| 1. |
- Stoltz Sjöström, Elisabeth, 1967-, et al.
(författare)
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Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants
- 2016
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - London, UK : BMJ. - 1359-2998 .- 1468-2052. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Poor weight gain during the first weeks of life in preterm infants is closely associated with the risk of developing the retinopathy of prematurity (ROP) and insufficient nutrition might be an important contributing factor. This study aimed to evaluate the effect of energy and macronutrient intakes during the first 4 weeks of life on the risk for severe ROP (stages 3-5). Study design A population-based study including all Swedish extremely preterm infants born before 27 gestational weeks during a 3-year period. Each infant was classified according to the maximum stage of ROP in either eye as assessed prospectively until full retinal vascularisation. The detailed daily data of actual intakes of enteral and parenteral nutrition and growth data were obtained from hospital records. Results Of the included 498 infants, 172 (34.5%) had severe ROP and 96 (19.3%) were treated. Energy and macronutrient intakes were less than recommended and the infants showed severe postnatal growth failure. Higher intakes of energy, fat and carbohydrates, but not protein, were significantly associated with a lower risk of severe ROP. Adjusting for morbidity, an increased energy intake of 10 kcal/kg/day was associated with a 24% decrease in severe ROP. Conclusions We showed that low energy intake during the first 4 weeks of life was an independent risk factor for severe ROP. This implies that the provision of adequate energy from parenteral and enteral sources during the first 4 weeks of life may be an effective method for reducing the risk of severe ROP in extremely preterm infants.
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| 2. |
- Austeng, Dordi, et al.
(författare)
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Regional differences in screening for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden : the EXPRESS study
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley-Blackwell. - 1755-375X .- 1755-3768. ; 92:4, s. 311-315
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The primary aim was to analyse regional incidences of retinopathy of prematurity (ROP) and frequencies of treatment and their relation to perinatal risk factors during a 3-year period. A secondary aim was to study adherence to the study screening protocol in the different regions.Methods: A population-based study of neonatal morbidity in extremely preterm infants in Sweden (EXPRESS) was performed during 2004-2007. Screening for ROP was to start at postnatal age 5weeks and to continue weekly until the retina was completely vascularized or until regression of ROP. Logistic regression analyses were used for evaluation of differences in incidence of Any ROP, ROP 3 or more and ROP Type 1 between the seven regions of the country.Results: The regional incidence of ROP varied between 54% and 92% for Any ROP, between 25% and 43% for ROP stage 3 or more and between 8% and 23% of infants with ROP Type 1, all of whom were treated. There was no significant difference between the regions regarding ROP Type 1, even when adjusting for known risk factors for ROP.Conclusion: The heterogeneity between the regions regarding the incidence of ROP was reduced with increasing severity of ROP, and there was no heterogeneity regarding frequency of treatment for ROP, which is the most important issue for the children. We cannot exclude observer bias regarding mild ROP and ROP stage 3 in this study.
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| 3. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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| 4. |
- Desai, S., et al.
(författare)
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Validation of WINROP (online prediction model) to identify severe retinopathy of prematurity (ROP) in an Australian preterm population: a retrospective study
- 2021
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Ingår i: Eye. - : Springer Science and Business Media LLC. - 0950-222X .- 1476-5454. ; 35, s. 1334-1339
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Retinopathy of prematurity (ROP) is the most common disease leading to blindness in extreme preterm infants. Current screening guidelines recommend frequent eye examinations. There is a dearth of trained ophthalmologists for these frequent screening procedures. The ANZNN neonatal network report (2013) found that only 6.4% of all screened infants had severe ROP and less than half received treatment. WINROP (online prediction model, Sweden) uses the postnatal weight gain (surrogate marker for low insulin-like growth factor IGF-1 and poor retinal vascular growth) to identify ROP requiring treatment and aims to reduce the number of examinations. Our objective was to validate the WINROP model in an Australian cohort of preterm infants. Methods Birth weight, gestational age, and weekly weight measurements were retrieved retrospectively along with the final ROP outcomes and plotted on the online WINROP software. Results The sensitivity, specificity, positive predictive value, and negative predictive value of WINROP were 85.7%, 59.0%, 6.98%, and 99.1% respectively for a cohort of 221 preterm infants (Median birth weight, 1040 g; Gestational age, 27.9 weeks). WINROP alarm was signaled in 42.6% of all infants. WINROP did not signal an alarm in one infant who needed treatment. This infant had intra ventricular hemorrhage grade 3-4 and temporary ventricular dilatation. Conclusions This is the first Australian study validating WINROP model. Our findings suggest that it lacked sensitivity to be used alone. However, adjusting the algorithm for the Australian population may improve the efficacy and reduce the number of examinations when used along with the current screening guidelines.
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| 5. |
- 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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| 6. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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Decreased Platelet Counts and Serum Levels of VEGF-A, PDGF-BB, and BDNF in Extremely Preterm Infants Developing Severe ROP
- 2021
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 118, s. 18-27
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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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| 7. |
- Hellström, Ann, 1959, et al.
(författare)
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Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants
- 2021
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. OBJECTIVE To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. MAIN OUTCOMES AND MEASURES Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. RESULTS A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. CONCLUSIONS AND RELEVANCE This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
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| 8. |
- Hellström, Ann, 1959, et al.
(författare)
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Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5years of age
- 2018
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 107:5, s. 811-821
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. Methods: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22+0 to 26+6weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30months. Results: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. Conclusion: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5years who were born extremely preterm.
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| 9. |
- Hellström, Ann, 1959, et al.
(författare)
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Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. Setting Eye and paediatric clinics in Sweden. Participants Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. Primary and secondary outcome measures Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. Results The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. Conclusions Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.
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| 10. |
- Holmström, Gerd E., et al.
(författare)
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Swedish National Register for Retinopathy of Prematurity (SWEDROP) and the Evaluation of Screening in Sweden
- 2012
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Ingår i: Archives of Ophthalmology. - Chicago, USA : American Medical Association (AMA). - 0003-9950. ; 130:11, s. 1418-1424
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. Methods: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. Results: In SWEDROP, there were 1791 infants born before a GA of 32weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (drop-out rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). Conclusions: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.
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