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| 4. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 5. |
- Ley, David, et al.
(författare)
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Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants : pharmacokinetics and short-term safety.
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 73:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background:In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP.Methods:In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded.Conclusion:In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.
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| 6. |
- Ley, David, et al.
(författare)
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Longitudinal infusion of insulin-like growth factor-I and IGF-binding protein-3 complex to five preterm infants: pharmacokinetics and short term safety.
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 63:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Background:In preterm infants, low levels of insulin like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP).Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and decrease prevalence of ROP.Methods:In a phase II pharmacokinetic and safety study, five infants (3 girls) with a median (range) gestational age (GA) of 26+6 (26+0 - 27+2) weeks and birth weight (BW) of 990 (900-1212) g received continuous intravenous infusion of rhIGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for median (range) 168h (47-168) in doses between 21 - 111 µg/kg/24h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (p<0.001) than model-predicted endogenous levels. Out of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within target range, 4 (5%) above and 33 (45%) were below. Predicted dose of rhIGF-I/rhIGFBP-3 to establish circulating levels of IGF-I within the intrauterine range in a 1000g infant was 75-100 µg/kg/24h. No hypoglycemia or other adverse effects were recorded.Conclusion:Continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3. Administration during study was safe.Pediatric Research (2012); doi:10.1038/pr.2012.146.
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| 7. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP: A substudy of the Mega Donna Mega trial
- 2022
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Ingår i: BMJ Open Ophthalmology. - : BMJ. - 2397-3269. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective The current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales (original: ROP-ActS and modified: mROP-ActS), describing increasing severity of ROP, versus the categorical variables severe ROP, stage, zone and plus disease were evaluated as discriminators of the effect of an ROP preventive treatment. Methods and analysis The Mega Donna Mega trial investigated ROP in infants born <28-week gestational age (GA), randomised to arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation or no supplementation. Of 207 infants, 86% with finalised ROP screening were included in this substudy. ROP-ActS versus standard variables were evaluated using Fisher's non-parametric permutation test, multivariable logistic and linear regression and marginal fractional response models. Results The AA:DHA group (n=84) and the control group (n=93) were well balanced. The maximum ROP-ActS measurement was numerically but not significantly lower in the AA:DHA group (mean: 4.0 (95% CI 2.9 to 5.0)) versus the control group (mean: 5.3 (95% CI 4.1 to 6.4)), p=0.11. In infants with any ROP, the corresponding scale measurements were 6.8 (95% CI 5.4 to 8.2) and 8.7 (95% CI 7.5 to 10.0), p=0.039. Longitudinal profiles of the scale were visually distinguished for the categories of sex and GA for the intervention versus control. Conclusions The preventive effect of AA:DHA supplementation versus no supplementation was better discriminated by the trial's primary outcome, severe ROP, than by ROP-ActS. The sensitivity and the linear qualities of ROP-ActS require further validations on large data sets and perhaps modifications. Trial registration number NCT03201588.
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| 8. |
- Yanagida, Keisuke, et al.
(författare)
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Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization
- 2020
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Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 52:6, s. 779-
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of b-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.
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| 9. |
- Fu, Z. F., et al.
(författare)
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Review: adiponectin in retinopathy
- 2016
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Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1862:8, s. 1392-1400
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Tidskriftsartikel (refereegranskat)abstract
- Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases. (C) 2016 Elsevier B.V. All rights reserved.
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| 10. |
- Fu, Zhongjie, et al.
(författare)
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FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP
- 2023
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 0969-6970 .- 1573-7209. ; 26:3, s. 409-21
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Tidskriftsartikel (refereegranskat)abstract
- Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).
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| 12. |
- Hellström, Ann, 1959, et al.
(författare)
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IGF-1 as a Drug for Preterm Infants : A Step-Wise Clinical Development
- 2017
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 23:38, s. 5964-5970
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants.METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 µg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included.RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 µg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days.CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.
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| 13. |
- Hellström, Ann, 1959, et al.
(författare)
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Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.
- 2016
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:6, s. 576-86
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Tidskriftsartikel (refereegranskat)abstract
- Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities.
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| 16. |
- Hellström, Ann, 1959, et al.
(författare)
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Weight Gain and Retinopathy of Prematurity
- 2013
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Ingår i: Pediatric Retina. Hartnett ME, Trese M, Capone A, et al. (eds.).. - Philadelphia : Lippincott Williams & Wilkins. - 9781451151404 ; , s. 533-542
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Bokkapitel (refereegranskat)
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| 17. |
- Hård, Anna Lena, et al.
(författare)
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Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk
- 2019
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:6, s. 998-1007
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This nonsystematic review examined differences in the composition of raw maternal breastmilk and pasteurised donor milk and possible health effects on preterm infants. Methods: We searched PubMed up to July 2018 for studies published in English that focused on four comparisons as follows: raw maternal milk versus donor milk, human milk before and after Holder pasteurisation, milk from mothers who delivered preterm and at term and milk collected during early and late lactation. We also searched for possible effects of the milk components, as well as the effects of maternal and donor milk on preterm infants’ health. Results: Raw maternal milk contained factors involved in antioxidant and anti-inflammatory defence, gut microbiome establishment and the maturation of immune defences, food tolerability and metabolism. Many of these factors were reduced or abolished in processed donor milk. Both maternal milk and donor milk have been associated with a reduced incidence of necrotising enterocolitis. High-dose feeding with maternal milk during the neonatal period reportedly reduced the risk of other morbidities and promoted growth and neurodevelopment. Conclusion: Many of the components in raw maternal breastmilk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants.
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| 18. |
- Klevebro, Susanna, et al.
(författare)
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Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants
- 2024
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 43:5, s. 1162-1170
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants. Methods: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center. Results: On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period. Conclusions: This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population. Clinical registration number: ClinicalTrials.gov (NCT03201588).
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| 19. |
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| 20. |
- Lundgren, Pia, 1967-, et al.
(författare)
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Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity
- 2019
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 86:2, s. 276-282
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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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| 21. |
- Lundgren, Pia, 1967-, et al.
(författare)
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Implementing Higher Oxygen Saturation Targets Reduced the Impact of Poor Weight Gain as a Predictor for Retinopathy of Prematurity
- 2018
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Ingår i: Acta Paediatrica. - Oxford, UK : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 107:5, s. 767-773
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Methods: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool. Results: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016. Conclusion: After the SpO2 target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops.
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| 24. |
- Lundgren, Pia, 1967-, et al.
(författare)
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Weight at first detection of retinopathy of prematurity predicts disease severity
- 2014
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Ingår i: British Journal of Ophthalmology. - London, UK : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 98:11, s. 1565-1569
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether postnatal weight at first detection of retinopathy of prematurity (ROP) can predict preterm infants who will develop severe ROP warranting treatment.Design: This modern, population-based cohort included 147 infants born at gestational age (GA) <32 weeks in the Gothenburg region during 2011–2012 and screened for ROP at Sahlgrenska University hospital. GA, birth weight (BW), and weekly postnatal weight from birth until postmenstrual age (PMA) 40 weeks data were retrospectively retrieved. Birth weight SD scores (BWSDS) were calculated. ROP data, including first detected ROP stage, maximal ROP stage, ROP treatment, and PMA at first detected sign of ROP were also retrieved. Weight SDS (WSDS) at first ROP detection was calculated.Results: Stepwise multivariate logistic regression analysis revealed that the best fit-model of risk factors for developing severe ROP warranting treatment included; GA (OR=0.28, CI 95% 0.12 to 0.66, p<0.01) and WSDS at first ROP detection (OR=0.22, CI 95% 0.05 to 0.89, p<0.05).Conclusions: Low weight and low WSDS at first ROP detection can be useful predictors for ROP warranting treatment.
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| 25. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Longitudinal Postnatal Weight and Insulin-like Growth Factor I Measurements in the Prediction of Retinopathy of Prematurity
- 2006
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Ingår i: Arch Ophthalmol. - : American Medical Association (AMA). ; 124:12, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether postnatal growth and development influence retinopathy of prematurity (ROP) and may be included in screening for ROP. Design We developed an algorithm to predict for individual infants the risk of later ROP development requiring treatment based on the postnatal longitudinal systemic factors of insulin-like growth factor I (IGF-I) level, IGF binding protein 3 level, and postnatal weight gain. We developed the algorithm based on 79 preterm infants considered at risk for ROP by standard criteria (gestational age, 23.6-31.7 weeks) in a longitudinal study measuring weight gain and serum IGF-I and IGF binding protein 3 levels weekly from birth until discharge from the hospital. We monitored deviations from reference models for weight and IGF-I level (preterm children who developed no or minimal ROP) to detect indications for treatable ROP by Early Treatment for Retinopathy of Prematurity study criteria. Results This monitoring method detected 6 (100%) of 6 infants in this cohort who required treatment for ROP with a warning signal at least 5 weeks before requiring treatment and at least 3 weeks before the onset of stage 3 ROP. The majority of infants (61/73 infants) requiring no treatment were also correctly identified. Conclusions Monitoring the postnatal factors of weight, IGF-I level, and IGF binding protein 3 level substantially enhances the clinician's ability to identify patients who will require treatment for ROP.
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