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1.
  • Ahearne, CE, et al. (författare)
  • Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy
  • 2016
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 110:4, s. 296-302
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> A <sup>1</sup>H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. <b><i>Objective:</i></b> To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. <b><i>Methods:</i></b> From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. <b><i>Results:</i></b> Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (&#x03C1;<sup>2</sup> = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p <i>< </i>0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). <b><i>Conclusions:</i></b> The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.
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2.
  • Almlen, A, et al. (författare)
  • Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity
  • 2007
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 92:3, s. 194-200
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. <i>Objectives:</i> To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol (68:31, w/w). <i>Methods:</i> Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. <i>Results:</i> Preparations containing ≧1% SP-C33 achieve minimum surface tension <5 mN/m indicating good biophysical activity, and increase tidal volumes in premature rabbit fetuses to the same level as a modified natural surfactant preparation does. Alveolar patency at end expiration, as evaluated by measurement of lung gas volumes, histological assessment of alveolar expansion and determination of alveolar volume density, was lower in the animals treated with synthetic surfactant than in those receiving modified natural surfactant. <i>Conclusions:</i> These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
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3.
  • Almlen, A, et al. (författare)
  • Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits
  • 2010
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:1, s. 91-99
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. <i>Objectives:</i> To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. <i>Methods:</i> Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. <i>Results:</i> Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. <i>Conclusions:</i> The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
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4.
  • Aman, J., et al. (författare)
  • Increased Fat Mass and Cardiac Septal Hypertrophy in Newborn Infants of Mothers with Well-Controlled Diabetes during Pregnancy
  • 2011
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 100:2, s. 147-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. Objective: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. Methods: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. Results: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. Conclusion: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.
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5.
  • Artlich, A, et al. (författare)
  • Single breath analysis of endogenous nitric oxide in the newborn
  • 2001
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 79:1, s. 21-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitric oxide (NO) is found in the exhaled gas of humans immediately after birth. However, variations of endogenous NO concentration during the breathing cycle have not been studied in newborns. We examined 24 newborns without acute respiratory compromise during spontaneous nasal breathing. Gas was sampled from the tip of a thin nasal catheter placed in the hypopharynx. Endogenous NO concentrations measured by chemiluminescence were assigned to the breathing cycle using synchronized CO<sub>2</sub> recording. Exhaled NO could reproducibly be measured at 1.9 ± 0.2 parts per billion (ppb, mean ± SEM). Autoinhaled nasal NO peaks during regular breathing were 12.0 ± 1.7 ppb and reached intermittent maxima of 52.2 ± 5.8 ppb. During regular breathing 6 infants exhibited sudden decreases of nasal NO peaks to periods with <50% amplitude suggesting transient shortage of autoinhaled nasal NO. We conclude that tidal NO analysis can be used to assess upper and lower airway NO production noninvasively during spontaneous breathing in the newborn.
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6.
  • Basabe-Burgos, O, et al. (författare)
  • Disulphide Bridges in Surfactant Protein B Analogues Affect Their Activity in Synthetic Surfactant Preparations
  • 2019
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 115:2, s. 134-141
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Limited supply and complicated manufacturing procedure of animal-derived surfactants make the development of synthetic surfactants warranted. The synthesis of surfactant protein (SP)-B and SP-C is complicated and several analogues have been developed. Mini-BLeu is an analogue that corresponds to the first and last helix of SP-B joined by a loop and linked by 2 disulphide bridges. SP-C33Leu is an SP-C analogue that can be cost-efficiently produced, but no such analogue has yet been described for SP-B. <b><i>Objective:</i></b> To design short SP-B analogues which lack disulphide bridges, are easy to produce and are efficacious in a preterm rabbit fetus model of neonatal RDS. <b><i>Methods:</i></b> Synthetic surfactants were prepared by adding 2 or 8% (w/w) of synthetic variants of Mini-B27, similar to Mini-BLeu but with a short loop, or different peptides covering helix 1 of SP-B to 2% (w/w) of SP-C33Leu in 80 mg/mL of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/egg yolk phosphatidylcholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 50: 40: 10 (by weight). Premature newborn rabbit fetuses were treated with 200 mg/kg of the surfactant preparations and ventilated with defined pressures for 30 min without positive end-expiratory pressure. Tidal volumes were registered during the experiments and lung gas volumes were measured at the end of the ventilation period. <b><i>Results:</i></b> Synthetic surfactant containing the Mini-B27 analogue with 2 disulphides gives similar lung gas volumes as treatment with an animal-derived surfactant preparation, but all other SP-B analogues gave lower lung gas volumes. All synthetic surfactants studied gave no significant differences in compliances except the surfactant containing the Mini-B27 analogue without cysteines that performed somewhat better at 30 min. <b><i>Conclusion:</i></b> The helix-loop-helix SP-B analogues tested in this study require the presence of 2 disulphide bridges for optimal activity in a rabbit RDS model.
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7.
  • Beltempo, Marc, et al. (författare)
  • Respiratory Management of Extremely Preterm Infants : An International Survey
  • 2018
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:1, s. 28-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies.OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration.METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015.RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%).CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.
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8.
  • Benterud, T, et al. (författare)
  • N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
  • 2017
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 111:1, s. 12-21
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. <b><i>Objectives:</i></b> To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-&#x03BA;B in the prefrontal cortex of neonatal pigs. <b><i>Methods:</i></b> Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. <b><i>Results:</i></b> Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-&#x03BA;B (measured as the fold-change of phosphorylated p65<sup>Ser 536</sup>), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01). <b><i>Conclusion:</i></b> The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-&#x03BA;B may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
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9.
  • Berg, Johan Henrik Martin, et al. (författare)
  • Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years : A Randomized Controlled Trial
  • 2021
  • Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 118:3, s. 282-288
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal.Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years.Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment.Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02.Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.
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10.
  • Berg, Johan Henrik Martin, et al. (författare)
  • Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years: A Randomized Controlled Trial.
  • 2021
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 118:3, s. 282-288
  • Tidskriftsartikel (refereegranskat)abstract
    • Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal.The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years.In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment.At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02.There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.
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11.
  • BLENNOW, M, et al. (författare)
  • Monoamine neurotransmitters and metabolites in the cerebrospinal fluid following perinatal asphyxia
  • 1995
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 67:6, s. 407-413
  • Tidskriftsartikel (refereegranskat)abstract
    • While the release of neurotransmitters is involved in the pathophysiology of brain damage following birth asphyxia, it also plays a role in endogenous defense against such damage. Levels of monoamines and the main cerebral monoamine metabolites in the cerebrospinal fluid (CSF) were measured in asphyxiated and control infants within 24 h after birth. The results indicate an increased turnover of noradrenaline (NA) and dopamine following asphyxia. Furthermore, the NA stores in the brain seem to be exhausted in some cases. We conclude that this increase in catecholamine turnover to some extent explains the clinical symptoms of hypoxic-ischemic encephalopathy and that it may reflect an intrinsic adaptive capacity to perinatal distress.
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12.
  • Blennow, M, et al. (författare)
  • Surfactant and noninvasive ventilation
  • 2015
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 107:4, s. 330-336
  • Tidskriftsartikel (refereegranskat)abstract
    • There is mounting evidence that early continuous positive airway pressure (CPAP) from birth is feasible and safe even in very preterm infants. However, many infants will develop respiratory distress syndrome (RDS) and require surfactant treatment. Combining a noninvasive ventilation approach with a strategy for surfactant administration is important to ensure optimal outcome, but questions remain about the optimal timing, mode of delivery and value of predictive tests for surfactant deficiency. Key findings in this review include the following: (1) a noninvasive ventilation strategy with CPAP from birth has a similar outcome to routine intubation in the delivery room; (2) prophylactic surfactant treatment has no advantage over early CPAP with selective surfactant administration; (3) surfactant during CPAP can be safely administered by rapid intubation-extubation (the INSURE method or via tracheal placement of a thin catheter), and (4) predictive tests for surfactant deficiency are being developed and might in future aid in directing surfactant treatment to infants at risk of developing severe RDS. A strategy for surfactant administration should be part of a noninvasive ventilation approach for preterm infants at risk of developing significant RDS. The different methods for surfactant administration during CPAP are reviewed here.
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13.
  • Bohlin, K, et al. (författare)
  • Continuous positive airway pressure and surfactant
  • 2008
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 93:4, s. 309-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Nasal continuous positive airway pressure (nCPAP) is an effective treatment of respiratory distress syndrome. Due to long-standing experience of early nCPAP as the primary respiratory support option in preterm infants, this approach is sometimes labeled ‘the Scandinavian Model’. Mechanical ventilation is potentially harmful to the immature lungs and cohort studies have demonstrated that centers using more CPAP and less mechanical ventilation have reduced rates of bronchopulmonary dysplasia. However, there is a lack of evidence in the form of larger, randomized controlled trials to prove the superiority of either method. Surfactant is essential in the treatment of respiratory distress syndrome and has generally been reserved for infants on mechanical ventilation. With the development of INSURE (INtubation SURfactant Extubation), in which surfactant is administered during a brief intubation followed by immediate extubation, surfactant therapy can be given during nCPAP treatment further reducing need for mechanical ventilation. In this review the history, current knowledge and techniques of CPAP and surfactant are discussed.
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14.
  • Bonamy, AKE, et al. (författare)
  • Patent Ductus Arteriosus Treatment in Very Preterm Infants: A European Population-Based Cohort Study (EPICE) on Variation and Outcomes
  • 2017
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 111:4, s. 367-375
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Spontaneous closure of patent ductus arteriosus (PDA) occurs frequently in very preterm infants and despite the lack of evidence for treatment benefits, treatment for PDA is common in neonatal medicine. <b><i>Objectives:</i></b> The aim of this work was to study regional variations in PDA treatment in very preterm infants (≤31 weeks of gestation), its relation to differences in perinatal characteristics, and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity. <b><i>Methods:</i></b> This was a population-based cohort study in 19 regions in 11 European countries conducted during 2011 and 2012. A total of 6,896 infants with data on PDA treatment were included. The differences in infant characteristics were studied across regions using a propensity score derived from perinatal risk factors for PDA treatment. The primary outcomes were a composite of BPD or death before 36 weeks postmenstrual age, or survival without major neonatal morbidity. <b><i>Results:</i></b> The proportion of PDA treatment varied from 10 to 39% between regions (<i>p</i> < 0.001), and this difference could not be explained by differences in perinatal characteristics. The regions were categorized according to a low (<15%, <i>n</i> = 6), medium (15-25%, <i>n</i> = 9), or high (>25%, <i>n</i> = 4) proportion of PDA treatment. Infants treated for PDA, compared to those not treated, were at higher risk of BPD or death in all regions, with an overall propensity score adjusted risk ratio of 1.33 (95% confidence interval 1.18-1.51). Survival without major neonatal morbidity was not related to PDA treatment. <b><i>Conclusions:</i></b> PDA treatment varies largely across Europe without associated variations in perinatal characteristics or neonatal outcomes. This finding calls for more uniform guidance for PDA diagnosis and treatment in very preterm infants.
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15.
  • Breindahl, M, et al. (författare)
  • The European database for subspecialist training in neonatology - transparency achieved
  • 2013
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 103:1, s. 74-82
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The European Society for Neonatology (ESN) developed a curriculum for subspecialist training in Europe recommending standards for national neonatal training programmes. We speculate whether these official recommendations are widely accepted or used in practice. <b><i>Objectives:</i></b> To characterize the variation in national neonatal training programmes, to enhance transparency, and to compare them to the ESN Curriculum. <b><i>Methods:</i></b> We constructed a database based on the backbone of the ESN Curriculum: (1) training – knowledge, (2) training – skills, (3) key competencies, (4) personal development, and (5) recording of progress. National neonatal representatives from all 30 member states of the Union of European Medical Specialties (UEMS) provided data on national training programmes. <b><i>Results:</i></b> Although only one country (3%) based its neonatology training entirely on the ESN Curriculum, we found high levels of uniformity among the UEMS member countries regarding knowledge, skills, and key competencies needed to practice neonatology at a tertiary care level. Discrepancy was encountered on ethical and legal issues and on personal development of the trainees. Mentoring and professional evaluation was generally not implemented in the participating countries. <b><i>Conclusions:</i></b> There is an awareness and readiness to focus on educational demands for neonatal trainees. Further discussions about the overall educational goals of neonatal training and the essence of practicing neonatology in each country are needed. The ESN will undertake this process to provide an updated and effective syllabus aimed to harmonize care and outcomes for babies and their families across Europe.
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16.
  • Calkovska, A, et al. (författare)
  • Biophysical and physiological properties of porcine surfactant enriched with polymyxin B
  • 2005
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 88:2, s. 101-108
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Objective:</i> We examined whether the biophysical and physiological properties of Curosurf<sup>®</sup> were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). <i>Methods:</i> Curosurf was diluted to 1–5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (γ<sub>min</sub>) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. <i>Results:</i> At surfactant concentration 2 mg/ml, γ<sub>min</sub> was high (17 ± 8.9 mN/m) but remained low (2.7 ± 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. <i>Conclusion:</i> Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.
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17.
  • Calkovska, A, et al. (författare)
  • Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits
  • 2016
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 109:3, s. 177-185
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. <b><i>Objectives:</i></b> To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. <b><i>Methods:</i></b> Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. <b><i>Results:</i></b> Treatment with Curosurf® or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (V<sub>T</sub>) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small V<sub>T</sub>, but after addition of both analogues V<sub>T</sub> was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-<i>sn</i>-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on V<sub>T</sub> and LGV as Curosurf. <b><i>Conclusions:</i></b> Phospholipid composition is important for V<sub>T</sub> while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding V<sub>T</sub> and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.
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18.
  • Chmielewska, Anna, et al. (författare)
  • Lean Tissue Deficit in Preterm Infants Persists up to 4 Months of Age : Results from a Swedish Longitudinal Study
  • 2020
  • Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 117:1, s. 80-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: At term-equivalent age, infants born prematurely are shorter, lighter and have more adipose tissue compared to term counterparts. Little is known on whether the differences in body composition persist in later age. Methods: We prospectively recruited 33 preterm infants (<32 weeks gestational age, mean gestational age 28.1 weeks) and 69 term controls. Anthropometry and body composition (air displacement plethysmography) were monitored up to 4 months of age. Nutrient intakes from preterm infants were collected from clinical records. Results: At 4 months of age preterm infants were lighter and shorter than term controls (mean weight-for-age z-score: –0.73 vs. 0.06, p = 0.001; mean length-for-age z-score: –1.31 vs. 0.29, p < 0.0001). The significantly greater percentage of total body fat seen in preterm infants at term-equivalent age (20.2 vs. 11.7%, p < 0.0001) was no longer observed at 4 months. A deficit of fat-free mass persisted until 4 months of age (fat-free mass at term-equivalent age: 2.71 vs. 3.18 kg, p < 0.0001; at 4 months: 4.3 vs. 4.78 kg, p < 0.0001). The fat mass index and fat-free mass index (taking length into account) did not differ between the groups. Nutrition had little effect on body composition. Higher protein intake at week 2 was a negative predictor of fat-free mass at discharge. Conclusions: At 4 months corrected age, preterm infants were both lighter and shorter than term controls and the absolute fat-free mass deficit remained until this age. Little effect of nutrition on body composition was observed.
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19.
  • Cunha-Goncalves, Doris, et al. (författare)
  • Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure
  • 2020
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 117:4, s. 467-473
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The ideal body position during surfactant nebulization is not known. Objective: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. Methods: Twenty-four 12- to 36-h-old full-termpiglets (1.3-2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (n = 6 each). All animals received 200 mg kg-1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. Results: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). Conclusions: In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.
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20.
  • Curstedt, T, et al. (författare)
  • A unique story in neonatal research: the development of a porcine surfactant
  • 2015
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 107:4, s. 321-329
  • Tidskriftsartikel (refereegranskat)abstract
    • Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf® (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by Christian Speer, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. Curosurf has also been compared with several synthetic and natural surfactants, and at a dose of 200 mg/kg Curosurf has been shown to be superior to either Survanta® or Curosurf used at a dose of 100 mg/kg. Recently, new-generation synthetic surfactants containing both phospholipids and proteins have been developed. After preclinical testing, CHF5633 (developed by Tore Curstedt and Jan Johansson in collaboration with Chiesi Farmaceutici) has undergone a preliminary first study in humans under the guidance of Christian Speer. If effective, this new surfactant preparation could revolutionize the treatment of preterm infants worldwide as it could be made consistently and safely in almost unlimited quantities. This story of a porcine surfactant preparation has been truly remarkable, and many thousands of preterm babies worldwide are now alive and well because of it.
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21.
  • Curstedt, T, et al. (författare)
  • New generation synthetic surfactants
  • 2013
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 103:4, s. 327-330
  • Tidskriftsartikel (refereegranskat)abstract
    • The treatment of preterm newborn rabbits with synthetic surfactants containing simple phospholipid mixtures and peptides gives similar tidal volumes to treatment with poractant alfa (Curosurf®). The addition of both surfactant protein B and C analogs to the phospholipid mixture will stabilize the alveoli, measured as lung gas volumes at end expiration, even if no positive end-expiratory pressure is applied. The effect on lung gas volumes seems to depend on the structure of the peptides as well as the phospholipid composition. It seems that synthetic surfactants containing two peptides and a more complex phospholipid composition will be able to replace natural surfactants within the near future, but more experiments need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants.
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22.
  • Curstedt, T, et al. (författare)
  • New synthetic surfactant - how and when?
  • 2006
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 89:4, s. 336-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.
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23.
  • Curstedt, T, et al. (författare)
  • New synthetic surfactants--basic science
  • 2005
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 87:4, s. 332-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface-active lipids to the air-liquid interface of the alveoli and are essential for alveolar stability and gas exchange. Synthetic surfactant preparations must contain at least one of these hydrophobic proteins, or analogs thereof, to have optimal effects when administered into the airways of patients with lung diseases. However, development of clinically active artificial surfactants has turned out to be more complicated than initially anticipated since the native hydrophobic proteins are structurally complex or unstable in pure form. The proteins have been replaced by different analogs which have the right conformation without forming oligomers. Increased understanding of the surfactant proteins will hopefully lead to development of effective synthetic surfactants which can be produced in large quantities for treatment of a wide range of respiratory disorders. Furthermore, the lipid composition seems to be important, as well as a high lipid concentration in the suspension. For successful treatment of many respiratory diseases, it is also desirable that the synthetic surfactant resists inactivation by plasma components leaking into the alveoli.
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24.
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25.
  • Darlow, Brian A, et al. (författare)
  • Variations in Oxygen Saturation Targeting, and Retinopathy of Prematurity Screening and Treatment Criteria in Neonatal Intensive Care Units : An International Survey
  • 2018
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:4, s. 323-331
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Rates of retinopathy of prematurity (ROP) and ROP treatment vary between neonatal intensive care units (NICUs). Neonatal care practices, including oxygen saturation (SpO2) targets and criteria for the screening and treatment of ROP, are potential contributing factors to the variations.OBJECTIVES: To survey variations in SpO2 targets in 2015 (and whether there had been recent changes) and criteria for ROP screening and treatment across the networks of the International Network for Evaluating Outcomes in Neonates (iNeo).METHODS: Online prepiloted questionnaires on treatment practices for preterm infants were sent to the directors of 390 NICUs in 10 collaborating iNeo networks. Nine questions were asked and the results were summarized and compared.RESULTS: Overall, 329/390 (84%) NICUs responded, and a majority (60%) recently made changes in upper and lower SpO2 target limits, with the median set higher than previously by 2-3% in 8 of 10 networks. After the changes, fewer NICUs (15 vs. 28%) set an upper SpO2 target limit > 95% and fewer (3 vs. 5%) a lower limit < 85%. There were variations in ROP screening criteria, and only in the Swedish network did all NICUs follow a single guideline. The initial retinal examination was carried out by an ophthalmologist in all but 6 NICUs, and retinal photography was used in 20% but most commonly as an adjunct to indirect ophthalmoscopy.CONCLUSIONS: There is considerable variation in SpO2 targets and ROP screening and treatment criteria, both within networks and between countries.
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26.
  • De Felice, C, et al. (författare)
  • Congenital oral mucosal abnormalities in true umbilical cord knots
  • 2004
  • Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 86:1, s. 34-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The pathogenesis and clinical significance of true umbilical cord knots remain controversial. Here, we tested the hypothesis of the presence of congenital oral mucosal changes in newborns with true umbilical cord knots. Study design: Seven consecutive infants with true umbilical cord knots and 50 gestational age- and sex-matched controls were enrolled. The proportion of oral frenulum abnormalities and the two-dimensional vascular network geometry [fractal dimension, D, at two scales: D(1-46), and D(1-15), with the relative Lempel-Ziv complexity, (L-Z)], were analyzed. Results: Infants with true umbilical cord knots showed significantly higher proportions of mandibular frenulum agenesis compared to controls (p = 0.000006). The oral vascular networks of these infants exhibited a significantly higher D(1-46) and D(1-15) (p < 0.0001, respectively), and higher L-Z values (p < 0.0001) than control networks. Conclusion: These findings indicate the presence of significant congenital oral mucosal changes in newborn infants with true umbilical cord knots, thus suggesting a previously unrecognized association between true umbilical cord knots and a subclinical extracellular matrix disorder. Copyright (C) 2004 S. Karger AG, Basel.
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27.
  • Donaldsson, S, et al. (författare)
  • Transition of Extremely Preterm Infants from Birth to Stable Breathing: A Secondary Analysis of the CORSAD Trial
  • 2023
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 120:2, s. 250-256
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Objective:</i></b> Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period. <b><i>Methods:</i></b> This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups. <b><i>Results:</i></b> Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD −16.5, 95% CI [−31.7 to −1.1], <i>p</i> 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD −15.6, 95% CI [−30.7 to −0.8], <i>p</i> 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups. <b><i>Conclusion:</i></b> In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.
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28.
  • Elsmén, Emma, et al. (författare)
  • Umbilical Cord Levels of Interleukin-1 Receptor Antagonist and Neonatal Outcome.
  • 2006
  • Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 89:4, s. 220-226
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies indicate that there may be infant gender differences in cytokine expression associated with differences in neonatal morbidity. Objective: We tested the hypothesis that umbilical cord interleukin-1 receptor antagonist (IL-1ra) correlates with infant gender and neonatal outcome in preterm infants. Study Design: IL-1ra was measured in cord blood taken from 58 preterm infants (33 males, 25 females) with gestational age less than 32 weeks. Receiver operating characteristics (ROC) curve were used for identifying IL-1ra values with high sensitivity and specificity for neonatal morbidity and adverse outcome, i.e., death or survival with severe intraventricular hemorrhage or periventricular leukomalacia. Results: In the female infants, but not the male infants, cord IL-1ra values correlated with postnatal depression, expressed as Apgar scores at 1 min (correlation coefficient, r(s); p value: -0.542; 0.005), 5 min (-0.571; 0.018), and 10 min (-0.442; 0.035); and postnatal age at intubation (-0.799; 0.001). The ROC area under the curve (AUC) was 0.735 for adverse outcome (p = 0.013), and 0.683 for bronchopulmonary dysplasia (p = 0.021) when all infants were included. However, there was a significant gender difference in the ROC curve for adverse outcome (p = 0.026), with AUC 0.640 (p = 0.240) in males and AUC 0.929 (p = 0.008) in females. Above a chosen cutoff at 13,500 ng/I for IL-1ra cord the sensitivity and specificity for predicting adverse outcome was 100 and 81%, respectively in females versus 50 and 84% in males. Conclusion: Increased levels of cord IL-1ra levels are associated with neonatal morbidity and adverse outcome in preterm infants. Comparable levels of IL-1ra have different predictive value depending on infant gender. Copyright (c) 2006 S. Karger AG, Basel.
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29.
  • Evilevitch, L., et al. (författare)
  • Three-Day Enteral Exposure to a Red Kidney Bean Lectin Preparation Enhances the Pancreatic Response to CCK Stimulation in Suckling Pigs.
  • 2005
  • Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 87:1, s. 20-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A reason for the digestive problems that often occur around early weaning in piglets could be that the pancreas is not yet fully developed and the enzymes required for degradation of the solid food are not secreted in enough amounts. Objectives: The aim of the study was to investigate the possibility of inducing pancreas maturation with enhanced enzyme secretion. Methods: 10-day-old suckling pigs were gavage fed with a red kidney bean lectin preparation for 3 days, and the pancreatic response to intravenous infusion of CCK-33 was measured in the anaesthetized animals fitted with pancreatic duct catheters. Results: The pancreatic fluid secretion, protein output, and the trypsin and amylase outputs were significantly increased in response to CCK stimulation after the lectin treatment, as compared to those of the control littermates (p le 0.05). In addition, the plasma insulin basal levels and those observed during CCK-33 stimulation were lower in the lectin-treated piglets. Conclusion: The results suggested that the lectin treatment led to an increase in the capacity for pancreatic enzyme secretion in the suckling piglets. An enhanced pancreatic function might help to ameliorate the problems that may appear in modern pig production which are associated with weaning.
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30.
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31.
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32.
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33.
  • Gudmundsdottir, Anna, et al. (författare)
  • Timing of Pharmacological Treatment for Patent Ductus Arteriosus and Risk of Secondary Surgery, Death or Bronchopulmonary Dysplasia: A Population-Based Cohort Study of Extremely Preterm Infants
  • 2015
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 107:2, s. 87-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The optimal timing of pharmacological treatment for patent ductus arteriosus (PDA) in extremely pre-term infants is unknown. Objective: To investigate whether timing of pharmacological PDA treatment is associated with a risk of secondary PDA surgery or death before 3 months of age, or bronchopulmonary dysplasia (BPD) in extremely preterm infants. Methods: In this population-based cohort of infants born before 27 gestational weeks in Sweden in 2004-2007, 290/585 infants (50%) received pharmacological PDA treatment. Cox proportional hazards regression estimated the hazard ratio (HR, with 95% confidence interval, Cl) of secondary PDA surgery or death as a composite outcome in relation to postnatal age at the start of pharmacological treatment: early (0-2 days); intermediate (3-6 days); late (>= 7 days). Furthermore, the odds ratio (OR, with 95% Cl) of BPD was estimated in relation to postnatal age at PDA treatment by conditional logistic regression. Results: The median postnatal age at the start of pharmacological PDA treatment was 4 days. 102 infants had secondary PDA surgery. Timing of PDA treatment was not associated with risk of PDA surgery or death; adjusted HRs were 0.89 (95% CI 0.57-1.39) after an intermediate start and 1.10(95% CI 0.53-2.28) after a late start, compared to an early start of treatment. Compared to the early start of PDA treatment, the intermediate start was not associated with any risk of BPD, while late PDA treatment was associated with a lower BPD risk; adjusted ORs were 0.83 (95% CI 0.42-1.64) and 0.28 (95% CI 0.13-0.61), respectively. Conclusion: Timing of pharmacological PDA treatment after extremely preterm birth is not associated with the risk of secondary PDA surgery or death. Moreover, expectant PDA management is not associated with an increased risk of BPD. (C) 2014 S. Karger AG, Basel
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34.
  • Hansen-Pupp, I, et al. (författare)
  • Transdermal Suctioning Technique for Serial Sampling of Interstitial Fluid in Newborn Infants.
  • 2005
  • Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 87:3, s. 197-202
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Overview:</i> Use of a suction-induced epidermal mini-erosion for serial sampling of dermal interstitial fluid (IF) in 16 newborn infants with gestational age ranging from 24 to 42 weeks is reported. <i>Results:</i> The mini-erosion formed reproducibly and electron microscopy showed that the split was located within the epidermis. IF was sampled serially by suctioning during 1–3 days without signs of stress or pain. IF sample volumes (10–50 µl) did not decrease with time. Glucose values in IF and blood were correlated (r<sub>s</sub> = 0.542; p = 0.000). IF glucose was lower than blood glucose on all 3 days. The epidermis regenerated within 4 ± 0.9 days (mean, SD) after sampling was terminated. There were no complications. <i>Conclusion:</i> Serial transdermal sampling was performed without stress or pain in newborn infants. Systemic and temporal differences between glucose measured in IF and blood were observed.
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35.
  • Hellgren, Gunnel, 1961, et al. (författare)
  • Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP
  • 2021
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 118, s. 18-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Thrombocytopenia has been identified as an independent risk factor for retinopathy of prematurity (ROP), although underlying mechanisms are unknown. In this study, the association of platelet count and serum platelet-derived factors with ROP was investigated. Methods: Data for 78 infants born at gestational age (GA) <28 weeks were included. Infants were classified as having no/mild ROP or severe ROP. Serum levels of vascular endothelial growth factor A, platelet-derived growth factor BB, and brain-derived neurotrophic factor were measured in serum samples collected from birth until postmenstrual age (PMA) 40 weeks. Platelet counts were obtained from samples taken for clinical indication. Results: Postnatal platelet counts and serum concentrations of the 3 growth factors followed the same postnatal pattern, with lower levels in infants developing severe ROP at PMA 32 and 36 weeks (p < 0.05-0.001). With adjustment for GA, low platelet counts and low serum concentrations of all 3 factors at PMA 32 weeks were significantly associated with severe ROP. Serum concentrations of all 3 factors also strongly correlated with platelet count (p < 0.001). Conclusion: In this article, we show that ROP, platelet counts, and specific pro-angiogenic factors correlate. These data suggest that platelet-released factors might be involved in the regulation of retinal and systemic angiogenesis after extremely preterm birth. Further investigations are needed.
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36.
  • Hellgren, Gunnel, 1961, et al. (författare)
  • Effect of Preterm Birth on Postnatal Apolipoprotein and Adipocytokine Profiles
  • 2015
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 108:1, s. 16-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Critical metabolic changes preparing for ex utero life may occur at the fetal age of approximately 28-32 weeks, and preterm birth <28 weeks postmenstrual age (PMA) may affect these pathways. Children born <28 weeks often have poorer outcomes possibly due to a major shift in metabolism, including nutritional supply and a shift in lipid-transporting particles and lipid profile. This shift may occur in apolipoprotein and adipocytokine levels, which may influence metabolism. Objective: To determine whether there is a shift in apolipoprotein and adipocytokine levels in neonates born at a gestational age (GA) of 28 and 32 weeks, respectively. Methods: Blood samples from 47 infants (GA 32 weeks, n = 30 and GA 28 weeks, n = 17) were collected at birth and, in the GA28 group, also at PMA 32 weeks. Apolipoproteins A-1, A-2, B, C-2, C-3, and E were analyzed, as well as adiponectin and leptin levels. Results: Serum levels of apolipoproteins A-1, C-2, C-3, and E were lower at birth in the GA28 group compared to the GA32 group. Adiponectin and leptin levels were low at birth in the GA28 group. In the GA28 group 4 weeks after birth, leptin levels were still low, whereas adiponectin levels had increased to levels similar to those found at birth in the GA32 group. Apolipoprotein A-1, C-2, C-3, and E levels were negatively correlated with days receiving total parenteral nutrition. Conclusion: There are significant differences in apolipoprotein and adipocytokine levels, which can be associated with GA and birth weight. The impact of these changes on neonatal and future morbidity remains to be determined. (C) 2015 S. Karger AG, Basel
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37.
  • Hellgren, Gunnel, 1961, et al. (författare)
  • Proliferative Retinopathy Is Associated with Impaired Increase in BDNF and RANTES Expression Levels after Preterm Birth.
  • 2010
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:4, s. 409-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Extremely preterm delivery is, amongst other complications, associated with retinopathy of prematurity (ROP). Untreated, ROP can progress to visual impairment and blindness due to an overgrowth of new vessels in the retina and vitreous cavity. Objective: The aim of this study was to identify cytokine markers within the first weeks of life that could be used to predict the risk for development of ROP later in life. Methods: Serum levels of 27 different cytokines in infants born at gestational weeks 23-30 were analyzed using a multiplex immunoassay method and compared between infants who did not develop ROP and infants who later developed proliferative ROP. In addition, mRNA levels of brain-derived neurotrophic factor (BDNF) in retinas from mice exposed to hyperoxia were analyzed using quantitative real-time PCR. Results: At birth, serum levels of IL-5 were higher in infants with no ROP compared to infants with proliferative ROP. 10-14 days after birth, serum levels of BDNF and RANTES were lower in infants who later developed proliferative ROP compared to infants who did not develop ROP. Furthermore, mRNA expression levels of BDNF in retinas from mice exposed to hyperoxia were significantly lower at postnatal day 15 compared to retinas from mice in room air. Conclusions: These results indicate that BDNF and RANTES may be important factors in the selective vulnerability of ROP development in preterm infants.
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38.
  • Hjalmarson, Ola, 1941, et al. (författare)
  • Effect of antenatal corticosteroid treatment on lung function in full-term newborn infants.
  • 2011
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 100:1, s. 32-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Antenatal treatment of pregnant women with corticosteroids in order to stimulate surfactant production has been shown to be effective. However, lung structure is also affected by the treatment. Objective: We tested the hypothesis that changes within lung acini, induced by maternal corticosteroid treatment, persist during lung development. Methods: Twenty-two healthy infants, whose mothers were treated with up to three doses of betamethasone at 25-33 weeks of pregnancy because of preterm labour, but where labour terminated and the infants were born at term, were studied at term and compared to a group of 50 healthy newborn infants without prenatal treatment with corticosteroids. Gas-mixing efficiency was measured in terms of moment ratio with a nitrogen washout method together with functional residual capacity. Mechanical parameters were assessed with the single occlusion technique. Results: There were no signs of disturbed gas mixing or changed lung volume or mechanics in the treated group. Conclusion: The result contributes to an emerging body of evidence that antenatal treatment with corticosteroids does not permanently affect lung structure or function.
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39.
  • Hofsten, von, Claes, et al. (författare)
  • Improved visual perception in very low birth weight infants on enhanced nutrient supply
  • 2015
  • Ingår i: Neonatalogy. - : S. Karger. - 1661-7800. ; 108, s. 30-37
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. <b><i>Objectives:</i></b> To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). <b><i>Methods:</i></b> A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. <b><i>Results:</i></b> Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). <b><i>Conclusion:</i></b> The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.
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40.
  • Huang, QW, et al. (författare)
  • Effects of inhaled nitric oxide and high-frequency ventilation in rabbits with meconium aspiration
  • 1999
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 76:6, s. 374-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To evaluate effects of inhaled nitric oxide (iNO) in experimental meconium aspiration treated with high-frequency (HFV) or conventional mechanical ventilation (CMV). Ventilated adult rabbits had meconium instilled intratracheally resulting in respiratory failure as evidenced by more than 50% reduction of dynamic lung compliance (Cdyn) and increase in mean oxygenation index (OI) from 1 to 16. The animals were then allocated to 2 groups treated without (control) or with iNO at 20 ppm (NO). In each group the animals were initially ventilated with CMV or HFV mode for 3 h and then in a crossover fashion with HFV or CMV for another 3 h (CMV→HFV, HFV→CMV), respectively. In the first 3 h of treatment, the animals subjected to HFV-CMV in the control, and those with both HFV-CMV and CMV-HFV in the NO group had significantly reduced OI. In the subsequent 3 h, the animals in the control group with CMV-HFV did not improve in OI and those with HFV-CMV had deteriorated. In the NO group with both CMV-HFV and HFV-CMV moderate improvement of OI was observed. Platelet aggregation capability and counts were significantly decreased and bleeding time prolonged in animals receiving iNO treatment. These results suggest that both HFV alone and a combined treatment of iNO with either CMV or HFV are more effective in improving blood oxygenation than that of CMV in this animal model. The influence of iNO on platelet aggregation should be considered.
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41.
  • Ingemarsson, Ingemar (författare)
  • Fetal monitoring during labor.
  • 2009
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 95:4, s. 342-346
  • Tidskriftsartikel (refereegranskat)abstract
    • For three decades, cardiotocography has been the basic technique for fetal surveillance during labor, but its impact on fetal well-being remains controversial. The benefits and disadvantages of fetal monitoring with cardiotocography during labor are reviewed. Special reference is made to the possible effect on the rate of neonatal seizures in newborns and their long-term outcome.
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42.
  • Jalde, FC, et al. (författare)
  • Neurally adjusted ventilatory assist and pressure support ventilation in small species and the impact of instrumental dead space
  • 2010
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 97:3, s. 279-285
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Neurally adjusted ventilatory assist (NAVA) is a pneumatically-independent mode of mechanical ventilation controlled by diaphragm electrical activity (EAdi), and has not yet been implemented in very small species. <i>Objectives:</i> The aims of the study were to evaluate the feasibility of applying NAVA in very small species and to compare this to pressure support ventilation (PSV) in terms of ventilatory efficiency and breathing pattern, and evaluate the impact of instrumental dead space on breathing pattern during both modes. <i>Methods:</i> Nine healthy rats (mean weight 385 ± 4 g) were studied while breathing on PSV or NAVA, at baseline or with added dead space. <i>Results:</i> A clear difference in breathing pattern between NAVA and PSV was observed during both baseline and dead space, where PSV – despite similar EAdi and tidal volume as during NAVA – caused shortened inspiratory time (p < 0.05) and increased the respiratory rate (p < 0.05). A higher minute ventilation (p < 0.05) in order to reach the same arterial CO<sub>2</sub> was observed. Ineffective inspiratory efforts occurred only during PSV and decreased with the dead space. <i>Conclusion:</i> This study demonstrates, in a small group of animals, that NAVA can deliver assist in very small species with a higher efficiency than PSV in terms of eliminating CO<sub>2</sub> for a given minute ventilation.
  •  
43.
  • Johansson, Jan, et al. (författare)
  • Different Effects of Surfactant Proteins B and C - Implications for Development of Synthetic Surfactants
  • 2010
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 97, s. 367-372
  • Forskningsöversikt (refereegranskat)abstract
    • Treatment of premature newborn rabbits with synthetic surfactants containing a surfactant protein C analogue in a simple phospholipid mixture gives similar tidal volumes as treatment with poractant alfa (Curosurf (R)) but ventilation with a positive end-expiratory pressure (PEEP) is needed for this synthetic surfactant to stabilize the alveoli at end-expiration. The effect on lung gas volumes seems to depend on the structure of the peptide since treatment with a synthetic surfactant containing the 21-residue peptide (LysLeu(4))(4)Lys (KL(4)) gives low lung gas volumes in experiments also performed with PEEP. Surfactant preparations containing both surfactant proteins B and C or their analogues prevent alveolar collapse at end-expiration even if ventilated without PEEP. Treatment of premature newborn rabbits with different natural surfactants indicates that both the lipid composition and the proteins are important in order to stabilize the alveoli at end-expiration. Synthetic surfactants containing two peptides may be able to replace natural surfactants within the near future but more trials need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants. Copyright (C) 2010 S. Karger AG, Basel
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44.
  •  
45.
  • Johansson, J, et al. (författare)
  • Synthetic surfactant protein analogues
  • 1998
  • Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 7474 Suppl 1, s. 9-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and SP-C, are presently obtained from animal lungs. Since structural information about SP-B and SP-C is available, it appears possible to design analogues that can replace the native proteins in synthetic surfactants. SP-C contains a single helix, but analogues with the poly-Val sequence of the native molecule do not fold into a native-like α-helical conformation. However, replacement of all Val with Leu yields efficient folding into a helical structure and Leu-based SP-C analogues effectively accelerate spreading of surfactant lipids and exhibit some physiological activity in animal models of RDS. The inferior in vivo activity of synthetic surfactants containing SP-C only compared to that of surfactant preparations derived from natural sources may be caused by a lack of covalently linked palmitoyl groups in the analogues and/or absence of SP-B. SP-B is significantly larger than SP-C and has a tertiary fold of several amphipathic helices in a dimeric structure. A single simplified amphipathic helical peptide containing only Leu and Lys does not mimic the surface properties of SP-B in vitro. These circumstances make the design of SP-B analogues from solely structural considerations less likely to be successful than in the case of SP-C.
  •  
46.
  • Karlsson, M, et al. (författare)
  • Liver enzymes cannot be used to predict liver damage after global hypoxia-ischemia in a neonatal pig model
  • 2009
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 96:4, s. 211-218
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> The term newborn pig is an established model for studying both brain and organ pathology after hypoxia-ischemia (HI). Serial liver enzyme activity is often used to predict liver injury but little is known about the relation between consecutive values of different liver enzymes and histologically verified liver injury. <i>Objective:</i> To determine whether plasma values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) differed between newborn pigs with liver injures and pigs with normal livers after a severe global HI insult. <i>Methods:</i> Nineteen ≤36-hour-old pigs underwent a 45-min global HI insult followed by 72-hour survival. Four histological sections from standardized areas within each liver were examined. Areas under the curve (AUC) for the enzymes were calculated and compared between pigs with pathological changes in the liver (n = 12) and pigs with normal liver histology (n = 7). <i>Results:</i> No differences in AUC for the enzyme values were seen between the groups. However, in pigs with liver injuries a transient significant increase in LDH at the end of the HI insult (928 U/l (567–1,031)) was seen compared to the baseline value (679 U/l (548–866), p = 0.010). Significantly more liver injury was seen in animals with the umbilical vein catheter (UVC) tip inserted into the liver (p = 0.040) compared to animals with the UVC tip located outside the liver. <i>Conclusions:</i> In newborn pigs subjected to global HI, only LDH increases alongside pathological changes in the liver. Normal values of ALT and AST do not exclude hepatic injury.
  •  
47.
  • Kistner, Anna, et al. (författare)
  • Retinopathy of Prematurity Is Associated with Increased Systolic Blood Pressure in Adults Who Were Born Preterm
  • 2017
  • Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 112:1, s. 87-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adults born preterm are at risk of developing cardiovascular morbidities. Objective: The aim of this study was to evaluate the relationship between retinopathy of prematurity (ROP) and blood pressure (BP) and salivary cortisol levels during adulthood. Methods: Sixty-nine subjects (mean age 22.6 years) were included. Subjects were adults who were: (a) ex-preterm infants with severe ROP (n = 22), born at gestational age (GA) < 30 weeks with a birth weight (BW) < 1,000 g, (b) ex-preterm infants with no/mild ROP (n = 21), born at GA < 28 weeks with a BW < 1,000 g, or (c) full-term controls (n = 26). Anthropometric data, office BP, ambulatory BP, and morning and evening salivary cortisol were analyzed. Results: As adults, ex-preterm infants with severe ROP had on average 7.4 mm Hg higher systolic office BP than those with no/mild ROP (p = 0.019) and controls (p = 0.007). A high cortisol level, tall height, and severe ROP were independent predictors of higher ambulatory systolic BP during adulthood in forward stepwise regression analysis, independent of GA. Conclusion: Our results indicate that preterm infants with severe abnormal retinal vascular development during the neonatal period may be at an increased risk for increased BP during adulthood. We found no differences between those with no/mild ROP as infants and controls with regard to BP data. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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48.
  • Klinger, Gil, et al. (författare)
  • Late-onset sepsis among extremely preterm infants of 24-28 weeks gestation : an international comparison in 10 high-income countries
  • 2024
  • Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis.Methods: We performed a retrospective populationbased cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Lateonset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network.Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis.Conclusions: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.
  •  
49.
  • Kruszewska, Danuta, et al. (författare)
  • Enteral crude red kidney bean (Phaseolus vulgaris) lectin--phytohemagglutinin--induces maturational changes in the enterocyte membrane proteins of suckling rats.
  • 2003
  • Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 84:2, s. 152-158
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to investigate the effect of enterally administered crude red kidney bean (Phaseolus vulgaris) lectin, PHA, on the expression of brush-border membrane vesicle (BBMV) proteins, in particular Na+/H+ exchangers (NHEs), in the small intestine of suckling rats. Gavage of PHA to 14-day-old rats for 3 days resulted in altered protein/glycoprotein patterns as analyzed by SDS-PAGE. Immunoblots demonstrated the appearance of two 71- and 27-kD protein bands indicative for NHE3 - one of the NHE isoforms - and PHA, respectively. PHA treatment also resulted in an augmented uptake of 22Na+ by the BBMV indicating an increase in NHE activity. Overall, the data suggests that enteral PHA exposure may induce maturational changes in enterocyte membrane proteins in young rats. In view of these findings, an investigation into the addition of PHA to infant formulas and weaning diets is warranted.
  •  
50.
  • Latheef, Faiza, et al. (författare)
  • The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants
  • 2021
  • Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 118:1, s. 73-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications.Methods: A retrospective cohort study in extremely preterm infants (gestational age <28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC.Results: A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found.Conclusion: The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.
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