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  • 1101.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fosdal, Inger
    Lindh, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Persson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wettrell, Göran
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Third Trimester Fetal Heart Rate Predicts Phenotype and Mutation Burden in the Type 1 Long QT Syndrome2015Ingår i: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 8, nr 4, s. 806-814Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background—Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype.

    Methods and Results—This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29–41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=−0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation; P<1.0×10–23). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute, P<0.0001.

    Conclusions—In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias.

  • 1102.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fetal heart rate reflects mutation burden and clinical outcome in twin probands with KCNQ1 mutations2018Ingår i: HeartRhythm case reports, ISSN 2214-0271, Vol. 4, nr 6, s. 237-240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present the case of a twin pregnancy of heterozygous andhomozygous long QT syndrome (LQTS) type 1 (LQT1)genotype, referred because of in utero bradycardia in thehomozygous twin at 19 weeks of gestation, with follow-upuntil.12 months of age. Fetal heart rate may predict bothgenotype and disease severity, as previously shown in2 LQTS founder populations.1This unique case report is acomparison of fetal heart rate and clinical outcome in twinprobands of heterozygous and homozygous genotype, in afamily without prior diagnosis of LQTS. In this setting, wediscuss the early management of LQTS and Jervell andLange-Nielsen syndrome (JLNS) detected in utero.

  • 1103.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome2015Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 49, nr 1, s. 7-13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives. To investigate the possible association between Jervell and Lange-Nielsen Syndrome (JLNS) genotype and vestibular dysfunction. Design. In 15 cases with JLNS, clinical data obtained from a semi-structured interview and full medical records were reviewed and post-rotatory nystagmus testing was performed. Results. All genotyped cases (n = 14) had double KCNQ1 mutations. Symptoms of impaired balance were reported in 14/14 deaf JLNS cases. Gross motor developmental delay (not walking without support at 18 months of age) was seen in 11/12 cases with available data (mean age for walking: 24 months). A pathologic post-rotatory test was seen in 9/9 tested subjects, and in 3 subjects clinical testing had been performed showing complete lack of vestibular function. Vestibular dysfunction was seen in deaf JLNS cases with (n = 5) and without (n = 9) cochlear implants, including subjective symptoms (5/5 vs. 9/9) and gross motor developmental delay (5/5 vs. 6/8). Conclusions. We identified a high frequency of symptoms and signs associated with vestibular dysfunction in deaf JLNS cases, irrespective of previous cochlear implantation. Disruption of endolymph homeostasis in the inner ear, including cochlea and vestibular system, by profound KCNQ1 function loss is the proposed mechanism.

  • 1104.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sandström, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome2013Ingår i: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 23, nr 3, s. 325-334Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim We investigated extra-cardiac clinical symptoms and signs in the rare Jervell and Lange-Nielsen Syndrome, characterised by impaired KCNQ1 function, a gene essential for gastric acid secretion. METHODS: All Swedish Jervell and Lange-Nielsen cases with double KCNQ1 mutations (14 cases) were investigated by medical record review, an interview, and were offered laboratory testing for iron-deficiency anaemia and gastrointestinal markers. RESULTS: A history of iron-deficiency anaemia in 12 of 14 patients and subjective gastrointestinal symptoms in 13 of 14 patients was revealed. Previous endoscopy in five cases had revealed no case of coeliac or inflammatory bowel disease but three cases of mucosal hyperplasia/dysplasia. Current signs of anaemia or iron substitution were present in 9 of 12 tested cases. Elevated levels of gastrin in seven of nine cases, pepsinogen in six of seven cases, and faecal calprotectin in nine of nine cases were present. A significant correlation between elevated gastrin levels and concurrent iron-deficiency and/or anaemia was revealed (p-value 0.039). CONCLUSIONS: A high frequency of extra-cardiac clinical symptoms and previous medical investigations was found. We propose that the Jervell and Lange-Nielsen Syndrome phenotypically includes gastrointestinal symptoms/signs and secondary iron-deficiency anaemia owing to hypochlorhydria on the basis of KCNQ1 mutations. The resultant elevated gastrin level is a potential risk factor for later gastrointestinal cancer. Clinical monitoring with regard to developing anaemia and hypergastrinaemia should be considered in the Jervell and Lange-Nielsen Syndrome.

  • 1105.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Persson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden2012Ingår i: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 14, nr 12, s. 1799-1806Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To explore the national prevalence, mutation spectrum, cardiac phenotype, and outcome of the uncommon Jervell and Lange-Nielsen syndrome (JLNS), associated with a high risk of sudden cardiac death.

    METHODS AND RESULTS: A national inventory of clinical JLNS cases was performed. Genotype and area of origin were ascertained in index families. Retrospective clinical data were collected from medical records and interviews. We identified 19 cases in 13 Swedish families. A JLNS prevalence >1:200 000 was revealed (five living cases <10 years of age). The mutation spectrum consisted of eight KCNQ1 mutations, whereof p.R518X in 12/24 alleles. Geographic clustering of four mutations (20/24 alleles) and similarities to Norway's mutation spectrum were seen. A high prevalence of heterozygotes was suggested. Three paediatric cases on β-blockers since birth were as yet asymptomatic. Seven symptomatic cases had suffered an aborted cardiac arrest and four had died suddenly. QTc prolongation was significantly longer in symptomatic cases (mean 605 ± 62 vs. 518 ± 50 ms, P = 0.016). β-Blockers reduced, but did not abolish, cardiac events in any previously symptomatic case. β-Blocker type, dosage, and compliance probably affect outcome significantly. Implantable cardioverter-defibrillator therapy (ICD, n = 6) was associated with certain complications; however, no case of sudden death.

    CONCLUSION: Founder effects could explain 83% of the Swedish JLNS mutation spectrum and probably contribute to the high JLNS prevalence found in preadolescent Swedish children. Due to the severe cardiac phenotype in JLNS, the importance of stringent β-blocker therapy and compliance, and consideration of ICD implantation in the case of therapy failure is stressed.

  • 1106.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Norberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Nordin, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Persson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    The Swedish long QT syndrome R518X/KCNQ1 founder population- origin and clinical phenotype: phenotypic variability partly explained by gender-specific effects of sequence variants in the NOS1AP geneManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: Genetic modifiers have been proposed to explain phenotypic variability in the long QT syndrome (LQTS). We investigate the origin and phenotype of the worldwide common R518X/KCNQ1 mutation in Sweden, as well as possible associations between p.R518X-LQTS phenotype and previously reported modifying sequence variants in the NOS1AP, KCNH2, KCNE1, SCN5A and KCNQ1(3’UTR) genes.

    Methods and Results: We identified 19 p.R518X families (101 mutation-carriers, whereof 15 Jervell and Lange-Nielsen (JLNS) cases and 86 LQTS cases). Analyses of microsatellite markers, genealogy and mutation age (ESTIAGE) identified a common northern origin ~700 years ago for 17/19 families and a high prevalence of Swedish p.R518X heterozygotes was suggested (DMLE). 

    Clinical phenotype ranged from severe in JLNS to relatively benign in LQTS (QTc 576±61 ms vs. 462±34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%).

    In p.R518X-LQTS males, two NOS1AP variants rs12143842 and rs16847548 were associated with a 29 ms QT prolongation (p=0.004), explaining 27% of QTc variability.

    Three derived 3’UTR-KCNQ1 variants, previously shown to suppress gene expression in an allele-specific manner, were found to segregate with the founder mutation.

    Conclusion: The R518X/KCNQ1 mutation is a Swedish founder mutation presenting with an expectedly severe phenotype in JLNS and an unusually mild phenotype in LQTS, although intra-familial variability remained. Gender-specific effects of NOS1AP sequence variants explained over a fourth of QTc variance in p.R518X-LQTS males, warranting further studies. Repressive 3’UTR-KCNQ1 sequence variants segregating within the founder haplotype could possibly contribute to its relative benignancy.

  • 1107.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Nordin, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Persson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Steen M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families2014Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 14, s. 22-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome-JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p. R518X mutation. Methods: The study included 19 Swedish p. R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software). Results: Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 +/- 61 ms vs. 462 +/- 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%). A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p. R518X heterozygotes was suggested (similar to 1: 2000-4000). Conclusions: R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

  • 1108.
    Winbo, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Physiology, University of Auckland, Auckland, New Zealand.
    Stattin, Eva-Lena
    Westin, Ida Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Norberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Persson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Steen M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sex is a moderator of the association between NOS1AP sequence variants and QTc in two long QT syndrome founder populations: a pedigree-based measured genotype association analysis2017Ingår i: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 18, artikel-id 74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1APsequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations.

    Methods: This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs.

    Results: A substantial variance in mean QTc was seen in genotype positives 476 ± 36 ms (Y111C 483 ± 34 ms; R518* 462 ± 34 ms) and genotype negatives 433 ± 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p < 0.001). In a multivariable analysis including the entire study population and adjusted for KCNQ1 genotype, sex and age, NOS1AP sequence variants rs12143842 and rs16847548 (but not rs4657139) were significantly associated with QT prolongation, +18 ms (p = 0.0007) and +17 ms (p = 0.006), respectively. Significant sex-interactions were detected for both sequent variants (interaction term r = 0.892, p < 0.001 and r = 0.944, p < 0.001, respectively). Notably, across the genotype groups, when stratified by sex neither rs12143842 nor rs16847548 were significantly associated with QTc in females (both p = 0.16) while in males, a prolongation of +19 ms and +8 ms (p = 0.002 and p = 0.02) was seen in multivariable analysis, explaining up to 23% of QTc variance in all males.

    Conclusions: Sex was identified as a moderator of the association between NOS1AP sequence variants and QTc in two LQT1 founder populations. This finding may contribute to QTc sex differences and affect the usefulness of NOS1AP as a marker for clinical risk stratification in LQTS.

  • 1109. Wit, J. M.
    et al.
    Ranke, M. B.
    Albertsson-Wikland, K.
    Carrascosa, A.
    Rosenfeld, R. G.
    Van Buuren, S.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Schoenau, E.
    Audi, L.
    Hokken-Koelega, A. C. S.
    Bang, P.
    Jung, H.
    Blum, W. F.
    Silverman, L. A.
    Cohen, P.
    Cianfarani, S.
    Deal, C.
    Clayton, P. E.
    de Graaff, L.
    Dahlgren, J.
    Kleintjens, J.
    Roelants, M.
    Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models2013Ingår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 79, nr 5, s. 257-270Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.

  • 1110. Wolthers, Benjamin Ole
    et al.
    Mogensen, Pernille R.
    Frandsen, Thomas L.
    Abrahamsson, Jonas
    Behrendtz, Mikael
    Heyman, Mats
    Lohi, Olli
    Norén-Nyström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ruud, Ellen
    Schmiegelow, Kjeld
    Insulin-dependent diabetes: a chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia2019Ingår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, nr 1, artikel-id e27437Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death. Here, we provide novel data on seven patients diagnosed with diabetes after pancreatitis and still requiring insulin treatment after a median follow-up of 4.2 years (range: 1.7-9.2). We describe the clinical course of pancreatitis and illustrate the association between pancreatic pseudocysts, older age, and development of insulin-dependent diabetes. Together, this study documents the persisting burden of pancreatitis in childhood ALL and underlines the need for plasma glucose level monitoring.

  • 1111. Wopereis, Harm
    et al.
    Van Ampting, Marleen
    Candy, David C. A.
    Peroni, Diego
    Vandenplas, Yvan
    Fox, Adam
    Nijhuis, Manon M. Oude
    Harthoorn, Lucien
    Michaelis, Louise J.
    Knol, Jan
    West, Christina E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Gut Microbiota Composition of Non-IgE Mediated Cow's Milk Allergic Infants before and after Dietary Management with a Synbiotics-Supplemented Amino Acid-Based Formula2017Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, nr 2, s. AB53-AB53Artikel i tidskrift (Refereegranskat)
  • 1112. Wopereis, Harm
    et al.
    van Ampting, Marleen T. J.
    Cetinyurek-Yavuz, Aysun
    Slump, Rob
    Candy, David C. A.
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Fox, Adam T.
    Shah, Neil
    Roeselers, Guus
    Harthoorn, Lucien F.
    Michaelis, Louise J.
    Knol, Jan
    West, Christina E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    A specific synbiotic-containing amino acid-based formula restores gut microbiota in non-IgE mediated cow's milk allergic infants: a randomized controlled trial2019Ingår i: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, artikel-id 27Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Altered gut microbiota is implicated in cow’s milk allergy (CMA) and differs markedly from healthy, breastfed infants. Infants who suffer from severe CMA often rely on cow’s milk protein avoidance and, when breastfeeding is not possible, on specialised infant formulas such as amino-acid based formulas (AAF). Herein, we report the effects of an AAF including specific synbiotics on oral and gastrointestinal microbiota of infants with non-IgE mediated CMA with reference to healthy, breastfed infants.

    Methods: In this prospective, randomized, double-blind controlled study, infants with suspected non-IgE mediated CMA received test or control formula. Test formula was AAF with synbiotics (prebiotic fructo-oligosaccharides and probiotic Bifidobacterium breve M-16V). Control formula was AAF without synbiotics. Healthy, breastfed infants were used as a separate reference group (HBR). Bacterial compositions of faecal and salivary samples were analysed by 16S rRNA-gene sequencing. Faecal analysis was complemented with the analysis of pH, short-chain fatty acids (SCFAs) and lactic acids.

    Results: The trial included 35 test subjects, 36 controls, and 51 HBR. The 16S rRNA-gene sequencing revealed moderate effects of test formula on oral microbiota. In contrast, the gut microbiota was substantially affected across time comparing test with control. In both groups bacterial diversity increased over time but was characterised by a more gradual increment in test compared to control. Compositionally this reflected an enhancement of Bifidobacterium spp. and Veillonella sp. in the test group. In contrast, the control-fed infants showed increased abundance of adult-like species, mainly within the Lachnospiraceaefamily, as well as within the Ruminococcus and Alistipes genus. The effects on Bifidobacterium spp. and Lachnospiraceae spp. were previously confirmed through enumeration by fluorescent in situ hybridization and were shown for test to approximate the proportions observed in the HBR. Additionally, microbial activity was affected as evidenced by an increase of l-lactate, a decrease of valerate, and reduced concentrations of branched-chain SCFAs in test versus control.

    Conclusions: The AAF including specific synbiotics effectively modulates the gut microbiota and its metabolic activity in non-IgE mediated CMA infants bringing it close to a healthy breastfed profile.

  • 1113.
    Wu, Junfang
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Zivkovic, Angela M.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation2016Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, nr 3, s. 626-632Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Low-molecular-weight metabolites in human milk are gaining increasing interest in studies of infant nutrition. In the present study, the milk metabolome from a single mother was explored at different stages of lactation. Metabolites were extracted from sample aliquots using either methanol water (MeOH/H2O) extraction or ultrafiltration. Nuclear magnetic resonance (NMR) spectroscopy was used for metabolite identification and quantification, and multi- and univariate statistical data analyses were used to detect changes over time of lactation. Compared to MeOH/H2O extraction, ultrafiltration more efficiently reduced the interference from lipid and protein resonances, thereby enabling the identification and quantification of 36 metabolites. The human milk metabolomes at the early (9-24 days after delivery) and late (31-87 days after delivery) stages of lactation were distinctly different according to multi- and univariate statistics. The late lactation stage was characterized by significantly elevated concentrations of lactose, choline, alanine, glutamate, and glutamine, as well as by reduced levels of citrate, phosphocholine, glycerophosphocholine, and N-acetylglucosamine. Our results indicate that there are significant compositional changes of the human milk metabolome also in different phases of the matured lactation stage. These findings complement temporal studies on the colostrum and transitional metabolome in providing a better understanding of the nutritional variations received by an infant.

  • 1114.
    Wu, Jungfang
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gouveia-Figueira, Sandra
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Zivkovic, Angela M
    Nording, Malin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Oxylipins, endocannabinoids, and related compounds in human milk: levels and effects of storage conditions2016Ingår i: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 122, s. 28-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presence of fatty acid derived oxylipins, endocannabinoids and related compounds in human milk may be of importance to the infant. Presently, clinically relevant protocols for storing and handling human milk that minimize error and variability in oxylipin and endocannabinoid concentrations are lacking. In this study, we compared the individual and combined effects of the following storage conditions on the stability of these fatty acid metabolites in human milk: state (fresh or frozen), storage temperature (4 °C, -20 °C or -80 °C), and duration (1 day, 1 week or 3 months). Thirteen endocannabinoids and related compounds, as well as 37 oxylipins were analyzed simultaneously by liquid chromatography coupled to tandem mass spectrometry. Twelve endocannabinoids and related compounds (2–111 nM) and 31 oxylipins (1.2 pM–1242 nM) were detected, with highest levels being found for 2-arachidonoylglycerol and 17(R)-hydroxydocosahexaenoic acid, respectively. The concentrations of most endocannabinoid-related compounds and oxylipins were dependent on storage condition, and especially storage at 4 °C introduced significant variability. Our findings suggest that human milk samples should be analyzed immediately after, or within one day of collection (if stored at 4 °C). Storage at -80 °C is required for long-term preservation, and storage at -20 °C is acceptable for no more than one week. These findings provide a protocol for investigating the oxylipin and endocannabinoid metabolome in human milk, useful for future milk-related clinical studies.

  • 1115. Yang, Zhenyu
    et al.
    Dewey, Kathryn G
    Lönnerdal, Bo
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Chaparro, Camila
    Adu-Afarwuah, Seth
    McLean, Erin D
    Cohen, Roberta J
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Allen, Lindsay H
    Brown, Kenneth H
    Comparison of plasma ferritin concentration with the ratio of plasma transferrin receptor to ferritin in estimating body iron stores: results of 4 intervention trials2008Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 87, nr 6, s. 1892-1898Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Efforts to develop global programs for the control of iron deficiency require simple, low-cost, and accurate indicators of iron status.

    Objective: We aimed to compare estimates of body iron (BI) stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transferrin receptor (TfR) to ferritin (BI-TfR/ferritin).

    Design: Data were analyzed from 4 previously completed, randomized intervention trials that enrolled infants, schoolchildren, or pregnant women (totaln = 1189, after excluding subjects with elevated C-reactive protein).

    Results: The correlation coefficients between BI-ferritin and BI-TfR/ferritin were >0.95 for all studies. The kappa index ranged from 0.5 to 1.0. All of the sensitivities of BI-ferritin for identifying persons with low iron stores (defined as BI-TfR/ferritin < 0 mg/kg body wt) were >0.90. All of the specificities were >0.90 except the study of pregnant women (specificity = 0.66). The effect sizes of iron intervention trials were significantly greater for change in iron reserves estimated by BI-TfR/ferritin than by BI-ferritin in 2 studies with larger effect sizes (1.11 compared with 1.00 and 1.56 compared with 1.44, respectively; P < 0.05) and 1 study with medium effect size (0.70 compared with 0.57; P < 0.05). However, there were no significant differences between estimates of these effect sizes for 1 study with a medium effect size and 1 study with a smaller effect size (0.78 compared with 0.83 and 0.37 compared with 0.35, respectively; P > 0.2).

    Conclusion: Plasma ferritin concentration alone provides a good approximation of total BI reserves, as estimated by BI-TfR/ferritin, on the basis of high correlation, sensitivity, and specificity among nonpregnant persons with unelevated C-reactive protein.

     

  • 1116. Yang, Zhenyu
    et al.
    Lönnerdal, Bo
    Adu-Afarwuah, Seth
    Brown, Kenneth H
    Chaparro, Camila M
    Cohen, Roberta J
    Domellöf, Magnus
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Pediatrik.
    Lartey, Anna
    Dewey, Kathryn G
    Prevalence and predictors of iron deficiency in fully breastfed infants at 6 mo of age: comparison of data from 6 studies.2009Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 89, nr 5, s. 1433-1440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Iron deficiency (ID) can occur among exclusively breastfed infants before 6 mo of age. OBJECTIVE: The objective was to determine which subgroups of fully breastfed infants are at highest risk of ID. DESIGN: We assessed the prevalence of ID (ferritin < 12 mug/L) and iron deficiency anemia (IDA; ferritin < 12 mug/L and hemoglobin < 105 g/L) and risk factors associated with ID and IDA at 6 mo among 404 fully breastfed infants with a birth weight >2500 g from 6 studies in Ghana, Honduras, Mexico, and Sweden. Infants with an elevated C-reactive protein concentration (8%) were excluded. RESULTS: The percentages of infants with ID were 6% in Sweden, 17% in Mexico, 13-25% in Honduras, and 12-37% in Ghana. The percentages with IDA were 2% in Sweden, 4% in Mexico, 5-11% in Honduras, and 8-16% in Ghana. With data pooled, the key predictors of ID (20%) were male sex [adjusted odds ratio (AOR): 4.6; 95% CI: 2.5, 8.5] and birth weight 2500-2999 g (AOR: 2.4; 95% CI: 1.4, 4.3). The predictors of IDA (8%) were male sex (AOR: 7.6; 95% CI: 2.5, 23.0), birth weight of 2500-2999 g (AOR: 3.4; 1.5, 7.5), and weight gain above the median since birth (AOR: 3.4; 95% CI: 1.3, 8.6). The combination of birth weight 2500-2999 g or male sex had a sensitivity of 91% for identifying ID and of 97% for identifying IDA. CONCLUSIONS: Among fully breastfed infants with a birth weight >2500 g, IDA is uncommon before 6 mo, but male infants and those with a birth weight of 2500-2999 g are at higher risk of ID and IDA.

  • 1117.
    Zachariadis, V
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gauffin, F
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kuchinskaya, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Heyman, M
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Schoumans, J
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blennow, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, B
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Barbany, G
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Ehrencrona, H
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Cavelier, L
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Palmqvist, L
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lönnerholm, G
    Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden.
    Nordenskjöld, M
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Johansson, B
    Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Nordgren, A
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial2011Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, nr 4, s. 622-628Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

  • 1118. Zachariadis, V.
    et al.
    Schoumans, J.
    Ofverholm, I.
    Barbany, G.
    Halvardsson, E.
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Johansson, B.
    Nordenskjold, M.
    Nordgren, A.
    Detecting dic(9;20)(p13.2;p11.2)-positive B-cell precursor acute lymphoblastic leukemia in a clinical setting using fluorescence in situ hybridization2014Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, nr 1, s. 196-198Artikel i tidskrift (Refereegranskat)
  • 1119.
    Zachrisson, I
    et al.
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Brismar, K
    Department of Endocrinology and Diabetology, Karolinska Hospital and Institute, Stockholm, Sweden.
    Carlsson-Skwirut, C
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wallensteen, M
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Bang, P
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.2000Ingår i: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 10, nr 6, s. 324-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

  • 1120. Zachrisson, I
    et al.
    Brismar, K
    Hall, K
    Wallensteen, M
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Determinants of growth in diabetic pubertal subjects1997Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, nr 8, s. 1261-1265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects.

    RESEARCH DESIGN AND METHODS: In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS).

    RESULTS: The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3-5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = -0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth.

    CONCLUSIONS: In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.

  • 1121.
    Zachrisson, I
    et al.
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Dahlquist, Gisela
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wallensteen, M
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Brismar, K
    Astrid Lindgren Children’s Hospital, Karolinska Hospital and Institute, Stockholm, Sweden.
    Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.2000Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 89, nr 9, s. 1044-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. CONCLUSION: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.

  • 1122. Zaman, S.
    et al.
    Lange, S.
    Jennische, E.
    Aamir, K.
    Silfverdal, Sven Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hanson, L. A.
    The antisecretory factor - an efficient tool for rapid recovery from early childhood diarrhoea2013Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, nr 9, s. E391-E391Artikel i tidskrift (Refereegranskat)
  • 1123. Zaman, Shakila
    et al.
    Aamir, Khalida
    Lange, Stefan
    Jennische, Eva
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hanson, Lars A.
    Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study2014Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, nr 6, s. 659-664Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim

    We studied the response to high doses of egg yolk containing antisecretory factor (B221((R)), Salovum((R))) in young children with acute diarrhoea, presenting to the Children's Hospital, Lahore, Pakistan.

    Methods

    In a randomised, placebo-controlled trial, 36 children aged 7 to 60months with acute diarrhoea of unknown aetiology, with mild-to-moderate dehydration, were randomised to the Salovum((R)) or placebo groups. Initially, 16 grams of Salovum((R)) or ordinary egg yolk (placebo) mixed in oral rehydration salts was given, followed by 8g every 5h until recovery. The number and consistency of stools were recorded.

    Results

    The two groups were comparable in age, gender, duration of diarrhoea, hydration and nutritional status, although the proportion with watery stools was higher in the Salovum((R)) group (p=0.04). Reduction in the frequency of stools was seen at 7 versus 18h (p<0.0001) and normalising of stool consistency was 10 versus 18h, p<0.03) in the Salovum((R)) and placebo groups. The overall effect was 35 versus 70h in the two groups (p=0.001). No side effects were reported.

    Conclusion

    High doses of AF in the form of Salovum((R)) effectively and safely reduce childhood diarrhoea of a likely broad aetiology.

  • 1124.
    Zamir, Itay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stoltz Sjöström, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Abrahamsson, T.
    Ahlsson, F.
    Hallberg, B.
    Pupp, I.
    Stjernkvist, K.
    Serenius, F.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Early-life hyperglycemia in extremely preterm infants affects neurodevelopment at 6 years of age2016Ingår i: EUROPEAN JOURNAL OF PEDIATRICS, ISSN 0340-6199, Vol. 175, nr 11, s. 1440-1440Artikel i tidskrift (Refereegranskat)
  • 1125.
    Zamir, Itay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stoltz Sjöström, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Edstedt Bonamy, Anna-Karin
    Mohlkert, Lilly-Ann
    Norman, Mikael
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm2019Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 86, nr 1, s. 115-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Adverse developmental programming by early-life exposures might account for higher blood pressure (BP) in children born extremely preterm. We assessed associations between nutrition, growth and hyperglycemia early in infancy, and BP at 6.5 years of age in children born extremely preterm.

    Methods: Data regarding perinatal exposures including nutrition, growth and glycemia status were collected from the Extremely Preterm Infants in Sweden Study (EXPRESS), a population-based cohort including infants born <27 gestational weeks during 2004–2007. BP measurements were performed at 6.5 years of age in a sub-cohort of 171 children (35% of the surviving children).

    Results: Higher mean daily protein intake (+1 g/kg/day) during postnatal weeks 1–8 was associated with 0.40 (±0.18) SD higher diastolic BP. Higher mean daily carbohydrate intake (+1 g/kg/day) during the same period was associated with 0.18 (±0.05) and 0.14 (±0.04) SD higher systolic and diastolic BP, respectively. No associations were found between infant growth (weight, length) and later BP. Hyperglycemia and its duration during postnatal weeks 1–4 were associated primarily with higher diastolic BP z-scores.

    Conclusions: These findings emphasize the importance of modifiable early-life exposures, such as nutrition and hyperglycemia, in determining long-term outcomes in children born extremely preterm.

  • 1126.
    Zamir, Itay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Tornevi, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Abrahamsson, Thomas
    Ahlsson, Fredrik
    Engström, Eva
    Hallberg, Boubou
    Hansen-Pupp, Ingrid
    Stoltz Sjöström, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hyperglycemia in extremely preterm infants: insulin treatment, mortality and nutrient intakes2018Ingår i: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 200, s. 104-110Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants.

    Study design: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data.

    Results: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05).

    Conclusions: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

  • 1127. Zhu, Lijun
    et al.
    Hou, Miao
    Sun, Bin
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Zhang, Li
    Yi, Jun
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Li, Xiaonan
    Testosterone Stimulates Adipose Tissue 11 beta-Hydroxysteroid Dehydrogenase Type 1 Expression in a Depot-Specific Manner in Children2010Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 7, s. 3300-3308Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol.

    Objective: Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment.

    Subjects and Methods: Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI SD score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined.

    Results: Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P < 0.05) in om adipose tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P < 0.001). However, there was no synergistic effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment.

    Conclusions: Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.

  • 1128. Åkeson, Pia Karlsland
    et al.
    Åkesson, Kristina E
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öhlund, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Vitamin D Intervention and Bone: A Randomized Clinical Trial in Fair- and Dark-skinned Children at Northern Latitudes2018Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 67, nr 3, s. 388-394Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of the study was to evaluate vitamin D status and effects of vitamin D intervention on bone mineral density (BMD) and content (BMC) in children with fair and dark skin in Sweden during winter.

    Methods: In a 2-center prospective double-blinded randomized intervention study 5- to 7-year-old children (n = 206) with fair and dark skin in Sweden (55 degrees N-63 degrees N) received daily vitamin D supplements of 25 mu g, 10 mu g, or placebo (2 mu g) during 3 winter months. We measured BMD and BMC for total body (TB), total body less head (TBLH), femoral neck (FN), and spine at baseline and 4 months later. Intake of vitamin D and calcium, serum 25-hydroxy vitamin D (S-25 [OH]D), and related parameters were analyzed.

    Results: Despite lower S-25(OH)D in dark than fair-skinned children, BMD of TB (P = 0.012) and TBLH (P = 0.002) and BMC of TBLH (P = 0.04) were higher at baseline and follow-up in those with dark skin. Delta (Delta) BMD and BMC of TB and TBLH did not differ between intervention and placebo groups, but FN-BMC increased more among dark-skinned children in the 25 mu g (P = 0.038) and 10 mu g (P = 0.027) groups compared to placebo. We found no associations between Delta S-25(OH)D, P-parathyroid hormone, P-alkaline phosphatase, and Delta BMD and BMC, respectively.

    Conclusions: BMD and BMC remained higher in dark- than fair-skinned children despite lower vitamin D status. Even though no difference in general was found in BMD or BMC after vitamin D intervention, the increase in FN-BMC in dark-skinned children may suggest an influence on bone in those with initially insufficient vitamin D status.

  • 1129.
    Öhlund, Inger
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Health implications of dietary intake in infancy and early childhood2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Swedish children are the healthiest in Europe. Through regular visits to well-baby clinics, infants and young children are checked and parents given information and advice on diet and other relevant matters for their child. For a long time, adequate nutrition during infancy and childhood has been focused on encouraging proper nutrition, preventing malnutrition and deficiency states, and obtaining optimal growth. Today, malnutrition and deficiency states in infants and children are rare. But other public health problems have arisen. Nutrition early in life is now thought to influence health and diseases even in adulthood. Thus promotion of a healthy diet in early life is important for preventing public health diseases such as iron deficiency, cardiovascular disease, obesity, and dental caries.

    Aims: This study investigates health implications of dietary intake in infancy and early childhood. More specific focus was on the associations between dietary fat intake and serum lipid levels in infants, early dietary intake, iron status, dental caries, and Body Mass Index (BMI) at 4 years of age. In addition, hereditary factors and changes over time were evaluated.

    Methods: Before 6 month of age, 300 healthy infants were recruited from well-baby clinics in Umeå. This thesis is based on secondary analysis of a prospective study in these infants run from 6-18 months and a follow-up of 127 of the children at 4 years. Between 6-18 months and at 4 years, dietary intakes were assessed, anthropometric measures performed, and venous blood samples taken. At 4 years, a dental examination was also performed and anthropometric data and blood samples were collected from parents and included in the study.

    Results: All but two infants were ever breastfed and at 6 months 73% were still breastfed. The quality of dietary fat was not within national recommendations. At 4 years, intake of vitamin D and selenium were below and intake of sugar and sweet products above the recommendations. In girls, but not boys, higher polyunsaturated fatty acid intake was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels. Iron status of the children was generally good and no child had iron deficiency anaemia (IDA). Children’s haemoglobin (Hb) levels tracked from infancy to 4 years and correlated with their mother’s Hb. Fortified infant products and meat were important sources of iron at both 12 months and 4 years. Children with frequent intake of cheese had less caries in this population with low caries prevalence. We found higher protein intake over time to be associated with higher Body Mass Index (BMI) at 4 years and high BMI at 4 years was associated with high BMI at 6 mo. There was also an association between the BMI of the child and that of its parents.

    Conclusions: BMI of the child and parents (especially the father), and iron status at 6 months were predictors of these variables at 4 years of age. The quality rather than the quantity of dietary fat in infancy affected serum lipid values. Even in a healthy and well-nourished group of Swedish infants and young children, quality of food and intake of nutrients are important for current and later health of the child.

  • 1130.
    Öhlund, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fett i barnets kost: kvalitet minst lika viktigt som kvantitet2011Ingår i: Nordisk Nutrition, ISSN 1654-8337, nr 1, s. 31-34Artikel i tidskrift (Övrigt vetenskapligt)
  • 1131.
    Öhlund, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hörnell, Agneta
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Serum lipid and apolipoprotein levels in 4-year-old children are associated with parental levels and track over time2011Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 65, nr 4, s. 463-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Objectives: There are only a few studies linking dietary fat intake to serum lipid levels in young children. Our objective was to prospectively evaluate serum lipid levels from infancy to early childhood, and to explore their possible association with dietary, growth and parental factors.

    Subjects/Methods: Children (n=127) followed from early infancy were examined for serum lipid levels, anthropometry and dietary intake at 4 years of age. We also studied possible associations with parental anthropometric and blood biochemistry data collected from 122 mothers' and 118 fathers' when children were 4 years of age.

    Results: Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and the apolipoprotein B/apolipoprotein A-1 ratio (apo B/apo A-1) showed significant tracking from infancy to 4 years. Furthermore, children's TC levels correlated with paternal TC level from 6 months to 4 years, but with maternal only at 4 years. In girls, both LDLC and HDLC correlated with parental LDLC and HDLC. In all children, intake of saturated fatty acids (SAFAs) was higher than recommended, and in 90% of the children polyunsaturated fatty acid (PUFA) intake was lower than recommended.

    Conclusions: Serum lipid levels values tracked from infancy to 4 years and were associated with parental values. Higher serum lipid levels at 4 years compared with 6-18 months of age may result from changes in the quality of dietary fat. We therefore suggest that intake of dietary fat in 4-year-old children should be more focused on quality. Furthermore, as there were strong associations between the child and parental serum lipid levels this supports the view that family-based rather than individual intervention is preferable.

  • 1132.
    Öhlund, Inger
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hörnell, Agneta
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    BMI at 4 years of age is associated with previous and current protein intake and with paternal BMI2010Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 64, nr 2, s. 138-145Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Objectives:To evaluate possible associations between body mass index (BMI) at 4 years of age, current and previous dietary intakes and parental BMI.Methods:A follow-up of dietary intake and anthropometry in 127 4-year-old children corresponding to 54% of children who completed an initial intervention study at 18 months of age.Results:Fourteen percent of the girls and 13% of the boys were overweight (age-adjusted BMI>/=25) and 2% of the girls and 3% of the boys were obese (age-adjusted BMI>/=30). Thirty-four percent and 9% of the fathers and 19 and 7% of the mothers were overweight and obese, respectively. BMI at 6-18 months was a strong predictor of BMI at 4 years. Univariate regression analyses revealed that intake of protein in particular, and also of total energy and carbohydrates at 17/18 months and at 4 years, was positively associated with BMI at 4 years. Although BMI at 6-18 months was the strongest predictor of BMI at 4 years, in the final multivariate models of the child's BMI, protein intake at 17-18 months and at 4 years, energy intake at 4 years and the father's-but not the mother's-BMI were also independent contributing factors.Conclusions:Among these healthy children, BMI at 4 years of age tracked from 6 to 18 months of age and were associated with previous and current protein intake as well as parental BMI, particularly that of the father.

  • 1133.
    Öhlund, Inger
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hörnell, Agneta
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dietary fat in infancy should be more focused on quality than on quantity2008Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 62, nr 9, s. 1058-1064Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The primary aim was to assess, the association of the quantity and quality of dietary fat intake from 6 to 12 months of age and serum lipids at 12 months.

    Subjects/Methods: Three hundred healthy term Swedish infants were recruited in a longitudinal prospective study at the age of 6 months; 276 remained in the study at 12 months. Food records and anthropometric data were collected monthly from 6 to 12 months; serum lipids were analysed at 6 and 12 months.

    Results: Swedish infants had a total fat intake within the Nordic recommendations, but intake of polyunsaturated fatty acids (PUFA) was low (5.6 percent of total energy (E%)) and intake of saturated fatty acids (SAFA) was high (15.1 E%). Higher PUFA intake was associated with lower total serum cholesterol (TC, B=−0.13, P=0.003), lower low-density-lipoprotein cholesterol (LDL-C, B=−0.12, P=0.004) and apolipoprotein B (B=−0.03) (P=0.034) in girls but not in boys. When data from the present study were compared to data from similar studies in Finland and Iceland, it appears that the quality of the dietary fat has greater impact on serum lipid levels than the quantity of fat in the diet.

    Conclusions: Higher PUFA and lower SAFA intakes may reduce TC and LDL-C early in life, particularly in girls. Further, with respect to lowering serum lipid concentrations in early childhood it seems appropriate to set focus on fat quality rather than the quantity.

  • 1134.
    Öhlund, Inger
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hörnell, Agneta
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Iron status and its relations to diet, growth and heredity in 4-years old, well-nourished Swedish children2007Ingår i: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), 2007Konferensbidrag (Övrigt vetenskapligt)
  • 1135.
    Öhlund, Inger
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Lif Holgerson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Bäckman, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Diet intake and caries prevalence in four-year-old children living in a low-prevalence country.2007Ingår i: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 41, nr 1, s. 26-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Preventive measures have dramatically decreased the prevalence of dental caries in children. However, risk factors for the disease in children living in low-prevalence areas remain elusive. In the present study we evaluated associations between dental caries, saliva levels of mutans streptococci and lactobacilli, and diet with special emphasis on the intake of fermentable carbohydrates and dairy products in 4-year-old children living in an area where the overall caries prevalence was low. Dietary intake was recorded in 234 infants as part of the Study of Infant Nutrition in Umea, Sweden (SINUS). Of these the parents of 124 children gave consent to participate in a follow-up at 4 years of age. Dietary intake, height and weight, dental caries, oral hygiene, including tooth brushing habits, presence of plaque and gingival inflammation, fluoride habits and numbers of mutans streptococci and lactobacilli in saliva were recorded. Using multivariate stepwise logistic regression, caries experience was negatively associated with intake frequency of cheese (OR = 0.67; 95% CI = 0.44-0.98) and positively associated with the salivary level of mutans streptococci (OR = 1.57; 95% CI = 1.21-2.03). Caries experience was not correlated with intake frequency or amounts of carbohydrate-containing foods, with any other particular food, or with daily intake of energy, carbohydrate or any other macro- or micronutrient. We conclude that cheese intake may have a caries-protective effect in childhood populations where the overall caries prevalence and caries experience are low and the children are regularly exposed to fluoride from toothpaste.

  • 1136.
    Öhlund, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Karlsland Åkeson, Pia
    Increased vitamin D intake differentiated according to skin color is needed to meet requirements in young Swedish children during winter: a double-blind randomized clinical trial2017Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, nr 1, s. 105-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dark skin and low exposure to sunlight increase the risk of vitamin D insufficiency in children. Objective: The aim of the study was to evaluate the amount of vitamin D needed to ascertain that most children >4 y of age attain sufficient serum25-hydroxyvitamin D [S-25(OH) D; i.e., >= 50 nmol/L] during winter regardless of latitude and skin color. Design: In a longitudinal, double-blind, randomized, food-based intervention study, 5- to 7-y-old children from northern (638 degrees N) and southern (558 degrees N) Sweden with fair (n = 108) and dark (n = 98) skin were included. Children, stratified by skin color by using Fitzpa-trick's definition, were randomly assigned to receive milk-based vitamin D-3 supplements that provided 2 (placebo), 10, or 25 mu g/d during 3 winter months. Results: Mean daily vitamin D intake increased from 6 to 17 mu g and 26 mu g in the intervention groups supplemented with 10 and 25 mu g, respectively. In the intention-to-treat analysis, 90.2% (95% CI: 81.1%, 99.3%) of fair-skinned children randomly assigned to supplementation of 10 mu g/d attained sufficient concentrations, whereas 25 mu g/d was needed in dark-skinned children to reach sufficiency in 95.1% (95% CI: 88.5%, 100%). In children adherent to the study product, 97% (95% CI: 91.3%, 100%) and 87.9% (95% CI: 76.8%, 99%) of fair-and dark-skinned children, respectively, achieved sufficient concentrations if supplemented with 10 mu g/d. By using 95% prediction intervals for 30 and 50 nmol S-25(OH) D/L, intakes of 6 and 20 mu g/d are required in fair-skinned children, whereas 14 and 28 mu g/d are required in children with dark skin. Conclusion: Children with fair and dark skin require vitamin D intakes of 20 and 28 mu g/d, respectively, to maintain S-25(OH) D >= 50 nmol/L, whereas intakes of 6 and 14 mu g/d, respectively, are required to maintain concentrations >= 30 nmol/L during winter.

  • 1137.
    Öhlund, Inger
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hörnell, Agneta
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Predictors of iron status in well-nourished 4-y-old children.2008Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 87, nr 4, s. 839-845Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Iron status in childhood is influenced by diet. Other factors affecting iron status at that age are unclear. OBJECTIVES: The objectives of the study were to evaluate iron status in 4-y-old children, to track that status from infancy to childhood, and to examine the associations of iron status with dietary factors, growth, and heredity. DESIGN: This study consisted of a longitudinal follow-up at age 4 y of children (n = 127) from the cohort of a study that began at age 6 mo. Blood samples and anthropometry were assessed in both children and their parents; food records were collected from children only. RESULTS: Dietary intake was not significantly correlated with hemoglobin concentrations, whereas the consumption of meat products had a positive effect on serum ferritin concentrations and mean corpuscular volume in boys (P = 0.015 and 0.04, respectively). The prevalences of anemia and iron deficiency were low, affecting 2 (1.8%) and 3 (2.8%) children, respectively; no child had iron deficiency anemia. There was significant within-subject tracking of hemoglobin and mean corpuscular volume from age 6 mo to 4 y. The mother's but not the father's hemoglobin correlated with the child's hemoglobin over time. CONCLUSIONS: Food choices had little effect on iron status. Hemoglobin concentrations and mean corpuscular volume were tracked from infancy to childhood. In healthy, well-nourished children with a low prevalence of iron deficiency, the mother's hemoglobin was significantly associated with that of her child, but the underlying mechanism is unclear.

  • 1138.
    Öhlund, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Serum 25-Hydroxyvitamin D Levels in Preschool-Age Children in Northern Sweden Are Inadequate After Summer and Diminish Further During Winter2013Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, nr 5, s. 551-555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objective: Despite studies indicating that vitamin D intake among Swedish children does not meet the recommendation, little is known of their vitamin D status. The aim of the present study was to examine vitamin D status in preschool-age children in relation to vitamin D intake, season, body mass index, and skin color. Methods: Preschool-age children (n = 90; mean age 54 +/- 7.1 months), all living in northern Sweden (latitude 63 degrees north), half of them with fair skin, half with darker complexion, were recruited from well-baby clinics. The study group was examined first in August-September (late summer) and then the following January-February (winter). Skin type, vitamin D intake, anthropometrics, serum 25-hydroxyvitamin D (S-25[OH] D), and serum parathyroid hormone were assessed. Results: Mean +/- SD S-25(OH) Din summer and winter were 60 +/- 15 nmol/L and 55 +/- 16 nmol/L, respectively (P < 0.001). Fifteen percent and 10% had S-25(OH) D >= 75 nmol/L, and 25% and 40% had S-25(OH) D < 50 nmol/L, respectively. The mean vitamin D intake was higher in dark-skinned compared with fair-skinned children. In spite of this, S-25(OH) D in dark-skinned children was lower compared with fair-skinned children during both seasons. The dietary intake of vitamin D was positively associated with S-25(OH) D levels. Conclusions: Vitamin D status is inadequate in preschool-age children living in northern Sweden, especially in dark-skinned children and during the winter despite vitamin D intakes meeting the recommendations, prompting strategies to improve intake of vitamin D in this population.

  • 1139.
    Öhlund, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Olsson, Cecilia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öhlund, Inger
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Dietary shortcomings in children on a gluten-free diet2010Ingår i: Journal of human nutrition and dietetics (Print), ISSN 0952-3871, E-ISSN 1365-277X, Vol. 23, nr 3, s. 294-300Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Coeliac disease (CD), or permanent gluten intolerance, is one of the most common chronic food-related diseases among children in Europe and the USA. The treatment is lifelong gluten-free diet (GFD) (i.e. the exclusion of wheat, rye and barley from the diet, which are important sources particularly of iron, dietary fibre and vitamin B). The present study aimed to evaluate dietary intakes of energy and nutrients in children and adolescents on GFD and compare these with intake of comparable age groups on a normal diet as well as current recommendations.

    Methods: Thirty children, 4-17 years of age with confirmed CD and on GFD were agreed to participate in this study at the Department of Pediatrics, Umeå University Hospital. Weight and height were used to calculate individual energy requirement according to Nordic Nutrition Recommendations 2004 (NNR-04). Dietary intake was assessed using 5-day food records and household measures were used for quantities. Twenty-five children completed their dietary record.

    Results: Thirteen of the 25 children did not meet the recommended energy intake and the dietary intakes were inadequate regarding quality of macronutrients and quantity of minerals and vitamins. The mean intakes of sucrose and saturated fatty acids were above and the intakes of dietary fibre, vitamin D, magnesium and selenium below the NNR-04. High intakes of sucrose and saturated fat and a low intake of dietary fibre were also noted in a previous national survey on healthy children on a normal diet. The nutrient density of vitamin D, riboflavin, niacin, thiamine, magnesium and selenium were lower among CD children than healthy children but, for iron and calcium, it was higher in CD children.

    Conclusions: Children on GFD appear to follow the same trends as healthy children on a normal diet, with high intakes of saturated fat and sucrose and low intakes of dietary fibre, vitamin D and magnesium compared to recommendations.

  • 1140.
    Öhlund, Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Antibiotic use before 1 year of age and development of allergic symptoms at 1, 4 and 13 years of age. A prospective Swedish birth cohort.2014Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 1141. Öhman, Annika
    et al.
    El-Segaier, Milad
    Bergman, Gunnar
    Hanséus, Katarina
    Malm, Torsten
    Nilsson, Boris
    Pivodic, Aldina
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sonesson, Sven-Erik
    Mellander, Mats
    Changing Epidemiology of Hypoplastic Left Heart Syndrome: Results of a National Swedish Cohort Study2019Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, nr 2, artikel-id e010893Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live-borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed. Methods and Results Neonates with hypoplastic left heart syndrome with aortic atresia born 1990-2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox-logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis. Conclusions We observed a decrease in incidence of live-borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live-borns who underwent surgery increased between time periods.

  • 1142. Örtqvist, Å
    et al.
    Blennow, M
    Carlsson, R-M
    Hansson, LÅ
    Lindberg, A
    Lindqvist, I
    Magnusson, M
    Nilsson, L
    Norlund, A
    Nyrén, O
    Olcén, P
    Olin, P
    Silfverdal, Sven Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Säwe, J
    Söderström, A
    Trollfors, B
    Vaccination of children: a children systematic review2010Ingår i: Acta Paediatrica. Supplement, ISSN 0803-5326, Vol. 99, nr s461, s. 1-192Artikel i tidskrift (Refereegranskat)
  • 1143.
    Österlund, J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Winberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    West, C. E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    A 10-year review found increasing incidence trends of emergency egg allergy reactions and food-induced anaphylaxis in children2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 2, s. 314-320Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Aim: International reports have suggested that food allergies and food‐induced anaphylaxis have increased in children. We investigated the incidence of emergency food reactions over a 10‐year period.

    Methods: This study retrospectively reviewed the medical records of children presenting to Umeå University hospital, Sweden, with an emergency food reaction from January 1, 2006 to December 31, 2015. Cases were identified using discharge codes for allergies and anaphylaxis. Anaphylaxis cases were included if they fulfilled the international criteria.

    Results: We found emergency food allergy reactions in 519 children (58% boys) from 2006–2015 at a median age of 1.3 years. One‐third were hospitalised (32%) including 71/99 cases of anaphylaxis. Milk and eggs were the most commonly identified triggers. Emergency reactions to eggs increased during the study period with a Spearman rank correlation coefficient of 0.770 (p < 0.01) and the figures for anaphylaxis were 0.745 (p = 0.013). The incidence of food‐induced anaphylaxis increased and was 30 per 100 000 person‐years for the study period.

    Conclusion: Most of the emergency reactions, treated by secondary care paediatricians and emergency physicians, were to milk and eggs. Allergic reactions to eggs increased from 2006 to 2015, as did food‐related anaphylaxis.

  • 1144.
    Österlund, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Incidence trends of emergency food reactions in children and adolescents in Northern Sweden: A 10-year retrospective study in Umeå2016Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 1145. Östman-Smith, Ingegerd
    et al.
    Sjöberg, Gunnar
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Larsson, Per
    Fernlund, Eva
    Predictors of risk for sudden death in childhood hypertrophic cardiomyopathy: the importance of the ECG risk score2017Ingår i: Open heart, E-ISSN 2053-3624, Vol. 4, nr 2, artikel-id e000658Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To establish which risk factors are predictive for sudden death in hypertrophic cardiomyopathy (HCM) diagnosed in childhood.

    Methods: A Swedish national cohort of patients with HCM diagnosed <19 years of age was collected between 1972 and 2014, consisting of 155 patients with available ECGs, with average follow-up of 10.9±(SD 9.0) years, out of whom 32 had suffered sudden death or cardiac arrest (SD/CA group). Previously proposed risk factors and clinical features, ECG and ultrasound measures were compared between SD/CA group and patients surviving >2 years (n=100), and features significantly more common in SD/CA group were further analysed with univariate and multivariate Cox hazard regression in the total cohort.

    Results: Ranked according to relative risk (RR) the ECG risk score >5 points had an RR of 46.5 (95% CI 6.6 to 331), sensitivity of 97% (83% to 100%) and specificity of 80% (71% to 88%) (p<0.0001), and was the best ECG predictor, predicting a 5-year risk of SD/CA of 30.6%. The following are other features with importantly raised RR: Detroit wall thickness Z-score >4.5: 9.9 (3.1 to 31.2); septal thickness ≥190% of upper limit of normal for age (septum in % of 95th centile for age (SEPPER) ≥190%): 7.9 (3.2 to 19.4); ventricular tachycardia: 9.1 (3.6 to 22.8); ventricular ectopics on exercise testing: 7.4 (2.7 to 20.2); and left ventricular outflow gradient (left ventricular outflow tract obstruction (LVOTO)) >50 mm Hg: 6.6 (4.0 to 11.0). Family history was non-significant. Multivariate Cox hazard analysis gives the following as early predictors: limb-lead QRS amplitude sum (p=0.020), SEPPER ≥190% (p<0.001) and LVOTO at rest (p=0.054); and for late predictors: last ECG risk score (p=0.002) and last Detroit Z-score (p=0.001). Both early (p=0.028) and late (p=0.037) beta-blocker doses reduced risk in the models.

    Conclusions: ECG phenotype as assessed by ECG risk score is important for risk of sudden death and should be considered for inclusion in risk stratification of paediatric patients with HCM.

  • 1146. Østergaard, Lars
    et al.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Berglund, Johan
    Flodmark, Carl-Erik
    West, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Bianco, Veronique
    Baine, Yaela
    Miller, Jacqueline M.
    A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: An open, randomised, controlled trial.2012Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, nr 4, s. 774-783Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The co-administration of the tetravalent meningococcal conjugate vaccine, MenACWY-TT, with a licensed hepatitis A and B vaccine, HepA/B (Twinrix(®)), was compared to their separate administration in this open, randomised, controlled study. Healthy subjects 11-17 years of age (n=611) were randomised (3:1:1) to receive both vaccines, MenACWY-TT alone or HepA/B alone. The co-administration of both vaccines was shown to be non-inferior to their individual administration. At seven months after the first vaccination, 99.4-100% of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1% of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity, safety and reactogenicity of either of the vaccines.

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