01 (95% CI 1.12-3.80). Neonatal infection was not associated with the risk of leukemia. The results remained unaltered after adjustment for potential confounders, and separate analyses for myeloid and lymphoid leukemia.

    CONCLUSIONS: We could document an association between exposure to maternal lower genital tract infection in utero, and a subsequent risk for childhood leukemia, which indicate the importance of an early exposure.

  • 347.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Section for Pediatrics, Uppsala University, Uppsala.
    Bellocco, Rino
    Cnattingius, Sven
    Jonzon, Anders
    Ekbom, Anders
    Supplementary oxygen and risk of childhood lymphatic leukaemia2002In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 91, no 12, p. 1328-1333Article in journal (Refereed)
    Abstract [en]

    AIM: Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population-based case-control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth-related factors.

    METHODS: Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Down's syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression.

    RESULTS: Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% Cl 1.21-6.82). The oxygen-related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16-10.80). Low Apgar scores at 1 and 5 min were associated with a non-significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth-related factors.

    CONCLUSION: Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.

  • 348.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital (Huddinge site), Stockholm, Sverige.
    Rane, Anders
    Halvorsen, Thomas
    Glosli, Heidi
    Henriksen, Tine Brink
    Haraldsson, Asgeir
    Kallio, Jaana
    Lepola, Pirkko
    Tardy development of safe medicines for children: a Nordic network offers new platform to reduce this inequity2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 6, p. 992-993Article in journal (Other academic)
  • 349.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Unit of Research Education and Development, Östersund Hospital, Östersund, Sweden.
    Soderstrom, Lars
    Huber, Daniel
    Axelsson, Inge
    Risk Factors for Pulmonary Arterial Hypertension in Children and Young Adults2017In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 52, no 5, p. 636-641Article in journal (Refereed)
    Abstract [en]

    Objectives: Pulmonary hypertension (PH) has been linked to preterm birth explained by congenital heart defects and pulmonary diseases. Working hypothesis: Other factors may influence the risk of PH among adolescences and children born premature. Study design: This national registry-based study assess risk of PH following premature birth adjusted for known risk factors. Patient-subject selection and methodology: All cases born 1993-2010, identified by diagnostic codes applicable to PH and retrieved from the Swedish Registry of Congenital Heart Disease (N = 67). Six controls were randomly selected and matched to each case by year of birth and hospital by the Swedish Medical Birth Register (N = 402). Maternal and infant data related to preterm birth, pulmonary diseases, and congenital defects were retrieved. The association between preterm birth and pulmonary hypertension was calculated by conditional logistic regression taking into account potential confounding factors. Results: One third of the cases and seven percent of the controls were born preterm in our study. Preterm birth was associated with PH, OR = 8.46 (95% CI 2.97-24.10) (P < 0.0001) even after adjusting for confounding factors. Other factors, such as acute pulmonary diseases, congenital heart defects, congenital diaphragm herniation, and chromosomal disorders were also associated with PH in the multivariate analysis. Conclusions: Children and young adults born preterm are known to have an increased risk of PH, previously explained by congenital heart defects and pulmonary diseases. By adjusting for such factors, our study indicates that new factors may play a role in the risk of developing PH among children born preterm. 

  • 350.
    Naumburg, Estelle
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women's and Children's Health, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden; Department of Paediatrics, Östersund County Hospital, Östersund, Sweden.
    Strömberg, Bo
    Kieler, Helle
    Prenatal characteristics of infants with a neuronal migration disorder: a national-based study2012In: International Journal of Pediatrics, ISSN 1687-9740, E-ISSN 1687-9759, p. 1-5, article id 541892Article in journal (Refereed)
    Abstract [en]

    The development of the central nervous system is complex and includes dorsal and ventral induction, neuronal proliferation, and neuronal migration, organization, and myelination. Migration occurs in humans in early fetal life. Pathogenesis of malformations of the central nervous system includes both genetic and environmental factors. Few epidemiological studies have addressed the impact of prenatal exposures. All infants born alive and included in the Swedish Medical Birth Register 1980-1999 were included in the study. By linkage to the Patient Register, 820 children with a diagnosis related to a neuronal migration abnormality were identified. Through copies of referrals for computer tomography or magnetic resonance imaging of the brain, the diagnosis was confirmed in 17 children. Median age of the mothers was 29 years. At the start of pregnancy, four out of 17 women smoked. Almost half of the women had a body mass index that is low or in the lower range of average. All infants were born at term with normal birth weights. Thirteen infants had one or more concomitant diseases or malformations. Two infants were born with rubella syndrome. The impact of low maternal body mass index and congenital infections on neuronal migration disorders in infants should be addressed in future studies.

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