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  • 1.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Using probiotics to prevent necrotising enterocolitis2017Inngår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, nr 11, s. 1718-1719Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 2.
    Abrahamsson, Thomas R.
    et al.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden.
    Jakobsson, Hedvig E.
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Anders F.
    Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden .
    Björkstén, Bengt
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; .
    Engstrand, Lars
    Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Jenmalm, Maria C.
    Department of Clinical and Experimental Medicine, Division of Pediatrics, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden.
    Low diversity of the gut microbiota in infants with atopic eczema2012Inngår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, nr 2, s. 434-440.e2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts.

    Objective: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development.

    Methods: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830).

    Results: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02).

    Conclusion: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.

  • 3.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Wu, Richard Y.
    University of Toronto, Canada.
    Sherman, Philip M.
    University of Toronto, Canada.
    Microbiota in Functional Gastrointestinal Disorders in Infancy: Implications for Management2017Inngår i: INTESTINAL MICROBIOME: FUNCTIONAL ASPECTS IN HEALTH AND DISEASE, KARGER , 2017, Vol. 88, s. 107-115Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel

  • 4.
    Adair, Brooke
    et al.
    School of Allied Health, Australian Catholic University, Fitzroy, Vic., Australia.
    Ullenhag, Anna
    Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Keen, Deb
    Autism Centre of Excellence, Griffith University, Mt Gravatt, Qld, Australia.
    Granlund, Mats
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för beteendevetenskap och socialt arbete. Högskolan i Jönköping, Högskolan för lärande och kommunikation, HLK, CHILD. Högskolan i Jönköping, Hälsohögskolan, HHJ. CHILD.
    Imms, Christine
    School of Allied Health, Australian Catholic University, Fitzroy, Vic., Australia.
    The effect of interventions aimed at improving participation outcomes for children with disabilities: a systematic review2015Inngår i: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 57, nr 12, s. 1093-1104Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Aim

    Enhancement of participation has been described as the ultimate outcome for health and educational interventions. The goal of this systematic review was to identify and critically appraise studies that aimed to improve the participation outcomes of children with disabilities.

    Method

    Nine databases that index literature from the fields of health, psychology, and education were searched to retrieve information on research conducted with children with disabilities aged between 5 years and 18 years. Articles were included if the author(s) reported that participation was an intended outcome of the intervention. The articles included were limited to those reporting high-level primary research, as defined by Australia's National Health and Medical Research Council evidence hierarchy guidelines. No restrictions were placed on the type of intervention being investigated.

    Results

    Seven randomized controlled or pseudo-randomized studies were included. Only three of these studies identified participation as a primary outcome. Both individualized and group-based approaches to enhancing participation outcomes appeared to be effective. Studies of interventions with a primary focus on body function or activity level outcomes did not demonstrate an effect on participation outcomes.

    Intepretation

    Few intervention studies have focused on participation as a primary outcome measure. Approaches using individually tailored education and mentoring programmes were found to enhance participation outcomes, while exercise programmes, where participation was a secondary outcome, generally demonstrated little effect.

  • 5.
    Adair, Brooke
    et al.
    Australian Catholic Univ, Ctr Disabil & Dev Res, Fitzroy, Vic, Australia..
    Ullenhag, Anna
    Mälardalens högskola, Akademin för hälsa, vård och välfärd.
    Rosenbaum, Peter
    McMaster Univ, Hamilton, ON, Canada..
    Granlund, Mats
    Jonkoping Univ, CHILD, SIDR, Sch Hlth Sci, Jonkoping, Sweden..
    Keen, Deb
    Griffith Univ, Autism Ctr Excellence, Mt Gravatt, Qld, Australia..
    Imms, Christine
    Australian Catholic Univ, Ctr Disabil & Dev Res, Fitzroy, Vic, Australia..
    Measures used to quantify participation in childhood disability and their alignment with the family of participation-related constructs: a systematic review2018Inngår i: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 60, nr 11, s. 1101-1116Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    AimWe aimed to identify measures used to assess the participation of disabled children and to map the measures' content to the family of participation-related constructs (fPRC) to inform future research and practice. MethodSix databases were searched to identify measures used to assess participation in health, psychology, and education research. Included studies involved children aged 0 to 18 years with a permanent impairment or developmental disability and reported use of a quantitative measure of participation. A second search sought relevant literature about each identified measure (including published manuals) to allow a comprehensive understanding of the measure. Measurement constructs of frequently reported measures were then mapped to the fPRC. ResultsFrom an initial yield of 32 767 articles, 578 reported one or more of 118 participation measures. Of these, 51 measures were reported in more than one article (our criterion) and were therefore eligible for mapping to the fPRC. Twenty-one measures quantified aspects of participation attendance, 10 quantified aspects of involvement as discrete scales, and four quantified attendance and involvement in a manner that could not be separated. InterpretationImproved understanding of participation and its related constructs is developing rapidly; thoughtful selection of measures in research is critical to further our knowledge base.

  • 6.
    Adair, Brooke
    et al.
    Centre for Disability and Development Research, Australian Catholic University, Fitzroy, Vic., Australia.
    Ullenhag, Anna
    Physiotherapy Department, Mälardalens University, Västerås, Sweden.
    Rosenbaum, Peter
    McMaster University, Hamilton, ON, Canada.
    Granlund, Mats
    Högskolan i Jönköping, Hälsohögskolan, HHJ. CHILD. Högskolan i Jönköping, Högskolan för lärande och kommunikation, HLK, CHILD. Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för socialt arbete. Högskolan i Jönköping, Hälsohögskolan, HHJ. Biomedicinsk plattform.
    Keen, Deb
    Autism Centre of Excellence, Griffith University, Mt Gravatt, Qld, Australia.
    Imms, Christine
    Centre for Disability and Development Research, Australian Catholic University, Fitzroy, Vic., Australia.
    Measures used to quantify participation in childhood disability and their alignment with the family of participation-related constructs: a systematic review2018Inngår i: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 60, nr 11, s. 1101-1116Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM:

    We aimed to identify measures used to assess the participation of disabled children and to map the measures' content to the family of participation-related constructs (fPRC) to inform future research and practice.

    METHOD:

    Six databases were searched to identify measures used to assess participation in health, psychology, and education research. Included studies involved children aged 0 to 18 years with a permanent impairment or developmental disability and reported use of a quantitative measure of participation. A second search sought relevant literature about each identified measure (including published manuals) to allow a comprehensive understanding of the measure. Measurement constructs of frequently reported measures were then mapped to the fPRC.

    RESULTS:

    From an initial yield of 32 767 articles, 578 reported one or more of 118 participation measures. Of these, 51 measures were reported in more than one article (our criterion) and were therefore eligible for mapping to the fPRC. Twenty-one measures quantified aspects of participation attendance, 10 quantified aspects of involvement as discrete scales, and four quantified attendance and involvement in a manner that could not be separated.

    INTERPRETATION:

    Improved understanding of participation and its related constructs is developing rapidly; thoughtful selection of measures in research is critical to further our knowledge base.

    WHAT THIS PAPER ADDS:

    The fPRC can support our rapidly evolving and expanding understanding of participation. Instruments selected to measure participation do not always align with emerging concepts. Matching research aims to a chosen measure's content will improve understanding of participation. Opportunities exist to develop validated participation measures, especially self-reported measures of involvement.

  • 7.
    Aden, U.
    et al.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden.
    Hugoson, P.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Kostilainen, K.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland..
    Mikkola, K.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland..
    Mårtensson, G.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Lagercrantz, H.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Westrup, B.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Fellman, V.
    Lund Univ, Pediat, Lund, Sweden..
    Huotilainen, Minna
    Uppsala universitet, Kollegiet för samhällsforskning (SCAS).
    The impacts of maternal singing during kangaroo care on mothers and infants2016Inngår i: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 175, nr 11, s. 1425-1425Artikkel i tidsskrift (Fagfellevurdert)
  • 8.
    Adolfsson, Margareta
    Högskolan i Jönköping, Högskolan för lärande och kommunikation, HLK, CHILD.
    ICF-CY in habilitation services for children2017Inngår i: An emerging approach for education and care: Implementing a worldwide classification of functioning and disability / [ed] S. Castro & O. Palikara, London: Routledge, 2017, s. 187-203Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Habilitation services is the name for interdisciplinary health care organisations in Sweden serving children and young people aged 0 to17 years with a wide range of disabilities categorised as mobility, behavioural, intellectual and multiple disabilities, their families and other networks. The construct of habilitation is used in childhood since it focuses on acquiring skills, whereas rehabilitation focuses on regaining lost skills. Despite this difference, the objective of services is consistent and the WHO definition of rehabilitation can apply to both: “A process aimed at enabling people with disabilities to reach and maintain their optimal physical, sensory, intellectual, psychological and social functional levels. Rehabilitation provides disabled people with the tools they need to attain independence and self-determination” (WHO, 2016). Habilitation teams include social, psychological, pedagogical and medical competencies with a marked preponderance of the latter (Figure 12.1).

  • 9. Agnafors, S.
    et al.
    Sydsjö, G.
    Comasco, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Bladh, M.
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Svedin, C.
    Behaviour problems in children-a longitudinal study of genetic and environmental factors2015Inngår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, s. S35-S35Artikkel i tidsskrift (Annet vitenskapelig)
  • 10.
    Agnafors, Sara
    et al.
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Comasco, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Dekeyser, Linda
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Svedin, Carl-Göran
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems: a longitudinal study2013Inngår i: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, artikkel-id 10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS:

    Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS:

    Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS:

    Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

  • 11.
    Agnafors, Sara
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Comasco, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuropsykofarmakologi.
    Svedin, Carl Göran
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Early predictors of behavioural problems in pre-schoolers: a longitudinal study of constitutional and environmental main and interaction effects2016Inngår i: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 16, artikkel-id 76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age 3, using a comparably large, representative, population-based sample. Methods: A total of 1,106 children, and their mothers, were followed from pregnancy to age 3. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms. Results: Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-by-gene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems. Conclusion: This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children.

  • 12.
    Agrasada, Grace V.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Postnatal Peer Counseling on Exclusive Breastfeeding of Low-birthweight Filipino Infants: Results of a Randomized Controlled Trial2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In a Manila hospital, 204 mothers were randomized into three groups: two intervention groups receiving home-based counseling visits, one of them (n=68) by counselors trained to use a locally developed, two-tiered program of breastfeeding counseling, and the other by counselors trained in general childcare (n=67), were compared with a control group of mothers (n=69) who did not receive any counseling. All infants were scheduled for seven visits to the hospital for follow-up. During hospital visits, maternal and infant body measurements were made and an independent interviewer asked the mothers individually to recall how the infant had been fed. One study physician, blind to participant groups, was consulted at all scheduled and unscheduled infant visits.

    At six months, 44% of the breastfeeding-counseled mothers, 7% of the childcare-counseled mothers and none of the mothers in the control group were exclusively breastfeeding. Twenty- four mothers breastfed exclusively during the first six months, of whom 22 received breastfeeding counseling and 2 had no breastfeeding counseling. Among 24 infants who were exclusively breastfed from birth to six months there were no episodes of diarrhea. All infants had gained in weight, length and head circumference. Mean maternal weight loss at six months was similar whether her breastfeeding was exclusive or partial.

    The reasons why mothers without breastfeeding counseling introduced non-breast milk feeding before six months reflected lack of knowledge and support. Breastfeeding support during the first six months focusing on how to prevent and solve breastfeeding problems, particularly during the first two weeks, will enable mothers to choose to breastfeed exclusively up to six months.

    This study has provided fundamental evidence of successful intervention by breastfeeding counseling to achieve six months of exclusive breastfeeding among term, low-birthweight infants. The locally developed training program in breastfeeding counseling, which successfully prepared volunteers to counsel mothers at home, could be incorporated into primary health care in the Philippines. Mothers who received breastfeeding counseling appreciated how this helped them to achieve their breastfeeding goals for the first six months. Improved breastfeeding practices as a result of breastfeeding counseling provided infants with protection from diarrhea and respiratory infections, contributing to their health and development.

  • 13.
    Ahl, Hanna
    et al.
    Skåne University Hospital, Lund, Sweden.
    Eriksson, Mats
    Örebro universitet, Institutionen för hälsovetenskaper.
    Norman, Elisabeth
    Lund University, Lund, Sweden.
    Sjöström Strand, Annica
    Lund University, Lund, Sweden.
    Olsson, Emma
    Örebro University Hospital, Örebro, Sweden.
    Bruschettini, Matteo
    Lund University, Lund, Sweden.
    Pain scales in clinical trials in newborn infants: a mapping of the evidence2018Annet (Annet vitenskapelig)
  • 14.
    Ahle, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Necrotising Enterocolitis: epidemiology and imaging2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.

    The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.

    Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.

    Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.

    The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.

    Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.

  • 15.
    Ahle, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Drott, Peder
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Elfvin, Anders
    Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Andersson, Roland E.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden .
    Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, PLoS ONE, ISSN 1932-6203, Vol. 13, nr 3, artikkel-id e0194352Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data.

    Study design

    All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age.

    Results

    In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age.

    Conclusion

    With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.

  • 16.
    Ahle, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Magnusson, Amanda
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Elfvin, Anders
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Andersson, Roland
    Department of Surgery, County Hospital Ryhov, Jönköping, Sweden.
    Space-time clustering of necrotizing enterocolitis supports the existence of transmissible causes.2017Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Problem Statement: Despite great efforts to prevent necrotizing enterocolitis (NEC) the incidence may in fact be increasing, and changes in the patient population over time seem to lead to changes in clinical presentation and risk factor spectrum as well. The presence of bacteria is an important prerequisite in the pathogenesis, but, rather than being caused by specific pathogens, inflammation and bacterial invasion are thought to be mediated through erroneous interaction between microbiota and innate immunity during colonization of the gut. There are, however, reports of episodic outbreaks of NEC, seasonal variation in incident rates, and clustering, suggesting a role for transmissible infectious agents or other environmental factors around the pregnant mother or newborn infant. In order to investigate evidence for such factors we have analyzed the occurrence of space-time clusters in Sweden over 23 years. Methods: A national register-based cohort of all children born between 1987 and 2009 in Sweden, diagnosed with NEC, was identified. The Knox test and Kulldorff’s scan method were used to analyze signs of space-time clusters at two geographical levels; the mother’s residential address and the delivery hospital. Time windows of seven, 14 and 21 days were used for closeness in time. Results: The Knox test showed clustering on hospital level in all studied temporal windows; seven days (p=0.022) 14 days (p=0.011) and 21 days (p=0.006), and Kulldorff’s scan method found seven significant clusters. On residential level, there was no indication of space-time interaction. When comparing two time periods, significant clustering on hospital level was found during 1987-1997, but not during 1998-2009. Conclusion: Space-time clustering was found on hospital level, but not on community level, suggesting a contagious environmental effect at and after delivery but not in the materno-fetal environment outside the hospital before birth. The decrease in clustering over time suggests that improved routines in neonatal care have minimized the risk of NEC precipitating contagions spreading between patients in the neonatal intensive care unit. The importance of such routines should not be forgotten while our efforts to bring down NEC incidence are directed towards other challenges.

  • 17.
    Ahle, Margareta
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Ringertz, Hans G.
    Department of Radiology, Stanford University Medical Center, Stanford, USA; Division of Diagnostic Radiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Rubesova, Erika
    Department of Radiology, Lucile Packard Children’s Hospital, Stanford University Medical Center, Stanford, USA.
    The role of imaging in the management of necrotising enterocolitis: a multispecialist survey and a review of the literature2018Inngår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, nr 9, s. 3621-3631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    To investigate current practices and perceptions of imaging in necrotising enterocolitis (NEC) according to involved specialists, put them in the context of current literature, and identify needs for further investigation.

    Methods

    Two hundred two neonatologists, paediatric surgeons, and radiologists answered a web-based questionnaire about imaging in NEC at their hospitals. The results were descriptively analysed, using proportion estimates with 95% confidence intervals.

    Results

    There was over 90% agreement on the value of imaging for confirmation of the diagnosis, surveillance, and guidance in decisions on surgery as well as on abdominal radiography as the first-choice modality and the most important radiographic signs. More variation was observed regarding some indications for surgery and the use of some ultrasonographic signs. Fifty-eight per cent stated that ultrasound was used for NEC at their hospital. Examination frequency, often once daily or more but with considerable variations, and projections used in AR were usually decided individually rather than according to fixed schedules. Predicting the need of surgery was regarded more important than formal staging.

    Conclusion

    Despite great agreement on the purposes of imaging in NEC and the most important radiographic signs of the disease, there was considerable diversity in routines, especially regarding examination frequency and the use of ultrasound. Apart from continuing validation of ultrasound, important objectives for future studies include definition of the supplementary roles of both imaging modalities in relation to other diagnostic parameters and evaluation of various imaging routines in relation to timing of surgery, complications, and mortality rate.

  • 18.
    Ahlsson, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Kaijser, Magnus
    Clincial Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Adami, Johanna
    Clincial Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lundgren, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Palme, Mårten
    Department of Economics, Stockholm University, Stockholm, Sweden.
    School performance after preterm birth2015Inngår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 26, nr 1, s. 106-111Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. METHODS: We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. RESULTS: Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31-33 weeks was on average 3.85 (95% confidence interval = -4.36 to -3.35) centiles lower than for children born at 40 weeks. For births at 22-24 weeks, the corresponding figure was -23.15 (-30.32 to -15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. CONCLUSIONS: Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

  • 19. Albertsson-Wikland, Kerstin
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jonsson, Björn
    Hochberg, Zeʼev
    Long-term response to growth hormone (GH) therapy in short children with a delayed infancy childhood transition (DICT)2011Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 69, s. 504-510Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transition of growth from infancy to childhood is associated with activation of the GH-IGF-I axis. Children with a delayed infancy-childhood-transition (ICT) are short as adults. Thus, age at ICT may impact on growth response to GH. The objective was to investigate associations between growth response to GH-treatment and ICT-timing in children with idiopathic short stature (ISS) in a randomized, controlled, multicenter trial, TRN 88-080. 147 pre-pubertal children (mean age, 11.5±1.4 yrs) were randomized to receive GH 33μg/kg/d (GH33, n=43), GH 67μg/kg/d (GH67, n=61) or no treatment (n=43). Data on growth to final height (FH) were analyzed after categorization into those with normal (n=76) or delayed ICT (n=71). Within the GH33 group, significant height gain at FH was only observed in children with a delayed ICT (p<0.001) with each month of delay corresponding to gain of 0.13 standard deviation score (SDS). For the GH67 group, the timing of the onset of the ICT had no impact on growth response. In conclusion, ISS children with a delayed ICT responded to standard-GH-dose (better responsiveness), whereas those with a normal ICT required higher doses to attain a significant height gain to FH.

  • 20. Albertsson-Wikland, Kerstin
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. berit.kristrom@umu.se.
    Lundberg, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Aronson, A. Stefan
    Gustafsson, Jan
    Hagenäs, Lars
    Ivarsson, Sten-A.
    Jonsson, Bjorn
    Ritzen, Martin
    Tuvemo, Torsten
    Westgren, Ulf
    Westphal, Otto
    Åman, Jan
    Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 3, s. 158-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height. Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS. Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.

  • 21.
    Albertsson-Wikland, Kerstin
    et al.
    Goteborg Pediat Growth Res Ctr, Dept Pediat, Inst Clin Sci, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Kriström, Berit
    Dept Clin Sci, Pediat Unit, Umeå Univ, Umeå, Sweden.
    Lundberg, Elena
    Dept Clin Sci, Pediat Unit, Umeå Univ, Umeå, Sweden.
    Aronson, A. Stefan
    Dept Pediat, Halmstad Cty Hosp, Halmstad, Sweden.
    Gustafsson, Jan
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Hagenäs, Lars
    Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden.
    Ivarsson, Sten-A.
    Dept Pediat, Lund Univ, Malmö, Sweden.
    Jonsson, Björn
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Ritzen, Martin
    Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden.
    Tuvemo, Torsten
    Dept Womens & Childrens Hlth, Uppsala Univ, Uppsala, Sweden.
    Westgren, Ulf
    Dept Pediat, Lund Univ, Malmo, Sweden.
    Westphal, Otto
    Goteborg Pediat Growth Res Ctr, Dept Pediat, Inst Clin Sci, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Åman, Jan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 3, s. 158-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

    Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.

    Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.

    Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.

  • 22.
    Albertsson-Wikland, Kerstin
    et al.
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Kriström, Berit
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Lundberg, Elena
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Aronson, A Stefan
    Department of Pediatrics, Halmstad Hospital, Sweden.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Hagenäs, Lars
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Ivarsson, Sten-A
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Jonsson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Ritzén, Martin
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Tuvemo, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Westgren, Ulf
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Westphal, Otto
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Aman, Jan
    School of Health and Medical Sciences, Örebro University, Sweden.
    Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 3, s. 158-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 23. Albertsson-Wikland, Kerstin
    et al.
    Martensson, Anton
    Savendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, nr 5, s. 2149-2159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment.

    Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA).

    Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010).

    Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982).

    Main Outcome Measures: Death.

    Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations.

    Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95.

    Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001).

    Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 24. Albertsson-Wikland, Kerstin
    et al.
    Mårtensson, Anton
    Sävendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Birth Characteristics Explain One Third of Expected Deaths in rhGH-treated Patients Diagnosed with IGHD, ISS & SGA2016Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, s. 49-49Artikkel i tidsskrift (Annet vitenskapelig)
  • 25.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Strömvall-Larsson, Eva
    Division of Cardiology, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Berggren, Håkan
    Division of Cardiothoracic Surgery, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Hanseus, Katarina
    Department of Paediatrics, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Johansson, Sune
    Paediatric Cardiac Surgical Unit, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Heart rate variability in children with fontan circulation: lateral tunnel and extracardiac conduit2012Inngår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 33, nr 2, s. 307-315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT.

  • 26. Allansson Kjölhede, Elin
    et al.
    Gustafsson, Per E.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Gustafsson, P. A.
    Nelson, N.
    Overweight and obese children have lower cortisol levels than normal weight children2014Inngår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, nr 3, s. 295-299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: The stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex. METHODS: Salivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6-12years using Salivette((R)) tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the children's height and weight, and these measurements were used to calculate their BMI. RESULTS: The children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex. CONCLUSION: Our findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children.

  • 27.
    Allbrand, Marianne
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Dept Obstet & Gynaecol, Örebro Univ Hosp, Örebro, Sweden.
    Björkqvist, Maria
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Dept Paediat, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Kerstin
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Dept Obstet & Gynaecol, Örebro University Hospital, Örebro, Sweden.
    Östlund, Ingrid
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Dept Obstet & Gynaecol, Örebro University Hospital, Örebro, Sweden.
    Åman, Jan
    Region Örebro län. Örebro universitet. Dept Paediat, Örebro University Hospital, Örebro, Sweden.
    Placental gene expression of inflammatory markers and growth factors: a case control study of obese and normal weight women2015Inngår i: Journal of Perinatal Medicine, ISSN 0300-5577, E-ISSN 1619-3997, Vol. 43, nr 2, s. 159-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women.

    Methods: Placental tissue samples from 32 obese women (body mass index, BMI >= 35.0 kg/m(2)) were compared with samples from 94 normal weight women (BMI 18.5-25.0 kg/m(2)) matched for age (+/- 1 year), gestational age (+/- 3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-alpha, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor.

    Results: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women.

    Conclusion: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.

  • 28.
    Allbrand, Marianne
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Åman, Jan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Lodefalk, Maria
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child2015Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr Suppl. 1, s. 47-48Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: The nutritional and hormonal state in utero may be a link between maternal obesity and obesity in the offspring. The gene expression in placentae in pregnancies complicated by diabetes is reduced for leptin, but increased for ghrelin. It is not known whether these genes’ expressions in placentae are altered in maternal obesity.

    Objectives and hypotheses: To compare obese and normal-weight women and their children concerning gene expressions of leptin and ghrelin in placentae; leptin, ghrelin, adiponectin, and C-peptide levels in cord blood, birth size and postnatal growth. Changes in the expression of these adipocytokines may lead to an altered hypothalamic sensitivity to leptin and ghrelin resulting in an increased risk of obesity in the offspring.

    Method: 32 women with pre-pregnancy obesity, but otherwise healthy, were compared to 32 matched, normal-weight controls. Full-term placenta biopsies were analysed with qPCR for leptin mRNA and ghrelin mRNA. Cord blood samples were examined with ELISA for leptin, ghrelin, adiponectin, and C-peptide concentrations. Birth size and postnatal growth of the children were collected from clinical registers at the Child Health Care Units.

    Results: The leptin and ghrelin gene expressions in placentae did not differ between obese and normal-weight women. The leptin concentration in cord blood was higher in children of obese mothers (P=0.021). It correlated with birth weight Z-score (r=0.467, P<0.001) and C-peptide level in cord blood (r=0.446, P<0.001). Children of obese women were slightly heavier at birth, but postnatal growth did not differ between groups. Children with birth weight  ≤−0.67 Z-score had higher ghrelin levels in cord blood than heavier children (P=0.042). The leptin level in cord blood correlated negatively with weight gain at 6 months (r=−0.332, P=0.009). The ghrelin level in cord blood correlated with weight gain at 3 months in girls (r=0.611, P=0.001), but not in boys. The adiponectin level in cord blood correlated negatively with length gain at 3 years in the obese group (r=−0.571, P=0.033), but not in the normal-weight group.

    Conclusion: Leptin and ghrelin placental gene expressions are not altered in obese women, but foetal adipocytokine production may influence early postnatal growth, possibly by influencing hunger signalling or insulin levels

  • 29.
    Alm, Fredrik
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Anaesthesia and Intensive Care, School of Health Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jaensson, Maria
    Örebro universitet, Institutionen för hälsovetenskaper.
    Lundeberg, Stefan
    Pain Treatment Service, Astrid Lindgren Children's Hospital, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Ericsson, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskaper.
    Adherence to Swedish guidelines for pain treatment in relation to pediatric tonsil surgery: A survey of the multidisciplinary team2017Inngår i: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 101, s. 123-131Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Pain management in children after tonsil surgery is essential, and optimal pain treatment has been discussed for many years. Data from the National Tonsil Register in Sweden (NTRS) and a national mapping system have demonstrated the need for national pain treatment guidelines for pediatric tonsil surgery. As a result, Swedish national guidelines, together with updated patient information on the website tonsilloperation.se, were developed and implemented in 2013.

    Objectives The objective of this study was to evaluate the professionals’ opinions of and adherence to pain treatment guidelines for pediatric tonsil surgery patients in a two-year follow-up.

    Method: This descriptive cross-sectional study was based on data from an inter-professional questionnaire, which was validated by an expert group using a content validity index (S-CVI 0.93). The questionnaire was sent to all Swedish ear, nose and throat (ENT) departments (n=49) that the NTRS identified as performing tonsil surgery on children younger than 18 years of age. In each clinic, we asked for responses from staff in each of the following professions: ENT physicians, anesthesia physicians, registered nurse anesthetists, and registered nurses in the ENT departments.

    Results: Respondents from 48 ENT departments participated, and 139/163 (85%) completed questionnaires were returned. The guidelines were reported as being clear, ensuring patient safety and providing optimal pharmacological treatment. Treatment was given according to the guidelines: Half of the departments gave pre- or intraoperative treatment with clonidine, betamethasone and high-dose paracetamol (acetaminophen). A multimodal pain approach (paracetamol and COX inhibitors) after hospital discharge was prescribed by all departments after tonsillectomy and, more extensively, after tonsillotomy. One-third of the departments prescribed paracetamol with a higher normal dose for the first three postoperative days. Half of the departments prescribed rescue analgesics, clonidine or opioids after tonsillectomy. None of the departments prescribed codeine or tramadol, drugs that are discouraged in the guidelines. The majority of the departments used the website tonsilloperation.se to provide information to the patients and their caregivers.

    Conclusion: The respondents' opinions of and the ENT departments adherence to the Swedish national guidelines were considered to be good. The national implementation process in Sweden has impacted the manner in which ENT departments treat pain after tonsil surgery.

  • 30.
    Al-Mashhadi, Ammar Nadhom Farman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    High Blood Pressure in Children with Hydronephrosis2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The most common cause of secondary hypertension is intrinsic renal disease, but little is known about the influence of hydronephrosis on blood pressure. In this thesis, the risk of development of hypertension in children with hydronephrosis was studied.

    Experimental and clinical studies were combined in order to investigate the risk of developing elevated blood pressure following conservative treatment of hydronephrosis, and to further explore underlying mechanisms. We started with a clinical study in children (study I), which in agreement with previous experimental studies, showed that blood pressure was lowered by surgical management of hydronephrosis. In parallel, an experimental study was conducted (study II) to investigate the involvement of renal sympathetic nerve activity in development of hypertension following induction of hydronephrosis caused by pelvo-ureteric junction obstruction. Renal denervation of the obstructed kidney attenuated hypertension and restored the renal excretion pattern, effects that were associated with reduced activity of both renal NADPH oxidase derived oxidative stress and components of the renin-angiotensin-aldosterone system.

    Based on the findings in studies I and II, we continued our studies in children with hydronephrosis, and including two control groups as comparisons with the hydronephrotic group (study III). In the same study, we further investigated potential mechanism(s) of hypertension by analyzing markers of oxidative stress and nitric oxide homeostasis in both urine and blood samples. We demonstrated increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which was restored to normal levels by surgical correction of the obstruction. Finally, in a retrospective cohort study, blood pressure of adult patients undergoing surgical management of hydronephrosis due to pelvo-ureteric junction obstruction was assessed (study IV). Similar to that demonstrated in the pediatric hydronephrotic population, blood pressure was significantly reduced by relief of the obstruction. In addition, blood pressure was increased again if the hydronephrosis recurred, and was reduced again following re-operation.

    It is concluded that conservative management of hydronephrosis in children is associated with a risk for development of high blood pressure, which can be reduced or even normalized by relief of the obstruction. The mechanism(s), at least in part, is coupled to increased oxidative stress.

  • 31.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Karanikas, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Nils
    Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden.
    Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis2015Inngår i: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, nr 2, s. 91.e1-91.e6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

  • 32.
    Almberg, Maria
    et al.
    Mobility Centre Gothenburg, Sweden.
    Selander, Helena
    Mobility Centre Gothenburg, Sweden.
    Falkmer, Marita
    Högskolan i Jönköping, Högskolan för lärande och kommunikation, HLK, CHILD. School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Vaz, Sharmila
    School of Occupational Therapy and Social Work, Faculty of Health Sciences, Curtin University, Perth, Australia.
    Cic