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1.
  • Stoltz Sjöström, Elisabeth, et al. (author)
  • Micronutrient Intakes Affect Early Growth in Extremely Preterm Infants : Preliminary Results from a Swedish Cohort
  • 2011
  • In: Pediatric Research. - : Nature Publishing Group. - 1530-0447 .- 0031-3998.
  • Conference paper (peer-reviewed)abstract
    • Background: Extremely preterm infants generally experience postnatal growth failure. It is still unclear if this is related to micronutrient intakes.Aim: To investigate the effect of micronutrient intakes (calcium, zinc, iron, phosphorus, sodium, potassium, chloride, magnesium, vitamin A, vitamin D, vitamin E, folate and vitamin B12) on growth during the first 28 days of life in extremely preterm infants.Method: From the EXPRESS cohort (all infants born < 27 gestational weeks between 2004-2007 in Sweden), those who survived the first 28 days were included (n=524). Daily parenteral and enteral intakes and anthropometric measurements were retrieved from hospital records.Results: Preliminary analyses of data from 333 infants (mean±SD gestational age 25.2±1.0 weeks, birth weight 753±168g) showed that macronutrient intakes were lower than recommended (energy 98±13kcal/kg/day, protein 2.9±0.4g/kg/day). Infants showed postnatal growth failure: mean standard deviation scores decreased by 2.2 for weight, 2.3 for length and 1.4 for head circumference. Intakes of micronutrients were generally low, e.g. adjusted enteral intakes of calcium were 66.6±21.4 mg/kg/day. The exception was iron, with a high parenteral intake of 2.7±1.6 mg/kg/day, mainly from blood transfusions. Adjusting for protein intake and other confounders, calcium intakes were positively correlated with head growth (r=+0.19, p=0.006) and iron intakes were negatively correlated with length gain (r=-0.18, p=0.009).Conclusions: Low calcium intakes and high iron intakes were associated with poor growth with regard to head circumference and length, respectively. If these results are confirmed, optimized micronutrient intakes may improve early growth in extremely preterm infants.
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  • Abelius, Martina S, et al. (author)
  • High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life
  • 2011
  • In: Pediatric Research. - 0031-3998 .- 1530-0447. ; 70:5, s. 495-500
  • Journal article (peer-reviewed)abstract
    • Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.
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  • Aburawi, Elhadi H., et al. (author)
  • Effects of N-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Coronary Flow in Children with Type 1 Diabetes Mellitus
  • 2011
  • In: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 70:227
  • Conference paper (peer-reviewed)abstract
    • Purposes: Dietary supplementation with N-3 Polyunsaturated Fatty Acids (n-3 PUFAs) could have beneficial effects on cardiovascular system in patients with type 1 diabetes mellitus (DM1). Methods: In a double-blind placebo controlled crossover study, 33 children with DM1 duration of more than one year were randomly and equally assigned to either n-3 PUFAs (2 gm/day, Nycoplus® Omega-3, 1000 mg) or placebo treatment for 8 weeks. Following a 4-week period recovery, the groups were crossovered with above treatments for another 8 weeks. Transthoracic Doppler echocardiography (TTDE) study was done on pre and post treatment visits, and after one month's treatment free recovery for left ventricular function and flow in the left anterior descending coronary artery (LAD). Results: Of recruited children 28 (85%) completed the study. n-3 PUFAs treatment was associated with increase in mean cardiac index (CI; from 2.7±0.4 to 3.7±0.8 l/min/m2, p< 0.0001) and left ventricular fractional shortening (FS; from 31±2.5 to 39±3%, p< 0.0001). The treatment decreased both LAD peak flow velocity (PFVd) from 96±17 to 68±12 cm/s, p< 0.0001 and LAD CF from 105±31 to 66±15 ml/min, p< 0.0001). One month after stopping the treatment CI decreased from 3.7±0.8 to 2.6±0.5 l/min/m2, p< 0.0001 and mean FS from 39±3 to 32±2, p< 0.0001. Mean PFVd increased from 68±12 to 90±12 cm/s, p< 0.0001 and CF from 66±15 to 108±30 ml/min, p< 0.0001. Conclusions: In patients with DM1 n-3 PUFA therapy increased cardiac index and LV systolic function. The basal coronary flow decrease improving the circumstances for better coronary flow reserve.
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  • Albertsson-Wikland, Kerstin, 1947, et al. (author)
  • Long-Term Response to GH Therapy in Short Children With a Delayed Infancy-Childhood Transition (DICT)
  • 2011
  • In: Pediatric Research. - 0031-3998 .- 1530-0447. ; 69:6, s. 504-510
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Albertsson-Wikland, Kerstin, et al. (author)
  • Long-term response to growth hormone (GH) therapy in short children with a delayed infancy childhood transition (DICT)
  • 2011
  • In: Pediatric Research. - 0031-3998 .- 1530-0447. ; 69, s. 504-510
  • Journal article (peer-reviewed)abstract
    • Transition of growth from infancy to childhood is associated with activation of the GH-IGF-I axis. Children with a delayed infancy-childhood-transition (ICT) are short as adults. Thus, age at ICT may impact on growth response to GH. The objective was to investigate associations between growth response to GH-treatment and ICT-timing in children with idiopathic short stature (ISS) in a randomized, controlled, multicenter trial, TRN 88-080. 147 pre-pubertal children (mean age, 11.5±1.4 yrs) were randomized to receive GH 33μg/kg/d (GH33, n=43), GH 67μg/kg/d (GH67, n=61) or no treatment (n=43). Data on growth to final height (FH) were analyzed after categorization into those with normal (n=76) or delayed ICT (n=71). Within the GH33 group, significant height gain at FH was only observed in children with a delayed ICT (p<0.001) with each month of delay corresponding to gain of 0.13 standard deviation score (SDS). For the GH67 group, the timing of the onset of the ICT had no impact on growth response. In conclusion, ISS children with a delayed ICT responded to standard-GH-dose (better responsiveness), whereas those with a normal ICT required higher doses to attain a significant height gain to FH.
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  • Berglund, Staffan, 1975-, et al. (author)
  • Effects of iron supplementation on auditory brainstem response in marginally LBW infants
  • 2011
  • In: Pediatric Research. - Baltimore : International Pediatrics Research Foundation, Inc. - 0031-3998 .- 1530-0447. ; 70:6, s. 601-606
  • Journal article (peer-reviewed)abstract
    • LBW infants are at risk of iron deficiency (ID), which is associated with impaired nervous system development and may lead to prolonged auditory brainstem response (ABR) latencies. We hypothesized that iron supplementation shortens ABR latencies in marginally LBW (MLBW, 2000-2500 g) infants. In a randomized, controlled trial, 285 healthy MLBW infants received 0, 1, or 2 mg iron/kg/d of iron supplements from 6 wk to 6 mo of age. ABR absolute wave V latencies and central conduction time (CCT) were measured at the endpoint. There were no significant differences between groups in ABR wave V latencies (n = 218). Furthermore, there were no significantly prolonged ABR latencies in infants with ID (n = 32). CCT was significantly higher in the 2 mg group than in the placebo group (n = 126). However, there were no significant correlations between CCT and iron intake or any iron status variable, suggesting that differences in CCT were not caused by iron. We conclude that iron supplements did not improve ABR latencies, and iron-deficient MLBW infants did not have impaired ABR latencies at 6 mo, suggesting that ABR is not a sensitive measure of impaired neurological development or that mild/moderate ID causes no such impairment in MLBW infants.
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  • Berglund, Staffan K, et al. (author)
  • Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants
  • 2014
  • In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 76:5, s. 477-482
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF. METHODS: We randomized 285 low-birth-weight infants (2,000-2,500g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth.
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  • Bragde, Hanna, 1979-, et al. (author)
  • Gene Expression Profiling of Duodenal Biopsies Discriminates Celiac Disease Mucosa From Normal Mucosa
  • 2011
  • In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 69:6, s. 530-537
  • Journal article (peer-reviewed)abstract
    • Celiac disease (CD) is identified by histopathologic changes in the small intestine which normalize during a gluten-free diet. The histopathologic assessment of duodenal biopsies is usually routine but can be difficult. This study investigated gene expression profiling as a diagnostic tool. A total of 109 genes were selected to reflect alterations in crypt-villi architecture, inflammatory response, and intestinal permeability and were examined for differential expression in normal mucosa compared with CD mucosa in pediatric patients. Biopsies were classified using discriminant analysis of gene expression. Fifty genes were differentially expressed, of which eight (APOC3, CYP3A4, OCLN, MAD2L1, MKI67, CXCL11, IL17A, and CTLA4) discriminated normal mucosa from CD mucosa without classification errors using leave-one-out cross-validation (n = 39) and identified the degree of mucosal damage. Validation using an independent set of biopsies (n = 27) resulted in four discrepant cases. Biopsies from two of these cases showed a patchy distribution of lesions, indicating that discriminant analysis based on single biopsies failed to identify CD mucosa. In the other two cases, serology support class according to discriminant analysis and histologic specimens were judged suboptimal but assessable. Gene expression profiling shows promise as a diagnostic tool and for follow-up of CD, but further evaluation is needed.
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  • Carlsson, Ylva, 1975, et al. (author)
  • Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury.
  • 2012
  • In: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 71:5, s. 566-72
  • Journal article (peer-reviewed)abstract
    • Intoduction:Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage.Methods:The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice.Results:HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33°C ) vs. normothermia (36°C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas.Discussion:In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
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  • Even, L., et al. (author)
  • Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand
  • 2014
  • In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 76:1, s. 109-114
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation. METHODS: Subjects of the study were 95 prepubertal children: 30 children with GH deficiency and 65 children with idiopathic short stature, aged 7.4 +/- 1.9 y (mean +/- SD) (trial registration number 98-0198-033). Bone maturation was assessed by the Greulich and Pyle method from X-rays obtained at the start and at 1 and 2 y of GH treatment, separately for carpals, long bones, and short bones, and was expressed as years of delay relative to chronological age. RESULTS: At GH start, the delay in bone maturation in the GH-deficient group was significantly greater for carpals (3.6 +/- 1.3 y) than for long (3.0 +/- 1.3 y) and short (1.7 +/- 1.1 y) bones. The delay was nonsignificantly greater for carpal bones in GH-deficient subjects than in subjects with idiopathic short stature (3.6 +/- 1.3 vs. 3.1 +/- 1.1 y, respectively) and was normalized after 2 y of GH treatment. CONCLUSION: The dominant effect of GH was on chondral osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal and long-bone maturation, which normalizes during 2 y of GH treatment, was typical in GH-deficient children. Therefore, separate carpal bone assessment in bone age reading is needed.
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  • Fagerås Böttcher, Malin, et al. (author)
  • Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children
  • 2011
  • In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 70:6, s. 572-577
  • Journal article (peer-reviewed)abstract
    • It is unknown why allergic symptoms do not develop in all sensitized children. We analyzed prospectively the postnatal secretory IgA (SIgA) development and whether high SIgA levels would protect sensitized infants from developing allergic symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically adjacent countries with different living conditions and allergy incidence. Total and SIgA levels increased with age, reaching adult levels at the age of 5. Virtually, all salivary IgA in Estonian children was in the secretory form, while a major part of IgA in Swedish saliva lacked the secretory component up to 2 y of age. In Sweden, high levels of salivary IgA without secretory component correlated inversely with house dust endotoxin levels. High SIgA levels were associated with less development of allergic symptoms in sensitized Swedish children. In conclusion, postnatal maturation of the salivary SIgA system proceeds markedly slower in Swedish than Estonian children, possibly as a consequence of low microbial pressure. SIgA may limit allergy-mediated tissue damage at mucosal surfaces in sensitized individuals.
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  • Furuhjelm, Catrin, et al. (author)
  • Th1 and Th2 chemokines, vaccine induced 1 immunity and allergic disease in infants  after maternal ω-3 fatty acid supplementation during pregnancy and lactation
  • 2011
  • In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 69:3, s. 259-264
  • Journal article (peer-reviewed)abstract
    • We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.
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