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1.
  • Abrahamsson, Thomas, et al. (författare)
  • Gut microbiota and allergy: the importance of the pregnancy period
  • 2015
  • Ingår i: Pediatric Research. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0031-3998 .- 1530-0447. ; 77:1, s. 214-219
  • Forskningsöversikt (refereegranskat)abstract
    • Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.
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  • Baraldi, Erika, 1982-, et al. (författare)
  • Clinical Protocol & Research Process of Stockholm Preterm Interaction-Based Intervention, SPIBI
  • 2019
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 86:Suppl., s. 54-55
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExtremely preterm (EPT) born children are at increased risk of cognitive and neurodevelopmental impairment, neuropsychiatric disorders and academic difficulties. Parents of EPT born children are extra vulnerable for anxiety, posttraumatic stress disorder and depression and the parent-child interaction is negatively affected by prematurity. There is some evidence that early interventions have beneficial effects on neurocognitive and motor outcomes (Spittle A et al 2015). Based on a previous intervention (Verkerk G et al 2012) and adjusted to the Swedish context with 480 days paid parental leave, we created a post–discharge intervention, SPIBI, for families of EPT born children.MethodThe aim of (SPIBI) is to improve the quality of the parent-child interaction, child development and parental mental health in families with EPT born children. . SPIBI is a randomized controlled beginning at discharge and lasting until the child is 12 months corrected age. The trial design is a two arm randomized trial with four recruiting sites in Stockholm. Intervention group (target, n=65) receives 10 visits and two telephone calls from a trained interventionist and the control group (target n=65) receives treatment as usual plus an extended follow-up program. The SPIBI-team has recruited and trained 6 multi-professional and NICU-experienced interventionists. The training takes one year (0.2 of full time) and the content was both theoretical and practical, including pilot-cases. ResultSPIBI is an ongoing research project, beginning the 1st of September 2018 and planning to end recruitment the 31st of August 2020 and finishing the home-visits in August 2021. By the end of April 2019, 33 eligible infants had been identified within the four neonatal units in Stockholm; of which 26 children approved and 7 children declined participation. At this stage, three children have dropped out of the study, because of severe social challenges and child death. Identified challenges have been social and medical vulnerability of the EPT-families, finding the optimal multi-professional balance of motoric, psychological, pedagogical and medical kernels of the intervention, ethical considerations when to ask families for participation, lack of long-term discharge-planning of the neonatal units and large geographical spread of NICUs as well as families.ConclusionIn conclusion, the protocol seem to be feasible and appreciated by parents in the target group. With regard to the small recruitment base, trials of this kind needs a long inclusion time. Since EPT-children and their parents displays a wide scope of difficulties and challenges, multi-professional cooperation is preferable, placing high demands of sensitivity, professional respect and time for long collaborative processes.
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3.
  • Berglund, Staffan K., et al. (författare)
  • Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years : a randomized controlled trial
  • 2018
  • Ingår i: Pediatric Research. - New York : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 83, s. 111-118
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Candy, David C. A., et al. (författare)
  • A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants
  • 2018
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 83:3, s. 677-686
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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6.
  • Chung, Jou Ku, et al. (författare)
  • Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants
  • 2017
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 81:3, s. 504-510
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.Results:Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).Conclusion:Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.
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  • Fredly, Siv, et al. (författare)
  • Noninvasive assessments of oxygen delivery from the microcirculation to skin in hypothermia-treated asphyxiated newborn infants
  • 2016
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 76:6, s. 902-906
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, noninvasive concept of assessing the capacity for oxygen delivery from the microcirculation to the cells of a tissue under investigation. The hypothesis was that mechanisms of reduced oxygen delivery due to reduced metabolism in cooled asphyxiated neonates could be characterized with this concept.METHODS:The skin of 28 asphyxiated newborn infants was studied on days 1 and 3 during TH and on day 4 following rewarming with laser Doppler perfusion measurements (LDPM), computer-assisted video microscopy (CAVM), and diffuse reflectance spectroscopy (DRS). Twenty-five healthy neonates served as a control group.RESULTS:The LDPM decreased during cooling (P < 0.01). Functional capillary density was higher both during and following TH compared with control infants (P < 0.01). Capillary flow velocities were reduced during TH (P < 0.05). The heterogeneity of the flow velocities was larger in the HIE infants than in the control infants. Tissue oxygen extraction was higher during TH (P < 0.01).CONCLUSION:This study indicates that assessments of skin microvascular density, capillary flow velocity, and oxygen extraction can be used to characterize reduced oxygen delivery to cells during TH
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12.
  • Grip, Tove, et al. (författare)
  • Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes
  • 2018
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 84:5, s. 726-732
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Hall, Ulrika Andersson, et al. (författare)
  • Maternal obesity and gestational diabetes mellitus affect body composition through infancy: the PONCH study
  • 2019
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 85:3, s. 369-377
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To determine how maternal obesity or gestational diabetes mellitus (GDM) affect infant body size and body composition during the first year of life. METHODS: Eighty three normal-weight (NW) women, 26 obese (OB) women, and 26 women with GDM were recruited during pregnancy. Infant body composition was determined by air-displacement plethysmography at 1 and 12 weeks, and anthropometric measurements made until 1 year of age. RESULTS: Girl infants born to OB women and women with GDM had a higher body-fat percentage (BF%) at 1 and 12 weeks of age than girls born to NW women. Girls had higher BF% than boys in OB and GDM groups only. Maternal HbA1c and fasting plasma glucose correlated with girl infant BF% at 1 week of age. Maternal weight at start of pregnancy correlated with birthweight in NW and OB groups, but not the GDM group. OB group infants showed greater BMI increases from 1 week to 1 year than both NW and GDM group infants. CONCLUSION: Results show that both maternal glycaemia and obesity are determinants of increased early life adiposity, especially in girls, with glycaemic levels being more influential than maternal weight for infants born to women with GDM.
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  • Hellgren, Gunnel, 1961, et al. (författare)
  • Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity.
  • 2016
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 79, s. 70-75
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP.
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  • Holmgren, Anton, et al. (författare)
  • Estimating secular changes in longitudinal growth patterns underlying adult height with the QEPS model: the Grow Up Gothenburg cohorts
  • 2018
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 84:1, s. 41-49
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Over the past 150 years, humans have become taller, and puberty has begun earlier. It is unclear if these changes are continuing in Sweden, and how longitudinal growth patterns are involved. We aimed to evaluate the underlying changes in growth patterns from birth to adulthood by QEPS estimates in two Swedish cohorts born in 1974 and 1990. METHODS: Growth characteristics of the longitudinal 1974 and 1990-birth cohorts (n = 4181) were compared using the QEPS model together with adult heights. RESULTS: There was more rapid fetal/infancy growth in girls/boys born in 1990 compared to 1974, as shown by a faster Etimescale and they were heavier at birth. The laterborn were taller also in childhood as shown by a higher Q-function. Girls born in 1990 had earlier and more pronounced growth during puberty than girls born in 1974. Individuals in the 1990 cohort attained greater adult heights than those in the 1974 cohort; 6 mm taller for females and 10 mm for males. CONCLUSION: A positive change in adult height was attributed to more growth during childhood in both sexes and during puberty for girls. The QEPS model proved to be effective detecting small changes of growth patterns, between two longitudinal growth cohorts born only 16 years apart.
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  • Holmgren, Anton, et al. (författare)
  • Pubertal height gain is inversely related to peak BMI in childhood.
  • 2017
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 81:3, s. 448-454
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundChildhood BMI may influence subsequent growth in height as well as the timing of puberty. The aim of the present study was to investigate associations between BMI in childhood and subsequent height gain/pubertal growth.MethodsLongitudinal growth data were used (GrowUp1990 Gothenburg cohort, n=1901). The QEPS growth-model was used to characterize height gain in relation to the highest BMISDS value between 3.5 and 8 years of age. Children were defined as overweight/obese (OwOb) or normal weight/underweight (NwUw), using the 2012 International Obesity Task Force criteria.ResultsA negative association between childhood BMISDS and pubertal height gain was observed. Already at birth, OwOb children were heavier than NwUw children, and had a greater height velocity during childhood. Onset of puberty was 3.5/3.0 months earlier in OwOb girls/boys, and they had 2.3/3.1cm less pubertal height gain from the QEPS-models specific P-function than NwUw children. Adult height was not related to childhood BMI.ConclusionWe found that pubertal height gain was inversely related to peak BMI in childhood. Higher childhood BMISDS was associated with more growth before onset of puberty, earlier puberty and less pubertal height gain, resulting in similar adult heights for OwOb and NwUw children.
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18.
  • Hövel, Holger, et al. (författare)
  • Auditory event-related potentials are related to cognition at preschool age after very preterm birth
  • 2015
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 77:4, s. 570-578
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Kamath-Rayne, Beena D, et al. (författare)
  • Neonatal resuscitation in global health settings : an examination of the past to prepare for the future.
  • 2017
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 82:2, s. 194-200
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Kaul, Ylva Fredriksson, et al. (författare)
  • Visual tracking in very preterm infants at 4 mo predicts neurodevelopment at 3 y of age
  • 2016
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 80:1, s. 35-42
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Krite Svanberg, Emilie, et al. (författare)
  • Diode laser spectroscopy for non-invasive monitoring of oxygen in the lungs of newborn infants.
  • 2016
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 79, s. 621-628
  • Tidskriftsartikel (refereegranskat)abstract
    • Newborn infants have pulmonary disorders with abnormal gas distribution, e. g. respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel non-invasive optical technique for rapid non-radiographic bedside detection of oxygen gas in the lungs of full-term newborn infants.
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  • Levy, P, et al. (författare)
  • Application of Neonatologist Performed Echocardiography in the Assessment and Management of Neonatal Heart Failure unrelated to Congenital Heart Disease
  • 2018
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 84:1Suppl 1, s. 78-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF.
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  • Lindholm, Annelie, 1975-, et al. (författare)
  • Body mass index classification misses to identify children with an elevated waist-to-height ratio at 5 years of age.
  • 2019
  • Ingår i: Pediatric Research. - New York, NY : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 85:1, s. 30-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Abdominal adiposity is an important risk factor in the metabolic syndrome. Since BMI does not reveal fat distribution, waist-to-height ratio (WHtR) has been suggested as a better measure of abdominal adiposity in children, but only a few studies cover the preschool population. The aim of the present study was to examine BMI and WHtR growth patterns and their association regarding their ability to identify children with an elevated WHtR at 5 years of age.A population-based longitudinal birth cohort study of 1540 children, followed from 0 to 5 years with nine measurement points. The children were classified as having WHtR standard deviation scores (WHtRSDS) <1 or ≥1 at 5 years. Student's t-tests and Chi-squared tests were used in the analyses.Association between BMISDS and WHtRSDS at 5 years showed that 55% of children with WHtRSDS ≥1 at 5 years had normal BMISDS (p<0.001). Children with WHtRSDS ≥1 at 5 years had from an early age significantly higher mean BMISDS and WHtRSDS than children with values <1.BMI classification misses every second child with WHtRSDS ≥1 at 5 years, suggesting that WHtR adds value in identifying children with abdominal adiposity who may need further investigation regarding cardiometabolic risk factors.
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  • Lindström, Linda, 1978-, et al. (författare)
  • Postnatal growth in children born small for gestational age with and without smoking mother
  • 2019
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 85:7, s. 961-966
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Lundgren, Pia, 1967-, et al. (författare)
  • Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity
  • 2019
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 86:2, s. 276-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP.Method: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L.Results: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant.Conclusions: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.
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  • Löfving, Anders, et al. (författare)
  • Reference intervals for reticulocyte hemoglobin content in healthy infants
  • 2018
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 84:5, s. 657-661
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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32.
  • Magnusson, Amanda, 1986, et al. (författare)
  • Increased risk of rickets but not fractures during childhood and adolescence following necrotizing enterocolitis among children born preterm in Sweden
  • 2019
  • Ingår i: Pediatric Research. - : NATURE PUBLISHING GROUP. - 0031-3998 .- 1530-0447. ; 86:1, s. 100-106
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age. METHODS: All infants born in Sweden between 1987 and 2009 with a gestational age amp;lt;32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed. RESULTS: In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007). CONCLUSIONS: This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.
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33.
  • Mohlkert, Lilly -Ann, et al. (författare)
  • Preterm arteries in childhood : dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm
  • 2017
  • Ingår i: Pediatric Research. - : NATURE PUBLISHING GROUP. - 0031-3998 .- 1530-0447. ; 81:2, s. 299-306
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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34.
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35.
  • Musilova, Ivana, et al. (författare)
  • Gastric fluid used to assess changes during the latency period in preterm prelabor rupture of membranes.
  • 2018
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 84, s. 240-247
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine changes in the intraamniotic environment during the latency period using paired amniotic and gastric fluid samples in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).A total of 34 women with singleton pregnancies complicated by PPROM prior to 34 weeks were included in the study. Amniotic fluid was obtained by transabdominal amniocentesis at the time of admission. Immediately after delivery, umbilical cord blood and gastric fluid were obtained.Microorganisms in amniotic and gastric fluid samples were found in 38% and 59% of women, respectively. Bedside IL-6 levels were higher in amniotic than in gastric fluid in pregnancies without fetal inflammatory response syndrome (FIRS) (263pg/mL vs. 50pg/mL; p<0.0001), but not in pregnancies with FIRS (318pg/mL vs. 444pg/mL; p=0.91). Funisitis and FIRS was associated with the highest bedside IL-6 levels in gastric fluid. A gastric fluid bedside IL-6 level of 275pg/mL was found to be the ideal cutoff value to predict funisitis and FIRS.The microbial and inflammatory status of the intraamniotic compartment changes during the latency period in PPROM. Bedside IL-6 assessment of gastric fluid may be useful in the rapid diagnosis of funisitis and FIRS.
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36.
  • Musilova, Ivana, et al. (författare)
  • Late preterm prelabor rupture of fetal membranes: fetal inflammatory response and neonatal outcome.
  • 2018
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998.
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTo characterize the influence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) on the intensity of the fetal inflammatory response and the association between the presence of the fetal inflammatory response syndrome (FIRS) and short-term neonatal morbidity in the preterm prelabor rupture of membranes (PPROM) between the gestational ages of 34 and 37 weeks.MethodsOne hundred and fifty-nine women were included in the study. The umbilical cord blood interleukin (IL)-6 concentrations were determined using enzyme-linked immunosorbent assay kits. FIRS was defined based on the umbilical cord blood IL-6 concentration and the presence of funisitis and/or chorionic plate vasculitis.ResultsWomen with both MIAC and IAI had the highest median umbilical cord blood IL-6 concentrations and highest rates of FIRS. Women with FIRS had the higher rates of early-onset sepsis and intraventricular hemorrhage grades I and II when FIRS was characterized based on the umbilical cord blood IL-6 concentrations and the histopathological findings.ConclusionThe presence of both MIAC and IAI was associated with a higher fetal inflammatory response and a higher rate of FIRS. Different aspects of short-term neonatal morbidity were related to FIRS when defined by umbilical cord blood IL-6 concentrations and the histopathology of the placenta.Pediatric Research advance online publication, 20 December 2017; doi:10.1038/pr.2017.300.
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37.
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38.
  • Olsson, Karl Wilhelm, 1985-, et al. (författare)
  • Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22–27 weeks’ gestation
  • 2019
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 86, s. 333-338
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundEarly 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.MethodsInfants 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.ResultsHigh 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.ConclusionsHigh 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.
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39.
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40.
  • Pasanen, Anu, et al. (författare)
  • NKG2D gene variation and susceptibility to viral bronchiolitis in childhood.
  • 2018
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 84, s. 451-457
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels.GWAS included a Finnish-Swedish case-control population (n=187), matched for age and site. We integrated GWAS variants (p<10-4) with QTL data. We subsequently verified allele-specific expression of identified QTLs by flow cytometry. Association of the resulting candidate loci with bronchiolitis was tested in three additional cohorts from Finland and Denmark (n=1201).Bronchiolitis-susceptibility variant rs10772271 resided within QTLs previously associated with NKG2D (NK group 2, member D) mRNA and protein levels. Flow cytometric analysis confirmed the association with protein level in NK cells. The GWAS susceptibility allele (A) of rs10772271 (odds ratio [OR]=2.34) corresponded with decreased NKG2D expression. The allele was nominally associated with bronchiolitis in one Finnish replicate (OR=1.50), and the other showed directional consistency (OR=1.43). No association was detected in Danish population CONCLUSIONS: The bronchiolitis GWAS susceptibility allele was linked to decreased NKG2D expression in the QTL data and in our expression analysis. We propose that reduced NKG2D expression predisposes infants to severe bronchiolitis.
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41.
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42.
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43.
  • Späth, Cornelia, et al. (författare)
  • Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants
  • 2017
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 81, s. 455-460
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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44.
  • Staaf, Johan, et al. (författare)
  • Initial hyperinsulinemia and subsequent beta-cell dysfunction is associated with elevated palmitate levels
  • 2016
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 80:2, s. 267-274
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  •  
45.
  • Starnberg, Josefine, 1991-, et al. (författare)
  • Lower cognitive test scores at age 7 in children born with marginally low birth weight
  • 2018
  • Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 83:6, s. 1129-1135
  • Tidskriftsartikel (refereegranskat)abstract
    • 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
  •  
46.
  • Szajewska, Hania, et al. (författare)
  • Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo : a randomized controlled trial
  • 2017
  • Ingår i: Pediatric Research. - : NATURE PUBLISHING GROUP. - 0031-3998 .- 1530-0447. ; 81:5, s. 752-758
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  •  
47.
  • Uijterschout, Lieke, et al. (författare)
  • Serum hepcidin in infants born after 32 to 37 wk of gestational age
  • 2016
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 79:4, s. 608-613
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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48.
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49.
  • Veneroni, Chiara, et al. (författare)
  • Oscillatory respiratory mechanics on the first day of life improves prediction of respiratory outcomes in extremely preterm newborns
  • 2019
  • Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 85:3, s. 312-317
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  •  
50.
  • Viitasalo, Anna, et al. (författare)
  • Association of MBOAT7 gene variant with plasma ALT levels in children: the PANIC study.
  • 2016
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 80:5, s. 651-655
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied for the first time among children differences in plasma alanine aminotransferase (ALT) among genotypes of the rs641738 polymorphism in the MBOAT7 gene that has been associated with increased risk of nonalcoholic fatty liver disease among adults. We also investigated the associations of a genetic risk score combining information from the MBOAT7, PNPLA3, and TM6SF2 polymorphisms with plasma ALT.
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