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  • 1.
    Albertsson-Wikland, Kerstin
    et al.
    Göteborg Pediatric Growth Research Center (GP-GRC), The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Kriström, Berit
    Department of Clinical Science, Umeå University, Sweden.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hochberg, Zeʼev
    Department of Pediatric Endocrinology, Meyer Children's Hospital at Rambam Medical Center, Haifa, Israel.
    Long-Term Response to GH Therapy in Short Children With a Delayed Infancy-Childhood Transition (DICT)2011In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 69, no 6, p. 504-510Article in journal (Refereed)
    Abstract [en]

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

  • 2. Appelkvist, E L
    et al.
    Venizelos, N
    Zhang, Y
    Parmryd, I
    Hagenfeldt, L
    Dallner, G
    Synthesis of mevalonate pathway lipids in fibroblasts from Zellweger and X-linked ALD patients.1999In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 46, no 3, p. 345-50Article in journal (Refereed)
    Abstract [en]

    Fibroblasts were cultured to determine the involvement of peroxisomes in cholesterol and dolichol synthesis. For this purpose, the behavior of cells from patients with Zellweger syndrome, with X-linked adrenoleukodystrophy, and from nondiseased control subjects was studied. Cells both after pretreatment with mevinolin and without pretreatment were incubated in a medium containing [3H]-mevalonate. In fibroblasts from patients with peroxisomal defects, the cholesterol content and mevalonate incorporation into cholesterol were decreased by 10-20% in comparison with control cells. Mevinolin pretreatment decreased the incorporation rate of [3H]-mevalonate into cholesterol but increased the labeling of ubiquinone and dolichol both in diseased and control cells. Squalene synthase activity was unchanged, whereas the activity of farnesyl-pyrophosphate synthase was increased in the diseased states. The results show that in patients with peroxisomal deficiency neither the amount nor the rate of synthesis of cholesterol and dolichol is reduced to any greater extent.

  • 3.
    Fjaertoft, Gustav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Foucard, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Neutrophils from term and preterm newborn infants express the high affinity Fcgamma-receptor 1 (CD64) during bacerial infections1999In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 45, no 6, p. 871-876Article in journal (Refereed)
    Abstract [en]

    The high affinity Fcgamma-receptor I (FcgammaRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcgammaRI. Stimulation through FcgammaRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcgammaRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcgammaRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcgammaRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcgammaRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcgammaRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcgammaRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.

  • 4.
    Fjaertoft, Gustav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Håkansson, Lena
    Ewald, Uwe
    Foucard, Tony
    Venge, Per
    Neutrophils from Term and Preterm Newborn Infants Express the High Affinity Fcγ-Receptor I (CD64) During Bacterial Infections1999In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 45, no 6, p. 871-876Article in journal (Refereed)
    Abstract [en]

    The high affinity Fcgamma-receptor I (FcgammaRI, CD64) is normally expressed only to a very low extent by neutrophils. During bacterial infections, however, neutrophils from adult patients significantly increase their expression of FcgammaRI. Stimulation through FcgammaRI is a highly effective way to improve various aspects of neutrophil function, including phagocytosis. In our study the expression of FcgammaRI on neutrophils from preterm (n = 9) and term (n = 3) newborn infants, children (n = 14), and adults (n = 6) during the early phase of an acute bacterial infection was investigated. Our results showed that neutrophils from newborn infants with bacterial infection expressed FcgammaRI to a significantly higher extent than both noninfected preterm (p < 0.001) and term (p < 0.001) newborn infants and that neutrophils from preterm neonates expressed FcgammaRI to the same extent as neutrophils from term neonates and older infants, children, and adults. No difference in the neutrophil cell surface expression of FcgammaRI during bacterial infections was found among newborn infants, children, and adults. Expression of FcgammaRI probably represents an important mechanism to improve neutrophil phagocytosis as well as other aspects of neutrophil function during bacterial infections, especially in preterm infants. Our study indicates that measurement of cell surface expression of FcgammaRI on neutrophils could be a useful indicator of severe bacterial infections in preterm and term neonates, as well as in older children and adults.

  • 5. Griesmaier, Elke
    et al.
    Enot, David Pierre
    Bachmann, Miriam
    Neubauer, Vera
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kiechl-Kohlendorfer, Ursula
    Keller, Matthias
    Systematic characterization of amplitude-integrated EEG signals for monitoring the preterm brain2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 73, no 2, p. 226-235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In preterm infants, the amplitude-integrated electroencephalogram (aEEG) is not established in clinical routine. The aim of this study was to derive normative data on aEEG parameters by means of longitudinal characterization and to evaluate the impact of gestational age (GA), postnatal age (PNA), postmenstrual age, sedation, and patent ductus arteriosus (PDA). METHODS: Recordings from 61 infants with GA 28-31 weeks were obtained during the first 72 h, then weekly until the age of 4 wk. Infants were divided into three groups: (i) no sedation, no PDA, (ii) sedation, no PDA, and (iii) sedation, PDA. Assessed parameters included background activity, cycling, amplitude, and log ratio of the maximum/minimum amplitude. RESULTS: GA and PNA had a significant impact within 72h. Sedation modified aEEG, and presence of PDA was associated with reduced aEEG scores within 72 h. The log ratio of the amplitude correlated with GA but was unaffected by sedation and PDA. CONCLUSION: Evaluation of electrocortical background activity within the first postnatal hours and longitudinally over days and weeks is important to better understand the postnatal factors impacting cerebral function in preterm infants. There is a need to agree on definitions and a standardized reporting system in order to permit comparisons between studies and establish aEEG as a method for routine monitoring of preterm infants.

  • 6.
    Gäreskog, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Wentzel, Parri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Altered Protein Kinase C Activation Associated with Rat Embryonic Dysmorphogenesis2004In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 56, no 6, p. 849-857Article in journal (Refereed)
    Abstract [en]

    It has been suggested that protein kinase C (PKC) is involved in the etiology of diabetic complications. The aim of the present study was to investigate the putative involvement of different PKC isoforms (alpha, beta1, beta 2, gamma, delta, epsilon, and zeta) in the embryopathy of diabetic rat pregnancy. Embryos were collected from normal and diabetic rats and assayed for PKC activity, PKC mRNA levels, and PKC protein distribution on gestational d 10 and 11. Embryos of diabetic rats showed markers of increased activity of PKC-alpha, PKC-beta1, PKC-gamma, PKC-delta, and PKC-zeta compared with embryos of normal rats on d 10. In addition, the malformed embryos had further increased PKC-gamma, and PKC-delta activity markers compared with nonmalformed embryos of diabetic rats on gestational d 10. In contrast, maternal diabetes caused only two alterations in PKC activity markers on gestational d 11, i.e. both PKC-alpha and PKC-zeta were decreased in embryos of diabetic rats. We found increased mRNA levels of PKC-beta 1 and PKC-zeta on d 10 in embryos of diabetic rats and decreased mRNA levels of PKC-gamma on d 11 in embryos of diabetic rats. Malformed embryos from diabetic rats showed increased distribution of PKC-beta 1 and PKC-beta 2 protein in the tissue compared with nonmalformed embryos from diabetic rats and embryos from normal rats. We conclude that diabetic rat embryopathy may be associated with increased activity and enhanced tissue distribution of several PKC isoforms in early organogenesis.

  • 7. Hansen-Pupp, Ingrid
    et al.
    Hovel, Holger
    Lofqvist, Chatarina
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fellman, Vineta
    Huppi, Petra S.
    Hellstrom, Ann
    Ley, David
    Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 74, no 5, p. 564-569Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. METHODS: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual beta coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. RESULTS: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) <85 (odds ratio (95% confidence interval): 0.6 (0.4-0.9), 0.96 (0.94-0.99), and 0.78 (0.6-0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. CONCLUSION: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age.

  • 8. Hovel, Holger
    et al.
    Partanen, Eino
    Tideman, Eva
    Stjernqvist, Karin
    Hellström-Westass, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Huotilainen, Minna
    Fellman, Vineta
    Auditory event-related potentials are related to cognition at preschool age after very preterm birth2015In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, no 4, p. 570-578Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Auditory event-related potentials (AERP) are neurophysiological correlates of sound perception and cognitive processes. Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome. METHODS: Seventy children (mean +/- SD gestational age 27.4 +/- 1.9 wk, birth weight 996 +/- 288 g) were investigated at age 4.3-5.3 y with psychological testing (WPPSI-R, four subtests of NEPSY), Electroencephalogram was recorded while they listened to a repeated standard tone, randomly replaced by one of three deviants. Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured. RESULTS: Better cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150-500 ms after stimulus change onset. Neonatal brain damage was associated with a negative displacement of AERP curves. Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows. CONCLUSION: AERP measures were associated with cognitive outcome. Neonatal morbidity mainly affects early cortical auditory encoding, while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction. Perinatal auditory environment might play a role in development of auditory processing.

  • 9. Kamath-Rayne, Beena D
    et al.
    Berkelhamer, Sara K
    KC, Ashish
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Ersdal, Hege L
    Niermeyer, Susan
    Neonatal resuscitation in global health settings: an examination of the past to prepare for the future.2017In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 82, no 2, p. 194-200Article in journal (Refereed)
    Abstract [en]

    As rates of childhood mortality decline, neonatal deaths account for nearly half of under-5 deaths worldwide. Intrapartum-related events (birth asphyxia) contribute to approximately one-quarter of neonatal deaths, many of which can be prevented by simple resuscitation and newborn care interventions. This paper reviews various lines of research that have influenced the global neonatal resuscitation landscape. A brief situational analysis of asphyxia-related newborn mortality in low-resource settings is linked to renewed efforts to reduce neonatal mortality in the Every Newborn Action Plan. Possible solutions to gaps in care are identified. Building on international scientific evidence, tests of educational efficacy, and community-based trials established the feasibility and effectiveness of training in resource-limited settings and identified successful implementation strategies. Implementation of neonatal resuscitation programs has been shown to decrease intrapartum stillbirth rates and early neonatal mortality. Challenges remain with respect to provider competencies, coverage, and quality of interventions. The combination of resuscitation science, strategies to increase educational effectiveness, and implemention of interventions with high coverage and quality has resulted in reduced rates of asphyxia-related neonatal mortality. Further efforts to improve coverage and implementation of neonatal resuscitation will be necessary to meet the 2035 goal of eliminating preventable newborn deaths.

  • 10.
    Kaul, Ylva Fredriksson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rosander, Kerstin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Hofsten, von, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Brodd, Katarina Strand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Kaul, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bohm, Birgitta
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Visual tracking in very preterm infants at 4 months predicts neurodevelopment at 3 years of age2016In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 80, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Typically developing infants track moving objects with eye and head movements in a smooth and predictive way at 4 mo of age, but this ability is delayed in very preterm infants. We hypothesized that visual tracking ability in very preterm infants predicts later neurodevelopment. METHOD: In 67 very preterm infants (gestational age<32wk), eye and head movements were assessed at 4 mo corrected age while the infant tracked a moving object. Gaze gain, smooth pursuit, head movements, and timing of gaze relative the object were analyzed off line. Results of the five subscales included in the Bayley Scales of Infant Development (BSID-III) at 3 y of age were evaluated in relation to the visual tracking data and to perinatal risk factors. RESULTS: Significant correlations were obtained between gaze gain and cognition, receptive and expressive language, and fine motor function, respectively, also after controlling for gestational age, severe brain damage, retinopathy of prematurity, and bronchopulmonary dysplasia. CONCLUSION: This is the first study demonstrating that the basic ability to visually track a moving object at 4 mo robustly predicts neurodevelopment at 3 y of age in children born very preterm.

  • 11.
    Khanolkar, Amal R.
    et al.
    Centre for Health Equity Studies, Karolinska Institutet/Stockholm University, Sweden.
    Sovio, Ulla
    Centre for Health Equity Studies, Karolinska Institutet/Stockholm University, Sweden.
    Bartlett, Jonathan W.
    Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
    Wallby, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Koupil, Ilona
    Centre for Health Equity Studies, Karolinska Institutet/Stockholm University, Sweden.
    Socioeconomic and early-life factors and risk of being overweight or obese in children of Swedish- and foreign-born parents2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 74, no 3, p. 356-363Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ethnic minorities/immigrants have differential health as compared with natives. The epidemic in child overweight/obesity (OW/OB) in Sweden is leveling oft but lower socioeconomic groups and immigrants/ethnic minorities may not have benefited equally from this trend. We investigated whether nonethnic Swedish children are at increased risk for being OW/OB and whether these associations are mediated by parental socioeconomic position (SEP) and/or early-life factors such as birth weight, maternal smoking, BMI, and breastfeeding. METHODS: Data on 10,628 singleton children (51% boys, mean age: 4.8 y, born during the period 2000-2004) residing in Uppsala were analyzed. OW/OB was computed using the International Obesity Task Force's sex- and age-specific cutoffs. The mother's nativity was used as proxy for ethnicity. Logistic regression was used to analyze ethnicity-OW/OB associations. RESULTS: Children of North African, Iranian, South American, and Turkish ethnicity had increased odds for being overweight/obese as compared with children of Swedish ethnicity (adjusted odds ratio (OR): 2.60 (95% confidence interval (CI): 1.57-4.27), 1.67 (1.03-2.72), 3.00 (1.86-4.80), and 2.90 (1.73-4.88), respectively). Finnish children had decreased odds for being overweight/obese (adjusted OR: 0.53 (0.32-0.90)). CONCLUSION: Ethnic differences in a child's risk for OW/OB exist in Sweden that cannot be explained by SEP or maternal or birth factors. As OW/OB often tracks into adulthood, more effective public health policies that intervene at an early age are needed.

  • 12. Ley, David
    et al.
    Hansen-Pupp, Ingrid
    Niklasson, Aimon
    Domellöf, Magnus
    Friberg, Lena E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Borg, Jan
    Löfqvist, Chatarina
    Hellgren, Gunnel
    Smith, Lois E H
    Hård, Anna-Lena
    Hellström, Ann
    Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety.2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 73, no 1, p. 68-74Article in journal (Refereed)
    Abstract [en]

    Background:In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP.Methods:In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded.Conclusion:In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.

  • 13.
    Lindström, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Bergman, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Mulic-Lutvica, Ajlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Postnatal growth in children born small for gestational age with and without smoking mother2019In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 85, no 7, p. 961-966Article in journal (Refereed)
    Abstract [en]

    Background: Maternal smoking impairs fetal growth; however, if postnatal growth differs between children born small for gestational age (SGA) with smoking and non-smoking mother is unknown.

    Methods: Cohort-study of term born children born appropriate for gestational age with non-smoking mother (AGA-NS, n=30,561), SGA (birthweight <10th percentile) with smoking mother (SGA-S, n=171) or SGA with non-smoking mother (SGA-NS, n=1761). Means of height and weight measurements, collected at birth, 1.5, 3, 4 and 5 years, were compared using a generalized linear mixed effect model. Relative risks of short stature (<10th percentile) were expressed as adjusted risk ratios (aRR).

    Results: At birth, children born SGA-S were shorter than SGA-NS, but they did not differ in weight. At 1.5 years, SGA-S had reached the same height as SGA-NS. At 5 years, SGA-S were 1.1 cm taller and 1.2 kg heavier than SGA-NS. Compared with AGA-NS, SGA-S did not have increased risk of short stature at 1.5 or 5 years, while SGA-NS had increased risk of short stature at both ages; aRRs 3.0 (95% CI 2.6;3.4) and 2.3 (95% CI 2.0;2.7), respectively.

    Conclusions: Children born SGA-S have a more rapid catch-up growth than SGA-NS. This may have consequences for metabolic and cardiovascular health in children with smoking mothers.

  • 14. Löfqvist, Chatarina
    et al.
    Niklasson, Aimon
    Engström, Eva
    Friberg, Lena E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Camacho-Hubner, Cecilia
    Ley, David
    Borg, Jan
    Smith, Lois E. H.
    Hellström, Ann
    A Pharmacokinetic and Dosing Study of Intravenous Insulin-Like Growth Factor-I and IGF-Binding Protein-3 Complex to Preterm Infants2009In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 65, no 5, p. 574-579Article in journal (Refereed)
    Abstract [en]

    In preterm infants, low levels of Insulin like growth factor I (IGF-I) have been associated with impaired growth and retinopathy of prematurity. Our objective was to study safety and pharmacokinetics of i.v. administered rhIGF-I with its binding protein 3 (rhIGFBP-3) to preterm infants. At 3 d chronological age, an i.v. 3 h infusion of rhIGF-1/rhIGFBP-3 was administered followed by serial measurements of IGF-I and IGFBP-3. Infants were evaluated for physiologic safety measurements. The individual dose of rhIGF-I ranged from I to 12 mu g/kg. The study was conducted at Queen Silvia Children's Hospital, Gothenburg, Sweden, between January and November 2007. Five patients (3 F) with mean (range) post menstrual age 27 wk (26-29) and birth weight 1022 g (810-1310) participated. IGF-I and IGFBP-3 levels before infusion were median (range) 18 (12-28) and 771 (651-1047) ng/mL, respectively. Immediately after study drug infusion, serum IGF-I and IGFBP-3 levels were 38 (25-59) and 838 (754-1182) ng/mL, respectively. Median (range) half-life for IGF-I and IGFBP-3 was 0.79 (0.59-1.42) and 0.87 (0.85-0.94) hours, respectively. Blood glucose, insulin, sodium, potassium, and physiologic safety measures were within normal ranges. The rhIGF-1/rhIGFBP-3 equimolar proportion was effective in increasing serum IGF-I levels and administration under these study conditions was safe and well tolerated.

  • 15.
    Löfving, Anders
    et al.
    Hosp Halland, Dept Pediat, Halmstad, Sweden.
    Domellöf, Magnus
    Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Andersson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition. Hosp Halland, Dept Pediat, Halmstad, Sweden.
    Reference intervals for reticulocyte hemoglobin content in healthy infants2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, no 5, p. 657-661Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Iron deficiency anemia in childhood is a serious public health problem worldwide. Reticulocyte hemoglobin content (Ret-He) is a novel biomarker of iron deficiency adopted for adults but there is a lack of reference intervals for Ret-He in infants. The aim of this study was to provide data from healthy infants. METHODS: Swedish infants (n = 456), born at term after normal pregnancies were included. Ret-He was measured at birth (umbilical cord sample), 48-72 h, 4 months, and 12 months. Reference intervals were calculated as +/- 2 standard deviations from the mean of Ret-He. RESULTS: Reference intervals for newborn Ret-He were 27.4 to 36.0 pg/L (N = 376) in the cord sample, 28.1-37.7 pg/L (N = 253) at 48-72 h, 25.6-33.4 pg/L (N = 341) at four months and 24.9-34.1 pg/L (N = 288) at 12 months. Ret-He was significantly lower among iron-deficient infants, at 4 months mean difference (95% Cl) -4.2 pg/L (-6.1 to -2.4) and at 12 months mean difference (95% Cl) -3.4 pg/L (-5.0 to -1.8). CONCLUSIONS: This longitudinal study presents Ret-He reference intervals based on non-anemic and non-iron-deficient infants and constitutes a step towards standardizing Ret-He as a pre-anemia biomarker of iron deficiency in children.

  • 16. Mannerkoski, Minna K.
    et al.
    Heiskala, Hannu J.
    Van Leemput, Koen
    Åberg, Laura E.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hämäläinen, Janne
    Autti, Taina H.
    Subjects with intellectual disability and familial need for full-time special education show regional brain alterations: a voxel-based morphometry study2009In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 66, no 3, p. 306-311Article in journal (Refereed)
    Abstract [en]

    Subjects attending full-time special education (SE) often have multifactorial background for their cognitive impairment, and brain MRI may show nonspecific changes. As voxel-based morphometry reveals regional volume differences, we applied this method to 119 subjects with cognitive impairments and familial need for full-time SE--graded into three levels from specific disorders of cognitive processes (level 1) to intellectual disability (IQ <70; level 3)--and to 43 age-matched controls attending mainstream education (level 0). Subjects in SE groups had smaller global brain white matter (WM), cerebrospinal fluid, and total brain volume than controls. Compared with controls, subjects with intellectual disabilities in SE level 3 showed greater regional gray matter volumes bilaterally in the ventral and dorsal anterior cingulate cortex and smaller regional gray matter volumes in the left thalamus and cerebellar hemisphere. Further, they had greater WM volume in the left frontoparietal region and smaller WM volumes in the posterior limbs of the internal capsules. Subjects in SE level 1 and 2 groups showed the same tendency, but the results were nonsignificant. In conclusion, compared with controls, subjects with intellectual disabilities showed in voxel-based morphometry analysis several regional brain alterations.

  • 17.
    Norman, Elisabeth
    et al.
    Dept. of Pediatrics, Lund University, Lund, Sweden.
    Rosén, Ingmar
    Dept. of Clinical Neurophysiology, Lund University Hospital, Lund, Sweden.
    Vanhatalo, Sampsa
    Dept. of Clinical Neurophysiology, Lund University Hospital, Lund, Sweden.
    Stjernqvist, Karin
    Dept. of Psychology, Lund University, Lund, Sweden.
    Okland, Ove
    Ålesund Hospital, Ålesund N-6006, Norway.
    Fellman, Vineta
    Dept. of Pediatrics, Lund University, Lund, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Electroencephalographic response to procedural pain in healthy term newborn infants2008In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 64, no 4, p. 429-34Article in journal (Refereed)
    Abstract [en]

    The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates, and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care.Seventy-two healthy term infants were investigated: Twenty-eight had a non skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n=16) or water (n=12) before the stimulus. 21 infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile (PIPP) scale. The stimulus evoked a significant increase in higher frequency components (10-30Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli.

  • 18. Norman, Elisabeth
    et al.
    Wikström, Sverre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rosen, Ingmar
    Fellman, Vineta
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants2013In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 73, no 1, p. 87-94Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation (RSI). METHODS: Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2-3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs. RESULTS: RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24h, and during the first 9h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure. CONCLUSION: Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.

  • 19.
    Olsson, Karl Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation2019In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 86, p. 333-338Article in journal (Refereed)
    Abstract [en]

    Background

    Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.

    Methods

    Infants born at 22–27 weeks’ gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.

    Results

    High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.

    Conclusions

    High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

  • 20. Perez-de-Sa, Valeria
    et al.
    Cunha-Goncalves, Doris
    Nordh, Anders
    Hansson, Stefan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ley, David
    Fellman, Vineta
    Werner, Olof
    High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep2009In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 65, no 1, p. 57-61Article in journal (Refereed)
    Abstract [en]

    The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n = 7) or with 100% oxygen for 3 (n = 6) or 30 min (n = 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (PO2) was 10.7 (1.8-56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue PO2 (PbtO2) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30-61) kPa, whereas in those given oxygen for just 3 min, PbtO2 peaked at 4.2 (2.9-46) kPa. The maximal PbtO2 in air-ventilated lambs was 2.9 (0.8-5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in PbtO2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia.

  • 21.
    Segerström, Lova
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fuchs, Dieter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bäckman, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Holmquist, Kajsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Azarbayjani, Faranak
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The Anti-VEGF Antibody Bevacizumab Potently Reduces the Growth Rate of High-Risk Neuroblastoma Xenografts2006In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 60, no 5, p. 576-581Article in journal (Refereed)
    Abstract [en]

    Neuroblastoma (NB) is a rapidly growing, well-vascularized childhood cancer that often presents with metastases. The overall five-year survival in NB is approximately 45% despite multimodality treatment, and therefore there is a clinical need for new therapeutic strategies. NB frequently overexpresses the angiogenic factor VEGF (vascular endothelial growth factor). The aim of this study was to investigate the effect of bevacizumab (Avastin, Genentech/Roche), a humanized anti-VEGF-A antibody, on NB growth in three different xenograft models, chosen to resemble high-risk NB. The human NB cell lines SK-N-AS, IMR-32 and SH-SY5Y, which are poorly differentiated and overexpress VEGF-A, were injected s.c. in immunodeficient mice. Bevacizumab was given intraperitoneally twice weekly at 5 mg/kg body weight, starting at a tumor volume of 0.3 mL. Bevacizumab significantly (p < 0.01-0.05) reduced NB growth in vivo without toxicity by causing a 30-63% reduction of angiogenesis, but had no effect on NB cell survival in vitro. Serum concentrations of VEGF-A increased two- to six-fold during bevacizumab therapy which did not result in faster tumor growth compared with control animals. Based on our experimental data we suggest consideration of bevacizumab in treatment of high-risk NB that does not respond to conventional therapy and that overexpresses VEGF.

  • 22.
    Späth, Cornelia
    et al.
    Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden..
    Sjöström, Elisabeth Stoltz
    Umea Univ, Dept Food & Nutr, Umea, Sweden..
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Domellöf, Magnus
    Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden..
    Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants2017In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, no 3, p. 455-460Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hyper- and hyponatremia occur frequently in extremely preterm infants. Our purpose was to investigate plasma sodium (P-Na) concentrations, the incidence of hyper and hyponatremia, and the impact of possible predisposing factors in extremely preterm infants. METHODS: In this observational study, we analyzed data from the EXtremely PREterm (< 27wk.) infants in Sweden Study (EXPRESS, n = 707). Detailed nutritional, laboratory, and weight data were collected retrospectively from patient records. RESULTS: Mean +/- SD P-Na increased from 135.5 +/- 3.0 at birth to 144.3 +/- 6.1 mmol/l at a postnatal age of 3 d and decreased thereafter. Fifty percent of infants had hypernatremia (P-Na > 145 mmol/l) during the first week of life while 79% displayed hyponatremia (P-Na < 135 mmol/l) during week 2. Initially, the main sodium sources were blood products and saline injections/infusions, gradually shifting to parenteral and enteral nutrition towards the end of the first week. The major deter, minant of P-Na and the risks of hyper- and hyponatremia was sodium supply. Fluid volume provision was associated with postnatal weight change but not with P-Na. CONCLUSION: The supply of sodium, rather than fluid volume, is the major factor determining P-Na concentrations and the risks of hyper- and hyponatremia.

  • 23.
    Staaf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ubhayasekera, Sarojini J. K. A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Chowdhury, Azazul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Initial hyperinsulinemia and subsequent beta-cell dysfunction is associated with elevated palmitate levels2016In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 80, no 2, p. 267-274Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The prevalence of obesity-related diabetes in childhood is increasing and circulating levels of nonesterified fatty acids may constitute a link. Here, the association between palmitate and insulin secretion was investigated in vivo and in vitro.

    METHODS: Obese and lean children and adolescents (n = 80) were included. Palmitate was measured at fasting; insulin and glucose during an oral glucose tolerance test (OGTT). Human islets were cultured for 0 to 7 d in presence of 0.5 mmol/l palmitate. Glucose-stimulated insulin secretion (GSIS), insulin content and apoptosis were measured.

    RESULTS: Obese subjects had fasting palmitate levels between 0.10 and 0.33 mmol/l, with higher average levels compared to lean subjects. While obese children with elevated palmitate (>0.20 mmol/l) had accentuated insulin levels during OGTT, obese adolescents with high palmitate had delayed first-phase insulin response. In human islets exposed to palmitate for 2 d GSIS was twofold enhanced, but after 7 d attenuated. Intracellular insulin content decreased time-dependently in islets cultured in the presence of palmitate and cleaved caspase 3 increased.

    CONCLUSION: The rapid accentuated and delayed insulin secretory responses observed in obese children and adolescents, respectively, with high palmitate levels may reflect changes in islet secretory activity and integrity induced by extended exposure to the fatty acid.

  • 24.
    Stålhammar, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Douhan Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Under Agarose Migration Assay: a Method to Study Graded Chemotactic Activity of Leukocytes in Newborn Infants2010In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 68, no suppl. 1, p. 427-427Article in journal (Refereed)
  • 25. van Kaam, AH
    et al.
    De Luca, D
    Hentschel, R
    Hutten, J
    Sindelar, R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thome, U
    Zimmermann, LJI
    Modes and strategies forproviding conventional mechanical ventilation in neonates2019In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed)
    Abstract [en]

    Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.

  • 26. van Kaam, Anton H
    Hentschel, R
    Hutten, J
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Thome, U
    Zimmermann, LJI
    Modes and strategies for providing conventional mechanical ventilation in neonates2019In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed)
    Abstract [en]

    Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.

  • 27.
    Veneroni, Chiara
    et al.
    Politecn Milano Univ, Dipartimento Elettron Informaz & Bioingn, Milan, Italy.
    Wallström, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Dellaca, Raffaele
    Politecn Milano Univ, Dipartimento Elettron Informaz & Bioingn, Milan, Italy.
    Oscillatory respiratory mechanics on the first day of life improves prediction of respiratory outcomes in extremely preterm newborns2018In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 85, no 3, p. 312-317Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to evaluate if lung mechanics measured by forced oscillatory technique (FOT) during the first day of life help identify extremely low gestational age newborns (ELGANs) at risk of prolonged mechanical ventilation (MV) and oxygen dependency.

    METHODS: Positive end-expiratory pressure (PEEP) was increased 2 cmH2O above the clinically set PEEP, then decreased by four 5-min steps of 1 cmH2O, and restored at the clinical value. At each PEEP, FOT measurements were performed bedside during MV. Changes in respiratory mechanics with PEEP, clinical parameters, and chest radiographs were evaluated.

    RESULTS: Twenty-two newborns (24+4 ± 1+4 wks gestational age (GA); birth weight 653 ± 166 g) on assist/control ventilation were studied. Infants were ventilated for 40 ± 36 d (range 1–155 d), 11 developed severe bronchopulmonary dysplasia (BPD) and one died before 28 d. Early lung mechanics correlated with days on MV, days of respiratory support, and BPD grade. Effects of increasing PEEP on oscillatory reactance assessed by FOT together with GA and radiographic score predicted days on MV (multilinear model, r2 = 0.73). A logistic model considering the same FOT parameter together with GA predicts BPD development.

    CONCLUSIONS: FOT can be applied bedside in ELGANs, where early changes in lung mechanics with PEEP improve clinical prediction of respiratory outcomes.

  • 28.
    Wentzel, Parri
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Eriksson, Ulf J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Diabetes in pregnancy: Uterine blood flow and embryonic development in the rat1995In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 38, no 4, p. 598-606Article in journal (Refereed)
    Abstract [en]

    The uterine blood flow to individual implantation sites was evaluated in early normal and diabetic rat pregnancy, and related to maternal metabolic state, length of gestation, and embryonic outcome. The aim was to search for a possible coupling between the flow rate and embryonic development. We studied pregnant rats of a malformation-prone Sprague-Dawley strain on gestational d 9, 10, 11, and 12, a time period which roughly corresponds to postconception wk 3-6 in human gestation. The blood flow in the uterus was estimated with the aid of a microsphere technique, and the embryos were evaluated with respect to morphology and uterine position. We found increased blood flow in the uterine and decidual tissue of the pregnant diabetic animals compared with normal pregnant rats on all days studied. The blood perfusion peaked on gestational d 10, both in normal and diabetic pregnancy. The implantations tended to be fewer, whereas the resorption and malformation rates were higher, in the left horn than in the right horn. The blood flow in the uterine and decidual tissues was increased in the left horn in diabetic d 10 tissue, as well as d 12 tissues, thereby suggesting that compromised embryonic development is associated with increased rather than decreased supply of nutrients to the implantation site. These findings are in concert with previous in vitro results suggesting that enhanced oxidative stress due to increased substrate availability is an important factor in diabetic teratogenesis.

  • 29.
    Ågren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Zelenin, Sergey
    Håkansson, Mattias
    Eklöf, Ann-Christine
    Aperia, Anita
    Nejsum, Lene N.
    Nielsen, Sören
    Sedin, Gunnar
    Transepidermal water loss in developing rats: Role of aquaporins in the immature skin2003In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 53, no 4, p. 558-565Article in journal (Refereed)
    Abstract [en]

    In the extremely preterm infant, high transepidermal water loss (TEWL) can result in severe dehydration. TEWL has been attributed to the structural properties of the epidermis but might also be influenced by mechanisms that facilitate water transport. To investigate whether aquaporins (AQP) may be involved in the extreme losses of water through immature skin, we examined the presence and cellular distributions of AQP-1 and AQP-3 in embryonic and adult rat skin by immunohistochemistry. The expression of AQP mRNA in skin was analyzed with the use of semiquantitative reverse transcription-PCR. In rat pups of different embryonic (E) and postnatal (P) ages (days), TEWL and skin hydration were measured. AQP-1 was detected in dermal capillaries, and AQP-3 was abundant in basal epidermal layers. Both AQP displayed several times higher expression in embryonic than in adult skin. TEWL was highest at embryonic day 18 (E18) (133 +/- 18 g/m2h) and lower at E20 (25 +/- 1 g/m2h) and P4 (9 +/- 2 g/m2h). Skin hydration measured as skin electrical capacitance paralleled TEWL, being highest in fetal skin (794 +/- 15 pF at E18) and decreasing to 109 +/- 11 pF at E20 and to 0 +/- 0 pF at P4. We conclude that, as in infants, water loss through the skin of rats decreases markedly with maturation during the perinatal period. The expression and cellular localization of the AQP are such that they might influence skin hydration and water transport and contribute to the high losses of water through the immature skin.

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