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      WINROP Identifies Severe Retinopathy of Prematurity at an Early Stage in a Nation-Based Cohort of Extremely Preterm Infants

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          Abstract

          Objective

          To evaluate the ability of a postnatal weight-gain algorithm (WINROP) to identify sight-threatening retinopathy of prematurity (ROP type 1) in a nation-based extremely preterm infant cohort.

          Methods

          This study enrolled all 707 live-born extremely preterm (gestational age [GA] <27 weeks) infants, born 2004–2007 in Sweden; the Extremely preterm Infants in Sweden Study (EXPRESS). WINROP analysis was performed retrospectively in 407 of the infants using weekly weight gain to assess the preterm infant’s risk of developing ROP type 1 requiring treatment. GA, birthweight (BW), and weekly postnatal weight measurements were entered into WINROP. WINROP signals with an alarm to indicate if the preterm infant is at risk for ROP type 1.

          Results

          In this extremely preterm population, WINROP correctly identified 96% (45/47) of the infants who required treatment for ROP type 1. The median time from alarm to treatment was 9 weeks (range, 4–20 weeks).

          Conclusions

          WINROP, an online surveillance system using weekly weight gain, identified extremely preterm infants at risk for ROP type 1 requiring treatment at an early stage and with high sensitivity in a Swedish nation-based cohort.

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          Most cited references27

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          Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.

          Early Treatment For Retinopathy Of Prematurity Cooperative Group (2003)
          To determine whether earlier treatment using ablation of the avascular retina in high-risk prethreshold retinopathy of prematurity (ROP) results in improved grating visual acuity and retinal structural outcomes compared with conventional treatment. Infants with bilateral high-risk prethreshold ROP (n = 317) had one eye randomized to early treatment with the fellow eye managed conventionally (control eye). In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. High risk was determined using a model based on the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a corrected age of 9 months, visual acuity was assessed by masked testers using the Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were examined for structural outcome. Outcomes for the 2 treatment groups of eyes were compared using chi2 analysis, combining data for bilateral and asymmetric cases. Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.5% to 14.5% (P =.01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type 1 ROP, defined as zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. The analysis supported a wait-and-watch approach to type 2 ROP, defined as zone I, stage 1 or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease. These eyes should be considered for treatment only if they progress to type 1 or threshold ROP. Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.
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            Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis.

            Kip Connor, John SanGiovanni, Chatarina Löfqvist … (2007)
            Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
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              Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.

              Anna-Lena Hård, Chatarina Löfqvist, Uwe Ewald … (2003)
              Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP. We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was
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                Author and article information

                Contributors
                Demetrios Vavvas: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 12 September 2013
                Volume: 8
                Issue: 9
                Electronic Location Identifier: e73256
                Affiliations
                [1 ]Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
                [2 ]Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
                [3 ]Tornbladsinstitute, Lund University Hospital, Lund, Sweden
                [4 ]Department of Neuroscience, Ophthalmology, Uppsala University, Uppsala, Sweden
                [5 ]Department of Ophthalmology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America
                Massachusetts Eye & Ear Infirmary, Harvard Medical School, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AH ALH CL. Performed the experiments: PL. Analyzed the data: PL CL. Wrote the manuscript: PL CL AH ALH. Responsible for the organisation and collection of ROP data of the EXPRESS study: GH. Responsible for the organisation and collection of weight data of the EXPRESS study: ESS MD. Performed and supervised database development of the EXPRESS study: KK. Reviewed the manuscript: GH MD LES ESS.

                Article
                Publisher ID: PONE-D-13-20050
                DOI: 10.1371/journal.pone.0073256
                PMC ID: 3771982
                PubMed ID: 24069180
                SO-VID: 4a77afc7-d2a8-48db-a289-218aebe39bf7
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 May 2013
                Date accepted : 17 July 2013
                Funding
                This study was supported by the Swedish Medical Research Council (grant #2008-2842, 2011-2432), Government grants (#ALFGB-137491), and VINNOVA (grant # 2009-01152, 2009-00221). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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