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Cruz NFSDA, Hudson JL, Sengillo JD, Shah SM, Lopez-Font F, Negron CI, Farah ME, Berrocal AM. Underlying Disease in Atypical Retinopathy of Prematurity. Am J Ophthalmol 2025; 274:67-75. [PMID: 40010420 DOI: 10.1016/j.ajo.2025.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/18/2025] [Accepted: 02/18/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND AND OBJECTIVE Retinopathy of prematurity (ROP), familial exudative vitreoretinopathy (FEVR), and telomere biology disorders (TBD) are classified as distinct diseases. However, emerging genetic research and evidence on multimodal imaging suggest a spectrum along which ROP may overlap with FEVR or TBD. DESIGN Retrospective case series. METHODS This was an institutional review board-approved, retrospective study. A literature review was performed, and medical records of all patients with phenotypic ROP evaluated by the pediatric retina service at Bascom Palmer Eye Institute from March 1, 2019 to July 30, 2023 were analyzed. RESULTS Eighteen patients with phenotypic and genetically confirmed FEVR or TBD were identified. Of these, the initial diagnosis was ROP with preterm gestational age (n = 11, 57.9%) or ROP at moderate to late preterm gestational age (n = 8, 42.1%). Final diagnosis for 15 patients (78.9%) was FEVR, and final diagnosis for 4 patients (21.1%) was TBD. The most common genetic variants in the FEVR group were identified in the genes LRP5 (n = 5, 33.3%) and FZD4 (n = 3, 20%), and in the TBD group, CTC1 (n = 3; 75%). The mean age at diagnosis was 5.7 years old (range 0.3-36.7 years). CONCLUSIONS The authors reinforce the classification of ROPER (ROP and FEVR) and introduce the term, ROPMERE (ROP and TBD), to classify these patients in a way that reflects their clinical presentation and underlying genetic diagnosis. Identification of this subset of patients will allow for sustained surveillance of infants with these diseases.
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Affiliation(s)
- Natasha F S DA Cruz
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States; Department of Ophthalmology (N.D.C., M.F.), Federal University of São Paulo, Escola Paulista de Medicina, São Paulo, Brazil; Department of Ophthalmology, Centro Ocular (N.D.C.), Belém, Brazil
| | - Julia L Hudson
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Jesse D Sengillo
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Serena M Shah
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Francisco Lopez-Font
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Catherin I Negron
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Michel E Farah
- Department of Ophthalmology (N.D.C., M.F.), Federal University of São Paulo, Escola Paulista de Medicina, São Paulo, Brazil
| | - Audina M Berrocal
- Department of Ophthalmology (N.D.C., J.H., J.S., S.S., F.L.F., C.N., A.B.), Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, United States.
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Lu E, Leung KY, Wong WHS, Lai CHY, Jalal K. Randomized Controlled Trial Comparing the Efficacy of Mydrin-P Microdrops Over Standard Dose Mydrin-P for Pupil Dilation in Retinopathy of Prematurity Examination. J Pediatr Ophthalmol Strabismus 2025:1-9. [PMID: 40423262 DOI: 10.3928/01913913-20250424-02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Abstract
PURPOSE To compare the efficacy of a reduced dose of Mydrin-P (0.5% tropicamide and 0.5% phenylephrine hydrochloride) (Santen Pharmaceutical) using micro-drops with standard Mydrin-P eye drops for retinopathy of prematurity (ROP) examinations. METHODS A prospective, randomized controlled, non-inferiority study was conducted in a single neonatal intensive care unit in Hong Kong. Eighteen infants with an estimated gestational age at birth of 32 weeks or less and/or birth weight of 1,500 g or less were recruited and randomized to receive either standard Mydrin-P eye drops or Mydrin-P microdrops (one-third of the standard dose). All patients were subsequently examined by an ophthalmologist for the presence of ROP. Serial pupil diameters and other clinical parameters were also measured after mydriatics were applied. RESULTS Eighteen infants with 46 eye examinations for ROP were included. All fundus examinations with microdrop instillation led to successful ROP assessments with no statistically significant difference compared to standard eye drops (P = .233). Mean pupil diameter did not differ between the microdrop (5.73 mm) and standard eye drop (5.47 mm) groups at the time of exami- nation. No statistically significant difference in systemic side effects was observed between the two groups. CONCLUSIONS Mydriatic Mydrin-P microdrops demonstrated similar efficacy compared to standard Mydrin-P eye drops and should replace standard Mydrin-P for ROP screening in preterm infants with potentially fewer side effects. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].
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El Emrani S, Jansen EJS, Goeman JJ, Termote JUM, Lopriore E, Schalij-Delfos NE, van der Meeren LE. Comprehensive assessment of placental inflammation: Novel approach in predicting retinopathy of prematurity. Early Hum Dev 2025; 204:106239. [PMID: 40086020 DOI: 10.1016/j.earlhumdev.2025.106239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025]
Abstract
The purpose of this study was to determine the independent association between placental inflammation and the development of retinopathy of prematurity (ROP). This retrospective cohort study included 591 neonates born with a gestational age (GA) ≤32 weeks and/or a birthweight (BW) ≤1500 g. Clinical data were retrospectively collected, and placentas were reexamined for acute (e.g. chorioamnionitis and funisitis) and chronic placental inflammation (e.g. chorioamnionitis, villitis of unknown etiology and chronic deciduitis). Severe acute chorioamnionitis was defined as the presence of confluent polymorphonuclear leukocytes or subchorionic microabscesses. Outcomes explored were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, necrotizing enterocolitis, and ROP. Acute histological chorioamnionitis and funisitis were associated with lower GA, lower SGA rates, increased duration of mechanical ventilation and increased ROP rates, while chronic chorioamnionitis and villitis were associated with higher GA and increased SGA rates. BW was significantly lower in neonates with chronic deciduitis. Subanalysis of placentas without maternal and fetal vascular malperfusion also showed increased rates of severe acute chorioamnionitis (42 % vs. 21 %), funisitis (61 % vs. 35 %) in neonates with ROP. Multivariable regression analysis revealed two placental inflammatory factors to be independently associated with ROP: severe acute chorioamnionitis (OR 2.1; 95 % CI 1.1-3.8) and funisitis (OR 1.7; 95 % CI 1.0-2.9). Structured placental evaluation of the presence of severe acute chorioamnionitis and funisitis is valuable in predicting the development of ROP. This increased risk of ROP development could be integrated into the neonatal treatment approach of high-risk neonates in a very early stage in order to reduce ROP.
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Affiliation(s)
- Salma El Emrani
- Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Division of Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
| | - Esther J S Jansen
- Division of Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jelle J Goeman
- Division of Medical statistics, Department of Biomedical Data Science, Leiden University Medical Center, Leiden, the Netherlands
| | - Jacqueline U M Termote
- Division of Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Enrico Lopriore
- Division of Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Lotte E van der Meeren
- Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands
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Maitra P, Kang EYC, Wu WC. Establishing an objective quantitative method for assessing the severity of plus disease in retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2025; 263:985-992. [PMID: 39870912 DOI: 10.1007/s00417-025-06743-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 12/10/2024] [Accepted: 01/10/2025] [Indexed: 01/29/2025] Open
Abstract
BACKGROUND To establish an objective method for assessing plus disease severity in retinopathy of prematurity. METHODS Six images of plus diseases that were color-coded according to severity and published in the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3) were analyzed. These images were individually processed, and the best-fit curve and vessel course in zone I were obtained using ImageJ software. Tortuosity indices (TIs) of the major vessels in the temporal quadrants were calculated. Data from real-world patients with no plus, pre-plus, and plus diseases were analyzed and compared with those of the ICROP. RESULTS The TIs of the arteries and veins, the sum of these TIs, and the artery/vein (A/V) TI ratios increased incrementally from grades 1 to 6. The trend revealed that the arterial tortuosity increased more than the venous tortuosity. The degree of venous tortuosity was similar from grades 3-5 but higher in grade 6. The A/V TI ratio increased in grades 1-3, stabilized in grades 3-5, and peaked in grade 6. Analysis of data from real-world patients showed increased TI of both arteries and veins, similar to the ICROP3. However, the A/V TI ratio did not show an increasing trend. CONCLUSION Objective methods for assessing disease severity can provide insights into the potential pathophysiological mechanisms of plus disease progression. Arterial tortuosity is more prominent than venous tortuosity. Venous features become more prominent as plus disease progresses, which may obscure the progression of arterial tortuosity.
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Affiliation(s)
- Puja Maitra
- Department of Vitreoretina Services, Aravind Eye Hospital, Chennai, India
| | - Eugene Yu-Chuan Kang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Ophthalmology, Linkou Medical Center, Chang Gung Memorial Hospital, No. 5, Fu-Hsin Rd, Taoyuan, Taiwan, 333
| | - Wei-Chi Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.
- Department of Ophthalmology, Linkou Medical Center, Chang Gung Memorial Hospital, No. 5, Fu-Hsin Rd, Taoyuan, Taiwan, 333.
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El Emrani S, Termote JUM, Jansen EJS, Goeman JJ, Lopriore E, Schalij-Delfos NE, van der Meeren LE. Difference in adverse neonatal outcomes between preterm singletons and twins possibly explained by placental abnormalities. Placenta 2025; 162:45-50. [PMID: 40010054 DOI: 10.1016/j.placenta.2025.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/12/2024] [Accepted: 02/14/2025] [Indexed: 02/28/2025]
Abstract
INTRODUCTION The purpose of this study was to compare microscopic placental characteristics between preterm twins and singletons, and between preterm monochorionic and dichorionic twins, in order to explore the effect of placental pathology on adverse neonatal outcomes. METHODS This study included 566 neonates born ≤32 weeks and/or ≤1500 g, of whom 429 were singletons and 137 were twins (38 monochorionic and 99 dichorionic). Clinical data was retrospectively collected, and placentas were prospectively examined for maternal vascular malperfusion, fetal vascular malperfusion and placental inflammation (acute and chronic). RESULTS Singletons had increased rates of maternal vascular malperfusion, fetal hypoxia, funisitis (in umbilical cord and chorial plate), chronic deciduitis, and villitis of unknown etiology compared to twins. Delayed villous maturation and ischemia were more frequently present in monochorionic placentas than in dichorionic. Singletons had a significant lower birthweight and were more often small for gestational age than twins. Multivariate linear regression analysis adjusting for singleton pregnancy, gestational hypertension and placental abnormalities showed that gestational hypertension (β = -114.8), infarct (β = -130.1), decidual necrosis (β = -115.4), fetal hypoxia (β = -59.3) and chronic deciduitis (β = -118.8) were independently associated with lower birthweight. Multivariate regression analysis revealed five independent risk factors of small for gestational age: gestational hypertension (OR 4.4), infarct (OR 3.7), decidual necrosis (OR 2.7), fetal hypoxia (OR 1.9) and villitis (OR 5.2). DISCUSSION Singleton pregnancies vary in histological placental abnormality rates from twin pregnancies. This study demonstrated that differences in birthweight and small for gestational age rates between preterm twins and singletons can be attributed to gestational hypertension and histological placental abnormalities.
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Affiliation(s)
- Salma El Emrani
- Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
| | - Jacqueline U M Termote
- Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Esther J S Jansen
- Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jelle J Goeman
- Medical Statistics, Department of Biomedical Data Science, Leiden University Medical Center, Leiden, the Netherlands
| | - Enrico Lopriore
- Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Lotte E van der Meeren
- Pathology, Leiden University Medical Center, Leiden, the Netherlands; Pathology, Erasmus Medical Center, Rotterdam, the Netherlands
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Chang E, Josan A, Purohit R, Aslam SA, Hartley C, Patel CK, Xue K. Retinal Vascularization Rate Predicts Retinopathy of Prematurity and Remains Unaffected by Low-Dose Bevacizumab Treatment. Am J Ophthalmol 2025; 275:74-87. [PMID: 40054545 DOI: 10.1016/j.ajo.2025.02.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/06/2025] [Accepted: 02/10/2025] [Indexed: 04/17/2025]
Abstract
PURPOSE To assess the rate of retinal vascularization derived from ultra-widefield (UWF) imaging-based retinopathy of prematurity (ROP) screening as predictor of type 1 ROP and characterize the effect of anti-vascular endothelial growth factor (anti-VEGF) therapy on vascularization rate. DESIGN Retrospective, consecutive cohort study. SUBJECTS The study included 132 eyes of 76 premature infants with a mean gestational age (GA) of 26.0 (±2.0 SD) weeks and birthweight (BW) of 815 (±264) g, who underwent longitudinal UWF imaging for ROP screening, at a level 3 neonatal unit in Oxford, United Kingdom. METHODS The extent of retinal vascularization on each UWF image was measured as the ratio between "disc-to-temporal vascular front" and "disc-to-fovea" distance along a straight line bisecting the vascular arcades. Measurements from ≥3 time points plotted against post-menstrual age (PMA) enabled calculation of temporal vascularization rate (TVR) for each eye. Using TVR, GA, and BW as predictors, a machine learning model was created to classify eyes as either group AB (no ROP and type 2 ROP) or group C (type 1 ROP). The model was validated in a withheld cohort of 32 eyes (19 infants), of which 8 eyes (5 infants) required treatment. TVR in 37 eyes (20 infants) was compared before and after ultra-low-dose (0.16 mg) intravitreal bevacizumab treatment. MAIN OUTCOME MEASURES The rate of retinal vascularization was determined. RESULTS Slower retinal vascularization correlated with increasing ROP severity, with TVR being 29% slower in group C eyes (n=50) than group AB eyes (n=33 no ROP and n=49 type 2 ROP) (P = .04). Our model correctly predicted ROP outcomes of 30/32 eyes, achieving a balanced accuracy of 95.8%. No significant change in TVR was found before and after bevacizumab treatment with mean posttreatment imaging follow-up of 7.7 (±7.9) weeks (P = .60 right eyes, P = .71 left eyes). CONCLUSIONS UWF imaging-based ROP screening enables quantification of retinal vascularization rate, which can provide early prediction of type 1 ROP independent of BW and GA. Rate of physiological retinal vascularization does not appear to be significantly affected by ultra-low-dose anti-VEGF treatment, which has significant implications for the development of peripheral avascular retina and timing of anti-VEGF intervention to prevent disease progression in high-risk infants.
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Affiliation(s)
- Emer Chang
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK
| | - Amandeep Josan
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford (A.J., K.X.), Oxford, UK
| | - Ravi Purohit
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK
| | - Sher A Aslam
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK
| | - Caroline Hartley
- Department of Paediatrics, University of Oxford (C.H.), Oxford, UK
| | - Chetan K Patel
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK
| | - Kanmin Xue
- From the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust (E.C., A.J., R.P., S.A.A., C.K.P., K.X.), Oxford, UK; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford (A.J., K.X.), Oxford, UK; Ophthalmology Department, Great Ormond Street Hospital for Children NHS Foundation Trust (K.X.), London, UK.
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Campbell-Yeo M, Mireault A, Bacchini F, Beltempo M, Shah PS, Alcock L, Comeau J, Dol J, Grant A, Gubbay J, Hughes B, Hundert A, Inglis D, Lalani Y, MacNeil M, Luu TM, Mitra S, Narvey M, O’Brien K, Robeson P, Science M, Canadian Neonatal Network (CNN) Investigators. Outcomes of Preterm Infants Admitted to Canadian NICUs Before and During the SARS-COV Pandemic. CHILDREN (BASEL, SWITZERLAND) 2025; 12:193. [PMID: 40003295 PMCID: PMC11854698 DOI: 10.3390/children12020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/23/2025] [Accepted: 01/28/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND To better elucidate the impact of the SARS-COV pandemic on neonatal outcomes, we compared the health outcomes of infants born preterm requiring care in a Canadian NICU before and during the SARS-COV pandemic. METHODS Using a retrospective cohort study, infants born between 23 and 32 weeks gestation who were admitted to tertiary Canadian NICUs before and during the pandemic were included. A total of 7280 infants were in the pre-pandemic cohort (admitted 1 April 2018-31 December 2019), and 7088 infants were in the pandemic cohort (admitted 1 April 2020-31 December 2021). The primary outcomes included major morbidity or mortality rates. Care strategies and treatments were compared across the two periods. The relative risk (RR) for the pandemic period, compared to the pre-pandemic period, was calculated using a Poisson regression model, adjusted for identified risk factors. RESULTS There were no significant differences in infant characteristics between the pre-pandemic and pandemic cohorts. The risk of mortality or major morbidity was comparable before and during the pandemic (37% pre-pandemic, 36% pandemic; RR = 1.01, 95% CI 0.92, 1.01). Individual risks for morbidity and mortality did not differ significantly between periods. There was a clinically significant decline in the receipt of the mothers' own milk exclusively at discharge during the pandemic (45% before and 37% during; RR 0.85, 95% CI 0.68, 1.06). CONCLUSIONS There were no significant differences in major morbidity or mortality rates in preterm infants between pre-pandemic and pandemic cohorts in Canadian NICUs.
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Affiliation(s)
- Marsha Campbell-Yeo
- Dalhousie University, Halifax, NS B3H 4R2, Canada
- MOM-LINC Laboratory, IWK Health, Halifax, NS B3K 6R8, Canada
- IWK Health, Halifax, NS B3K 6R8, Canada
| | - Amy Mireault
- MOM-LINC Laboratory, IWK Health, Halifax, NS B3K 6R8, Canada
| | - Fabiana Bacchini
- Canadian Premature Babies Foundation, Toronto, ON M8X 1Y3, Canada
| | - Marc Beltempo
- McGill University Health Centre—Montreal Children’s Hospital, Montreal, QC H4A 3J1, Canada
| | - Prakesh S. Shah
- Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
- Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Lynsey Alcock
- MOM-LINC Laboratory, IWK Health, Halifax, NS B3K 6R8, Canada
| | | | | | - Amy Grant
- Maritime SPOR Support Unit, Halifax, NS B3H 0A2, Canada
| | - Jonathan Gubbay
- BC Children’s Hospital, Vancouver, BC V6H 3N1, Canada
- Laboratory Medicine, Department of Pathology, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Brianna Hughes
- MOM-LINC Laboratory, IWK Health, Halifax, NS B3K 6R8, Canada
- Faculty of Nursing, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada
| | | | | | - Yasmin Lalani
- Canadian Premature Babies Foundation, Toronto, ON M8X 1Y3, Canada
- Humber River Health, Toronto, ON M3M 0B2, Canada
| | - Morgan MacNeil
- Dalhousie University, Halifax, NS B3H 4R2, Canada
- MOM-LINC Laboratory, IWK Health, Halifax, NS B3K 6R8, Canada
| | - Thuy Mai Luu
- Département de Pédiatrie, Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC H3T 1C5, Canada
| | - Souvik Mitra
- BC Children’s Hospital, Vancouver, BC V6H 3N1, Canada
| | - Michael Narvey
- Department of Pediatrics, Children’s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Karel O’Brien
- Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
- Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Paula Robeson
- Children’s Healthcare Canada, Ottawa, ON K2A 3W9, Canada
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Wang W, Freedman SF, Wallace DK, Prakalapakorn SG. Quantitative comparison of vascular characteristics of plus disease images published over time: International Classification of Retinopathy of Prematurity. J AAPOS 2025; 29:104101. [PMID: 39746533 DOI: 10.1016/j.jaapos.2024.104101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 08/06/2024] [Accepted: 08/25/2024] [Indexed: 01/04/2025]
Abstract
Plus disease was first defined in the original International Classification of retinopathy of prematurity (ICROP) publication in 1984. Over time, the definition of plus disease has evolved, and each ensuing ICROP publication has included example plus disease images. Because plus disease is often present when treatment is indicated, it is important to evaluate whether the retinal vascular characteristics (ie, dilation and tortuosity) depicted in these example images have remained the same or changed over time. Using a semiautomated computer program to trace and quantitatively analyze the retinal vessels in all example plus disease images published in three iterations of ICROP over time, the most recent ICROP publication (ICROP3) consistently exhibited the lowest amount of vascular dilation and tortuosity. This suggests a potential shift towards less tortuous and dilated retinal vessels in example plus disease images published in ICROP3, possibly indicating a lowering of the threshold for diagnosing plus disease and treatment of retinopathy of prematurity.
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Affiliation(s)
- Weiliang Wang
- Duke-National University of Singapore Medical School, Singapore
| | - Sharon F Freedman
- Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
| | - David K Wallace
- Department of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - S Grace Prakalapakorn
- Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
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Fevereiro-Martins M, Aguiar L, Inácio Â, Cardoso C, Santos AC, Marques-Neves C, Guimarães H, Pinto R, Bicho M. Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal. Biomedicines 2025; 13:110. [PMID: 39857694 PMCID: PMC11761889 DOI: 10.3390/biomedicines13010110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 12/27/2024] [Accepted: 01/02/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Retinopathy of prematurity (ROP) is a leading cause of vision impairment in preterm infants, with its pathogenesis linked to oxygen exposure. Red blood cell (RBC) transfusions, commonly performed in neonatal intensive care units (NICUs), reduce fetal hemoglobin (HbF) fraction, altering oxygen dynamics and potentially contributing to ROP. We aimed to investigate the relationship between RBC transfusions, HbF percentage, and ROP, evaluating HbF as a potential predictive biomarker. Methods: A multicenter, prospective study was conducted across eight Portuguese NICUs, involving infants born at <32 weeks gestational age (GA) or <1500 g. ROP staging followed the International Classification of ROP (ICROP2). Clinical data were collected during hospitalization, and HbF fractions were measured from blood samples in the first four weeks of life using standardized methods. Infants were stratified by ROP presence and treatment requirement. Statistical analysis was performed using SPSS 28.0, with p < 0.05. Results: Eighty-two infants (mean GA: 28.1 ± 2.1 weeks, birth weight: 1055.8 ± 258.3 g) were included. Among them, 29 (35.4%) presented ROP and 4 (4.9%) required treatment. Infants with ROP had more RBC transfusions and lower HbF percentages than those without ROP (p < 0.05). Lower HbF was associated with more RBC transfusions (p < 0.001). Kaplan-Meier survival curves showed a higher ROP risk in infants with reduced HbF (p < 0.05). Conclusions: Low HbF percentage in the first four weeks of life may increase ROP risk in preterm infants. HbF could serve as a biomarker for ROP prediction. Interventions preserving HbF may reduce ROP risk. Further studies are needed to validate HbF as a biomarker and refine prevention strategies.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
- Department of Ophthalmology, Cuf Descobertas Hospital, Rua Mário Botas, 1998-018 Lisbon, Portugal
| | - Laura Aguiar
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
| | - Ângela Inácio
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
| | - Carlos Cardoso
- Clinical Analysis Laboratory Dr. Joaquim Chaves, Rua Aníbal Bettencourt, nº3, Edificio CORE, 2790-225 Carnaxide, Portugal; (C.C.); (R.P.)
| | - Ana Carolina Santos
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
| | - Carlos Marques-Neves
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
- Center for the Study of Vision Sciences, University Ophthalmology Clinic, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
| | - Hercília Guimarães
- Department of Gynecology, Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal;
| | - Rui Pinto
- Clinical Analysis Laboratory Dr. Joaquim Chaves, Rua Aníbal Bettencourt, nº3, Edificio CORE, 2790-225 Carnaxide, Portugal; (C.C.); (R.P.)
| | - Manuel Bicho
- Ecogenetics and Human Health Unit, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisbon, Portugal; (L.A.); (Â.I.); (A.C.S.); (C.M.-N.); (M.B.)
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
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Ünal AC, Akıdan M, Erol MK. A comparation of three different anti-VEGF drugs in development of persistent avascular retina in premature children. Sci Rep 2024; 14:31097. [PMID: 39732747 DOI: 10.1038/s41598-024-82445-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 12/05/2024] [Indexed: 12/30/2024] Open
Abstract
Our current prospective cross-sectional study aimed to investigate the effect of anti-vascular endothelial growth factor (VEGF) drugs used in the treatment of retinopathy of prematurity on retinal maturation and persistent avascular retina (PAR). Retinal imaging was performed with Optos confocal laser ophthalmoscopy for 100 patients aged 4 to 8 years who were screened and treated for retinopathy of prematurity (ROP) during the neonatal period. The ROP examination findings (stage and zone) and treatment history (age in weeks at time of treatment and anti-VEGF drug used) from the neonatal period were reviewed. Retinal vascularization was assessed in fundus images using the green filter on the Optos device and the presence of PAR was evaluated by two investigators. Relationships between the rate of PAR, age in weeks at time of treatment, and type of anti-VEGF drug used were analyzed statistically. The study included 196 eyes of 100 patients. Sixty-four eyes were analyzed in Group 1 (no ROP), 23 eyes in Group 2 (ROP, no treatment), and 108 eyes in Group 3 (treated group; anti-VEGF treatment of ROP with ranibizumab, bevacizumab, or aflibercept). The number of eyes with PAR in these groups was 2 (3.7%), 4 (17.4%), and 45 (41.7%), respectively. PAR was detected in 30 of 44 eyes treated with aflibercept. The rate of PAR was higher after aflibercept treatment (68.2%) with statistical significance (p = 0.000). This study showed that the prevalence of PAR differs between anti-VEGF drugs. Patients treated with aflibercept have a higher risk of late complications and should be followed closely.
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Affiliation(s)
- Ayşe Cengiz Ünal
- Department of Ophthalmology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, 07050, Turkey.
| | - Melih Akıdan
- Department of Ophthalmology, Antalya Akseki State Hospital, Antalya, Turkey
| | - Muhammet Kazım Erol
- Department of Ophthalmology, University of Health Sciences, Antalya Education and Research Hospital, Antalya, 07050, Turkey
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Chang YH, Kang EYC, Chen KJ, Wang NK, Liu L, Hwang YS, Lai CC, Wu WC. Long-term surgical outcomes and prognostic factors for advanced-stage retinopathy of prematurity after vitrectomy. Br J Ophthalmol 2024; 109:126-132. [PMID: 39375028 DOI: 10.1136/bjo-2023-323723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 06/02/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND/AIMS The aims of this study is to evaluate the anatomic, visual outcomes and associated prognostic factors in patients with advanced retinopathy of prematurity (ROP) following vitrectomy. METHODS A retrospective cohort study of patients with ROP who underwent vitrectomy from 2005 to 2016 was conducted. All the patients had a follow-up period of at least 5 years. Univariate and multivariable logistic regression analyses were used to explore the factors related to unfavourable outcomes. RESULTS In total, 81 eyes of 51 patients were included. The mean age at last follow-up was 10.2 years. The anatomic success rate was 96.3% (26/27) for stage 4A, 90.9% (20/22) for stage 4B and 31.3% (10/32) for stage 5 ROP (p<0.01). The mean logMAR best corrected visual acuity of the stage-4A eyes was the highest, followed by those of stage-4B and stage-5 eyes (0.8, 1.5 and 2.6 for stages 4A, 4B and 5, respectively; p<0.01). High myopia (≤ -5.0 D) was noted in 70.8% and 71.4% of stage-4A and stage-4B eyes, respectively. Cataract was the most common complication (25.9%), followed by corneal opacity (17.3%), strabismus (16.1%), and phthisis (16.1%). Stage of the disease was a poor prognostic factor in all vitrectomised eyes (p<0.01). Vitrectomy combined lensectomy was a significant predictor for poor anatomic outcomes for stage-4 eyes (p=0.03). Presence of plus disease was also a possible factor affecting the surgical outcomes. CONCLUSION The long-term surgical outcomes of the eyes with stage 4A and 4B ROP were favourable. Management of stage 5 ROP remained challenging.
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Affiliation(s)
- Yin-Hsi Chang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Eugene Yu-Chuan Kang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuan-Jen Chen
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Nan-Kai Wang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, Columbia University, New York, NY, USA
| | - Laura Liu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yih-Shiou Hwang
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Chun Lai
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Chi Wu
- Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Butt F, Mohamad H, Abusallout N, Zaineh A, El Khatib F, Abdulrahman S, Hamwi S, Rahmani M, Alabdullatif M. Comparison of Efficacy of Beractant (SURVANTA®) and Poractant Alfa (CUROSURF®) in Preterm Infants With Respiratory Distress Syndrome in Tawam Hospital, Al Ain, UAE: A Retrospective Study. Cureus 2024; 16:e74790. [PMID: 39737314 PMCID: PMC11683160 DOI: 10.7759/cureus.74790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 11/29/2024] [Indexed: 01/01/2025] Open
Abstract
Introduction Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality among preterm infants, necessitating effective treatment strategies. This study compared the efficacy of Beractant (SURVANTA®) to Poractant alfa (CUROSURF®) in treating RDS in preterm infants admitted to Tawam Hospital in the UAE. Methodology This retrospective study included preterm infants from 23+0 to 36+6 weeks of gestation with a diagnosis of RDS and treatment by Beractant or Poractant alfa within 48 hours of life between January 2020 and March 2023. Data collected from electronic medical records of Tawam Hospital include infant and maternal demographics, primary outcome parameters, such as bronchopulmonary dysplasia (BPD) and/or mortality, and secondary outcome parameters, such as surfactant redosing, air leak syndrome, and other complications. Results A total of 258 infants met the inclusion criteria: 178 were treated with Beractant, and 80 were treated with Poractant alfa. After adjusting the confounding factors, the occurrence of bronchopulmonary dysplasia (BPD) was not statistically significant, showing rates of 68.7% (n=46) in the Poractant group and 47.5% (n=75) in the Beractant group (p=0.71). Likewise, there was no significant difference in mortality rates between the two groups, with 22.5% (n=18) in the Poractant group and 11.8% (n=21) in the Beractant group (p=0.33). Furthermore, the combined incidence of BPD or mortality was also not statistically significant, recorded at 53.4% (n=95) for the Beractant group compared to 73.8% (n=59) for the Poractant group (p=0.93). However, the need for surfactant redosing and air leak syndrome was significantly lower in the Poractant group compared to the Beractant group, 26.2% (n=21) vs 45.5% (n=81), p < 0.00001 and 8.8% (n=7) vs 14.6% (n=26), p = 0.05, respectively. There was no difference in the incidence of other outcomes such as pulmonary hemorrhage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), significant patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP) that required treatment. Conclusion There was no significant difference in the rates of bronchopulmonary dysplasia or mortality between Poractant alfa (CUROSURF®) and Beractant (SURVANTA®) in preterm infants suffering from respiratory distress syndrome. Poractant alfa (CUROSURF®) showed a reduced need for surfactant redosing and a lower incidence of air leak syndrome. However, the rates of other outcomes, including significant patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), and necrotizing enterocolitis (NEC), were comparable in both treatment groups. Further randomized prospective studies are necessary to evaluate these types of surfactants and investigate their efficacy as well as both short- and long-term outcomes.
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Affiliation(s)
- Fahad Butt
- Neonatology, Tawam Hospital, Al Ain, ARE
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Alabdullatif M, Butt F, BenAyad A, Rahmani A. Survival Rate and Short-Term Outcomes of Periviable Preterm Infants: A Single-Center Experience From the United Arab Emirates. Cureus 2024; 16:e73877. [PMID: 39697939 PMCID: PMC11652957 DOI: 10.7759/cureus.73877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 11/17/2024] [Indexed: 12/20/2024] Open
Abstract
The limit of periviability is constantly changing as infants born at 22-25 weeks of gestation increasingly survive. The data from our region are limited due to the small numbers of these infants among the NICU population. In this study, we evaluated the survival rates and short-term outcomes among preterm neonates between 22 and 24 weeks of gestation admitted to Tawam Hospital, United Arab Emirates. Our retrospective analysis included 100 cohorts of newborns from 22 to 25 weeks of gestation throughout the eight-year period in our level 3 NICU. We evaluated the use and effects of prenatal steroids and intrapartum antibiotics, in addition to perinatal complications, and examined their outcomes (survival, length of stay, and major morbidities). The survival rate of our periviable neonates was 18% (N = 18/100). Only one 22-week infant out of 32 cases (3%) survived during the study period in 2023. In contrast, the survival rate of infants of 23- and 24-week gestational age was 10% (N = 4/40) and 46% (N = 13/28), respectively. Although our focus in this study was to evaluate the survival of neonates who were born at around the limits of viability, we also reported the short-term outcomes at our single center, including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). Our data demonstrate that the trend of increasing survival with higher gestational age continues to improve over time. However, there was a significant risk of short-term co-morbidities for those who survived. Further studies are required to have robust data on short and long-term outcomes for this population. The information provided by this study could be essential for counseling parents, enabling them to participate actively in formulating their infants' care plans. It may also help parents and healthcare professionals reach a more informed and collaborative decision regarding active resuscitation and subsequent care plans for these periviable neonates.
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Affiliation(s)
| | - Fahad Butt
- Neonatology, Tawam Hospital, Al Ain, ARE
| | | | - Aiman Rahmani
- Pediatrics and Neonatology, Tawam Hospital, Al Ain, ARE
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Binenbaum G, Stahl A, Coyner AS, He J, Ying GS, Ostmo S, Chan RVP, Toth C, Vinekar A, Campbell JP. P Score: A Reference Image-Based Clinical Grading Scale for Vascular Change in Retinopathy of Prematurity. Ophthalmology 2024; 131:1297-1303. [PMID: 38795976 PMCID: PMC11499040 DOI: 10.1016/j.ophtha.2024.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 05/16/2024] [Accepted: 05/17/2024] [Indexed: 05/28/2024] Open
Abstract
PURPOSE The International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), acknowledged that plus-like retinopathy of prematurity (ROP) vascular changes occurs along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photograph reference image set for grading plus-like changes and compared intergrader agreement of the set with standard grading with no plus, preplus, and plus disease. DESIGN Retinal photographic grading and expert consensus opinion. PARTICIPANTS The development set included 34 international ICROP3 committee members. The validation set included 30 ophthalmologists with ROP expertise (15 ICROP3 committee members and 15 non-ICROP3 members) METHODS: Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on the 34 ICROP3 committee members' gradings and consensus image reviews, were used to establish standard photographs for the plus (P) score. Study participants graded 150 fundus photographs 2 ways, separated by a 1-week washout period: (1) no plus, preplus, or plus disease and (2) choosing the closest P score image. MAIN OUTCOME MEASURES Intergrader agreement measured by intraclass correlation coefficient. RESULTS Intergrader agreement was higher using the P score (intraclass correlation coefficient, 0.75; 95% confidence interval, 0.71-0.79) than no plus, preplus, or plus disease (intraclass correlation coefficient, 0.67; 95% confidence interval, 0.62-0.72). Mean ± standard deviation P scores for images with mode gradings of no plus, preplus, and plus disease were 2.5 ± 0.7, 4.8 ± 0.8, and 7.4 ± 0.8, respectively. CONCLUSIONS Intergrader agreement of plus-like vascular change in ROP using the P score is high. We now incorporate this 9-image reference set into ICROP3 for use in clinician daily practice alongside zone, stage, and plus assessment. P score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of the International Classification of Retinopathy of Prematurity. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Affiliation(s)
- Gil Binenbaum
- Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Andreas Stahl
- Department of Ophthalmology, University Medicine Greifswald, Greifswald, Germany
| | - Aaron S Coyner
- Casey Eye Institute, Oregon Health and Science University, Portland, Oregon
| | - Jocelyn He
- Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Gui-Shuang Ying
- Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan Ostmo
- Casey Eye Institute, Oregon Health and Science University, Portland, Oregon
| | - R V Paul Chan
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois
| | - Cynthia Toth
- Department of Ophthalmology, Duke University, Durham North Carolina
| | - Anand Vinekar
- Department of Pediatric Retina, Narayana Nethralaya Eye Institute, Bangalore, Karnataka, India
| | - J Peter Campbell
- Casey Eye Institute, Oregon Health and Science University, Portland, Oregon
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Seo YM, Kim SY, Youn YA. Improved Outcomes following a Conservative Approach to Hemodynamically Significant Patent Ductus Arteriosus: A Comparison across Two Periods. Cardiology 2024:1-9. [PMID: 39317174 DOI: 10.1159/000541477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/07/2024] [Indexed: 09/26/2024]
Abstract
INTRODUCTION Patent ductus arteriosus (PDA) is a commonly encountered morbidity that occurs inversely with gestational age. In response to the growing trend of avoiding PDA ligation and prophylactic interventions, our center adopted a conservative approach starting in September 2020. This approach involves more precise fluid restriction for hemodynamically significant (hs) PDA. This study aimed to evaluate whether a conservative approach to hsPDA has led to a reduction in adverse clinical outcomes for very low birth weight infants (VLBWIs) during the period of conservative treatment. METHODS Since more conservative approach to hsPDA was adopted since September 2020, the two periods were divided into period 1 (January 2015 to August 2020) and period 2 (September 2020 to June 2023). Fluid therapy was carefully monitored and advanced from day 1 in all VLBWI, and a more conservative approach as fluid restriction was attempted in hsPDA during period 2. RESULTS Of the 540 VLBWI with hsPDA, 348 infants were born and diagnosed with hsPDA. Period 2 demonstrated a significantly higher rate of medical treatment (79.17% vs. 19.51%) and lower PDA ligation (54.17% vs. 78.05%). Period 2 showed a greater adherence to conservative fluid restriction compared to period 1. Bronchopulmonary dysplasia (BPD) and BPD ≥ moderate, sepsis, necrotizing enterocolitis (≥ grade 2), IVH (grade ≥3) were notably lower in period 2 with lower mortality. In regard to PDA-related treatment, primary PDA ligation was significantly higher in period 1. The secondary PDA ligation after medical failure and more conservative fluid restriction were significantly higher in period 2. At corrected age of 18-24 months, cognitive score was significantly lower in VLBWI born in period 1 compared to those born in period 2. CONCLUSION Our study demonstrated that a conservative approach to hsPDA led to better clinical outcomes and improved cognitive scores at a corrected age of 18-24 months compared to the period of active PDA ligation. This conservative strategy, involving more precise fluid restriction and the judicious use of appropriate diuretics, has shown to improve clinical outcomes with minimal intervention.
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Affiliation(s)
- Yu-Mi Seo
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sae Yun Kim
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Ah Youn
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Fevereiro-Martins M, Santos AC, Marques-Neves C, Bicho M, Guimarães H, on behalf of the GenE-ROP Study Group. Retinopathy of Prematurity in Eight Portuguese Neonatal Intensive Care Units: Incidence, Risk Factors, and Progression-A Prospective Multicenter Study. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1154. [PMID: 39457121 PMCID: PMC11505647 DOI: 10.3390/children11101154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND/OBJECTIVES Retinopathy of prematurity (ROP) is a retinal neovascular disease affecting preterm infants. Identifying risk factors for its development and progression is critical for effective screening and prevention. This study aimed to analyze the incidence of ROP and identify key risk factors for its development and progression. METHODS We conducted a prospective, observational cohort study on 455 neonates (gestational age [GA] < 32 weeks or birth weight < 1500 g) across eight Portuguese NICUs. RESULTS ROP incidence was 37.8%, with 4.6% requiring treatment. Multivariate analysis identified low GA and the number of red blood cell (RBC) transfusions as significant factors for ROP development and progression. After adjusting for these variables, platelet transfusions, high maximum fraction of inspired oxygen (FiO2) in the second week, and surfactant use remained significantly associated with ROP development, while early and late sepsis, maternal chronic hypertension, and delayed enteral nutrition were associated with progression to ROP requiring treatment. CONCLUSIONS These findings underscore the importance of addressing low GAs and adult RBC transfusions in ROP risk management and suggest that maximum FiO2, platelet transfusions, and sepsis also play crucial roles. Larger studies are needed to validate these results and explore preventive interventions, particularly regarding the impact of multiple adult RBC transfusions on fetal hemoglobin percentages.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
- Department of Ophthalmology, Cuf Descobertas Hospital, Rua Mário Botas, 1998-018 Lisboa, Portugal
| | - Ana Carolina Santos
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
| | - Carlos Marques-Neves
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Center for the Study of Vision Sciences, University Ophthalmology Clinic, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal
| | - Manuel Bicho
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
| | - Hercília Guimarães
- Department of Gynecology—Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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El Emrani S, Jansen EJS, Goeman JJ, Termote JUM, Lopriore E, Schalij-Delfos NE, van der Meeren LE. Enhancing the Retinopathy Of Prematurity Risk Profile Through Placental Evaluation of Maternal and Fetal Vascular Malperfusion. Invest Ophthalmol Vis Sci 2024; 65:9. [PMID: 39230991 PMCID: PMC11379085 DOI: 10.1167/iovs.65.11.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/06/2024] Open
Abstract
Purpose To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP). Methods This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. Results Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0-3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1-3.9) and funisitis (OR = 1.8; 95% CI, 1.0-3.1). Conclusions Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible.
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Affiliation(s)
- Salma El Emrani
- Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
- Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - Esther J S Jansen
- Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jelle J Goeman
- Medical statistics, Department of Biomedical Data Science, Leiden University Medical Center, Leiden, The Netherlands
| | - Jacqueline U M Termote
- Neonatology, Wilhelmina Children's Hospital, Department of Women and Neonate, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Enrico Lopriore
- Neonatology, Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Lotte E van der Meeren
- Pathology, Leiden University Medical Center, Leiden, The Netherlands
- Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
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Kıran Yenice E, Kara C, Erdaş ÇB. Automated detection of type 1 ROP, type 2 ROP and A-ROP based on deep learning. Eye (Lond) 2024; 38:2644-2648. [PMID: 38918566 PMCID: PMC11385231 DOI: 10.1038/s41433-024-03184-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 06/27/2024] Open
Abstract
PURPOSE To provide automatic detection of Type 1 retinopathy of prematurity (ROP), Type 2 ROP, and A-ROP by deep learning-based analysis of fundus images obtained by clinical examination using convolutional neural networks. MATERIAL AND METHODS A total of 634 fundus images of 317 premature infants born at 23-34 weeks of gestation were evaluated. After image pre-processing, we obtained a rectangular region (ROI). RegNetY002 was used for algorithm training, and stratified 10-fold cross-validation was applied during training to evaluate and standardize our model. The model's performance was reported as accuracy and specificity and described by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS The model achieved 0.98 accuracy and 0.98 specificity in detecting Type 2 ROP versus Type 1 ROP and A-ROP. On the other hand, as a result of the analysis of ROI regions, the model achieved 0.90 accuracy and 0.95 specificity in detecting Stage 2 ROP versus Stage 3 ROP and 0.91 accuracy and 0.92 specificity in detecting A-ROP versus Type 1 ROP. The AUC scores were 0.98 for Type 2 ROP versus Type 1 ROP and A-ROP, 0.85 for Stage 2 ROP versus Stage 3 ROP, and 0.91 for A-ROP versus Type 1 ROP. CONCLUSION Our study demonstrated that ROP classification by DL-based analysis of fundus images can be distinguished with high accuracy and specificity. Integrating DL-based artificial intelligence algorithms into clinical practice may reduce the workload of ophthalmologists in the future and provide support in decision-making in the management of ROP.
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Affiliation(s)
- Eşay Kıran Yenice
- Department of Ophthalmology, University of Health Sciences, Etlik Zübeyde Hanım Maternity and Women's Health Teaching and Research Hospital, Ankara, Turkey.
| | - Caner Kara
- Department of Ophthalmology, Etlik City Hospital, Ankara, Turkey
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Sugie M, Nawa N, Noguchi Y, Taki A, Kashimada A, Honda I, Koyama A, Okazaki K, Kondo M, Miyahara H, Ito K, Yamauchi T, Kondo T, Honda-Ozaki F, Kusuda S, Morioka C, Fujiwara T, Morio T, Kashimada K. Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity. J Pediatr 2024; 272:114085. [PMID: 38703992 DOI: 10.1016/j.jpeds.2024.114085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/30/2024] [Accepted: 04/28/2024] [Indexed: 05/06/2024]
Abstract
OBJECTIVE To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.
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Affiliation(s)
- Manabu Sugie
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan; Neonatal Intensive Care Unit, Tsuchiura Kyodo General Hospital, Tsuchiura-city, Ibaraki
| | - Nobutoshi Nawa
- Department of Global Health Promotion, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Yusuke Noguchi
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Atsuko Taki
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Ayako Kashimada
- Department of Medical Education Research and Development, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Izumi Honda
- Department of Obstetrics and Gynecology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Akira Koyama
- Department of Obstetrics and Gynecology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Kaoru Okazaki
- Department of Neonatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Masatoshi Kondo
- Department of Neonatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Hiroyuki Miyahara
- Neonatal Intensive Care Unit, Tsuchiura Kyodo General Hospital, Tsuchiura-city, Ibaraki
| | - Kazuyuki Ito
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Takeru Yamauchi
- Neonatal Intensive Care Unit, Tsuchiura Kyodo General Hospital, Tsuchiura-city, Ibaraki
| | - Tsutomu Kondo
- Neonatal Intensive Care Unit, Tsuchiura Kyodo General Hospital, Tsuchiura-city, Ibaraki
| | - Fumiko Honda-Ozaki
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Satoshi Kusuda
- Department of Pediatrics, Kyorin University, Tokyo, Japan; The Neonatal Research Network of Japan (NRNJ), Shinjuku-ku, Tokyo
| | - Chikako Morioka
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Takeo Fujiwara
- Department of Global Health Promotion, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Tomohiro Morio
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Kenichi Kashimada
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
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Baig S, Das P, Podaralla N, Evangelista A, Kaur I, Bhandari V. Correlation of Polymorphonuclear Cell Burden and Microbial Growth to the Inflammatory Cytokines in Tracheal Aspirates from Ventilated Preterm Infants. Am J Perinatol 2024; 41:1388-1395. [PMID: 36773600 DOI: 10.1055/a-2033-5536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
OBJECTIVE The significance of the presence of microorganisms and polymorphonuclear cells in the tracheal aspirates (TAs) of ventilated preterm infants is not well known. Our aim was to correlate information about the presence of polymorphonuclear cells with microbial growth and the cytokine milieu in the TAs of infants who have been intubated for >7 days. STUDY DESIGN TAs were collected from infants who had been intubated for 7 days or longer. Respiratory cultures were performed, and infants were stratified based on the presence and abundance of polymorphonuclear cells and microbial growth. Cytokines were measured in the TAs of each of the respective groups. RESULTS In the 19 infants whose TAs were collected, the presence of at least moderate WBC with presence of microbial growth was positively associated with the presence of interleukin (IL)-10, IL-1β, IL-8, and tumor necrosis factor (TNF)-α. The presence of at least moderate WBC, with or without microbial growth, was correlated positively with the presence of IL-8 and TNF-α. CONCLUSION There are higher levels of proinflammatory cytokines (especially, IL-10, IL-1β, and TNF-α) in TAs with higher cell counts and presence of microbial growth. The findings suggest that the presence of microbial growth correlated with inflammatory burden and warrant a larger study to see if treatment of microbial growth can ameliorate the inflammatory burden. KEY POINTS · Concomitant evaluation of inflammatory cells, microbial growth, and cytokines in tracheal aspirates.. · Moderate TA WBC with presence of microbial growth associated with IL-10, IL-1β, IL-8, and TNF-α.. · Moderate TA WBC, with/without microbial growth, correlated with the presence of IL-8 and TNF-α.. · Higher levels of IL-10, IL-1β, and TNF-α correlated with higher TA cell counts and microbial growth..
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Affiliation(s)
- Sophia Baig
- Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
| | - Pragnya Das
- Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
| | - Niharika Podaralla
- Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
| | - Alan Evangelista
- Department of Pathology & Laboratory Medicine, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
| | - Ishminder Kaur
- Section of Infectious Diseases, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
| | - Vineet Bhandari
- Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania
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21
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Kim SY, Youn YA. Gut Dysbiosis in the First-Passed Meconium Microbiomes of Korean Preterm Infants Compared to Full-Term Neonates. Microorganisms 2024; 12:1271. [PMID: 39065040 PMCID: PMC11279035 DOI: 10.3390/microorganisms12071271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 06/14/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Since gestational age (GA) is an important factor influencing the presence of specific microbiomes, we aimed to characterize the core microbiomes of preterm infants compared to full-term (FT) infants. This study investigated the differences in microbiota composition between very preterm (VP), moderate-to-late preterm (MLP), and FT neonates by examining the core microbiomes of a large cohort of Korean neonates. Meconium samples from 310 neonates with a GA range of 22-40 weeks were collected, and 16S rRNA analyses were performed; 97 samples were obtained from the FT, 59 from the VP, and 154 from the MLP group. Firmicutes, Bacteroidetes, and Proteobacteria were the phylum-level core microbiomes. Infants born before 37 weeks showed a disruption in the core microbiomes. At the phylum level, the relative abundance of Bacteroidetes was positively (r = 0.177, p = 0.002) correlated with GA, while that of Proteobacteria was negatively (r = -0.116, p = 0.040) correlated with GA. At the genus level, the relative abundances of Bacteroides and Prevotella were positively correlated with GA (r = 0.157, p = 0.006; r = 0.160, p = 0.005). The meconium of preterm infants exhibited significantly lower α-diversities than that of FT infants. β-diversities did not appear to differ between the groups. Overall, these findings underscore the importance of GA in shaping the early gut microbiome.
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Affiliation(s)
| | - Young-Ah Youn
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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22
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Kim SY, Shin J, Oh MY, Youn YA. Enhanced Survival of 22-25 Week Preterm Infants After Proactive Care Implementation: A Comparative Analysis of Two Time Periods. Indian J Pediatr 2024:10.1007/s12098-024-05164-4. [PMID: 38836963 DOI: 10.1007/s12098-024-05164-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 05/09/2024] [Indexed: 06/06/2024]
Abstract
OBJECTIVES To investigate the impact of proactive perinatal care on periviable preterm infants before and after its implementation. METHODS This retrospective cohort study was conducted over a period of 10 y, from 2013 to 2019, referred to as Phase I, and from 2020 to 2022, referred to as Phase II. A total of 162 eligible infants born between 220/7 and 256/7 wk of gestation were included in this analysis. RESULTS A total of 125 infants were born in phase I, and 37 infants in phase II received proactive care with minimal handling. The mortality decreased from 54.4% to 24.3% (P = 0.001). The composite outcomes of severe brain injury or death, sepsis or death and necrotizing enterocolitis or death were also improved with proactive care. Gestational age [adjusted odds ratio (aOR) 0.900; 95% confidence interval (CI), 0.836-0.970], air leak syndrome (aOR 4.958; 95% CI, 1.681-14.624), massive pulmonary hemorrhage (aOR 4.944; 95% CI, 2.055-11.893), and birth in phase II (aOR 0.324; 95% CI, 0.115-0.912) were independently associated with mortality. CONCLUSIONS The implementation of proactive care with minimal handling resulted in an increased survival rate and a reduction in the combined morbidities between the two time periods. The provision of proactive perinatal care with minimal handling is crucial for improving both the survival rates and clinical outcomes of these vulnerable infants.
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Affiliation(s)
- Sae Yun Kim
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Jeongmin Shin
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Moon Yeon Oh
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Young-Ah Youn
- Department of Pediatrics, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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Padhi TR, Bhunia S, Shah M, Sahu S, Das T, Bhusal U, Singh A, Samantaray B, Patro K, Devi S, Routray D, Mohamed A, Pradhan L, Jalali S. OUTCOME OF EYES TREATED FOR RETINOPATHY OF PREMATURITY IN POSTERIOR ZONE I: An Eastern India Study. Retina 2024; 44:1073-1082. [PMID: 38346099 DOI: 10.1097/iae.0000000000004067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 01/28/2024] [Indexed: 05/21/2024]
Abstract
PURPOSE To analyze the outcomes of eyes treated for retinopathy of prematurity in posterior Zone I. METHODS In a part retrospective (9 years) and part prospective (1 year) interventional study, we analyzed eyes treated for retinopathy of prematurity in posterior Zone I with a minimum follow-up for 6 months. RESULTS This study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) g, respectively. The treatment included intravitreal anti-vascular endothelial growth factor as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in eight eyes, either alone (n = 3) or in combination with surgery (n = 5). With anti-vascular endothelial growth factor alone, 30.68% (n = 27) eyes responded favorably, and the remaining 69.32% (n = 59) eyes needed retreatment (laser in the majority). At the final follow-up, 89.9% (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation ( P < 0.0001) and the presence of well-defined central vascular trunks ( P = 0.001). CONCLUSION Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior Zone I retinopathy of prematurity.
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Affiliation(s)
- Tapas R Padhi
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Souvik Bhunia
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Miloni Shah
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Suman Sahu
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Taraprasad Das
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, India
| | - Utpal Bhusal
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Aveenash Singh
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | | | - Krishna Patro
- Department of Ophthalmology, SCB Medical College, Cuttack, India
| | - Sabita Devi
- Department of Ophthalmology, MKCG Medical College, Berhampur, India
| | - Dipanweeta Routray
- Department of Community Medicine, Dharanidhar Medical College Hospital, Keonjhar, India; and
| | - Ashik Mohamed
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | | | - Subhadra Jalali
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, India
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Chen S, Zhao X, Wu Z, Cao K, Zhang Y, Tan T, Lam CT, Xu Y, Zhang G, Sun Y. Multi-risk factors joint prediction model for risk prediction of retinopathy of prematurity. EPMA J 2024; 15:261-274. [PMID: 38841619 PMCID: PMC11147992 DOI: 10.1007/s13167-024-00363-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 04/17/2024] [Indexed: 06/07/2024]
Abstract
Purpose Retinopathy of prematurity (ROP) is a retinal vascular proliferative disease common in low birth weight and premature infants and is one of the main causes of blindness in children.In the context of predictive, preventive and personalized medicine (PPPM/3PM), early screening, identification and treatment of ROP will directly contribute to improve patients' long-term visual prognosis and reduce the risk of blindness. Thus, our objective is to establish an artificial intelligence (AI) algorithm combined with clinical demographics to create a risk model for ROP including treatment-requiring retinopathy of prematurity (TR-ROP) infants. Methods A total of 22,569 infants who underwent routine ROP screening in Shenzhen Eye Hospital from March 2003 to September 2023 were collected, including 3335 infants with ROP and 1234 infants with TR-ROP among ROP infants. Two machine learning methods of logistic regression and decision tree and a deep learning method of multi-layer perceptron were trained by using the relevant combination of risk factors such as birth weight (BW), gestational age (GA), gender, whether multiple births (MB) and mode of delivery (MD) to achieve the risk prediction of ROP and TR-ROP. We used five evaluation metrics to evaluate the performance of the risk prediction model. The area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) were the main measurement metrics. Results In the risk prediction for ROP, the BW + GA demonstrated the optimal performance (mean ± SD, AUCPR: 0.4849 ± 0.0175, AUC: 0.8124 ± 0.0033). In the risk prediction of TR-ROP, reasonable performance can be achieved by using GA + BW + Gender + MD + MB (AUCPR: 0.2713 ± 0.0214, AUC: 0.8328 ± 0.0088). Conclusions Combining risk factors with AI in screening programs for ROP could achieve risk prediction of ROP and TR-ROP, detect TR-ROP earlier and reduce the number of ROP examinations and unnecessary physiological stress in low-risk infants. Therefore, combining ROP-related biometric information with AI is a cost-effective strategy for predictive diagnostic, targeted prevention, and personalization of medical services in early screening and treatment of ROP.
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Affiliation(s)
- Shaobin Chen
- Faculty of Applied Sciences, Macao Polytechnic University, Gomes Street, Macao, China
| | - Xinyu Zhao
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518040 China
| | - Zhenquan Wu
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518040 China
| | - Kangyang Cao
- Faculty of Applied Sciences, Macao Polytechnic University, Gomes Street, Macao, China
| | - Yulin Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518040 China
| | - Tao Tan
- Faculty of Applied Sciences, Macao Polytechnic University, Gomes Street, Macao, China
| | - Chan-Tong Lam
- Faculty of Applied Sciences, Macao Polytechnic University, Gomes Street, Macao, China
| | - Yanwu Xu
- School of Future Technology, South China University of Technology, Guangzhou, Guangzhou; Pazhou Lab, China
| | - Guoming Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518040 China
| | - Yue Sun
- Faculty of Applied Sciences, Macao Polytechnic University, Gomes Street, Macao, China
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, 5612 AP The Netherlands
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Kiechl-Kohlendorfer U, Simma B, Berger A, Urlesberger B, Wald M, Haiden N, Fuiko R, Ndayisaba JP. Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group. Acta Paediatr 2024; 113:1278-1287. [PMID: 38433292 DOI: 10.1111/apa.17187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/24/2024] [Accepted: 02/22/2024] [Indexed: 03/05/2024]
Abstract
AIM The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.
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Affiliation(s)
| | - Burkhard Simma
- Department of Paediatrics, Academic Teaching Hospital, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Angelika Berger
- Division of Neonatology, Paediatric Intensive Care and Neuropediatric, Department of Paediatrics and Adolescent Medicine, Comprehensive Centre for Paediatrics, Medical University of Vienna, Vienna, Austria
| | - Berndt Urlesberger
- Division of Neonatology, Department of Paediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria
| | - Martin Wald
- Division of Neonatology, Department of Paediatrics and Adolescent Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Nadja Haiden
- Department of Neonatology, Kepler University Hospital Linz, Linz, Austria
| | - Renate Fuiko
- Division of Neonatology, Paediatric Intensive Care and Neuropediatric, Department of Paediatrics and Adolescent Medicine, Comprehensive Centre for Paediatrics, Medical University of Vienna, Vienna, Austria
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Kim S, Kim SY, Shin JA, Youn YA. Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18-24 months in very low birth weight infants. BMC Pediatr 2024; 24:376. [PMID: 38822298 PMCID: PMC11140864 DOI: 10.1186/s12887-024-04860-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/28/2024] [Indexed: 06/02/2024] Open
Abstract
BACKGROUND Patent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA). PURPOSE This study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation. METHODS A total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18-24 months of age were included in this study analysis. RESULTS Out of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18-24 months. CONCLUSION In our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18-24 months.
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Affiliation(s)
- Sol Kim
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Sae Yun Kim
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Ju-Ae Shin
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Young-Ah Youn
- Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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Kim MS, Koh JW, Shin J, Kim SY. Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea. J Clin Med 2024; 13:2930. [PMID: 38792471 PMCID: PMC11122437 DOI: 10.3390/jcm13102930] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.
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Affiliation(s)
| | | | | | - Sae Yun Kim
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea; (M.S.K.); (J.W.K.); (J.S.)
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Hanif AM, Jian Y, Young BK, Campbell JP. Implementation of optical coherence tomography in retinopathy of prematurity screening. Curr Opin Ophthalmol 2024; 35:252-259. [PMID: 38205941 PMCID: PMC11034813 DOI: 10.1097/icu.0000000000001030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
PURPOSE OF REVIEW In this review, we explore the investigational applications of optical coherence tomography (OCT) in retinopathy of prematurity (ROP), the insights they have delivered thus far, and key milestones for its integration into the standard of care. RECENT FINDINGS While OCT has been widely integrated into clinical management of common retinal diseases, its use in pediatric contexts has been undermined by limitations in ergonomics, image acquisition time, and field of view. Recently, investigational handheld OCT devices have been reported with advancements including ultra-widefield view, noncontact use, and high-speed image capture permitting real-time en face visualization. These developments are compelling for OCT as a more objective alternative with reduced neonatal stress compared to indirect ophthalmoscopy and/or fundus photography as a means of classifying and monitoring ROP. SUMMARY OCT may become a viable modality in management of ROP. Ongoing innovation surrounding handheld devices should aim to optimize patient comfort and image resolution in the retinal periphery. Future clinical investigations may seek to objectively characterize features of peripheral stage and explore novel biomarkers of disease activity.
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Affiliation(s)
- Adam M. Hanif
- Ophthalmology, Oregon Health & Science University, Portland, Oregon
| | - Yifan Jian
- Ophthalmology, Oregon Health & Science University, Portland, Oregon
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Lee HM, Shin J, Kim SY, Kim SY. Factors affecting length of stay according to bronchopulmonary dysplasia severity: a nationwide cohort study in Korea. World J Pediatr 2024; 20:470-480. [PMID: 38356035 PMCID: PMC11136859 DOI: 10.1007/s12519-023-00794-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 12/24/2023] [Indexed: 02/16/2024]
Abstract
BACKGROUND Longer hospitalizations for preterm infants with bronchopulmonary dysplasia (BPD) delay developmental outcomes, increase the risk for hospital-acquired complications, and exert a substantial socioeconomic burden. This study aimed to identify factors associated with an extended length of stay (LOS) at different levels of severity of BPD. METHODS A cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis. RESULTS A total of 4263 infants were diagnosed with BPD. For mild BPD, infants requiring surgical treatment for patent ductus arteriosus needed a longer LOS [eadjusted β coefficients (adj β) 1.041; 95% confidence interval (CI): 0.01-0.08] and hydrocephalus (eadj β 1.094; 95% CI 0.01-0.17). In moderate BPD, infants administered steroids or with intraventricular hemorrhage required a longer LOS (eadj β 1.041; 95% CI 0.00-0.07 and eadj β 1.271; 95% CI 0.11-0.38, respectively). In severe BPD, infants with comorbidities required a longer LOS: pulmonary hypertension (eadj β 1.174; 95% CI 0.09-0.23), administrated steroid for BPD (eadj β 1.116; 95% CI 0.07-0.14), sepsis (eadj β 1.062; 95% CI 0.01-0.11), patent ductus arteriosus requiring surgical ligation (eadj β 1.041; 95% CI 0.00-0.08), and intraventricular hemorrhage (eadj β 1.016; 95% CI 0.05-0.26). Additionally, the higher the clinical risk index score, the longer the LOS needed for infants in all groups. CONCLUSIONS The factors affecting LOS differed according to the severity of BPD. Individualized approaches to reducing LOS may be devised using knowledge of the various risk factors affecting LOS by BPD severity.
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Affiliation(s)
- Hye Mi Lee
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeongmin Shin
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sae Yun Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
- Department of Pediatrics, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, 07345, Republic of Korea.
| | - So Young Kim
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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30
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Shemesh R, Strauss T, Zaslavsky-Paltiel I, Lerner-Geva L, Reichman B, Wygnanski-Jaffe T. Perinatal and neonatal risk factors for retinopathy of prematurity in very low birthweight, very preterm twins: a population-based study. Eye (Lond) 2024; 38:902-909. [PMID: 37925560 PMCID: PMC10965998 DOI: 10.1038/s41433-023-02801-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 09/28/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023] Open
Abstract
OBJECTIVE To determine the effect of perinatal and neonatal risk factors on retinopathy of prematurity (ROP) and to examine the association of fertility treatments on the risk for ROP in very low birth weight (VLBW) preterm twins. METHODS The population-based observational study consisted of VLBW twins born at 24-29 weeks gestational age (GA). Data from the Israel national database (1995-2020) were applied. Univariate and multivariable logistic regression using the General Estimating Equation were used for assessment of risk factors. RESULTS The study population comprised 4092 infants of whom 2374 (58%) were conceived following fertility treatments. ROP was diagnosed in 851 (20.8%) infants. The odds for ROP approximately doubled with each week decrease in GA: at 24 weeks, Odds Ratio (OR) 58.00 (95% confidence interval (CI) 31.83-105.68); 25 weeks, OR 25.88 (95% CI 16.76-39.96); 26 weeks, OR 12.69 (95% CI 8.84-18.22) compared to 29 weeks GA. Each decrease in one birthweight z-score was associated with 1.82-fold increased risk for ROP (OR, 1.82, 95% CI 1.59-2.08). Infertility treatments were not associated with ROP. Neonatal morbidities significantly associated with ROP were surgical necrotizing enterocolitis (NEC) (OR, 2.04, 95% CI 1.31-3.19); surgically treated patent ductus arteriosus (PDA) (OR, 1.63, 95% CI 1.12-2.37); sepsis (OR, 1.43, 95% CI 1.20-1.71) and bronchopulmonary dysplasia (OR, 1.52, 95% CI 1.22-1.90). CONCLUSION Among preterm VLBW twins, poor intrauterine growth and surgical interventions for NEC and PDA were associated with high odds for ROP. This study does not support an association of fertility treatments with increased risk for ROP.
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Affiliation(s)
- Rachel Shemesh
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel
| | - Tzipi Strauss
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neonatology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel
| | - Inna Zaslavsky-Paltiel
- Women and Children's Health Research Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Liat Lerner-Geva
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Women and Children's Health Research Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Brian Reichman
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Women and Children's Health Research Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Tamara Wygnanski-Jaffe
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
- Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel.
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Almutairi M, Chechalk K, Deane E, Fox R, Janes A, Maguire-Henry T, McCabe D, O'Connor C, Quirk J, Swan E, White K, McCreery K, Isweisi E, Stewart P, Branagan A, Roche EF, Meehan J, Molloy EJ. Biomarkers in retinopathy of prematurity: a systematic review and meta-analysis. Front Pediatr 2024; 12:1371776. [PMID: 38571701 PMCID: PMC10987861 DOI: 10.3389/fped.2024.1371776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 03/01/2024] [Indexed: 04/05/2024] Open
Abstract
Aim Retinopathy of prematurity is a significant global cause of childhood blindness. This study aims to identify serum biomarkers that are associated with the development of ROP. Methods A systematic review and meta-analysis was conducted using PRISMA guidelines. Three databases were searched (Pubmed, Scopus and Web of Science) from 2003 to March 2023. Only studies investigating serum biomarker levels in preterm infants (<37 weeks gestation) were included. Results Meta-analysis suggests that low serum IGF-1 levels have a strong association with the development of ROP [SMD (95% CI) of -.46 [-.63, -.30], p < .001]. Meta-analysis suggests that higher serum glucose levels were associated with the development of ROP [SMD (95% CI) of 1.25 [.94, 1.55], p < .001]. Meta-analysis suggests that thrombocytopenia is associated with the development of ROP [SMD (95% CI) of -.62 [-.86, -.37], p < .001]. Conclusion Low levels of serum IGF-1, high levels of serum glucose and thrombocytopenia all appear to have the strongest association with the development of ROP out of the 63 biomarkers investigated in this review. These associations highlight their potential use as diagnostic biomarkers in ROP, though further research is needed to establish the exact relationship between these biomarkers and disease pathogenesis.
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Affiliation(s)
- Mariam Almutairi
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Katherine Chechalk
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Emelia Deane
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Rebecca Fox
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Ava Janes
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Tidgh Maguire-Henry
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Devin McCabe
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Cole O'Connor
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Joseph Quirk
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Evan Swan
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Katherine White
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Kathryn McCreery
- Paediatric Ophthalmology, Children's Health Ireland (CHI) at Crumlin, Dublin, Ireland
| | - Eman Isweisi
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Philip Stewart
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
| | - Aoife Branagan
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Paediatrics, Coombe Hospital, Dublin, Ireland
| | - Edna F. Roche
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland
- Endocrinology, Children's Health Ireland (CHI) at Tallaght, Dublin, Ireland
| | - Judith Meehan
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland
- Trinity College Dublin, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St James Hospital, The University of Dublin, Dublin, Ireland
| | - Eleanor J. Molloy
- Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Paediatrics, Coombe Hospital, Dublin, Ireland
- Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, Ireland
- Endocrinology, Children's Health Ireland (CHI) at Tallaght, Dublin, Ireland
- Trinity College Dublin, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St James Hospital, The University of Dublin, Dublin, Ireland
- Neurodisability, Children’s Health Ireland (CHI) at Tallaght, Dublin, Ireland
- Neonatology, Children's Health Ireland (CHI) at Crumlin, Dublin, Ireland
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32
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Sola A, Leslie Altimier, Teresa Montes Bueno M, Muñoz CE. Monitoring SpO 2: The Basics of Retinopathy of Prematurity (Back to Basics) and Targeting Oxygen Saturation. Crit Care Nurs Clin North Am 2024; 36:69-98. [PMID: 38296377 DOI: 10.1016/j.cnc.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2024]
Abstract
Oxygen (O2) is a drug frequently used in newborn care. Adverse effects of hypoxia are well known but the damaging effects of excess oxygen administration and oxidative stress have only been studied in the last 2 decades. Many negative effects have been described, including retinopathy of prematurity . Noninvasive pulse oximetry (SpO2) is useful to detect hypoxemia but requires careful evaluation and understanding of the frequently changing relationship between O2 and hemoglobin to prevent hyperoxemia. Intention to treat SpO2 ranges should be individualized for every newborn receiving supplemental O2, according to gestational age, post-natal age, and clinical condition.
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Affiliation(s)
- Augusto Sola
- Iberoamerican Society of Neonatology (SIBEN), 2244 Newbury Drive, Wellington, FL 3341, USA.
| | - Leslie Altimier
- Cardinal Glennon Children's Hospital, 1465 South Grand Avenue, St. Louis, MO 63104, USA
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Tachikawa T, Ueno R, Mita T, Yuzurihara D, Noda T. Corneal refractive error and astigmatism in patients aged 6 to 18 years with a history of retinopathy of prematurity and birth weight of <1500 g. Jpn J Ophthalmol 2024; 68:42-49. [PMID: 38001368 DOI: 10.1007/s10384-023-01026-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/05/2023] [Indexed: 11/26/2023]
Abstract
PURPOSE To investigate corneal refractive power (CR) and astigmatism (AS) in 6- to 18-year-old children with a history of retinopathy of prematurity (ROP) and birth weight of <1500 g who either did or did not undergo retinal photocoagulation (PC). STUDY DESIGN Retrospective study. METHODS We examined 143 eyes of 77 children in 2021. The children were divided into three groups for evaluation of CR and AS: those with a birth weight of ≥2500 g (normal birth weight [NBW] group, 13 eyes) as controls, those with spontaneously resolved ROP (sr-ROP group, 27 eyes), and those who underwent PC for treatment of ROP (PC-ROP group, 103 eyes). Swept-source anterior segment optical coherence tomography was used to analyze the cornea. RESULTS The median CR in the NBW, sr-ROP, and PC-ROP groups was 42.2 (41.3, 42.8) diopters (D), 44.5 (43.2, 45.5) D, and 45.2 (43.8, 46.6) D, respectively. The median AS in the NBW, sr-ROP, and PC-ROP groups was 1.2 (1.0, 1.5) D, 1.1 (0.8, 1.6) D, and 2.1 (1.4, 2.7) D. In the PC-ROP group, the with-the-rule astigmatic axis was 97%. In all three groups, a strong positive correlation was found between the mean anterior and posterior CR (NBW: r=0.795, sr-ROP: r=0.842, PC-ROP: r=0.890) and AS (NBW: r=0.883, sr-ROP: r=0.841, PC-ROP: r=0.860). CONCLUSION CR was significantly higher in the sr-ROP (p=0.013) and PC-ROP (p<0.001) groups than in the NBW group. The PC-ROP group had significantly more AS than the sr-ROP group. There was a strong correlation between the anterior and posterior CR and AS.
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Affiliation(s)
- Takako Tachikawa
- Department of Ophthalmology, Tokyo Metropolitan Ohtsuka Hospital, Minami-Ohtsuka 2-8-1, Toshima-ku, Tokyo, 170-8476, Japan.
| | - Ritsuko Ueno
- Department of Ophthalmology, Tokyo Metropolitan Ohtsuka Hospital, Minami-Ohtsuka 2-8-1, Toshima-ku, Tokyo, 170-8476, Japan
| | - Tetsuko Mita
- Department of Ophthalmology, Tokyo Metropolitan Ohtsuka Hospital, Minami-Ohtsuka 2-8-1, Toshima-ku, Tokyo, 170-8476, Japan
| | - Daisuke Yuzurihara
- Department of Ophthalmology, Tokyo Metropolitan Ohtsuka Hospital, Minami-Ohtsuka 2-8-1, Toshima-ku, Tokyo, 170-8476, Japan
| | - Toru Noda
- Department of Ophthalmology, NHO Tokyo Medical Center, Tokyo, Japan
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Mohr FH, Fischer HS, Czernik C, Müller B, Bührer C. Retinal blood flow velocities in infants with retinopathy of prematurity after intravitreal administration of bevacizumab. Eur J Ophthalmol 2024; 34:95-101. [PMID: 37218176 PMCID: PMC10757389 DOI: 10.1177/11206721231178062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/08/2023] [Indexed: 05/24/2023]
Abstract
BACKGROUND/OBJECTIVES Progression of retinopathy of prematurity (ROP) is associated with increased retinal blood flow velocities. We investigated changes of central retinal arterial and venous blood flow after intravitreal administration of bevacizumab. SUBJECTS/METHODS Prospective observational study using serial ultrasound Doppler imaging in preterm infants with bevacizumab-treated ROP. Eyes were examined 1 [0-2] days before injection (median [interquartile range]), and at three time points after injection (1 [1-2] days, 6 [3-8] days, and 17 [9-28] days). Preterm infants with ROP stage 2 displaying spontaneous regression served as controls. RESULTS In 21 eyes of 12 infants with bevacizumab-treated ROP, peak arterial systolic velocity declined from 13.6 [11.0-16.3] cm/s prior to intravitreal bevacizumab to 11.2 [9.4-13.9] cm/s, 10.6 [9.2-13.3] cm/s and 9.3 [8.2-11.0] cm/s at discharge (p = .002). There was also a decline of the arterial velocity time integral (from 3.1 [2.3-3.9] cm to 2.9 [2.4-3.5], 2.7 [2.3-3.2] cm and 2.2 [2.0-2.7], p = .021) and mean velocity in the central retinal vein (from 4.5 [3.6-5.8] cm/s to 3.7 [2.6-4.1] cm/s, 3.5 [3.0-4.3] cm/s, and 3.2 [2.8-4.6] cm/s, p = .012). Arterial end-diastolic velocity and resistance index remained unchanged. Blood flow velocities in bevacizumab-treated eyes examined before injection were significantly higher than those measured in untreated eyes that ultimately showed spontaneous regression of ROP. Sequential examinations in these controls did not reveal any declines of retinal blood flow velocities. CONCLUSION Increased retinal arterial and venous blood flow velocities in infants with threshold ROP decline following intravitreal bevacizumab injection.
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Affiliation(s)
- Franziska H Mohr
- Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Department of Pediatric Pulmonology, Immunology, and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Hendrik S Fischer
- Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Czernik
- Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Bert Müller
- Department of Ophthalmology, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Bührer
- Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
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Padhi TR, Shah M, Sahoo S, Das T, Bhusal U, Singh A, Bhunia S, Nayak S, Nayak S, Panchal B, Agrawal K, Samantaray B, Devi S, Rao K, Pradhan L, Mohamed A, Jalali S. Characteristics of posterior zone I retinopathy of prematurity. Eye (Lond) 2023; 37:3776-3780. [PMID: 37253857 PMCID: PMC10697929 DOI: 10.1038/s41433-023-02603-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 05/12/2023] [Accepted: 05/22/2023] [Indexed: 06/01/2023] Open
Abstract
OBJECTIVE To report the demographic profile and clinical characteristics of retinopathy of prematurity (ROP) in posterior Zone I. METHODS In a partly retrospective (ten years) and partly prospective (one year) study, we analysed the demographic profile and clinical characteristics of babies with ROP in posterior Zone I. RESULTS The study included 130 eyes of 67 infants with a mean gestational age and birth weight of 29.3 (±2.2) weeks and 1217.3 (±381.9) grams, respectively. All babies had received unblended oxygen. In 47 of 51 (91.1%) babies, the weekly weight gain was <100 g (details were not available in 16 babies). The ROP subtypes included aggressive, threshold, hybrid, stage 4, and atypical types in 78 (60%), 20 (15.4%), 11 (8.5%), 15 (11.5%), and 6 (4.6%) eyes, respectively. Fibrovascular proliferation, when present, was prominent nasally, occasionally overriding the disc margin. Extensive arteriovenous tortuosity was more prominent than vascular dilatation. Atypical observations included bleb-like detachment (6 eyes; 4.6%) and candle wax-like preretinal deposits (23 eyes; 17.7%). CONCLUSIONS Retinopathy of Prematurity in posterior Zone I in this cohort was strongly associated with 100% unblended oxygen supplementation, poor weight gain, and multiple systemic co-morbidities. ROP in posterior zone 1 has a distinct profile with several atypical characteristics different from ROP in other zones.
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Affiliation(s)
- Tapas R Padhi
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India.
- Miriam Hyman Children's Eye Care Centre (MHCECC), Bhubaneswar, India.
| | - Miloni Shah
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Suman Sahoo
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Taraprasad Das
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, India
| | - Utpal Bhusal
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Abinash Singh
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Souvik Bhunia
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Sameer Nayak
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Mithu Tulsi Chanrai Campus), Bhubaneswar, India
| | - Sameera Nayak
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kode Venkatadri Chowdary Campus), Vijayawada, India
| | - Bhavik Panchal
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (GMRV Campus), Visakhapatnam, India
| | - Komal Agrawal
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, India
| | | | - Sabita Devi
- Department of Ophthalmology, MKCG Medical College, Berhampur, India
| | - Krishna Rao
- Department of Ophthalmology, SCB Medical College, Cuttack, India
| | | | - Ashik Mohamed
- Miriam Hyman Children's Eye Care Centre (MHCECC), Bhubaneswar, India
| | - Subhadra Jalali
- Anant Bajaj Retina Institute, L V Prasad Eye Institute (Kallam Anji Reddy Campus), Hyderabad, India
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36
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Zhang Y, Chai X, Fan Z, Zhang S, Zhang G. Research hotspots and trends in retinopathy of prematurity from 2003 to 2022: a bibliometric analysis. Front Pediatr 2023; 11:1273413. [PMID: 37854031 PMCID: PMC10579817 DOI: 10.3389/fped.2023.1273413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 09/22/2023] [Indexed: 10/20/2023] Open
Abstract
Background In order to understand the research hotspots and trends in the field of retinopathy of prematurity (ROP), our study analyzed the relevant publications from 2003 to 2022 by using bibliometric analysis. Methods The Citespace 6.2.R3 system was used to analyze the publications collected from the Web of Science Core Collection (WoSCC) database. Results In total, 4,957 publications were included in this study. From 2003 to 2022, the number of publications gradually increased and peaked in 2022. The United States was the country with the most publications, while Harvard University was the most productive institution. The top co-cited journal PEDIATRICS is published by the United States. Author analysis showed that Hellström A was the author with the most publications, while Good WV was the top co-cited author. The co-citation analysis of references showed seven major clusters: genetic polymorphism, neurodevelopmental outcome, threshold retinopathy, oxygen-induced retinopathy, low birth weight infant, prematurity diagnosis cluster and artificial intelligence (AI). For the citation burst analysis, there remained seven keywords in their burst phases until 2022, including ranibizumab, validation, trends, type 1 retinopathy, preterm, deep learning and artificial intelligence. Conclusion Intravitreal anti-vascular endothelial growth factor therapy and AI-assisted clinical decision-making were two major topics of ROP research, which may still be the research trends in the coming years.
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Affiliation(s)
- Yulin Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Xiaoyan Chai
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Zixin Fan
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Sifan Zhang
- Department of Biology, New York University, New York, NY, United States
| | - Guoming Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
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van 't Westende C, Twilhaar ES, Stam CJ, de Kieviet JF, van Elburg RM, Oosterlaan J, van de Pol LA. The influence of very preterm birth on adolescent EEG connectivity, network organization and long-term outcome. Clin Neurophysiol 2023; 154:49-59. [PMID: 37549613 DOI: 10.1016/j.clinph.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/01/2023] [Accepted: 07/13/2023] [Indexed: 08/09/2023]
Abstract
OBJECTIVE The aim of this study was to explore differences in functional connectivity and network organization between very preterm born adolescents and term born controls and to investigate if these differences might explain the relation between preterm birth and adverse long-term outcome. METHODS Forty-seven very preterm born adolescents (53% males) and 54 controls (54% males) with matching age, sex and parental educational levels underwent high-density electroencephalography (EEG) at 13 years of age. Long-term outcome was assessed by Intelligence Quotient (IQ), motor, attentional functioning and academic performance. Two minutes of EEG data were analysed within delta, theta, lower alpha, upper alpha and beta frequency bands. Within each frequency band, connectivity was assessed using the Phase Lag Index (PLI) and Amplitude Envelope Correlation, corrected for volume conduction (AEC-c). Brain networks were constructed using the minimum spanning tree method. RESULTS Very preterm born adolescents had stronger beta PLI connectivity and less differentiated network organization. Beta AEC-c and differentiation of AEC-c based networks were negatively associated with long-term outcomes. EEG measures did not mediate the relation between preterm birth and outcomes. CONCLUSIONS This study shows that very preterm born adolescents may have altered functional connectivity and brain network organization in the beta frequency band. Alterations in measures of functional connectivity and network topologies, especially its differentiating characteristics, were associated with neurodevelopmental functioning. SIGNIFICANCE The findings indicate that EEG connectivity and network analysis is a promising tool for investigating underlying mechanisms of impaired functioning.
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Affiliation(s)
- C van 't Westende
- Amsterdam UMC, Department of Child Neurology, Amsterdam, the Netherlands
| | - E S Twilhaar
- Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, F-75004 Paris, France
| | - C J Stam
- Amsterdam UMC, Department of Clinical Neurophysiology, Amsterdam, the Netherlands
| | - J F de Kieviet
- Amsterdam Rehabilitation Research Center, Reade, Amsterdam, the Netherlands
| | - R M van Elburg
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatrics, Emma Children's Hospital Amsterdam UMC Follow-Me Program & Emma Neuroscience Group, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands; Amsterdam UMC, Department of Amsterdam Gastroenterology & Metabolism, Amsterdam, the Netherlands
| | - J Oosterlaan
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatrics, Emma Children's Hospital Amsterdam UMC Follow-Me Program & Emma Neuroscience Group, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands; Amsterdam Rehabilitation Research Center, Reade, Amsterdam, the Netherlands
| | - L A van de Pol
- Amsterdam UMC, Department of Child Neurology, Amsterdam, the Netherlands.
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Fevereiro-Martins M, Santos AC, Marques-Neves C, Guimarães H, Bicho M. Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study. Graefes Arch Clin Exp Ophthalmol 2023; 261:2997-3006. [PMID: 37129632 PMCID: PMC10543149 DOI: 10.1007/s00417-023-06072-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 01/27/2023] [Accepted: 04/11/2023] [Indexed: 05/03/2023] Open
Abstract
PURPOSE To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). METHODS Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. RESULTS A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. CONCLUSION In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
- Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
- Departamento de Oftalmologia, Hospital Cuf Descobertas, Rua Mário Botas, 1998-018 Lisbon, Portugal
| | - Ana Carolina Santos
- Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
| | - Carlos Marques-Neves
- Centro de Estudos das Ciências da Visão, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
- Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
| | - Hercília Guimarães
- Departamento de Ginecologia - Obstetrícia e Pediatria, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Manuel Bicho
- Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisbon, Portugal
- Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisbon, Portugal
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Xu CL, Adu-Brimpong J, Moshfeghi HP, Rosenblatt TR, Yu MD, Ji MH, Wang SK, Zaidi M, Ghoraba H, Michalak S, Callaway NF, Kumm J, Nudleman E, Wood EH, Patel NA, Stahl A, Lepore D, Moshfeghi DM. Telemedicine retinopathy of prematurity severity score (TeleROP-SS) versus modified activity score (mROP-ActS) retrospective comparison in SUNDROP cohort. Sci Rep 2023; 13:15219. [PMID: 37709791 PMCID: PMC10502047 DOI: 10.1038/s41598-023-42150-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 09/06/2023] [Indexed: 09/16/2023] Open
Abstract
Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP's totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.
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Affiliation(s)
- Christine L Xu
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Joel Adu-Brimpong
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | | | - Tatiana R Rosenblatt
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA
| | - Michael D Yu
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Marco H Ji
- Department of Ophthalmology, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Sean K Wang
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Moosa Zaidi
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Hashem Ghoraba
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Suzanne Michalak
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Natalia F Callaway
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Jochen Kumm
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA
| | - Eric Nudleman
- Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA
| | | | - Nimesh A Patel
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
| | - Andreas Stahl
- Department of Ophthalmology, University Medicine Greifswald, Greifswald, Germany
| | - Domenico Lepore
- Department of Geriatrics and Neuroscience, Catholic University of the Sacred Heart, A. Gemelli Foundation IRCSS, Rome, Italy
| | - Darius M Moshfeghi
- Department of Ophthalmology, Horngren Family Vitreoretinal Center, Byers Eye Institute, Stanford University School of Medicine, 2452 Watson Ct., Rm 2277, Palo Alto, CA, 94303, USA.
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Ramanathan A, Athikarisamy SE, Lam GC. Artificial intelligence for the diagnosis of retinopathy of prematurity: A systematic review of current algorithms. Eye (Lond) 2023; 37:2518-2526. [PMID: 36577806 PMCID: PMC10397194 DOI: 10.1038/s41433-022-02366-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 11/23/2022] [Accepted: 12/09/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND/OBJECTIVES With the increasing survival of premature infants, there is an increased demand to provide adequate retinopathy of prematurity (ROP) services. Wide field retinal imaging (WFDRI) and artificial intelligence (AI) have shown promise in the field of ROP and have the potential to improve the diagnostic performance and reduce the workload for screening ophthalmologists. The aim of this review is to systematically review and provide a summary of the diagnostic characteristics of existing deep learning algorithms. SUBJECT/METHODS Two authors independently searched the literature, and studies using a deep learning system from retinal imaging were included. Data were extracted, assessed and reported using PRISMA guidelines. RESULTS Twenty-seven studies were included in this review. Nineteen studies used AI systems to diagnose ROP, classify the staging of ROP, diagnose the presence of pre-plus or plus disease, or assess the quality of retinal images. The included studies reported a sensitivity of 71%-100%, specificity of 74-99% and area under the curve of 91-99% for the primary outcome of the study. AI techniques were comparable to the assessment of ophthalmologists in terms of overall accuracy and sensitivity. Eight studies evaluated vascular severity scores and were able to accurately differentiate severity using an automated classification score. CONCLUSION Artificial intelligence for ROP diagnosis is a growing field, and many potential utilities have already been identified, including the presence of plus disease, staging of disease and a new automated severity score. AI has a role as an adjunct to clinical assessment; however, there is insufficient evidence to support its use as a sole diagnostic tool currently.
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Affiliation(s)
- Ashwin Ramanathan
- Department of Paediatrics, Perth Children's Hospital, Perth, Australia
| | - Sam Ebenezer Athikarisamy
- Department of Neonatology, Perth Children's Hospital, Perth, Australia.
- School of Medicine, University of Western Australia, Crawley, Australia.
| | - Geoffrey C Lam
- Department of Ophthalmology, Perth Children's Hospital, Perth, Australia
- Centre for Ophthalmology and Visual Science, University of Western Australia, Crawley, Australia
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Fevereiro-Martins M, Santos AC, Marques-Neves C, Guimarães H, Bicho M, On Behalf Of The GenE-Rop Study Group. Genetic Modulation of the Erythrocyte Phenotype Associated with Retinopathy of Prematurity-A Multicenter Portuguese Cohort Study. Int J Mol Sci 2023; 24:11817. [PMID: 37511576 PMCID: PMC10380881 DOI: 10.3390/ijms241411817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/15/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 β (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
- Department of Ophthalmology, Cuf Descobertas Hospital, Rua Mário Botas, 1998-018 Lisboa, Portugal
| | - Ana Carolina Santos
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
| | - Carlos Marques-Neves
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Center for the Study of Vision Sciences, Ophthalmology Clinic, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal
| | - Hercília Guimarães
- Department of Gynecology-Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Manuel Bicho
- Ecogenetics and Human Health Unit, Environmental Health Institute-ISAMB, Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal
- Institute for Scientific Research Bento Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal
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Yehiam SZ, Simkin SK, Al-Taie R, Wong M, Battin M, Dai S. Incomplete peripheral retinal vascularisation in retinopathy of prematurity: is it the consequence of changing oxygen saturation? Front Pediatr 2023; 11:1203068. [PMID: 37416821 PMCID: PMC10320580 DOI: 10.3389/fped.2023.1203068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 06/07/2023] [Indexed: 07/08/2023] Open
Abstract
Background We wish to determine the prevalence and risk factors of incomplete peripheral avascular retina (IPAR) in children screened for retinopathy of prematurity (ROP) and its association with oxygen saturation (SpO2) targets. Methods A retrospective review of retinal images of premature infants born and screened for ROP in Auckland Region, New Zealand, between January 2013 and December 2017 was conducted. Images were reviewed to determine if avascular retina was present at their final ROP screening. The prevalence of peripheral avascular retina was compared among infants born prior to (Group 1) and after (Group 2) 2015 when the SpO2 target was increased. Infants with any concurrent ocular pathology or who had received ROP treatment were excluded. Results In total, 62 (12.8%) of the total of 486 infants (247 in Group 1; 239 in Group 2) were found to have IPAR at their last ROP screening. Group 1 had more statistically significant infants with IPAR compared to Group 2 (39/247 infants and 23/239 infants respectively; p = 0.043). Conclusions Incomplete peripheral retinal vascularisation occurred at a prevalence of 12.8% in infants at risk of ROP. Higher SpO2 targets did not increase the prevalence of incomplete peripheral retinal vascularisation. Low gestational age and low birth weight are likely risk factors for the development of avascular retina. Further research into the risk factors associated with incomplete peripheral retinal vascularisation and the associated long-term outcomes is needed.
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Affiliation(s)
- Sigal Zmujack Yehiam
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Samantha K. Simkin
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Rasha Al-Taie
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- Neonatal Intensive Care, Counties Manukau District Health Board, Auckland, New Zealand
| | - Maisie Wong
- Neonatal Intensive Care, Counties Manukau District Health Board, Auckland, New Zealand
| | - Malcolm Battin
- Neonatal Intensive Care, Newborn Services, Auckland City Hospital, Auckland, New Zealand
| | - Shuan Dai
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- Children’s Health Queensland Hospital and Health Service, Queensland Children’s Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
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Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates. Cochrane Database Syst Rev 2023; 6:CD004205. [PMID: 37338074 PMCID: PMC10282162 DOI: 10.1002/14651858.cd004205.pub4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
Abstract
BACKGROUND Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. OBJECTIVES To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. DATA COLLECTION AND ANALYSIS We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. MAIN RESULTS We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. AUTHORS' CONCLUSIONS Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.
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Affiliation(s)
- Mohan Pammi
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Khalid N Haque
- (Formerly) Division of Neonatology, Department of Child Health, Queen Mary's Hospital for Children, Wrythe Lane, Carshalton, UK
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Sanjuán Riera L, Peralta Calvo J, Hernández Rivas L, Klein Burgos C, Roca Cabau M. Functional results in children with retinopathy of prematurity treated with intravitreal bevacizumab. ARCHIVOS DE LA SOCIEDAD ESPANOLA DE OFTALMOLOGIA 2023:S2173-5794(23)00088-9. [PMID: 37285960 DOI: 10.1016/j.oftale.2023.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 04/27/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND/AIM The aim of the study is to describe the efficacy and to determine the functional outcome in terms of visual acuity and refractive defect of a single dose of intravitreal bevacizumab in patients with high-risk ROP type 1. METHODS In this retrospective clinical study patients diagnosed between December 2013 and January 2018 with high-risk pre-threshold ROP type 1 and treated with intravitreal bevacizumab were selected. All patients were treated following the established protocol at our centre. Those patients with less than three-year follow-up were excluded. Visual acuity and cycloplegic refraction in the last visit were registered. Treatment efficacy was defined as the absence of retreatment with intravitreal anti-VEGF or laser during follow-up. RESULTS A total of 38 infants (76 eyes) were included in the analysis. Twenty infants (40 eyes) completed visual acuity testing. Mean age was 6 years (IQR: 4-9). Median visual acuity was 0.8 (IQR: 0.5-1). Thirty-four eyes (85%) had good visual acuity (greater than or equal to 0.5). Thirty-seven patients (74 eyes) had cycloplegic refraction measured. Median spherical equivalent at the last visit was +0.94 (IQR: -0.25; 1.88). Treatment success rate was 96.05%. CONCLUSION Intravitreal bevacizumab treatment showed good functional outcome in patients with high-risk ROP type 1. In our study, good response to treatment was observed with a success rate over 95%.
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Affiliation(s)
| | | | | | - C Klein Burgos
- Servicio de Oftalmología, Hospital La Paz, Madrid, Spain
| | - M Roca Cabau
- Servicio de Oftalmología, Hospital La Paz, Madrid, Spain
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Prasad M, Ingolfsland EC, Christiansen SP. Modifiable Risk Factors and Preventative Strategies for Severe Retinopathy of Prematurity. Life (Basel) 2023; 13:life13051075. [PMID: 37240719 DOI: 10.3390/life13051075] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/13/2023] [Accepted: 04/13/2023] [Indexed: 05/28/2023] Open
Abstract
Severe ROP is characterized by the development of retinal fibrovascular proliferation that may progress to retinal detachment. The purpose of this report is to review five of the most common and well-studied perinatal and neonatal modifiable risk factors for the development of severe ROP. Hyperoxemia, hypoxia, and associated prolonged respiratory support are linked to the development of severe ROP. While there is a well-established association between clinical maternal chorioamnionitis and severe ROP, there is greater variability between histologic chorioamnionitis and severe ROP. Neonatal sepsis, including both bacterial and fungal subtypes, are independent predictors of severe ROP in preterm infants. Although there is limited evidence related to platelet transfusions, the risk of severe ROP increases with the number and volume of red blood cell transfusions. Poor postnatal weight gain within the first six weeks of life is also strongly tied to the development of severe ROP. We also discuss preventative strategies that may reduce the risk of severe ROP. Limited evidence-based studies exist regarding the protective effects of caffeine, human milk, and vitamins A and E.
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Affiliation(s)
- Minali Prasad
- Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA
| | - Ellen C Ingolfsland
- Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Stephen P Christiansen
- Departments of Ophthalmology and Pediatrics, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA 02118, USA
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Fevereiro-Martins M, Marques-Neves C, Guimarães H, Bicho M. Retinopathy of prematurity: A review of pathophysiology and signaling pathways. Surv Ophthalmol 2023; 68:175-210. [PMID: 36427559 DOI: 10.1016/j.survophthal.2022.11.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 11/15/2022] [Accepted: 11/18/2022] [Indexed: 11/25/2022]
Abstract
Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is characterized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and nitrosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced retinal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about signaling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.
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Affiliation(s)
- Mariza Fevereiro-Martins
- Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Investigação Científica Bento da Rocha Cabral, Lisboa, Portugal; Departamento de Oftalmologia, Hospital Cuf Descobertas, Lisboa, Portugal.
| | - Carlos Marques-Neves
- Centro de Estudos das Ci.¼ncias da Visão, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
| | - Hercília Guimarães
- Departamento de Ginecologia-Obstetrícia e Pediatria, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
| | - Manuel Bicho
- Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Investigação Científica Bento da Rocha Cabral, Lisboa, Portugal.
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Effect of maternal age on neonatal outcomes in very low birth weight singleton infants: a population-based study. J Perinatol 2023; 43:424-429. [PMID: 36739362 DOI: 10.1038/s41372-023-01620-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 03/23/2022] [Accepted: 01/20/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND Little is known on the impact of maternal age (MA) on very low birth weight (VLBW) infants' outcomes. We tested the hypothesis that at both ends of MA there are increased adverse neonatal outcomes in VLBW infants. METHODS We used the Israel National Neonatal Network VLBW (≤1500 g) database. Maternal age was stratified as: <20, 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses were univariate and multivariable logistic regression analysis. RESULTS After adjustment, the infant outcomes of older mothers were similar to those of the reference group for mortality, RDS, severe ROP, NEC and sepsis. Mothers < 20 and 20-24 years old had higher odds of IVH grades 3-4 (OR 1.45, 95% CI 1.09-1.93 and OR 1.26, 95% CI 1.10-1.45, respectively), and BPD (OR 1.55, 95% CI 1.13-2.13 and OR 1.40, 95% CI 1.22-1.62, respectively). There were higher odds for PVL in infants of <20 year-old mothers (OR 1.83, 95% CI 1.26-2.65) and in infants of 35-39 year-old mothers (OR 1.38, 95% CI 1.12-1.69). Poor composite outcomes were significantly higher in the youngest maternal age categories (<20-year-old mothers (OR 1.63, 95% CI 1.28-2.08), and 20-24-year-old (OR 1.28, 95% CI 1.15-1.43). CONCLUSIONS Neonatal outcomes differ in relation to maternal age among very low birth weight newborns, with adverse outcomes more predominant in infants of younger mothers.
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Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen. J Clin Med 2023; 12:jcm12031228. [PMID: 36769876 PMCID: PMC9918247 DOI: 10.3390/jcm12031228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 01/19/2023] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).
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Retinopathy of prematurity in preterm infants: A prospective study of prevalence and predictors in Northern India. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2023. [DOI: 10.1016/j.cegh.2023.101230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Dani C, Cecchi A, Ciarcià M, Miselli F, Luzzati M, Remaschi G, Bona MD, la Marca G, Boni L. Enteral and Parenteral Treatment with Caffeine for Preterm Infants in the Delivery Room: A Randomised Trial. Paediatr Drugs 2023; 25:79-86. [PMID: 36301511 PMCID: PMC9810558 DOI: 10.1007/s40272-022-00541-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Early treatment with caffeine in the delivery room (DR) has been proposed to decrease the need for mechanical ventilation (MV) by limiting episodes of apnoea and improving respiratory mechanics in preterm infants. Our aim was to verify the hypothesis that intravenous or enteral administration of caffeine can be performed in the preterm infant in the DR. METHODS Infants with 25±0-29±6 weeks of gestational age were enrolled and randomised to receive 20 mg/kg of caffeine citrate intravenously, via the umbilical vein, or enterally, through an orogastric tube, within 10 min of birth. Caffeine blood level was measured at 60 ± 15 min after administration and 60 ± 15 min before the next dose (5 mg/kg). The primary endpoint was evaluation of the success rate of intravenous and enteral administration of caffeine in the DR. RESULTS Nineteen patients were treated with intravenous caffeine and 19 with enteral caffeine. In all patients the procedure was successfully performed. Peak blood level of caffeine 60 ± 15 min after administration in the DR was found to be below the therapeutic range (5 µg/mL) in 25 % of samples and above the therapeutic range in 3%. Blood level of caffeine 60 ± 15 min before administration of the second dose was found to be below the therapeutic range in 18% of samples. CONCLUSIONS Intravenous and enteral administration of caffeine can be performed in the DR without interfering with infants' postnatal assistance. Some patients did not reach the therapeutic range, raising the question of which dose is the most effective to prevent MV. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier NCT04044976; EudraCT number 2018-003626-91.
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Affiliation(s)
- Carlo Dani
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy.
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
| | - Alessandra Cecchi
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Martina Ciarcià
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Francesca Miselli
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Michele Luzzati
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Giulia Remaschi
- Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Maria Della Bona
- Laboratory of Clinical Chemistry and Pharmacology of the Meyer Children's Hospital IRCCS, Florence, Italy
| | - Giancarlo la Marca
- Laboratory of Clinical Chemistry and Pharmacology of the Meyer Children's Hospital IRCCS, Florence, Italy
| | - Luca Boni
- SC Epidemiologia Clinica, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino of Genova, Genoa, Italy
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