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  • 51.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Meeting iron needs for infants and children2014In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 17, no 3, p. 267-272Article, review/survey (Refereed)
    Abstract [en]

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

  • 52.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Chmielewska, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Starnberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Norman, Mikael
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, p. 111-118Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 53.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Centre of Excellence for Paediatric Research EURISTIKOS, Department of Paediatrics, School of Medicine, University of Granada, Avda. De Madrid 11, 18012 Granada, Spain.
    García-Valdes, Luz
    Torres-Espinola, Francisco J.
    Segura, Maria Teresa
    Martínez-Zaldivar, Cristina
    Aguilar, Maria J.
    Agil, Ahmad
    Lorente, Jose A.
    Florido, Jesús
    Padilla, Carmen
    Altmäe, Signe
    Marcos, Acensión
    Carmen López-Sabater, M.
    Campoy, Cristina
    Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE)2016In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 16, article id 207Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 54.
    Berglund, Staffan K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Björn, Matias
    Lindberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Norman, Mikael
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Marginally low birth weight increases the risk of underweight and short stature at three and a half years of age2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 6, p. 610-617Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 55.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindberg, Josefine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Bjorn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants2014In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, no 5, p. 477-482Article in journal (Refereed)
    Abstract [en]

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

  • 56.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 390-395Article in journal (Refereed)
    Abstract [en]

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

  • 57.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    The Department of Nutrition, University of California, Davis, CA, USA.
    Westrup, Björn
    The Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 6, p. 1553-1561Article in journal (Refereed)
    Abstract [en]

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

  • 58.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Bjorn
    Department of Women and Child Health, Karolinska Institute, SE-182 88 Stockholm, Sweden.
    Haraldsson, Elisabet
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Engstrom, Berit
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation on auditory brainstem response in marginally LBW infants2011In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 6, p. 601-606Article in journal (Refereed)
    Abstract [en]

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

  • 59.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron supplements reduce the risk of iron deficiency anemia in marginally low birth weight infants2010In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 126, no 4, p. e874-e883Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 60.
    Berglund, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Division of Neonatology, Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effects of iron supplementation of LBW infants on cognition and behavior at 3 years2013In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 131, p. 47-55Article in journal (Refereed)
    Abstract [en]

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

  • 61.
    Bergström, E
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Hernell, O
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics.
    Obesity and insulin resistance in childhood and adolescence.2005In: From Preventive Nutrition: The Comprehensive Guide for Health Professionals, third ed, Humana Press Inc. Totowa, NJ , 2005, p. 293-316Chapter in book (Other academic)
  • 62.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Blomquist, Hans K Son
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Is the prevalence of overweight and obesity declining among 4-year-old Swedish children?2009In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 12, p. 1956-1958Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the trend in overweight and obesity prevalence among 4-year-old Swedish children. METHODS: Height and weight data registered at the regular health check up at the child health centres in the county of Västerbotten during the years 2007/2008 (2225 boys and 2156 girls) were analysed and compared with data from 2002/2003 (2231 boys and 2176 girls). Overweight and obesity were estimated using the International Obesity Task Force cut-off values (ISO BMI). RESULTS: In both boys and girls, overweight prevalence (ISO BMI > 25) decreased over the 5-year period, boys from 17.2% to 14.2% and girls from 22.3% to 19.0%. Among girls, there was also a decrease in obesity prevalence (ISO BMI > 30) from 5.7% to 3.1%. CONCLUSION: The result of this study indicates that the overweight and obesity epidemic among Swedish pre-school children may be levelling off.

  • 63.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Epidemiological studies of childhood diabetes and important health complications to the disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims: The overall aim of this thesis was to increase knowledge regarding the occurrence of childhood onset T1D and T2D in Sweden and in relation to that describe and elucidate important aspects on two grave complications to diabetes; end-stage renal disease (ESRD) and mortality. The two first studies included in this thesis aimed to describe and analyze the cumulative incidence of childhood onset T1D in Sweden and to assess the occurrence of undetected T2D in Swedish children. The aim with the third study was to describe the cumulative incidence of ESRD, and to analyze how ESRD risk differs with age at-onset and sex. The aim of the fourth study was to show how parental socioeconomic status (SES) affects all cause mortality in Swedish patients with childhood onset T1D.

    Study populations: The foundation for the studies on T1D was data from the Swedish Childhood Diabetes Registry (SCDR). When studying ESRD we also included adult onset T1D cases from the Diabetes Incidence Study in Sweden (DISS). The study on T2D was a population-based screening study where BMI was measured in 5528 school-children and hemoglobin A1c was measured in children with overweight according to international age and sex specific BMI cut-offs. To study ESRD and mortality, we linked the SCDR to various nationwide registers containing individual information on SES, mortality and ESRD.

    Results: The incidence rates of childhood onset T1D has continued to increase in Sweden 1977–2007. Age- and sex-specific incidence rates varied from 21.6 (95% CI 19.4–23.9) during 1978–1980 to 43.9 (95% CI 40.7– 47.3) during 2005–2007. Cumulative incidence by birth-cohorts has shifted to a younger age at-onset over the first 22 years of incidence registration. From the year 2000 there was a significant reverse in this trend (p<0.01). In contrast to the increase of T1D, we found no evidence of undetected T2D among Swedish school children. Despite a relatively high incidence in T1D in Sweden there is low cumulative incidence of ESRD, 3.3% at maximum 30 years of duration. We found difference between the sexes regarding long-term risk of developing ESRD that was dependent on the age at onset of T1D. When analyzing how socioeconomic status affects mortality in different age at death groups, we found that having parents that received income support increased mortality up to three times in those who died after 18 years of age.

    Conclusion: The incidence of childhood onset T1D continued to increase in Sweden 1978-2007. Between the years 1978-1999 there was a shift to a younger age at-onset, but from the year 2000 there is a change in this shift indicating a possible trend break. The prevalence of T2D among Swedish children up to 12 years of age is probably very low. There is still a low cumulative incidence of T1D associated ESRD in Sweden. The risk of developing ESRD depends on age at-onset of T1D, and there is a clear difference in risk between men and woman. Excess mortality among subjects with childhood onset T1D still exists, and low parental socioeconomic status additionally increased mortality in this group.

  • 64.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of parental socioeconomic status on excess mortality in subjects with childhood onset type-1 diabetesManuscript (preprint) (Other academic)
    Abstract [en]

    Aims/Hypothesis: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all cause mortality in a population based cohort of childhood onset T1D.

    Methods: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) January 1 1978 to December 31 2008 were included (n=14 409). The SCDR was linked to the Swedish Cause of Death Register (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA). SES measures (education and income support) wtypeere retrieved from the LISA for the years 1990-2010. Mortality data were retrieved from the CDR as of December 31, 2010.

    Results: At a mean follow-up of 24.4 years (maximum 47.5), 238 deaths occurred in a total of 357 048 person-years at risk. In crude analyses, low maternal education predicted mortality for male cases only (p=0.046), while parental income support predicted mortality in both sexes (p<0.001 for both). In Cox models stratified by age at death groups and adjusted for age at onset and sex, parental income support predicted mortality among young adults ( ≥18 years of age) but not for children. Including the adult patient´s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥ 24 years of age when adjusting for age at onset, sex and parental SES.

    Conclusions/Interpretation: Low parental SES, mirrored by the need of income support, increases mortality risk in childhood onset type-1 diabetics who died after the age of 18 years.

  • 65.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Högberg, Lotta
    Linköping Univ, Dept Clin & Expt Med, Div Pediat, Linköping, Sweden.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Five-region study finds no evidence of undiagnosed type 2 diabetes in Swedish 11- to 13-year-olds2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, p. 1078-1082Article in journal (Refereed)
    Abstract [en]

    AIM: Childhood obesity is now an established public health problem in most developed countries, and there is concern about a parallel increase of type 2 diabetes. The aim of this study was to estimate the prevalence of undiagnosed type 2 diabetes in overweight Swedish school children from 11 to 13 years of age.

    METHODS: Body mass index (BMI) was measured in 5528 schoolchildren in the 6th grade, from 11 to 13 years of age, in five different regions in Sweden. Overweight was defined by international age- and sex-specific BMI cut-offs, corresponding to adult BMI cut-offs of 25 kg/m(2) at 18 years of age (ISO-BMI ≥25, n = 1275). Haemoglobin A1c (HbA1c) was measured in 1126 children with ISO-BMI ≥25. Children with a Diabetes Control and Complications Trial aligned HbA1c ≥6.1% on two occasions underwent an oral glucose tolerance test (OGTT) to establish the diabetes diagnosis.

    RESULTS: Of 1126 children with ISO-BMI ≥25, 24 (2.1%) had at least one HbA1c value ≥6.1%. Three of them had HbA1c ≥6.1% on two occasions, and all of them had a normal OGTT.

    CONCLUSION: In this cross-sectional, population-based screening study of a high-risk group of 11- to 13-year-old Swedish school children, we found no indication of undiagnosed diabetes or impaired glucose tolerance.

  • 66.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Högberg, Lotta
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Screening for undiagnosed type-2 diabetes in Swedish 6th grade school childrenManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: To estimate the prevalence of undiagnosed type-2 diabetes in overweight Swedish school children 11-13 years old.

    Methods: BMI was measured in 5 528 school-children (11-13 years of age) attending the 6th grade, in five different regions in Sweden. Overweight was defined by international age-sex specific BMI cut-offs, corresponding to adult BMI cut-offs of 25 kg/m² at 18 years of age (ISO-BMI ≥25, n=1 275). Haemoglobin A1c (HbA1c) was measured in 1 126 children with ISO-BMI ≥25. Children with a DCCT-aligned HbA1c ≥ 6.1% on two occasions underwent an oral glucose-tolerance test (OGTT) to establish diabetes diagnosis.

    Results: Twenty four children (2.1%) had at least one HbA1c-value ≥6.1%. Three of them had HbA1c ≥6.1% on two occasions and all of them had a normal OGTT.

    Conclusion: In this cross-sectional population-based screening study of a high risk group of 11-13 years old Swedish school children we found no indication of undiagnosed diabetes or impaired glucose tolerance.Key

  • 67. Bhatia, Jatinder
    et al.
    Griffin, Ian
    Anderson, Diane
    Kler, Neelam
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Selected macro/micronutrient needs of the routine preterm infant2013In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 162, no 3, p. S48-S55Article in journal (Refereed)
    Abstract [en]

    Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data. (J Pediatr 2013;162:S48-55).

  • 68. Biagio, L.
    et al.
    Swanepoel, D. W.
    Laurent, Claude
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Speech-Language Pathology and Audiology, University of Pretoria, South Africa.
    Lundberg, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Paediatric otitis media at a primary healthcare clinic in South Africa2014In: SAMJ South African Medical Journal, ISSN 0256-9574, E-ISSN 2078-5135, Vol. 104, no 6, p. 431-435Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No published studies on the prevalence of paediatric otitis media at primary healthcare clinics (PHCs) in South Africa (SA) are available. OBJECTIVE: To examine the point prevalence of otitis media in a paediatric population in a PHC in Johannesburg, SA, using otomicroscopy. METHODS: A sample of 140 children aged 2 - 16 years (mean 6.4; 44.1% females) were recruited from patients attending the PHC. Otomicroscopy was completed for each of the participants' ears by a specialist otologist using a surgical microscope. RESULTS: Cerumen removal was necessary in 36.0% of participants (23.5% of ears). Otitis media with effusion was the most frequent diagnosis (16.5%). Chronic suppurative otitis media (CSOM) was diagnosed in 6.6% of children and was the most common type of otitis media in participants aged 6 - 15 years. Acute otitis media was only diagnosed in the younger 2 - 5-year age group (1.7%). Otitis media was significantly more prevalent among younger (31.4%) than older children (16.7%). CONCLUSION: CSOM prevalence, as classified by the World Health Organization, was high. Consequently diagnosis, treatment and subsequent referral protocols may need to be reviewed to prevent CSOM complications.

  • 69.
    Birkeland, Anna-Lena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Psychosocial aspects of living with congenital heart disease: child, family, and professional perspectives2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The vast majority of infants born with congenital heart disease (CHD) reach adulthood because of the developments in cardiology in recent decades. This thesis aims to describe the psychosocial situation of child/adolescent cardiac patients and their families, investigate the situation faced by parents and siblings initially and over time, investigate the approaches paediatric cardiologists use in encountering the family, and describe the teamwork occurring in paediatric cardiology teams (PCTs) in Sweden.

    Theoretical framework: The theoretical framework was based on a quality of life model applied to children, a stress-coping model, and a psychosocial approach including support, profession, and teamwork.

    Methods: The research combines quantitative data collection/analysis and qualitative research interviews/content analysis.

    Results:

    Complexity: The three grades of medical complexity differed regarding the number and severity of psychosocial symptoms, the children with the most complex CHD having the most severe symptoms. The most frequent symptoms in the whole patient group regarding various spheres were: healthcare and treatment-related needs in the external sphere, family symptoms in the interpersonal sphere, and mental/psychosomatic symptoms in the personal sphere.

    Coping: Being informed of a child’s/sibling’s heart disease has emotional consequences, so information, communication, and support are essential. Breaking the news of a child’s disease can be described as a turning point still significant after ten years. The professionalism of the doctor’s approach in breaking the news is crucial.

    Profession: Among paediatric cardiologists, how to break bad news to a family is an important concern, evident in findings regarding the significance of trust and confidence and the use of various emotional positions. Paediatric cardiologists commonly wish to be skilled at handling this situation, and attaining the needed skills calls for reflection, education, and sharing experience.

    Team: PCTs in Sweden aim and try to work in a structured way. In PCTs, there is a need for leadership, resource coordination, coaching, and a forum for joint reflection. Dependence on the physician on the team was identified in all PCTs. The challenge of managing increasing complexity at both the family and system levels requires interprofessional teams.

    Conclusions: These studies illustrate the psychosocial complexity and the need of psychosocial support. Emotional consequences, communication, information and support are essential both for the children, parents/families and for the professionals. To manage this complexity organizational alteration action plans are required. There is a need for a forum to stimulate dialogue and common reflection in the local PCT and at the regional and national centres.

  • 70.
    Birkeland, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hällgren Graneheim, Ulla
    Umeå University, Faculty of Medicine, Department of Nursing.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Dahlgren, Lars
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Facing bad news: a case study focusing on families having a child with congenital heart diseaseManuscript (preprint) (Other academic)
  • 71.
    Birkeland, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlgren, Lars
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Teamwork in Swedish paediatric cardiology: a national exploratory study examining function and dynamicsManuscript (preprint) (Other academic)
  • 72.
    Birkeland, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    The complexity of the psychosocial situation in children and adolescents with heart disease2005In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 94, no 10, p. 1495-1501Article in journal (Refereed)
    Abstract [en]

    Aim: To describe the psychosocial situation of children/adolescents with heart disease and their families, an inventory method was worked out.

    Methods: Ninety-seven children/adolescents with congenital heart disease (CHD) were graded into three categories with respect to complexity of CHD. Group I included 42 patients with malformations requiring standardized operations. Group II included 20 patients with more complicated malformations, and group III included 35 patients with very complex malformations. The patients were compared with controls without heart disease, matched for age and gender. The psychosocial impact of CHD was measured by the inventory.

    Results: The most frequent problems in the patient group were healthcare and treatment-related needs (71/97) in the external sphere, family symptoms (68/97) in the interpersonal sphere, and somatic symptoms (19/97) in the personal sphere. Corresponding numbers in the controls were treatment-related needs (15/97), family (9/97) and somatic symptoms (25/97). Fifty per cent of the symptoms in the patient groups were mild, 30% moderate and 20% severe. The most severe symptoms were found in the interpersonal sphere, where family symptoms constituted the most severe variable. The frequency of severe problems in the personal sphere was 11% in the patients and 1% in the controls. This inventory method differentiates the grades of medical complexity both regarding number and severity of psychosocial symptoms. It indicates severe personal problems in the most complex group and shows that they have severe personal problems independent of family problems.

    Conclusion: This study elucidates the psychosocial complexity in children/adolescents with CHD, which has clinical implications in developing a psychosocial care programme.

  • 73.
    Bjerg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berthold, Malin
    Mattsson, Lars
    Borres, Magnus P
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
    A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren2015In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 6, p. 557-563Article in journal (Refereed)
    Abstract [en]

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

  • 74.
    Blind, Per Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Carboxylic ester hydrolase in acute pancreatitis: a clinical and experimental study1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diagnosis of acute pancreatitis (AP) is erroneous in up to one third of patients when based on clinical criteria and elevated serum amylase values. Furthermore, according to autopsy reports fatal pancreatitis remains clinically undiagnosed in 22 to 86 % of hospitalised patients. Consequently, search for better methods for the diagnosis of AP seems not only justified but urgent. The pancreas secretes an nonspecific lipase, the carboxylic ester hydrolase (CEH) with molecular properties different from other pancreatic secretory enzymes. These differences may imply that sites and rates of clearances from blood of pancreatic enzymes differ. Except for the pancreas this enzyme is secreted from the lactating mammary gland with milk.

    A sensitive and reproducible sandwich-ELISA for quantitative determination of CEH was developed. When establishing referent values it was noted that in individuals aged 20 to 65 years serum concentrations of CEH did not depend on age, gender, the time of the day or duration from food intake to blood sampling, or use of nicotine. The mammary gland did not contribute significantly to basal serum levels of CEH; enzyme levels in lactating women or women with mammary tumours were identical to those of the reference population.

    Seventy percent of patients with the diagnosis AP, based on elevated serum amylase levels and abdominal pain, had elevated CEH values. Among the patients with elevated amylase alone a probable cause of pancreatitis was lacking in the majority of patients. Contrastingly, a likely cause of AP could be identified in all patients presenting with abdominal pain and elevated CEH levels alone. These findings suggested that an elevated CEH level indicated AP more reliably than an elevated amylase level.

    In patients with AP diagnosed by contrast enhanced computed tomography (CECT) alone, or combined with histopathological diagnosis, serum CEH levels were elevated on admission in all but one patient, and in all within the next 24 h. Furthermore, in patients with severe pancreatitis CEH levels remained at a raised level from the second to at least the 10:th day following admission, whereas a significant decrease was noted in patients with mild pancreatitis. In contrast, serum amylase values were higher in patients with mild pancreatitis during the observation period than in those with severe pancreatitis. CEH levels were higher in patients with three or more Ranson signs than in those with less than three signs from the first day after admission. CEH levels were within referent range in 164 patients without known pancreatic disease admitted due to abdominal emergency conditions, or due to planned surgery for chronic extrapancreatic gastrointestinal diseases, and 16 patients having CECT without pathological findings in the pancreas. This suggests that AP can be excluded with very high degree of probability in presence of non-elevated CEH levels.

    A sandwich ELISA for determination of Guinea pig CEH and a model for graded pancreatitis in the same species were developed. CEH levels showed proportional to severity of inflammation, thus confirming previous clinical observations. CEH levels in bile were proportional to inflammation, while it was absent in urine. Amylase levels in urine were identical regardless of severity of inflammation, but low in bile. These results suggested differences in sites and rates of clearance between the two enzymes.

    Seemingly elevated CEH levels allowed identification of clinically significant pancreatitis following ERCP, which amylase levels did not.

    The presented studies have shown that quantitative determination in serum of CEH by the described method is a more reliable test for the diagnosis of AP than determination of amylase activity. The differences between CEH and amylase are, at least partly, due to differences in molecular properties determining rates and routes of clearances of the two enzymes from serum.

  • 75. Bolk, Jenny
    et al.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hafstrom, Maria
    Aden, Ulrika
    Serenius, F.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Developmental Coordination Disorder and Its Association With Developmental Comorbidities at 6.5 Years in Apparently Healthy Children Born Extremely Preterm2018In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 172, no 8, p. 765-774Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE There are concerns that apparently healthy extremely preterm children face a risk of developing motor impairments, such as developmental coordination disorder. OBJECTIVE To evaluate the prevalence of developmental coordination disorder and associated comorbidities in a national cohort of apparently healthy children born at 22 to 26 gestational weeks, compared alongside term-born peers. DESIGN, SETTING, AND PARTICIPANTS This prospective, population-based cohort study included all children who were consecutively born at 22 to 26 gestational weeks in Sweden from April 1, 2004, through March 31, 2007. At 6.5 years, 441 preterm children were evaluated alongside 371 controls. A total of 275 preterm children (62.4%) and 359 term-born children (96.8%) did not have neurodevelopmental disabilities. Motor assessments were completed for 229 of 275 preterm children (83.3%) and 344 of 359 (95.8%) term-born children, who composed the final study sample. MAIN OUTCOMES AND MEASURES Developmental coordination disorder was defined as a score of the fifth percentile or lower on the Movement Assessment Battery for Children-Second Edition scale, using control group scores. Assessment tools included the Wechsler Intelligence Scale for Children-Fourth Edition, the Brown Attention-Deficit Disorder Scales, the Five to Fifteen questionnaire, and the Strengths and Difficulties questionnaire. RESULTS Of the 229 extremely preterm children and 344 term-born controls who underwent motor assessments, 115 (50.2%) and 194 (56.4%) were boys, respectively. Developmental coordination disorder was present in 85 of 229 (37.1%) preterm children and in 19 of 344 controls (5.5%) (adjusted odds ratio [OR], 7.92; 99% CI, 3.69-17.20). When preterm children with developmental coordination disorder were compared with term-born peers, the risk was increased for total behavioral problems, internalizing, externalizing, attentional problems, hyperactivity, perceptual problems, executive dysfunction, and poor social skills, with adjusted ORs varying from 2.66 (99% CI, 1.09-6.48) for time concepts to 9.06 (99% CI, 3.60-22.8) for attentional problems (all P < .01). When preterm children with and without developmental coordination disorder were compared, preterm children with developmental coordination disorder had more behavioral problems; the adjusted OR for total behavioral problems was 2.71 (99% CI, 1.15-6.37); for externalizing problems, 2.80 (99% CI, 1.10-7.12); for inattention, 3.38 (99% CI, 1.39-8.18); and for combined attention/hyperactivity problems, 3.68 (99% CI, 1.47-9.16) (all P < .01). Parents underestimated the children's motor problems and only a few of the children had received psychological care or physiotherapy. CONCLUSIONS AND RELEVANCE Children who were born extremely preterm faced a high risk for developmental coordination disorder with associated comorbidities. Our findings support the importance of a structured follow-up of motor function, behavior, and cognition. 

  • 76. Bolk, Jenny
    et al.
    Kaul, Ylva Fredriksson
    Hellstrom-Westas, Lena
    Stjernqvist, Karin
    Padilla, Nelly
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Uppsala University Hospital, Uppsala, Sweden.
    Hellgren, Kerstin
    Aden, Ulrika
    National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 831-837Article in journal (Refereed)
    Abstract [en]

    Aim: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. Methods: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). Results: The mean (SD) VMI score was 87 (+/- 12) in preterm children compared to 98 (+/- 11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. Conclusion: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

  • 77. Bonamy, Anna-Karin Edstedt
    et al.
    Mohlkert, Lilly-Ann
    Hallberg, Jenny
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Blood Pressure in 6-Year-Old Children Born Extremely Preterm2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 8, article id e005858Article in journal (Refereed)
    Abstract [en]

    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

  • 78. Bonamy, Anna-Karin Edstedt
    et al.
    Stjernqvist, Karin
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    [Extremely premature infants could be a new risk group in adult care].2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 42, p. 2548-2552Article in journal (Refereed)
  • 79.
    Borssen, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Lars
    Karrman, Kristina
    Abrahamsson, Jonas
    Behrendtz, Mikael
    Heldrup, Jesper
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e65373-Article in journal (Refereed)
    Abstract [en]

    Background: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided.

    Design and Methods: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32).

    Results: Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP- (low methylation). CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes.

    Conclusions: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

  • 80.
    Borssén, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    DNA methylation as a prognostic marker i acute lymphoblastic leukemia2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Most ALL cases originate from immature B-cells (BCP-ALL) and are characterized by reoccurring structural genetic aberrations. These aberrations hold information of the pathogenesis of ALL and are used for risk stratification in treatment. Despite increased knowledge of genetic aberrations in pediatric T-cell ALL (T-ALL), no reliable molecular genetic markers exist for identifying patients with higher risk of relapse. The lack of molecular prognostic markers is also evident in patients with relapsed ALL. During the last decades, aberrant epigenetic mechanisms including DNA methylation have emerged as important components in cancer development. Telomere maintenance is another important factor in malignant transformation and is crucial for long-term cell survival. Like DNA methylation, telomere length maintenance has also been implicated to reflect outcomes for patients with leukemia.

    In this thesis, the prognostic relevance of DNA methylation and telomere length was investigated in pediatric ALL at diagnosis and relapse. The telomere length (TL) was significantly shorter in diagnostic ALL samples compared to normal bone marrow samples collected at cessation of therapy, reflecting the proliferation associated telomere length shortening. Prognostic relevance of TL was shown in low-risk BCP-ALL patients where longer telomeres at diagnosis were associated with higher risk of relapse.

    Genome-wide methylation characterization by arrays in diagnostic T-ALL samples identified two distinct methylation subgroups denoted CIMP+ (CpG Island Methylator Phenotype high) and CIMP- (low). CIMP- T-ALL patients had significantly worse outcome compared to CIMP+ cases. These results were confirmed in a Nordic cohort treated according to the current NOPHO-ALL2008 protocol.  By combining minimal residual disease (MRD) status at treatment day 29 and CIMP status at diagnosis we could further separate T-ALL patients into risk groups.

    Likewise, the CIMP profile could separate relapsed BCP-ALL patients into risk groups, where the CIMP- cases had a significantly worse outcome compared to CIMP+ cases.  From these data we conclude that DNA methylation subgrouping is a promising prognostic marker in T-ALL, as well as in relapsed BCP-ALL two groups where reliable prognostic markers are currently missing. By elucidating the biology behind the different CIMP profiles, the pathogenesis of ALL will be further understood and may contribute to new treatment strategies.

  • 81.
    Borssén, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haider, Zahra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Norén-Nyström, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schmiegelow, Kjeld
    Åsberg, Ann E.
    Kanerva, Jukka
    Madsen, Hans O.
    Marquart, Hanne
    Heyman, Mats
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Department of Paediatrics, University Hospital of Trondheim, Norway.
    DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia2016In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, no 7, p. 1185-1192Article in journal (Refereed)
    Abstract [en]

    Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.

  • 82. Braegger, Christian
    et al.
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellof, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Vitamin D in the Healthy European Paediatric Population2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 6, p. 692-701Article in journal (Refereed)
    Abstract [en]

    In recent years, reports suggesting a resurgence of vitamin D deficiency in the Western world, combined with various proposed health benefits for vitamin D supplementation, have resulted in increased interest from health care professionals, the media, and the public. The aim of this position paper is to summarise the published data on vitamin D intake and prevalence of vitamin D deficiency in the healthy European paediatric population, to discuss the health benefits of vitamin D and to provide recommendations for the prevention of vitamin D deficiency in this population. Vitamin D plays a key role in calcium and phosphate metabolism and is essential for bone health. There is insufficient evidence from interventional studies to support vitamin D supplementation for other health benefits in infants, children, and adolescents. The pragmatic use of a serum concentration >50 nmol/L to indicate sufficiency and a serum concentration <25 nmol/L to indicate severe deficiency is recommended. Vitamin D deficiency occurs commonly among healthy European infants, children, and adolescents, especially in certain risk groups, including breast-fed infants, not adhering to the present recommendation for vitamin D supplementation, children and adolescents with dark skin living in northern countries, children and adolescents without adequate sun exposure, and obese children. Infants should receive an oral supplementation of 400 IU/day of vitamin D. The implementation should be promoted and supervised by paediatricians and other health care professionals. Healthy children and adolescents should be encouraged to follow a healthy lifestyle associated with a normal body mass index, including a varied diet with vitamin D-containing foods (fish, eggs, dairy products) and adequate outdoor activities with associated sun exposure. For children in risk groups identified above, an oral supplementation of vitamin D must be considered beyond 1 year of age. National authorities should adopt policies aimed at improving vitamin D status using measures such as dietary recommendations, food fortification, vitamin D supplementation, and judicious sun exposure, depending on local circumstances.

  • 83. Bronsky, Jiri
    et al.
    Campoy, Cristina
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Nataša Fidler
    Gerasimidis, Konstantinos
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Moltu, Sissel Jennifer
    Verduci, Elvira
    Vora, Rakesh
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition2019In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 68, no 5, p. 742-760Article in journal (Refereed)
    Abstract [en]

    Background: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. Methods: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. Results: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. Conclusions: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.

  • 84.
    Browaldh, Lars
    et al.
    Sachsska barnsjukhuset, Södersjukhuset, Stockholm.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Agardh, Daniel
    barnmedicinska kliniken Malmö och Lund, Skånes universitetssjukhus.
    Stenhammar, Lars
    Vrinnevisjukhuset, Norrköping.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Celiaki är en vanlig sjukdom som är lätt att missa2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 11, p. 484-488Article in journal (Refereed)
    Abstract [sv]

    Celiaki ansågs länge som en ovanlig barnsjukdom, men är en vanlig sjukdom som drabbar alla åldrar.  Genomförda screeningar av normalbefolkningen visar att merparten inte fått dia­gnos eller behandling. Den kliniska bilden varierar: alltifrån diffusa besvär eller inga symtom alls till allvarliga gastrointestinala symtom med grav avmagring och tillväxtrubbning till följd av malabsorption. Klinisk misstanke om eller hereditet för celiaki bör föranleda analys av specifika serologiska markörer. Gastroskopi med tunntarmsbiopsi bör övervägas för att bekräfta eller utesluta diagnosen.

  • 85.
    Bruce, Elisabeth
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Institutionen för omvårdnad i Örnsköldsvik.
    Lilja, Catrine
    Umeå University, Faculty of Medicine, Department of Nursing. Institutionen för omvårdnad i Örnsköldsvik.
    Sundin, Karin
    Umeå University, Faculty of Medicine, Department of Nursing. Institutionen för omvårdnad i Örnsköldsvik.
    Mothers' lived experiences of support when living with young children with congenital heart defects2014In: Journal for specialists in pediatric nursing, ISSN 1744-6155, 1539-0136, Vol. 19, no 1, p. 54-67Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to illuminate the meanings of support as disclosed by mothers of children with congenital heart defects (CHD).

    DESIGN AND METHOD: Narrative interviews were conducted with 10 mothers of children with CHD. A phenomenological-hermeneutic method was used for interpretation of the transcribed interviews.

    RESULTS: The comprehensive understanding of mothers' lived experiences of support emerged as the experiences of receiving good support, receiving "poor support," and absence of support.

    PRACTICE IMPLICATIONS: Mothers receiving person-centered and family-centered care feel more supported and are more likely to adapt to the stresses of parenting a child with CHD.

  • 86. Bruck, Wolfram M
    et al.
    Redgrave, Michele
    Tuohy, Kieran M
    Lönnerdal, Bo
    Graverholt, Gitte
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gibson, Glenn R
    Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants2006In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 43, no 5, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Objective: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived healthpromoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, a-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study.

    Patients and Methods: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-Jac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation.

    Results: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a. predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora.

    Conclusions: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed).

  • 87.
    Brugård Konde, Åsa
    et al.
    Livsmedelsverket.
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Mat för spädbarn 0-1 år2012In: Barnläkaren, ISSN 1651-0534, no 5, p. 6-8Article in journal (Other academic)
  • 88.
    Brånalt, Jens
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Pulmonary function in children with congenital diaphragmatic hernia at the age of seven.2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 89. Burström, Åsa
    et al.
    Bratt, Ewa-Lena
    Frenckner, Björn
    Nisell, Margret
    Hanséus, Katarina
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öjmyr-Joelsson, Maria
    Adolescents with congenital heart disease: their opinions about the preparation for transfer to adult care2017In: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 176, no 7, p. 881-889Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to explore what adolescents with congenital heart disease (CHD) view as important in the preparation for the transfer to adult care. We performed interviews in four focus groups with adolescents (14-18 years old) at four university hospitals in Sweden. Data was analysed using qualitative content analysis. The analysis revealed one main category; Becoming a manager of the condition and four subcategories; Sufficient knowledge about the health, Be a participant in the care, Parental support, and Communicate with others about the health. The adolescents' ages differentiated the discussion in the groups. The older adolescents seemed to have more interest in transition planning, information and transfer. The younger described more frustrations about communication and handling the disease. Conclusion: To become a manager of the CHD in daily life, the adolescents want disease specific knowledge, which should be communicated in a developmentally appropriate way. Adolescents want to participate and be involved in the transition process. They need support and guidance in how to communicate their CHD. Parental support is fundamental but it change over time. Moreover, peer-support is becoming more significant during the transition process.

  • 90.
    Buttner, Barbara E.
    et al.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Witthoft, Cornelia M.
    Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Effect of type of heat treatment of breastmilk on folate content and pattern2014In: Breastfeeding medicine, ISSN 1556-8253, Vol. 9, no 2, p. 86-91Article in journal (Refereed)
    Abstract [en]

    Background: Breastmilk is the recommended aliment for preterm infants. Milk banks provide donated breastmilk for the neonatal care of preterm infants when mother's own milk is not is available. To avoid pathogen transmission, donated breastmilk is heat-treated according to different procedures before administration. There is varying information on the effect of heat treatment on folate in breastmilk. Sufficient folate intake, however, is essential for normal growth and brain development. This study determined and compared the effects of different heat treatments on breastmilk folate content and pattern of individual folate forms. Materials and Methods: Donated Swedish breastmilk samples were heat-treated according to three procedures: two low temperature treatments (57 degrees C, 23 minutes; 62.5 degrees C, 12 minutes) and a rapid high temperature treatment (heating to 73 degrees C in boiling water). The folate content and pattern were determined before and after treatment by high-performance liquid chromatography. Results: The folate content in 38 untreated Swedish breastmilk samples was 15046nmol/L. Two different folate vitamers were detected: 5-methyltetrahydrofolate (78 +/- 7%) and tetrahydrofolate (22 +/- 7%). Heat treatment affected only tetrahydrofolate stability and decreased folate content by 15-24%; however, the effects on folate content did not differ among the investigated heat treatment procedures. Conclusions: Folate losses during heat treatment of human milk were considered acceptable. Yet, native folate content of heat-treated, non-fortified breastmilk supplied only 25% of the recommended daily intake for preterm infants.

  • 91.
    Bäcklund, Catharina
    et al.
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Larsson, Christel
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Problems in enhancing physical activity among overweight and obese children2010Conference paper (Refereed)
    Abstract [en]

    Introduction: Physical inactivity is regarded as one of the main factors that have contributed to the rapid increase in prevalence of childhood obesity in recent decades. The aim of this study was to evaluate whether participation in a family-based multifactor intervention program could increase physical activity among overweight and obese children.

    Methods: 105 children, mean age 10.5 years (SD±1.09), with overweight and obesity living in northern Sweden were recruited and randomized into an intervention or control group. The intervention group was invited to participate in a program aiming at improving lifestyle regarding food habits and physical activity. The children’s physical activity was measured during 4 days at baseline and after 1 year with SenseWear Armband.

    Results: There were no statistically significant differences between the groups neither at either baseline or 1 year, regarding energy expenditure, steps/day, time being sedentary (< 3 MET), and time being active at different MET-levels. For all children, time being active ≥ 3 MET significantly decreased with 44.5 (111) min/d from baseline to 1-year. Despite the decrease in physical activity, the children were physically active ≥ 3 MET during 4.1 (1.6) h/d at 1-year.

    Conclusion: Physical activity decreased with increased age among overweight and obese children, despite extensive effort of intervention. To make future interventions worthwhile it is important to consider the participant’s physical activity level before entering the study, when planning and setting up the intervention program; to comprise the participant’s individual goals regarding physical activity; and to focus specifically on decreasing time being sedentary.

  • 92. Böttcher, Malin
    et al.
    Norin, Elisabeth
    Sandin, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Midtvedt, Tore
    Björkstén, Bengt
    Microflora-associated characteristics in faeces from allergic and nonallergic infants2000In: Clinical and experimental allergy, Vol. 30, no 11, p. 1591-1596Article in journal (Refereed)
  • 93. Candy, David C. A.
    et al.
    Van Ampting, Marleen T. J.
    Nijhuis, Manon M. Oude
    Wopereis, Harm
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Fox, Adam T.
    Shah, Neil
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Garssen, Johan
    Harthoorn, Lucien F.
    Knol, Jan
    Michaelis, Louise J.
    A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, no 3, p. 677-686Article in journal (Refereed)
    Abstract [en]

    Background: Prebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow’s milk allergy (CMA).

    Methods: This multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.

    Results: A total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.

    Conclusion: AAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.

  • 94. Carlsson, Goran
    et al.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordenskjold, Magnus
    Henter, Jan-Inge
    Fadeel, Bengt
    Ovarian failure in HAX1-deficient patients: is there a gender-specific difference in pubertal development in severe congenital neutropenia or Kostmann disease?2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 1, p. 78-82Article in journal (Refereed)
    Abstract [en]

    Aim Severe congenital neutropenia (SCN) is a rare disorder of myelopoiesis characterized by neutropenia, recurrent bacterial infections and a maturation arrest of the myelopoiesis in the bone marrow. Homozygous mutations in the HAX1 gene were described in patients with autosomal recessive SCN or Kostmann disease. Some of these patients display neurological disease. We noted, during the course of clinical management of patients with Kostmann disease, insufficient pubertal development in female patients, but not in our male patients. The study objective was to provide a detailed account of this phenotype and its possible relation to HAX1 mutations. Methods Detailed clinical histories and laboratory investigations of three patients with Kostmann disease belonging to the original kindred in northern Sweden described by Rolf Kostmann are reported. Results We report one male patient with normal puberty and two female patients with insufficient pubertal development. Elevated levels of LH and FSH were recorded in both patients. All three patients harbour the same p.Glu190X mutation in the HAX1 gene. Conclusions We show for the first time that female patients with Kostmann disease display primary gonadal insufficiency. This suggests a possible role for HAX1 in the development and/or function of the human ovary.

  • 95.
    Carlsson, R. M.
    et al.
    Göteborg, Sweden; Public Health Agency of Sweden, Sweden.
    Gustafsson, L.
    Public Health Agency of Sweden, Sweden.
    Hallander, H. O.
    Public Health Agency of Sweden, Sweden.
    Ljungman, M.
    Public Health Agency of Sweden, Sweden.
    Olin, P.
    Public Health Agency of Sweden, Sweden.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Public Health Agency of Sweden, Sweden.
    Nilsson, L.
    Public Health Agency of Sweden, Sweden; Linköping, Sweden.
    Netterlid, E.
    Public Health Agency of Sweden, Sweden; Malmö, Sweden.
    Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years2015In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 33, no 31, p. 3717-3725Article in journal (Refereed)
    Abstract [en]

    Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.

  • 96.
    Carlsson, Sofia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gut motility and early stooling pattern in relation to development of necrotising enterocolitis in preterm infants2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 97. Casper, Charlotte
    et al.
    Hascoet, Jean-Michel
    Ertl, Tibor
    Gadzinowski, Janusz S.
    Carnielli, Virgilio
    Rigo, Jacques
    Lapillonne, Alexandre
    Couce, Maria L.
    Vagero, Marten
    Palmgren, Ingrid
    Timdahl, Kristina
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0156071Article in journal (Refereed)
    Abstract [en]

    Introduction Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. Patients and Methods LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. Results In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. Conclusions Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants.

  • 98.
    Challis, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Larsson, Linn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Serenius, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Elfvin, Anders
    Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 5, p. 835-841Article in journal (Refereed)
    Abstract [en]

    Aim: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS)

    Methods: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004–2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC.

    Results: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%.

    Conclusion: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

  • 99.
    Chaplin, John Eric
    et al.
    Gothenburg.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jonsson, Björn
    Uppsala.
    Tuvemo, Torsten
    Uppsala.
    Albertsson-Wikland, Kerstin
    Gothenburg .
    Growth Hormone Treatment Improves Cognitive Function in Short Children with Growth Hormone Deficiency2015In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 83, no 6, p. 390-399Article in journal (Refereed)
    Abstract [en]

    Background/Aims: We investigated the association between cognition and growth hormone (GH) status and GH treatment in short prepubertal children with broadly ranging GH secretion. Methods: A total of 99 children (age 3-11 years), 41 with GH deficiency (GHD) and 58 with idiopathic short stature (ISS), were randomized to a fixed dose (43 mu g/kg/day) or a prediction model-guided individualized dose (17-100 mu g/kg/day) and followed up for 24 months. In a longitudinal and mixed within-and between-subjects study, we examined clinical effect size changes, measured by Cohen's d, in full-scale IQ (FSIQ) and secondary IQ indices. Results: Significant increases giving medium effect size in FSIQ (p = 0.001, Cohen's d = 0.63), performance IQ (p = 0.001, Cohen's d = 0.65) and processing speed (p = 0.005, Cohen's d = 0.71) were found in the GH-deficient group. In contrast, perceptual organization only increased in the ISS group (p = 0.001, Cohen's d = 0.53). Baseline IQ was normally distributed with small but significant differences between the groups: GH-deficient children had lower FSIQ (p = 0.042) and lower performance IQ (p = 0.021). Using multiple regression analysis, 40% of the variance in delta processing speed scores (0-24 months) was explained by GH(max) and IGF-I-SDS at baseline. Conclusion: IQ, specifically fluid intelligence, increased in the GH-deficient children. The pretreatment status of the GH/IGF-I axis was significantly predictive for these changes. (C) 2015 S. Karger AG, Basel

  • 100.
    Charisopoulou, Dafni
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    Koulaouzidis, George
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Molecular & Clinical Sciences Research Institute, St George University, London, UK.
    Abnormal ventricular repolarization in long QT syndrome carriers is related to short left ventricular filling time and attenuated stroke volume response during exercise2018In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 35, no 8, p. 1116-1123Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Long QT syndrome (LQTS) carriers are characterized by abnormal ventricular repolarization, prolonged systole, and mechanical dispersion. Prolonged left ventricular (LV) systole has been shown to result in disproportionate shortening of LV filling in other conditions. The aim of this study was to assess LV filling, diastolic function, and stroke volume (SV) response to dynamic exercise, in a group of LQTS carriers.

    METHODS: Forty-seven LQTS carriers (45 ± 15 years, 20 symptomatic) and 35 healthy individuals underwent bicycle stress echocardiogram. Electrocardiographic and echocardiographic measurements were obtained at rest, peak exercise, and 4 minutes into recovery.

    RESULTS: Long QT syndrome carriers and controls did not differ in age, gender, heart rate, QRS duration, or LV ejection fraction. At rest, LQTS carriers had longer QTc and shorter filling time (FT). At peak exercise, QTc increased and remained longer than controls at recovery. A negative correlation was found between QTc and FT (r = -.398, P = .001) with greater fall in FT in LQTS carriers than in controls at peak exercise (-23% ± 10 vs +2% ± 3, P < .0001). FT correlated with SV (r = +.27, P = .001), which increased more in controls than in LQTS carriers (+32% ± 4 vs +2% ± 1, P < .05). These differences were more pronounced in symptomatic LQTS carriers who had shorter FT and smaller SV at peak exercise and during recovery compared to asymptomatics (P < .05).

    CONCLUSIONS: Long QT syndrome carriers have longer QTc, but also shorter FT. These disturbances worsen at peak exercise (particularly in symptomatics) compromising LV filling and SV, hence a potential pathomechanism for adverse events.

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