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  • 501. Torres-Espinola, Francisco J
    et al.
    Berglund, Staffan K
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    García-Valdés, Luz M
    Segura, M Teresa
    Jerez, Antonio
    Campos, Daniel
    Moreno-Torres, Rosario
    Rueda, Ricardo
    Catena, Andrés
    Peréz-García, Miguel
    Campoy, Cristina
    Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age: A Follow Up from the PREOBE Cohort2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0133010Article in journal (Refereed)
    Abstract [en]

    Background: Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring. Objective: The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life. Design This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment. Results: At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the off-spring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups. Conclusions: Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.

  • 502. Turck, Dominique
    et al.
    Michaelsen, Kim F.
    Shamir, Raanan
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Kolacek, Sanja
    Mihatsch, Walter
    Moreno, Luis A.
    van Goudoever, Johannes
    World Health Organization 2006 Child Growth Standards and 2007 Growth Reference Charts: A Discussion Paper by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 2, p. 258-264Article in journal (Refereed)
    Abstract [en]

    Growth charts are essential for evaluating children's health including their nutrition; however, the evaluation of child growth trajectories and consequently the decision to intervene are highly dependent on the growth charts used. The aim of this discussion paper of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition is to provide information on the background and rationale of the World Health Organization (WHO) 2006 child growth standards and WHO 2007 growth reference charts, describe their development, outline their main innovative aspects, discuss potential limitations, and make recommendations. WHO 2006 child growth standards (0-5 years) are based on prospectively collected data describing the growth of healthy infants who were breast-fed according to WHO recommendations, showing a pattern of linear growth, which is remarkably consistent between different countries and ethnic groups. WHO 2007 growth reference charts (5-19 years) are based mainly on a re-analysis of National Centre for Health Statistics data from 1977, without information on feeding. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recommends that WHO child growth standards should be used to monitor growth in all children in the age range 0 to 2 years in Europe, whether breast- or formula-fed, and that they should be considered to be used in the age range 2 to 5 years. Implementation of the WHO child growth standards should be preceded by evaluation of the implication of their use on national healthcare policies. Health professionals should be guided on their use and interpretation and an adequate communication strategy should be available locally to ensure that parents receive clear and consistent advice. The decision on whether to implement the WHO growth references (5-19 years) should be made by national bodies because the growth pattern during the 5- to 19-year period differs between populations.

  • 503.
    Tärnvik, Arne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Sundqvist, G
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gustafsson, H
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Meningitis caused by Fusobacterium necrophorum.1986In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 5, no 3, p. 353-355Article in journal (Refereed)
  • 504.
    Törnell, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ekeus, C.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Thunberg, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Högberg, U.
    Low Apgar score, neonatal encephalopathy and epidural analgesia during labour: a Swedish registry-based study2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 4, p. 486-495Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Maternal intrapartum fever (MF) is associated with neonatal sequelae, and women in labour who receive epidural analgesia (EA) are more likely to develop hyperthermia. The aims of this study were to investigate if EA and/or a diagnosis of MF were associated to adverse neonatal outcomes at a population level. METHODS: Population-based register study with data from the Swedish Birth Register and the Swedish National Patient Register, including all nulliparae (n = 294,329) with singleton pregnancies who gave birth at term in Sweden 1999-2008. Neonatal outcomes analysed were Apgar score (AS) < 7 at 5 min and ICD-10 diagnosis of neonatal encephalopathy (e.g. convulsions or neonatal cerebral ischaemia). Multivariate logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: EA was used in 44% of the deliveries. Low AS or encephalopathy was found in 1.26% and 0.39% of the children in the EA group compared with 0.80% and 0.29% in the control group. In multivariate analysis, EA was associated with increased risk with low AS, AOR 1.27 (95% CI 1.16-1.39), but not with diagnosis of encephalopathy, 1.11 (0.96-1.29). A diagnosis of MF was associated with increased risk for both low AS, 2.27 (1.71-3.02), and of neonatal encephalopathy, 1.97 (1.19-3.26). CONCLUSION: Diagnosis of MF was associated with low AS and neonatal encephalopathy, whereas EA was only associated with low AS and not with neonatal encephalopathy. The found associations might be a result of confounding by indication, which is difficult to assess in a registry-based population study.

  • 505. Udo, Camilla
    et al.
    Kreicbergs, Ulrika
    Axelsson, Bertil
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Unit of Clinical Research Centre‐Östersund.
    Björk, Olle
    Lövgren, Malin
    Physicians working in oncology identified challenges and factors that facilitated communication with families when children could not be cured2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 12, p. 2285-2291Article in journal (Refereed)
    Abstract [en]

    Aim: We explored physicians' experiences of communicating with families when their child had cancer and a cure was no longer an option, by focusing on barriers and facilitating factors.

    Methods: Physicians from the six cancer centres in Sweden took part in focus group discussions between December 2017 and May 2018, and the data were analysed using qualitative content analysis. Focus groups enabled us to gather individual and shared perspectives.

    Results: The 35 physicians (20 male) had a mean age of 47 (range 31-74) and a mean of 11 years' experience in oncology, ranging from under one year to 43 years. They reported communication challenges when a cure was not possible, namely: emotional and mental drain, lack of mutual understanding and uncertainty about communication skills. They also reported facilitating factors: flexibility in complex conversations, the child's position in the conversations, continuity and trusting relationships, support from colleagues and having discussed the potentially life-threatening nature of cancer from the very start of treatment.

    Conclusion: Training to overcome communication issues could support the early integration of palliative care.

  • 506.
    Uggla, C.
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    IMPACT-III is a valid and reliable questionnaire for assessing health-related quality of life in Swedish children with inflammatory bowel disease2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 2, p. 347-353Article in journal (Refereed)
    Abstract [en]

    Aim: This study examined the reliability, validity and factor structure of the Swedish version of the IMPACT-III questionnaire for assessing health-related quality of life in children with inflammatory bowel disease.

    Methods: We recruited 202 participants aged eight to 18years, who were enrolled from 16 of the 23 paediatric gastroenterology clinics across Sweden during 2010-2013. This cross-sectional study compared two versions of the IMPACT-III questionnaire - one with six factors and 35 items and one with four factors and 19 items - plus the Paediatric Quality of Life Inventory 4.0 Generic Core Scale. Disease activity was assessed and defined as active or inactive.

    Results: The mean total score for the six-factor IMPACT-III scale was 143.7/175, with a standard deviation (SD) of 17.9. There was a significant difference in mean total scores between the 133 children with inactive disease (147.8, SD: 14.9) and the 52 with active disease (133.0, SD: 20.3). Confirmatory factor analysis showed that the four-factor scale was more robust than the original six-factor scale. Concurrent validity and discriminant validity were high for both versions.

    Conclusion: The Swedish version of the IMPACT-III questionnaire was valid and reliable, but the shorter, four-factor version is quicker and may be more convenient in clinical settings.

  • 507. Uijterschout, L
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Abbink, M
    Berglund, Staffan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    van Veen, I
    Vos, P
    Rövekamp, L
    Boersma, B
    Hudig, C
    Vos, R
    van Goudoever, J B
    Brus, F
    Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age2015In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 69, no 5, p. 598-602Article in journal (Refereed)
    Abstract [en]

    Background/objectives: Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life.

    Subjects/methods: In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation.Results:ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week.

    Conclusions: Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

  • 508. Uijterschout, Lieke
    et al.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Berglund, Staffan K
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Abbink, Micky
    Vos, Paul
    Rövekamp, Lyanne
    Boersma, Bart
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hudig, Cisca
    van Goudoever, Johannes B
    Brus, Frank
    Serum hepcidin in infants born after 32 to 37 wk of gestational age2016In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 79, no 4, p. 608-613Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additional indicator of ID in preterm infants, next to ferritin.

    METHODS: In a prospective observational study, we analyzed serum hepcidin in 111 infants born after 32+0 to 36+6 wk gestational age during the first 4 mo of life.

    RESULTS: Hepcidin concentrations decreased during the first 4 mo of life, and concentrations were lower in infants with ID compared to those without ID. Infants who developed ID at the age of 4 mo had already significantly lower levels of hepcidin at 1.5 mo of age, while ferritin was already significantly lower at the age of 1 wk.

    CONCLUSION: Hepcidin concentrations of late preterm infants decrease during the first 4 mo of life. This decrease, which parallels a decrease of ferritin concentration, we interpret as a physiological response, aiming to increase iron availability. Hepcidin concentrations are lower in infants with ID compared with those without ID, with a notable change already observed at 1.5 mo of age. Hepcidin can be used as an early marker of ID, although an additive value of hepcidin over ferritin in the diagnosis of ID is not present.

  • 509. Uljterschout, Lieke
    et al.
    Swinkels, Dorine W.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hudig, Cisca
    Tjalsma, Harrold
    Vos, Rimke
    van Goudoever, Johannes B.
    Brus, Frank
    Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y2014In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, no 4, p. 409-414Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation. METHODS: We included 400 healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.

  • 510.
    Vaezghasemi, Masoud
    et al.
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Eurenius, Eva
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Richter Sundberg, Linda
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Social-emotional problems among Swedish three-year-olds: an Item Response Theory Analysis2019In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 29, no Suppl 4, p. 367-368Article in journal (Other academic)
    Abstract [en]

    Background: Young children’s social-emotional problems can have a long-term effect if not treated early. In order to deepen our knowledge about children’s social and emotional functioning, we utilized the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) among 3-year-olds in Sweden aiming: 1) to identify ASQ:SE items that are most commonly endorsed by children with high level of social-emotional problems; and 2) to assess whether certain ASQ:SE items differs between boys and girls at the same level of social-emotional problems.

    Methods: During 2014-2017 data was collected from 7179 three-year-old children through Child Health Care in a northern county of Sweden within the Salut Child Health Promotion Programme. Item Characteristic Curve (ICC) and Differential Item Functioning (DIF) were used to identify the characteristics of children with high social-emotional problems and to determine whether an item exhibit uniform between boys and girls at the same level of social-emotional problems.

    Results: Items regarding interest in sexual words, too little sleep, disinterest in things around, unhappiness and self-injury were more commonly endorsed by children with high levels of social-emotional problems. Additionally, on the same level of social-emotional problem girls were more likely to score high in items regarding difficulties to occupy herself, clinging behaviour and repetitive behaviour while boys were more likely to score high in items regarding difficulty to name friends, difficulty to express feelings and destruction of things on purpose.

    Conclusions: This study has increased our knowledge about Swedish young children’s social emotional functioning already at the age of three by detecting which items are most closely connected to high level of social-emotional problems and differences between boys and girls. However, whether the results detected in this analysis are reflecting their parents’ expectations more than child behaviour requires further investigations.

    Key messages

    • Children with high level of social-emotional problems were rated high on items regarding interest in sexual words, too little sleep, disinterest in things around, unhappiness and self-injury.

    • On equal levels of social-emotional problems, girls were more often reported with internalizing problematic behaviours and boys were more often reported with externalizing problematic behaviours.

  • 511. van den Akker, Chris H P
    et al.
    van Goudoever, Johannes B
    Szajewska, Hania
    Embleton, Nicholas D.
    Hojsak, Iva
    Reid, Daan
    Shamir, Raanan
    BerniCanani, Roberto
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Guarino, Alfredo
    Indrio, Flavia
    Kolaček, Sanja
    Mihatsch, Walter A.
    Orel, Rok
    Vandenplas, Yvan
    Weizman, Zvi
    Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 67, no 1, p. 103-122Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy.

    METHODS: A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA.

    RESULTS: Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains.

    CONCLUSIONS: This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.

  • 512.
    van den Berg, Johannes
    Umeå University, Faculty of Medicine, Department of Nursing.
    Neonatala transporter i Sverige: hur långt har vi kommit?2009In: BarnBladet, ISSN 0349-1994, Vol. 34, no 4, p. 15-18Article in journal (Other academic)
  • 513.
    van den Berg, Johannes
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Back transport of infants to community hospitals: 12 years´ experience of an intervention to prepare parents for their infants´ transfer from neonatal intensive care to community hospital2011In: Journal of Neonatal Nursing, ISSN 1355-1841, E-ISSN 1878-089X, Vol. 17, no 3, p. 116-125Article in journal (Refereed)
    Abstract [en]

    Effective regionalized neonatal intensive care includes back transport of stable infants to community hospitals. This transition can be pleasant or frightening for the family, and psychological preparation is critical. The aim of this study was to evaluate an intervention performed in collaboration with the neonatal intensive care unit (NICU) and community hospitals (CH) in the northern health care region of Sweden. Questionnaires were sent to families who had an infant transported from NICU to CH and discharged to home over three periods from 1994 to 2007. Families rated information about the CH more accurate, reception at the CH better, and their preparation for the transition better when they were contacted by the CH during their stay at the NICU. Both NICU and CH staff have a responsibility to facilitate back transport by promoting communication between families and staff at the hospital to which they are to be transported.

  • 514. van der Pals, Maria
    et al.
    Myléus, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hammarroth, Solveig
    Högberg, Lotta
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Carlsson, Annelie
    Body mass index is not a reliable tool in predicting celiac disease in children2014In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 14, p. 165-Article in journal (Refereed)
    Abstract [en]

    Background: Untreated celiac disease is traditionally believed to be associated with malabsorption and underweight. However, studies describing body mass index (BMI) in individuals at the time of diagnosis have shown contradictory results. We investigated the differences in weight, height, and BMI in 12- year-old children with screening-detected celiac disease compared to their healthy peers.

    Methods: In a population-based screening study of 12,632 12-year-old children, blood samples were analyzed for markers of celiac disease. Children with elevated markers were referred for a small bowel biopsy. Weight and height were measured in 239 out of 242 children with screening-detected celiac disease (57.3% girls) and in 12,227 children without celiac disease (48.5% girls). BMI was categorized according to the International Obesity Task Force. Age- and sex-specific cut-off points for underweight, normal weight, and overweight were used.

    Results: Children with celiac disease weighed less and were shorter than their peers (median weight 45.2 kg, interquartile range (IQR) 40.2-52.2 kg vs. 47.0 kg, IQR 41.1-54.4 kg, respectively, p = 0.01; median height 156.5 cm, IQR 151.0-162.0 cm vs. 157.5 cm, IQR 152.0-163.0 cm, respectively, p = 0.04). In comparing those with celiac disease to their healthy peers, 4.2% vs. 5.2% were underweight, 82.0% vs. 72.8% were normal weight, and 13.8% vs. 21.9% were overweight, respectively. There was no association between being underweight and the risk of having undiagnosed celiac disease (Odds ratio (OR) 1.3, 95% CI 0.7-2.4), but the risk was significantly lower among overweight children (OR 0.56, 95% CI 0.4-0.8). Median BMI was slightly lower among the children with screening-detected celiac disease compared to their healthy peers (18.6 kg/m(2), IQR 17.1-19.8 kg/m(2) vs. 18.8 kg/m(2), IQR 17.2-21.1 kg/m(2), respectively, p = 0.05), but most of the celiac disease cases had a normal BMI.

    Conclusions: At a population level, children with celiac disease weigh less, are shorter, and have a lower BMI compared to their peers without celiac disease, and this emphasizes the importance of early recognition and treatment of the condition. However, at an individual level, growth parameters are not reliable in establishing the diagnosis.

  • 515. Van der Wielen, Marie
    et al.
    Giaquinto, Carlo
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Huelsse, Christel
    Huet, Frédéric
    Littmann, Martina
    Maxwell, Melanie
    Talayero, José M P
    Todd, Peter
    Vila, Miguel T
    Cantarutti, Luigi
    Van Damme, Pierre
    Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.2010In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 11, p. 22-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. METHODS: Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. RESULTS: 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, > or = 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. CONCLUSIONS: Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

  • 516. van Goudoever, Johannes B.
    et al.
    Carnielli, Virgilio
    Darmaun, Dominique
    de Pipaon, Miguel Sainz
    Braegger, Christian
    Bronsky, Jiri
    Cai, Wei
    Campoy, Cristina
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas
    Fewtrell, Mary
    Fidler Mis, Natasa
    Franz, Axel
    Goulet, Olivier
    Hartman, Corina
    Hill, Susan
    Hojsak, Iva
    Iacobelli, Silvia
    Jochum, Frank
    Joosten, Koen
    Kolacek, Sanja
    Koletzko, Berthold
    Ksiazyk, Janusz
    Lapillonne, Alexandre
    Lohner, Szimonetta
    Mesotten, Dieter
    Mihalyi, Krisztina
    Mihatsch, Walter A.
    Mimouni, Francis
    Christian, Molgaard
    Moltu, Sissel J.
    Nomayo, Antonia
    Picaud, Jean Charles
    Prell, Christine
    Puntis, John
    Riskin, Arieh
    Saenz De Pipaon, Miguel
    Senterre, Thibault
    Shamir, Raanan
    Simchowitz, Venetia
    Szitanyi, Peter
    Tabbers, Merit M.
    Van Den Akker, Chris H. B.
    Van Kempen, Anne
    Verbruggen, Sascha
    Wu, Jiang
    Weihui, Yan
    ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Amino acids2018In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 37, no 6, p. 2315-2323Article in journal (Refereed)
  • 517. Vandenplas, Yvan
    et al.
    Alarcon, Pedro
    Fleischer, David
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kolacek, Sanja
    Laignelet, Hugo
    Lönnerdal, Bo
    Raman, Rita
    Rigo, Jacques
    Salvatore, Silvia
    Shamir, Raanan
    Staiano, Annamaria
    Szajewska, Hania
    Van Goudoever, Hans J.
    von Berg, Andrea
    Lee, Way S.
    Should Partial Hydrolysates Be Used as Starter Infant Formula?: A Working Group Consensus2016In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 62, no 1, p. 22-35Article, review/survey (Refereed)
    Abstract [en]

    Partially hydrolyzed formulas (pHFs) are increasingly used worldwide, both in the prevention of atopic disease in at-risk infants and in the therapeutic management of infants with functional gastrointestinal manifestations. Because prevention is always preferable to treatment, we reviewed the literature aiming to find an answer for the question whether pHF may be recommended for feeding all infants if breast-feeding is not possible. PubMed and Cochrane databases were searched up to December 2014. In addition, to search for data that remained undetected by the searches, we approached authors of relevant articles and major producers of pHFs asking for unpublished data. Because few data were found, nonrandomized, controlled trials and trials in preterm infants were included as well. Overall, only limited data could be found on the efficacy and safety of pHF in healthy term infants. Available data do not indicate that pHFs are potentially harmful for healthy, term infants. With respect to long-term outcomes, particularly referring to immune, metabolic and hormonal effects, data are, however, nonexistent. From a regulatory point of view, pHFs meet the nutrient requirements to be considered as standard formula for term healthy infants. Cost, which is different from country to country, should be considered in the decision-making process. Based on limited available data, the use of pHF in healthy infants is safe with regard to growth. The lack of data, in particular for metabolic consequences and long-term outcomes, is, however, the basis for our recommendation that health authorities should develop and support long-term follow-up studies. Efficacy and long-term safety data are required before a recommendation of this type of formula for all infants can be made.

  • 518. Vellodi, A
    et al.
    Tylki-Szymanska, A
    Davies, E H
    Kolodny, E
    Bembi, B
    Collin-Histed, T
    Mengel, E
    Erikson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schiffmann, R
    Management of neuronopathic Gaucher disease: revised recommendations2009In: Journal of Inherited Metabolic Disease, ISSN 0141-8955, E-ISSN 1573-2665, Vol. 32, no 5, p. 660-664Article in journal (Refereed)
    Abstract [en]

    The original guidelines drawn up for the management of the neuronopathic forms of Gaucher disease were felt to be in need of revision; in particular, the role of high-dose enzyme replacement therapy (120 IU/kg of body weight every 2 weeks) in stabilizing neurological disease. The existing published evidence was analysed; it was concluded that it did not support the role of high-dose ERT, although this might be required to treat severe visceral disease.

  • 519. Vesikari, Timo
    et al.
    Richardus, Jan Hendrik
    Berglund, Johan
    Korhonen, Tiina
    Flodmark, Carl-Erik
    Lindstrand, Ann
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bambure, Vinod
    Caplanusi, Adrian
    Dieussaert, Ilse
    Roy-Ghanta, Sumita
    Vaughn, David W.
    Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine Two Open-label, Randomized Trials2015In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 34, no 7, p. 774-782Article in journal (Refereed)
    Abstract [en]

    Background: During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1) pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1) pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1) pdm09 vaccine. Methods: Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1) pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1) pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. Results: At day 0, >93.9% of all children had HI titers >= 1:40 for the A(H1N1) pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1) pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. Conclusion: AS03-adjuvanted A(H1N1) pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1) pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03adjuvanted A(H1N1) pdm09 vaccine.

  • 520. Vesikari, Timo
    et al.
    Silfverdal, Sven Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Boisnard, Florence
    Thomas, Stephane
    Mwawasi, Grace
    Reynolds, Donna
    Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of a Fully Liquid Combination Diphtheria-Tetanus Toxoid-Five-Component Acellular Pertussis (DTaP5), Inactivated Poliovirus (IPV), and Haemophilus influenzae Type b (Hib) Vaccine Compared with a DTaP3-IPV/Hib Vaccine Administered at 3, 5, and 12 Months of Age2013In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 20, no 10, p. 1647-1653Article in journal (Refereed)
    Abstract [en]

    This study compared the levels of immunogenicity and safety of diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP5-IPV-Hib) and DTaP3-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP5-IPV-Hib to DTaP3-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP5-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.)

  • 521. Vesikari, Timo
    et al.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jordanov, Emilia
    Feroldi, Emmanuel
    A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-,5-and 11-to 12-month Schedule2017In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 36, no 1, p. 87-93Article in journal (Refereed)
    Abstract [en]

    Background: To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age.

    Methods: Phase III, randomized, active-controlled, observer-blind, multi-center study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRPNT: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports.

    Results: Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP similar to T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP similar to T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated.

    Conclusions: These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

  • 522.
    Vestman, Nelly Romani
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Holgerson, Pernilla Lif
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kressirer, Christine A
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Tanner, Anne CR
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Characterization and in vitro properties of oral lactobacilli in breastfed infants2013In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, p. 193-Article in journal (Refereed)
    Abstract [en]

    Background: Lactobacillus species can contribute positively to general and oral health and are frequently acquired by breastfeeding in infancy. The present study aimed to identify oral lactobacilli in breast and formula-fed 4 month-old infants and to evaluate potential probiotic properties of the dominant Lactobacillus species detected. Saliva and oral swab samples were collected from 133 infants who were enrolled in a longitudinal study (n=240) examining the effect of a new infant formula on child growth and development. Saliva was cultured and Lactobacillus isolates were identified from 16S rRNA gene sequences. Five L. gasseri isolates that differed in 16S rRNA sequence were tested for their ability to inhibit growth of selected oral bacteria and for adhesion to oral tissues. Oral swab samples were analyzed by qPCR for Lactobacillus gasseri.

    Results: 43 (32.3%) infants were breastfed and 90 (67.7%) were formula-fed with either a standard formula (43 out of 90) or formula supplemented with a milk fat globule membrane (MFGM) fraction (47 out of 90). Lactobacilli were cultured from saliva of 34.1% breastfed infants, but only in 4.7% of the standard and 9.3% of the MFGM supplemented formula-fed infants. L. gasseri was the most prevalent (88% of Lactobacillus positive infants) of six Lactobacillus species detected. L. gasseri isolates inhibited Streptococcus mutans binding to saliva-coated hydroxyapatite, and inhibited growth of S. mutans, Streptococcus sobrinus, Actinomyces naeslundii, Actinomyces oris, Candida albicans and Fusobacterium nucleatum in a concentration dependent fashion. L. gasseri isolates bound to parotid and submandibular saliva, salivary gp340 and MUC7, and purified MFGM, and adhered to epithelial cells. L. gasseri was detected by qPCR in 29.7% of the oral swabs. Breastfed infants had significantly higher mean DNA levels of L. gasseri (2.14 pg/uL) than infants fed the standard (0.363 pg/uL) or MFGM (0.697 pg/uL) formula.

    Conclusions: Lactobacilli colonized the oral cavity of breastfed infants significantly more frequently than formulafed infants. The dominant Lactobacillus was L. gasseri, which was detected at higher levels in breastfed than formula-fed infants and displayed probiotic traits in vitro.

  • 523.
    Videholm, Samuel
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Unit of Research, Development, and Education, Östersund Hospital, Östersund, Sweden.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Reniers, Georges
    Maternal weight and infections in early childhood: a cohort study2019In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 104, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to examine this association between maternal weight during pregnancy and the incidence of hospitalisations for infectious diseases during early childhood. Design A population-based cohort study. Setting A national cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register and the Longitudinal integration database for health insurance and labour market studies. Patients 693 007 children born in Sweden between 1998 and 2006. Main outcome measures Number of hospitalisations for infectious diseases during the first 5 years of life, overall and for categories of infectious diseases (lower respiratory, enteric, upper respiratory, genitourinary, perinatal, skin and soft tissue, neurological and eye, digestive tract, bloodstream and other infections). Results Overweight (body mass index (BMI) 25.0-29.9) and obesity (BMI >= 30) during pregnancy were associated with a higher overall incidence of hospitalisations for infectious diseases, adjusted incidence rate ratio (IRR) 1.05 (95% CI 1.03 to 1.06) and adjusted IRR 1.18 (95% CI 1.16 to 1.21). Overweight and obesity during pregnancy were strongly associated with perinatal infections, adjusted IRR 1.34 (95% CI 1.25 to 1.44) and adjusted IRR 1.72 (95% CI 1.57 to 1.88). In contrast, we found no association between maternal weight during pregnancy and infections of skin and soft tissue, the nervous system, the digestive tract or the bloodstream. Conclusions We observed an association between overweight and obesity during pregnancy, and hospitalisations for infectious diseases during early childhood.

  • 524.
    Videhult, Frida K.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhlund, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Body mass but not vitamin D status is associated with bone mineral content and density in young school children in northern Sweden2016In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 60, article id 30045Article in journal (Refereed)
    Abstract [en]

    Background: High latitude of residence where sun exposure is limited affects vitamin D status. Although vitamin D levels have been associated with poor bone health, cut-off values for optimising bone health are yet to be decided. Objective: To assess vitamin D intake and status among young school children living at latitude 63-64 degrees N, in northern Sweden and to examine the association between vitamin D status and bone mineral content (BMC) and bone mineral density (BMD). Design: In a cross-sectional study, diet was assessed by a 4-day food diary and a food frequency questionnaire in 8- to 9-year-old children (n = 120). Energy, vitamin D, and calcium intakes were calculated. Physical activity was assessed using a pedometer for 7 days. Serum 25-hydroxyvitamin D (S-25[OH]D) levels were analysed by high-pressure liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry (n = 113). BMC and BMD were assessed by dual energy X-ray absorptiometry scan. Height and weight were measured by standard procedures and BMI z-score was calculated using WHO AnthroPlus programme. Results: The majority of children, 91%, did not reach the recommended vitaminDintake of 7.5 mu g/day and 50% had insufficient S-25[OH]D levels defined as <50 nmol/l. The highest concentrations of S-25[OH]D were observed during the summer months (p = 0.01). Body mass (p < 0.01) but not S-25[OH]D was associated with measures of BMC and BMD. Furthermore, boys had higher total BMC (p = 0.01), total body less head BMC (p = 0.02), fat free mass (p < 0.01), and a higher degree of physical activity (p = 0.01) compared to girls. Conclusions: Body mass was related to BMC and BMD measures in a population of prepubertal school children living at high latitudes in Sweden. Despite insufficient S-25[OH]D levels and low vitamin D intake, this did not appear to affect bone parameters. Prospective studies with repeated assessment of vitamin D status are needed to examine cut-off values for optimising bone health.

  • 525. Vogt, Hartmut
    et al.
    Lindstrom, Karolina
    Bråbäck, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hjern, Anders
    Preterm Birth and Inhaled Corticosteroid Use in 6- to 19-Year-Olds: A Swedish National Cohort Study2011In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 127, no 6, p. 1052-1059Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Preterm birth is associated with respiratory morbidity later in life, including asthma. Previous studies have mainly focused on asthma in early childhood in children born extremely preterm. In this study, we examined the risk of asthma in a national cohort of schoolchildren grouped according to degree of immaturity expressed as completed gestational weeks at birth. METHODS: This was a register study in a Swedish national cohort of 1 100 826 children 6 to 19 years old. Retrieval of at least 1 prescription of inhaled corticosteroids (ICS) during 2006 was used as the main indicator for asthma. Logistic regression was used to test hypotheses, with adjustment for multiple socioeconomic and perinatal indicators. RESULTS: Degree of immaturity, expressed as completed gestational weeks at birth, had an inverse dose-response relationship with ICS use. Compared with children born between 39 and 41 weeks' gestation, the odds ratio for ICS use increased with the degree of prematurity, from 1.10 (95% confidence interval: 1.08-1.13) for children born in weeks 37 to 38, to 2.28 (95% confidence interval: 1.96-2.64) for children born in weeks 23 to 28, after adjustment for confounders. The increase in ICS use with decreasing gestational age at delivery was similar in boys and girls, and declined with older age. CONCLUSION: Preterm birth increased the risk of ICS use in these 6- to 19-year-olds by degree of immaturity, from extremely preterm to early term birth. Pediatrics 2011; 127:1052-1059

  • 526.
    von Knorring, Anne-Liis
    Umeå University, Faculty of Medicine.
    Adoption studies on psychiatric illness: epidemiological, environmental and genetic aspects1983Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this study is to evaluate the outcome of adoptions and to study the gene-environment influences on psychiatric illness as well as sick-leave patterns. The material consists of 2 966 adopted persons born between 1917 and 1949, their 5 932 adoptive parents and 5 438 identified biological parents.Adopted persons had a higher incidence of personality disorders and substance abuse than non-adopted controls. Adopted men also had an increased incidence of neuroses. Adopted women had an increased sick-leave because of somatic complaints, especially upper respiratory tract infections and abdominal complaints of short duration. Somatization i.e. more than 2 sick-leaves/year because of somatic complaint together with nervous complaints was more frequent among adopted women. Women with somatization could be separated into 2 types according to the pattern of sick-leave. Type 1 ("high frequency") had frequent sick-leaves for psychiatric, abdominal and back complaints. They also had a high frequency of alcohol abuse. Type 2 ("diversiform") had more diverse complaints and had fewer sick-leaves because of nervous complaints.High frequency somatizers had biological fathers with teenage onset of criminality and frequent registrations for alcohol abuse. Diversiform somatizers had the same genetic background as adopted men with petty criminality or male limited alcoholism.No specific genetic influences on treated depression or substance abuse were found in this study. However, a non-specific vulnerability of the biological mother influenced on the risk of depression and substance abuse among adopted women.There were some indications that placement in the adoptive home between 6 and 12 months of age was associated with reactive neurotic depression in adult life. Otherwise early negative experiences in term of unstable placements before adoption did not significantly influence on psychiatric illness in adulthood.Affective disorders in the adoptive father were associated with treatment for depressions or substance abuse in the adoptee. Low social status in the part of the adoptive father increased the risk of somatization of both types in the adoptee.

  • 527. Wackernagel, Dirk
    et al.
    Gustafsson, Anna
    Edstedt Bonamy, Anna-Karin
    Reims, Annika
    Ahlsson, Fredrik
    Elfving, Maria
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hansen Pupp, Ingrid
    Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥ 35 weeks2020In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 109, no 1, p. 31-44Article, review/survey (Refereed)
    Abstract [en]

    Aim: Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age >= 35 + 0 weeks.

    Methods: A PubMed search-based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations.

    Results: Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold-based screening and treatment protocol presented as a flow chart was developed.

    Conclusion: An updated and evidence-based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia-related long-term sequelae.

  • 528.
    Waenerlund, Anna-Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Stenmark, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Bergström, Erik
    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.
    Öhman, Ann
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Petersen, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    School experiences may be important determinants of mental health problems in middle childhood: a Swedish longitudinal population-based study2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 4, p. 407-415Article in journal (Refereed)
    Abstract [en]

    AimLittle is known about the association between school experiences and mental health in young schoolchildren. This study explored the cross-sectional and prospective associations between children's school experiences and mental health in middle childhood. MethodsWe gathered comprehensive population-based data on the school experiences and mental health of 592 schoolchildren attending grades three and six in Sweden (ages approximately nine and 12 years). The KIDSCREEN questionnaire was used to measure school experiences in both age groups while the Child Behavior Checklist and the Strengths and Difficulties Questionnaire measured mental health in grades three and six, respectively. ResultsChildren with problematic school experiences in grade three had an approximately two times higher odds for concurrent total, internalised, externalised, attention-hyperactivity and social problems. They also had a 1.5-2.5 higher odds for these mental health problems three years later. Likewise, there was an association between problematic school experiences in grade three and lower levels of prosocial behaviour three years later. These associations were shown in both boys and girls, but were particularly pronounced in girls. ConclusionThis study indicated that school experiences in young schoolchildren may be important determinants of concurrent and later mental health problems.

  • 529.
    Waernbaum, Ingeborg
    et al.
    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.
    Low mean temperature rather than few sunshine hours are associated with an increased incidence of type 1 diabetes in children2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 1, p. 61-65Article in journal (Refereed)
    Abstract [en]

    The well-known north-south gradient and the seasonal variability in incidence of childhood type1 diabetes indicate climatological factors to have an effect on the onset. Both sunshine hours and a low temperature may be responsible. In the present study we tried to disentangle these effects that tend to be strongly connected.

    Exposure data were sunshine hours and mean temperature respectively obtained from eleven meteorological stations in Sweden which were linked to incidence data from geographically matched areas. Incident cases during 1983-2008 were retrieved from the population based Swedish childhood diabetes register. We used generalized additive models to analyze the incidence as a function of mean temperature and hours of sun adjusted for the time trend, age and sex.

    In our data set the correlation between sun hours and temperature was weak (r=0.36) implying that it was possible to estimate the effect of these variables in a regression model. We fit a general additive model with a smoothing term for the time trend. In the model with sun hours we found no significant effect on T1 incidence (p=0.17) whereas the model with temperature as predictor was significant (p=0.05) when adjusting for the time trend, sex and age. Adding sun hours in the model where mean temperature was already present did not change the effect of temperature.

    There is an association with incidence of type1 diabetes in children and low mean temperature independent of a possible effect of sunshine hours after adjustment for age, sex and time trend. The findings may mirror the cold effect on insulin resistance and accords with the hypothesis that overload of an already ongoing beta cell destruction may accelerate disease onset.

  • 530.
    Waernbaum, Ingeborg
    et al.
    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.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Perinatal risk factors for type 1 diabetes revisited: a population-based register study2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 7, p. 1173-1184Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Single-centre studies and meta-analyses have found diverging results as to which early life factors affect the risk of type 1 diabetes during childhood. We wanted to use a large, nationwide, prospective database to further clarify and analyse the associations between perinatal factors and the subsequent risk for childhood-onset type 1 diabetes using a case–control design.

    Methods: The Swedish Childhood Diabetes Register was linked to the Swedish Medical Birth Register and National Patient Register, and 14,949 cases with type 1 diabetes onset at ages 0–14 years were compared with 55,712 matched controls born from the start of the Medical Birth Register in 1973 to 2013. After excluding confounders (i.e. children multiple births, those whose mother had maternal diabetes and those with a non-Nordic mother), we used conditional logistic regression analyses to determine risk factors for childhood-onset type 1 diabetes. We used WHO ICD codes for child and maternal diagnoses.

    Results: In multivariate analysis, there were small but statistically significant associations between higher birthweight z score (OR 1.08, 95% CI 1.06, 1.10), delivery by Caesarean section (OR 1.08, 95% CI 1.02, 1.15), premature rupture of membranes (OR 1.08, 95% CI 1.01, 1.16) and maternal urinary tract infection during pregnancy (OR 1.39, 95% CI 1.04, 1.86) and the subsequent risk of childhood-onset type 1 diabetes. Birth before 32 weeks of gestation was associated with a lower risk of childhood-onset type 1 diabetes compared with full-term infants (OR 0.54, 95% CI 0.38, 0.76), whereas birth between 32 and 36 weeks’ gestation was associated with a higher risk (OR 1.24, 95% CI 1.14, 1.35). In subgroup analyses (birth years 1992–2013), maternal obesity was independently associated with subsequent type 1 diabetes in the children (OR 1.27, 95% CI 1.15, 1.41) and rendered the association with Caesarean section non-significant. In contrast to previous studies, we found no association of childhood-onset type 1 diabetes with maternal–child blood-group incompatibility, maternal pre-eclampsia, perinatal infections or treatment of the newborn with phototherapy for neonatal jaundice. The proportion of children with neonatal jaundice was significantly higher in the 1973–1982 birth cohort compared with later cohorts.

    Conclusions/interpretation: Perinatal factors make small but statistically significant contributions to the overall risk of childhood-onset type 1 diabetes. Some of these risk factors, such as maternal obesity, may be amendable with improved antenatal care. Better perinatal practices may have affected some previously noted risk factors over time.

  • 531. Webb, Charlotta
    et al.
    Myléus, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hammarroth, Solveig
    Högberg, Lotta
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenhammar, Lars
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Carlsson, Annelie
    High adherence to a gluten-free diet in adolescents with screening-detected celiac disease2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 1, p. 54-59Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the gluten-free diet (GFD) adherenceafter one year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 12 year olds were invited to participate in apopulation-based CD screening (ETICS- Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This sub-study included the 210 children with TG2-IgAevaluated both at the initialbiopsy occasion and at the one-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After one year, 83% (179/210) had normalizedTG2-IgA levels (<5U/mL). Among those who had >50 U/mL at diagnosis,25% (16/63) still had elevated TG2-IgA but for the majority their initial values were more than halved. Most reported a high level ofGFD adherence ('always' 75%(158/193) and 'often' 14%(30/193)), and 75% (145/193) reported always adhereingcombined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely, however, a majority of these initially had the highestTG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12yearolds. Almost all had normalized serology and reported GFD adherenceat the one-year follow-up. However, a few adolescents whoreported GFD adherence still had elevated TG2-IgA levelssuggesting more severe disease and/or non-adherence.

  • 532. Webb, Charlotta
    et al.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Myléus, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Halvarsson, Britta
    Högberg, Lotta
    Lagerqvist, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sandström, Olof
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenhammar, Lars
    Carlsson, Annelie
    Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 6, p. 787-791Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) guidelines cover this group of patients.

    METHODS: This is a sub-study of a cross-sectional CD screening study, ETICS (Exploring the Iceberg of Celiacs in Sweden), a two-phased study performed during 2005-2006 and 2009-2010. The 13,279 participating children had a blood test obtained and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with the assessment of the biopsy.

    RESULTS: There were 267 children included, of whom 230 were diagnosed with CD. Out of all children, 67 children had low tTG-IgA levels (<5 U/mL), whereof 55% had Marsh 3 lesions. All children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, i.e. 50 U/mL, were diagnosed with CD. Lowering the cut-off to 3 U/mL, all but one child with 30 U/mL got CD diagnosis.

    CONCLUSION: By adapting the revised ESPGHAN criteria, biopsies could have been omitted in a fourth of all cases. Our results indicate, that the criteria might be useful even on screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.

  • 533. Wennström, Lovisa
    et al.
    Edslev, Pernille Wendtland
    Abrahamsson, Jonas
    Nørgaard, Jan Maxwell
    Fløisand, Yngvar
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Gustafsson, Göran
    Heldrup, Jesper
    Hovi, Liisa
    Jahnukainen, Kirsi
    Jonsson, Olafur Gisli
    Lausen, Birgitte
    Palle, Josefine
    Zeller, Bernward
    Holmberg, Erik
    Juliusson, Gunnar
    Stockelberg, Dick
    Hasle, Henrik
    Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries2016In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, no 1, p. 83-92Article in journal (Refereed)
    Abstract [en]

    Background: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited. Procedure: We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries. Results: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor. Conclusions: No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.

  • 534.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Feeding Lactobacillus paracasei ssp. paracasei strain F19 to infants during weaning: effects on adaptive immunity and gut microbial function2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Gut microbial composition has been associated with immune-mediated diseases. Breastfeeding yields a microbiota rich in bifidobacteria and promotes colonization by lactobacilli. Bifidobacteria and lactobacilli are considered health-promoting and are used as probiotics, i.e. live microbial food supplements which when ingested in adequate amounts confer a beneficial effect on the host. During weaning the developing gut immune system is exposed to an increasing variety of antigens from both foods and gut microbiota.

    Aims: We aimed to determine if daily feeding of 1x108 colony-forming units (CFU) of the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (LF19) to healthy term infants from 4 to 13 months of age could maintain some of the beneficial effects conferred by breastfeeding on gut microbial composition, with possible effects on gut microbial function, T cell function, Th1/Th2 immune balance and eczema incidence.

    Study design: Infants were randomized to daily intake of cereals with (n=89) or without LF19 (n=90) from 4-13 months of age. Clinical outcome measures were monitored by diaries and a questionnaire. Stool and blood samples were obtained at 4, 6½, 9, 13 and 5½, 6½, 12 and 13 months of age, respectively. Stool samples were analyzed for lactobacilli counts by conventional culture methods and the presence of LF19 was verified by randomly amplified polymerase chain reaction (RAPD-PCR). Fecal short-chain fatty acid (SCFA) pattern, a proxy for gut microbial function, was determined by gas-liquid chromatography. After polyclonal or specific activation of T cells, the cytokine mRNA expression levels [interleukin 2 (IL2), IFN-, IL4 and IL10] were determined on isolated mRNA by quantitative real time reverse transcriptase-PCR. Serum concentrations of total and specific IgE antibodies, Haemophilus influenzae type b, diphtheria and tetanus toxoid specific IgG antibodies were analyzed by enzyme immunoassay.

    Results: Feeding LF19 maintained high fecal lactobacilli counts during weaning. Persistent colonization with LF19 induced differences in the fecal SCFA pattern. The cumulative incidence of eczema was lower in the probiotic group, in conjunction with a higher IFN-γ/IL4 mRNA ratio in polyclonally activated T cells. Even though there was an effect by LF19 on Th1/Th2 immune balance, there was no effect on IgE sensitization. Infants in both groups increased their capacity to express both Th1 and Th2 cytokines during the second half of infancy but the expression was still lower than that of adults. Infants in the probiotic group had lower IL2 levels after polyclonal T cell activation at 13 months of age compared with infants in the placebo group. Infants fed LF19 did not have fewer infections, but had fewer days with antibiotic prescription compared with infants fed placebo. In addition, compared to placebo, persistent colonization by LF19 enhanced specific vaccine responses to protein antigens during the course of vaccination.

    Conclusions: We conclude that feeding LF19 was safe, based on no observed adverse effects in our study. Infants in both groups demonstrated maturation of adaptive immune responses during weaning. Adding probiotics in complementary foods during weaning reduced the risk of eczema by 50%, with a concomitant shift towards an enhanced Th1/Th2 ratio. The reduction of eczema might be explained by probiotic effects on both T cell-mediated immune responses and reinforced gut microbial function.

  • 535.
    West, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Introduction of Complementary Foods to Infants2017In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 70, p. 47-54Article in journal (Refereed)
    Abstract [en]

    While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance. Many international infant feeding guidelines already recommend complementary foods, including allergenic foods, to be introduced from 4 to 6 months of age irrespective of family history risk. Interim guidelines from 10 International Pediatric Allergy Associations state that healthcare providers should recommend the introduction of peanut-containing products into the diets of infants at high risk of allergic disease in countries where peanut allergy is prevalent. Direct translation of the results obtained from a cohort of high-risk infants to the general population has proved difficult, and issues regarding feasibility, safety, and cost-effectiveness have been raised. Five randomized placebo-controlled trials have assessed the effects of early egg exposure in infancy with varying results. In a recent comprehensive meta-analysis, there was moderate-certainty evidence that early versus late introduction of egg was associated with a reduced egg allergy risk. Although promising, optimal timing, doses, and if the feeding regimen should be stratified according to infant allergy risk remain to be determined. The single study that assessed introduction of multiple foods from 3 months whilst breastfeeding compared with exclusive breastfeeding until 6 months of age showed no reduction in food allergy prevalence. Future research should aim at optimizing infant feeding regimens and support a tolerogenic gastrointestinal microenvironment during the period of food allergen introduction. 

  • 536.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Prebiotics in infancy and childhood; clinical research warranted2011In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 106, no 11, p. 1628-1629Article in journal (Refereed)
  • 537.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Probiotics for allergy prevention2016In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 7, no 2, p. 171-179Article, review/survey (Refereed)
    Abstract [en]

    Probiotics, given either as a supplement or in infant foods, have been evaluated in randomised controlled trials for allergy prevention. Here, the aim is to give an overview of the results from these primary prevention studies and to discuss current strategies. In most studies, single strains or a mixture of strains of lactic acid bacteria and bifidobacteria have been used - prenatally, postnatally or perinatally. Several meta-analyses have reported a moderate benefit of probiotics for eczema prevention, and the most consistent effect has been observed with a combined perinatal intervention in infants at high risk of allergic disease due to familial predisposition. In a recent meta-analysis, the use of multi-strain probiotics appeared to be most effective for eczema prevention. No preventive effect has been shown for other allergic manifestations. As long-term follow-up data on later onset allergic conditions (asthma and allergic rhinitis) are available only from a few of the initiated studies, reports from ongoing follow-up studies that are adequately powered to examine long-term outcomes are anticipated to provide more insight. Arguably, the differences in many aspects of study design and the use of different probiotic strains and combinations have made direct comparison difficult. To date, expert bodies do not generally recommend probiotics for allergy prevention, although the World Allergy Organization (WAO) in their recently developed guidelines suggests considering using probiotics in pregnant women, during breastfeeding and/or to the infant if at high risk of developing allergic disease (based on heredity). However, in concordance with other expert bodies, the WAO guideline panel stressed the low level of evidence and the need for adequately powered randomised controlled trials and a more standardised approach before clinical recommendations on specific strains, dosages and timing can be given.

  • 538.
    West, Christina E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The role of prebiotics in infectious and inflammatory conditions in infancy and childhood2010In: Infantil, Vol. 1, no 1Article in journal (Other academic)
  • 539.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dunstan, Janet
    McCarthy, Suzi
    Metcalfe, Jessica
    D'Vaz, Nina
    Meldrum, Suzanne
    Oddy, Wendy H
    Tulic, Meri K
    Prescott, Susan L
    Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes2012In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 4, no 11, p. 1747-1758Article in journal (Refereed)
    Abstract [en]

    Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease. We investigated associations between maternal intakes of β-carotene, vitamin C, vitamin E, copper and zinc, and infant allergic outcomes. Antioxidant intakes of pregnant women (n = 420) assessed prospectively by a food frequency questionnaire, were examined in relation to allergic outcomes at 1 year of age (n = 300). The main relationships with allergic outcomes were seen with dietary vitamin C and copper. Specifically, higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze. After adjustment for potential confounders the relationship with wheeze remained statistically significant. There was also an inverse linear relationship between vitamin C and food allergy. Higher dietary copper intake was associated with reduced risk of eczema, wheeze and any allergic disease. The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis, and there was also an inverse linear relationship between copper and food allergy. However, these relationships were only seen for nutrients present in food. There were no relationships between β-carotene, vitamin E or zinc and any allergic outcomes. In summary, this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze, and that copper intake is associated with reduced risk of several allergic outcomes.

  • 540.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. inFLAME Global Network (Worldwide Universities Network), West New York, NJ, USA.
    Dzidic, Majda
    Prescott, Susan L.
    Jenmalm, Maria C.
    Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention2017In: Allergology International, ISSN 1323-8930, E-ISSN 1440-1592, Vol. 66, no 4, p. 529-538Article, review/survey (Refereed)
    Abstract [en]

    Large-scale biodiversity loss and complex changes in social behaviors are altering human microbial ecology. This is increasingly implicated in the global rise in inflammatory diseases, most notably the "allergy epidemic" in very early life. Colonization of human ecological niches, particularly the gastrointestinal tract, is critical for normal local and systemic immune development and regulation. Disturbances in composition, diversity and timing of microbial colonization have been associated with increased allergy risk, indicating the importance of strategies to restore a dysbiotic gut microbiota in the primary prevention of allergic diseases, including the administration of probiotics, prebiotics and synbiotics. Here, we summarize and discuss findings of randomized clinical trials that have examined the effects of these microbiome-related strategies on short and long-term allergy preventative effects - including new guidelines from the World Allergy Organization which now recommend probiotics and prebiotics for allergy prevention under certain conditions. The relatively low quality evidence, limited comparative studies and large heterogeneity between studies, have collectively hampered recommendations on specific probiotic strains, specific timing and specific conditions for the most effective preventive management. At the same time the risk of using available products is low. While further research is needed before specific practice guidelines on supplement probiotics and prebiotics, it is equally important that the underlying dietary and lifestyle factors of dysbiosis are addressed at both the individual and societal levels.

  • 541.
    West, Christina E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöstedt, M
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Probiotic effects on T-cell maturation in infants during weaning.2012In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, no 4, p. 540-549Article in journal (Refereed)
    Abstract [en]

    Background: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema.

    Objective: To investigate the impact of feeding LF19 on T-cell maturation.

    Methods: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 10colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages.

    Results: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05).

    Conclusion and Clinical Relevance: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.

  • 542.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jenmalm, Maria C.
    Transfer of Probiotic Bacteria From Mother to Child: A Matter of Strain Specificity?2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 61, no 2, p. 157-158Article in journal (Other academic)
  • 543.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kvistgaard, Anne Staudt
    Peerson, Janet M.
    Donovan, Sharon M.
    Peng, Yong-mei
    Lönnerdal, Bo
    Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial2017In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 82, no 1, p. 63-71Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human milk is rich in osteopontin (OPN), which has immunomodulatory functions. METHODS: In a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing similar to 50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group. RESULTS: The F130 group had increased T-cell proportions compared with the SF (P = 0.036, average effect size 0.51) and F65 groups (P = 0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups. CONCLUSION: OPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at similar to 50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

  • 544.
    West, Christina E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Lundin, D.
    Engstrand, L.
    Tulic, M. K.
    Prescott, S. L.
    Gut microbiome and innate immune response patterns in IgE-associated eczema2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 9, p. 1419-1429Article in journal (Refereed)
    Abstract [en]

    BackgroundGut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling. ObjectiveWe examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5years in predisposed children due to maternal atopy [, trial ID ACTRN12606000280505]. MethodsMicrobial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1week, 1month and 12months in infants (n=10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5years of age (n=10). Microbiome data at 1week and 1month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6months of age. ResultsThe relative abundance of Gram-positive Ruminococcaceae was lower at 1week of age in infants developing IgE-associated eczema, compared with controls (P=0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, P=0.042) and TNF- (-0.597, P=0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF- (rs=-0.629, P=0.024). This relationship persisted at 1month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF- (rs=-0.697, P=0.038) and Enterobacteriaceae and IL-6 (rs=-0.709, P=0.035). Mothers whose infants developed IgE-associated eczema had lower -diversity of Bacteroidetes (P=0.04) although this was not seen later in their infants. At 1year, -diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P=0.002). Conclusion and clinical relevanceOur findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR-ligands and subsequent development of IgE-associated eczema.

  • 545.
    West, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersson, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöstedt, Marianne
    Maturation of T cell function in the human infant and effects thereon of probiotic feeding during weaningManuscript (Other academic)
  • 546. Westin, Vera
    et al.
    Klevebro, Susanna
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vanpée, Mirelille
    Hallberg, Boubou
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Improved nutrition for extremely preterm infants: a population based observational study2018In: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 23, p. 245-251Article in journal (Refereed)
    Abstract [en]

    Background and aims Extremely preterm (EPT) infants are at high risk for malnutrition due to immaturity and medical complications and they often accumulate nutritional deficits and experience growth faltering during treatment at neonatal intensive care units (NICUs). Enhanced intake of energy and protein during the first weeks of life improves weight gain and head circumference growth. The optimal nutritional strategy for these infants' health and long-term development remains unknown. Nutritional regiments have been identified as a potential area for improvement in Swedish NICUs. The aim of this study was to evaluate changes in nutritional intake over time during the first 56 postnatal days in EPT (<27 gestational weeks; n = 316) infants, who were treated in NICUs during 2004–2011 in Stockholm, using a population-based study approach.

    Methods Several different nutritional interventions were implemented over the 8-year period. Nutrition and growth data were obtained retrospectively from hospital records. All intakes of enteral and parenteral nutrients were retrieved daily during the first 28 postnatal days and on days 35, 42, 49 and 56.

    Results Energy intake (median) increased from 77 kcal/kg/d during the 2004–2005 period to 98 kcal/kg/d during the 2010–2011 period on days 4–6. Median protein intake increased from 2.4 g/kg/d during 2004–2005 to 3.6 g/kg/d during 2010–2011. Energy and protein intake during postnatal days 0–6 increased continuously over the 8 years and protein intake increased during all 56 postnatal days. Full enteral feeds were reached earlier and the proportion of enteral feeds during the first week was higher during 2008–2009 compared to all other years. A significant improvement in growth was primarily noted by comparing the 2004–2005 period to subsequent years.

    Conclusions Neonatal nutrition improved significantly in Stockholm from 2004 to 2011. Above all, parenteral nutrition was initiated more promptly during the first week and was provided at higher quantities. However, many of the EPT infants born during the later years still did not reach the recommended macronutrient intake levels. A significant weight gain improvement was observed between 2004–2005 and 2006–2011.

  • 547.
    Westin, Vera
    et al.
    Karolinska Institutet, Stockholm.
    Stoltz Sjöström, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Ahlsson, Fredrik
    Uppsala University, Uppsala.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Karolinska Institutet, Stockholm.
    Perioperative nutrition in extremely preterm infants undergoing surgical treatment for patent ductus arteriosus is suboptimal2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 3, p. 282-288Article in journal (Refereed)
    Abstract [en]

    AIM: To evaluate perioperative nutrition in extremely preterm infants undergoing surgery for patent ductus arteriousus (PDA).

    METHODS: Population-based study of extremely preterm infants born in Sweden during 2004-2007 and operated on for PDA. Data on perioperative nutrition was obtained from hospital records. All enteral and parenteral nutrients and blood products were used to calculate daily nutritional intakes, starting three days before and ending three days after surgery. Data are mean (95% confidence intervals).

    RESULTS: Study infants (n=140) had a mean gestational age of 24.8 weeks and mean birth weight was 723 gram. Energy and macronutrient intakes were below minimal requirements before, during and after PDA surgery. On the day of surgery, energy intake was 78(74-81) kcal/kg/d, protein 2.9(2.7-3.2) g/kg/d, fat 2.5(2.3-2.7) g/kg/d and carbohydrate intake was 10.7(10.2-11.2) g/kg/d. Nutrition did not vary in relation to GA, but infants operated early (0-6 days after birth) received poorer nutrition than infants operated at older age. Fluid intake was 164(159-169) mL/kg/d, and it did not vary during the week of surgery.

    CONCLUSIONS: Perioperative nutrition in extremely preterm infants undergoing PDA surgery in Sweden is suboptimal and needs to be improved. The significance of malnutrition for outcome after PDA surgery remains unclear and requires further investigation.

  • 548.
    Wikland, Kerstin Albertsson
    et al.
    International Pediatric Growth Research Center, Department of Pediatrics University of Göteborg, SE-41685 Göteborg.
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosberg, Sten
    International Pediatric Growth Research Center, Department of Pediatrics University of Göteborg, SE-41685 Göteborg.
    Svensson, Birgitta
    International Pediatric Growth Research Center, Department of Pediatrics University of Göteborg, SE-41685 Göteborg.
    Nierop, Andreas F. M.
    Muvara bv, Tijmtuin 8, 2353 PH Leiderdorp, the Netherlands.
    Validated multivariate models predicting the growth response to GH treatment in individual short children with a broad range in GH secretion capacities.2000In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 48, no 4, p. 475-484Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to develop and validate models that could predict the growth responses to GH therapy of individual children. Models for prediction of the initial one and 2-y growth response were constructed from a cohort of 269 prepubertal children (Model group) with isolated GH deficiency or idiopathic short stature, using a nonlinear multivariate data fitting technique. Five sets of clinical information were used. The "Basic model" was created using auxological data from the year before the start of GH treatment and parental heights. In addition to Basic model data, the other four models included growth data from the first 2 y of life, or IGF-I, or GH secretion estimated during a provocation test (AITT) or a spontaneous GH secretion profile. The performance of the models was validated by calculating the differences between predicted and observed growth responses in 149 new GH treated children (Validation group) who fulfilled the inclusion criteria used in the original cohort. The SD of these differences (SD(res)) in the validation group was compared with the SD(res) for the model group. For the 1st y, the SD(res) for the Basic model was 0.28 SDscores. The lowest SD(res) (0.19 SDscores), giving the most narrow prediction interval, was achieved adding the 24h GH profile and data on growth from the first 2 y of life to the Basic model. The models presented permit estimation of GH responsiveness in children over a broad range in GH secretion, and with an accuracy of the models substantially better than when using maximal GH response during an provocation test. The predicted individual growth response, calculated using a computer program, can serve as a guide for evidence-based decisions when selecting children to GH treatment.

  • 549.
    Wikström, Malin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Erythema Toxicum Neonatorum, early microbial exposure and immunological activity2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 550.
    Winberg, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Epidemiology of food hypersensitivity in school children: Validation with double-blind placebo-controlled food challenges and biomarkers2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: This thesis focuses on the incidence and remission of reported food hypersensitivity in schoolchildren followed from 8 to 12 -years of age and the prevalence of hypersensitivity to milk, egg, cod and wheat among 12-year olds investigated by reported data, clinical investigation and double-blind placebo-controlled food challenges and biomarkers.

    Methods: The studies are mainly based on a population based cohort recruited in 2006 from three municipalities in Northern Sweden. All children in first and second grade, aged 7-8 years, were invited to a parental questionnaire study and 2585 (96% of invited) participated. The children in two of the municipalities were also invited to a skin prick test with airborne allergens. At age 11-12 years, there was a follow-up of the cohort using the same methods, with the addition of a child interview and assessment of body mass index (BMI).

    At the follow-up, children who reported milk hypersensitivity were invited to structured interviews and children reporting complete elimination of milk, egg, cod or wheat due to perceived hypersensitivity were invited to a clinical examination and blood sampling. According to test results, the children were categorized into different food hypersensitivity phenotypes according to preset criteria. Children categorized as current food allergy were then invited to further evaluation with a double-blind placebo-controlled food-challenge using newly developed recipes. Before their use, the recipes were successfully validated regarding detectable sensorial differences between the active and placebo substances in a separate cohort of healthy schoolchildren (n=275).

    Before and after the challenge series blood samples were collected for analyses of cytokine mRNA expression in peripheral blood mononuclear cells including hallmark cytokines for the humoral allergy-promoting T helper (Th) 2 response, cellular cytotoxicity-promoting Th1 response, inflammatory-, and T regulatory responses. Fecal inflammatory biomarkers were also analyzed before and after the challenge series.

    Results: Reported food hypersensitivity increased from 21% at age 7-8 years to 26% at 11-12 years. There was a high incidence (15%) as well as a high remission (33%) of reported food hypersensitivity. Risk factors associated with incidence and remission were different for milk hypersensitivity and hypersensitivity to foods other than milk. The agreement between reported symptoms to milk, egg, cod, wheat, soy and peanut and sensitization to the culprit food was poor. At 11 to 12-years of age the prevalence of reported allergy to milk, egg, cod or wheat was 4.8% while the allergy prevalence according to clinical evaluation was 1.4%. This figure was further halved when evaluated with double-blind placebo-controlled food challenges.

    The majority of children with reported allergy to milk, egg, cod and wheat were categorized as other food hypersensitivity phenotypes, the most common being probable lactose intolerance (40%) and outgrown food allergy (19%). Even though reported milk hypersensitivity among the 11-12 year olds was 14.5%, only 3% were categorized as current milk allergy. Current and outgrown milk allergy was associated with other atopic disorders and a lower BMI (OR 0.8, 95% CI 0.80-0.98). Before the challenge series, the mRNA expression of the cytokines IL-13 and IL-10 were higher among children with a positive compared to a negative challenge outcome.

    Conclusion: Reported food hypersensitivity was common among school children in Northern Sweden and increased from 7-8 years to 11-12 years of age, and both the incidence and remission of reported hypersensitivity was high. There was an 8-fold difference in the prevalence of allergy to milk, egg, cod or wheat when reported data was assessed by clinical examinations and double-blind placebo-controlled food challenges. Allergy to milk, egg, cod and wheat was an uncommon cause of complete avoidance of these foods due to perceived hypersensitivity. Some of the analyzed biomarkers might serve as prognostic markers for symptomatic, IgE-mediated food allergy but need further validation.

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