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  • 1. Albertsson-Wikland, Kerstin
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jonsson, Björn
    Hochberg, Zeʼev
    Long-term response to growth hormone (GH) therapy in short children with a delayed infancy childhood transition (DICT)2011Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 69, s. 504-510Artikel i tidskrift (Refereegranskat)
    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 (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.

  • 2.
    Andersson, Yvonne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lindquist, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Bergström, S
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland.1997Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 41, nr 3, s. 380-3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.

  • 3.
    Berglund, Staffan K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Chmielewska, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Starnberg, Josefine
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Björn
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Norman, Mikael
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, s. 111-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 4.
    Berglund, Staffan K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lindberg, Josefine
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Bjorn
    Department of Women and Child Health, Division of Neonatology, Karolinska Institute, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants2014Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, nr 5, s. 477-482Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 5.
    Berglund, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Westrup, Bjorn
    Department of Women and Child Health, Karolinska Institute, SE-182 88 Stockholm, Sweden.
    Haraldsson, Elisabet
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Engstrom, Berit
    Department of Audiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Domellof, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of iron supplementation on auditory brainstem response in marginally LBW infants2011Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, nr 6, s. 601-606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 6. Björkstén, B
    et al.
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sidenvall, R
    The effect of human colostrum on neutrophil function.1979Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 13, nr 6, s. 737-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Strains of Escherichia coli were opsonized in human colostrum via heat stable opsonins and the classic complement pathway, but colostrum lacked capacity to opsonize E. coli via the alternative pathway. There was no bacteriostatic activity against serum sensitive E. coli strains, although specific antibodies against the strains were present. Neutrophils suspended in colostrum had normal chemotaxis and this was not altered by treating the colostrum with HCl.

  • 7. Candy, David C. A.
    et al.
    Van Ampting, Marleen T. J.
    Nijhuis, Manon M. Oude
    Wopereis, Harm
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Fox, Adam T.
    Shah, Neil
    West, Christina E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Garssen, Johan
    Harthoorn, Lucien F.
    Knol, Jan
    Michaelis, Louise J.
    A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, nr 3, s. 677-686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 8.
    Dahlquist, Gisela
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Källén, B
    Early neonatal events and the disease incidence in nonobese diabetic mice.1997Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 42, nr 4, s. 489-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiologic studies have shown that perinatal events are associated with an increased risk for type 1 (insulin-dependent) diabetes in childhood. We used nonobese diabetic mice to examine whether neonatal separation from the mother with or without phototherapy would affect the incidence of diabetes in this genetically susceptible mouse model. The newborn pups were taken from their mothers for two 4-h periods during each of five successive days. One group of animals was just taken from their mothers and were left lying in daylight in the cage, whereas another group was exposed to identical light as used for treatment of neonatal jaundice in infants. Treatment resulted in a 30% death rate. For animals surviving more than 3 mo the incidence of diabetes was significantly higher in both treatment groups compared with control animals, allowed to stay with their mother. The odds ratio for treatment versus control, stratifying for sex, was 3.42 (95% confidence interval, 1.57-7.74). Histologic insulitis did not differ between treated and untreated animals when examined either at clinical diabetes onset or at 8 mo of age. Blood glucose values at 8 mo of age (in animals without clinical diabetes) did not differ between-treated and untreated animals. It is concluded that neonatal separation of the nonobese diabetic mice from their mothers will lead to a significantly increased risk for diabetes. This increase in risk seems to be associated with the induction of metabolic alterations leading to increased peripheral insulin need rather than with an increased rate of beta cell destruction.

  • 9. Even, Lea
    et al.
    Andersson, Bjorn
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Albertsson-Wikland, Kerstin
    Hochberg, Ze'ev
    Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand2014Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, nr 1, s. 109-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 10.
    Grip, Tove
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dyrlund, Thomas S.
    Ahonen, Linda
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hyötyläinen, Tuulia
    Knip, Mikael
    Lönnerdal, Bo
    Oresic, Matej
    Timby, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, nr 5, s. 726-732Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Supplementation of formula with bovine milk fat globule membranes has been shown to narrow the gap in immunological and cognitive development between breast-fed and formula-fed infants.

    METHOD: In a double-blinded randomized controlled trial 160 formula-fed infants received an experimental formula (EF), supplemented with bovine milk fat globule membranes, or standard formula until 6 months of age. A breast-fed reference group was recruited. Lipidomic analyses were performed on plasma and erythrocyte membranes at 6 months and on serum at 4 and 12 months of age.

    RESULTS: At 6 months of age, we observed a significant separation in the plasma lipidome between the two formula groups, mostly due to differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC), and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs and PCs. Already at 4 months, a separation in the serum lipidome was evident where SMs and PCs contributed. The separation was not detected at 12 months.

    CONCLUSIONS: The effect of MFGM supplementation on the lipidome is likely part of the mechanisms behind the positive cognitive and immunological effects of feeding the EF previously reported in the same study population.

  • 11. Ley, David
    et al.
    Hansen-Pupp, Ingrid
    Niklasson, Aimon
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Friberg, Lena E
    Borg, Jan
    Löfqvist, Chatarina
    Hellgren, Gunnel
    Smith, Lois EH
    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 safety2013Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 73, nr 1, s. 68-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In preterm infants, low levels of insulin-like growth factor-I (IGF-1) 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 mu g/kg/24h.

    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 mu g/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.

  • 12. Löfving, Anders
    et al.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hellström-Westas, Lena
    Andersson, Ola
    Reference intervals for reticulocyte hemoglobin content in healthy infants2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 84, nr 5, s. 657-661Artikel i tidskrift (Refereegranskat)
    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% CI) −4.2 pg/L (−6.1 to −2.4) and at 12 months mean difference (95% CI) −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.

  • 13. Mohlkert, Lilly -Ann
    et al.
    Hallberg, Jenny
    Broberg, Olof
    Hellström, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Halvorsen, Cecilia Pegelow
    Sjoberg, Gunnar
    Bonamy, Anna -Karin Edstedt
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norman, Mikael
    Preterm arteries in childhood: dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm2017Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, nr 2, s. 299-306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Preterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-y-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term. METHODS: Children born extremely preterm (EXP, n = 176, birthweights: 348-1,161 g) and at term (CTRL, n = 174, birth weights: 2,430-4,315 g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (CIMT), and the stiffness index of the CCA and aorta. RESULTS: Arteries were 5-10% narrower in EXP than in CTRL (P < 0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD = 0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL. CONCLUSION: In 6-y-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.

  • 14.
    Späth, Cornelia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stoltz Sjöström, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Ahlsson, Fredrik
    Uppsala universitet.
    Ågren, Johan
    Uppsala universitet.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants2017Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, s. 455-460Artikel i tidskrift (Refereegranskat)
    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 (< 27 wk.) 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 determinant 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.

  • 15.
    Starnberg, Josefine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norman, Mikael
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Westrup, Björn
    Division of Neonatology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Berglund, Staffan K
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lower cognitive test scores at age 7 in children born with marginally low birth weight2018Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 83, nr 6, s. 1129-1135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Being born with very low birth weight (<1500 g) is associated with poorer neurocognition later in life. The aim of this study was to explore neurodevelopmental functions in those born with marginally LBW (2000–2500 g).

    Methods: This was originally a randomized controlled trial investigating the effects of early iron supplementation in 285 marginally LBW children. Herein, we explored the combined marginally LBW group and compared their results to 95 normal birth weight (NBW; 2501–4500 g) controls in an observational design. At 7 years, a pediatric psychologist tested the children using Wechsler Intelligence Scale for Children (WISC IV), Beery–Buktenica developmental test of Visual–Motor Integration (Beery VMI), and Test of Everyday Attention for Children (TEA-Ch).

    Results: The marginally LBW children had lower verbal comprehension intelligence quotient (IQ) (104 vs. 107, P=0.004), lower VMI scores (96.5 vs. 100, P=0.028), and lower total mean TEA-Ch scores (8.5 vs. 9.7, P=0.006), compared to controls. Also, the marginally LBW children group had a higher proportion of children below −1 SD for VMI and TEA-Ch.

    Conclusions: Marginally LBW children had lower verbal comprehension IQ, lower visual–motor integration, and lower attention performance than NBW children, suggesting an increased risk of cognitive difficulties in early school age

  • 16. Szajewska, Hania
    et al.
    Ruszczynski, Marek
    Szymanski, Henryk
    Sadowska-Krawczenko, Iwona
    Piwowarczyk, Anna
    Rasmussen, Preben Bodstrup
    Kristensen, Mette Bach
    West, Christina E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial2017Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 81, nr 5, s. 752-758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.

  • 17.
    Timby, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, California.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes2014Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, nr 4, s. 394-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Some of the health advantages of breast-fed as compared to formula-fed infants have been suggested to be due to metabolic programming effects resulting from early nutrition. METHODS: In a prospective double-blinded randomized trial, 160 infants <2 mo of age were randomized to experimental formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF) until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion and at 4, 6, and 12 mo of age. RESULTS: During the intervention, the EF group had higher total serum cholesterol concentration than the SF group, reaching the level of the BFR group. The EF group had a low-density lipoprotein to high-density lipoprotein ratio not significantly different from the SF group but lower than the BFR group. CONCLUSION: Supplementation of infant formula with MFGM modified the fat composition of the formula and narrowed the gap between breast-fed and formula-fed infants with regard to serum lipid status at 12 mo.

  • 18. Uijterschout, Lieke
    et al.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Berglund, Staffan K
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Abbink, Micky
    Vos, Paul
    Rövekamp, Lyanne
    Boersma, Bart
    Lagerqvist, Carina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hudig, Cisca
    van Goudoever, Johannes B
    Brus, Frank
    Serum hepcidin in infants born after 32 to 37 wk of gestational age2016Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 79, nr 4, s. 608-613Artikel i tidskrift (Refereegranskat)
    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.

  • 19. Uljterschout, Lieke
    et al.
    Swinkels, Dorine W.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lagerqvist, Carina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    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 y2014Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 76, nr 4, s. 409-414Artikel i tidskrift (Refereegranskat)
    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.

  • 20.
    West, Christina E.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    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 trial2017Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 82, nr 1, s. 63-71Artikel i tidskrift (Refereegranskat)
    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.

  • 21.
    Wikland, Kerstin Albertsson
    et al.
    International Pediatric Growth Research Center, Department of Pediatrics University of Göteborg, SE-41685 Göteborg.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    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.2000Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 48, nr 4, s. 475-484Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Zamir, Itay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stoltz Sjöström, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Edstedt Bonamy, Anna-Karin
    Mohlkert, Lilly-Ann
    Norman, Mikael
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm2019Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 86, nr 1, s. 115-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

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