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1.
N Engl J Med ; 388(16): 1501-1511, 2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37075142

RESUMEN

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).


Asunto(s)
Recien Nacido Extremadamente Prematuro , Enfermedades del Prematuro , Oximetría , Humanos , Lactante , Recién Nacido , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/etiología , Displasia Broncopulmonar/etiología , Circulación Cerebrovascular , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/mortalidad , Enfermedades del Prematuro/terapia , Oximetría/métodos , Cerebro , Ultrasonografía , Retinopatía de la Prematuridad/etiología , Enterocolitis Necrotizante/etiología , Sepsis Neonatal/etiología
2.
BMC Genomics ; 25(1): 415, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671350

RESUMEN

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.


Asunto(s)
Oxígeno , Proteómica , Retinopatía de la Prematuridad , Factor A de Crecimiento Endotelial Vascular , Animales , Oxígeno/metabolismo , Ratones , Proteómica/métodos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Espectrometría de Masas en Tándem , Ontología de Genes , Cromatografía Liquida , Retina/metabolismo , Retina/efectos de los fármacos , Retina/patología
3.
Development ; 148(9)2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33960384

RESUMEN

Angiogenesis in the developing mammalian retina requires patterning cues from astrocytes. Developmental disorders of retinal vasculature, such as retinopathy of prematurity (ROP), involve arrest or mispatterning of angiogenesis. Whether these vascular pathologies involve astrocyte dysfunction remains untested. Here, we demonstrate that the major risk factor for ROP - transient neonatal exposure to excess oxygen - disrupts formation of the angiogenic astrocyte template. Exposing newborn mice to elevated oxygen (75%) suppressed astrocyte proliferation, whereas return to room air (21% oxygen) at postnatal day 4 triggered extensive proliferation, massively increasing astrocyte numbers and disturbing their spatial patterning prior to the arrival of developing vasculature. Proliferation required astrocytic HIF2α and was also stimulated by direct hypoxia (10% oxygen), suggesting that astrocyte oxygen sensing regulates the number of astrocytes produced during development. Along with astrocyte defects, return to room air also caused vascular defects reminiscent of ROP. Strikingly, these vascular phenotypes were more severe in animals that had larger numbers of excess astrocytes. Together, our findings suggest that fluctuations in environmental oxygen dysregulate molecular pathways controlling astrocyte proliferation, thereby generating excess astrocytes that interfere with retinal angiogenesis.


Asunto(s)
Astrocitos/metabolismo , Proliferación Celular/fisiología , Neovascularización Patológica/metabolismo , Neovascularización Fisiológica/fisiología , Oxígeno/metabolismo , Retina/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Astrocitos/citología , Astrocitos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Hipoxia/metabolismo , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Oxígeno/farmacología , Retina/anomalías , Retina/metabolismo , Retina/patología , Vasos Retinianos/metabolismo , Retinopatía de la Prematuridad
4.
Am J Pathol ; 193(11): 1683-1690, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36780985

RESUMEN

Retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, is strongly associated with gestational age and weight at birth. Yet, many extremely preterm infants never develop ROP or develop only mild ROP with spontaneous regression. In addition, a myriad of other factors play a role in the retinal pathology, one of which may include the early gut microbiome. The complications associated with early gestational age include dysbiosis of the dynamic neonatal gut microbiome, as evidenced by the development of often concomitant conditions, such as necrotizing enterocolitis. Given this, alongside growing evidence for a gut-retina axis, there is an increasing interest in how the early intestinal environment may play a role in the pathophysiology of ROP. Potential mechanisms include dysregulation of vascular endothelial growth factor and insulin-like growth factor 1. Furthermore, the gut microbiome may be impacted by other known risk factors for ROP, such as intermittent hypoxia and sepsis treated with antibiotics. This mini-review summarizes the literature supporting these proposed avenues, establishing a foundation to guide future studies.


Asunto(s)
Microbioma Gastrointestinal , Retinopatía de la Prematuridad , Recién Nacido , Humanos , Recien Nacido Prematuro , Retinopatía de la Prematuridad/etiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Edad Gestacional , Factores de Riesgo
5.
Am J Pathol ; 193(12): 2001-2016, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37673326

RESUMEN

Bronchopulmonary dysplasia (BPD), also called chronic lung disease of immaturity, afflicts approximately one third of all extremely premature infants, causing lifelong lung damage. There is no effective treatment other than supportive care. Retinopathy of prematurity (ROP), which impairs vision irreversibly, is common in BPD, suggesting a related pathogenesis. However, specific mechanisms of BPD and ROP are not known. Herein, a neonatal mouse hyperoxic model of coincident BPD and retinopathy was used to screen for candidate mediators, which revealed that granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3, was up-regulated significantly in mouse lung lavage fluid and plasma at postnatal day 14 in response to hyperoxia. Preterm infants with more severe BPD had increased plasma G-CSF. G-CSF-deficient neonatal pups showed significantly reduced alveolar simplification, normalized alveolar and airway resistance, and normalized weight gain compared with wild-type pups after hyperoxic lung injury. This was associated with a marked reduction in the intensity, and activation state, of neutrophilic and monocytic inflammation and its attendant oxidative stress response, and protection of lung endothelial cells. G-CSF deficiency also provided partial protection against ROP. The findings in this study implicate G-CSF as a pathogenic mediator of BPD and ROP, and suggest the therapeutic utility of targeting G-CSF biology to treat these conditions.


Asunto(s)
Displasia Broncopulmonar , Hiperoxia , Retinopatía de la Prematuridad , Lactante , Recién Nacido , Animales , Humanos , Ratones , Displasia Broncopulmonar/patología , Recien Nacido Prematuro , Células Endoteliales/patología , Pulmón/patología , Hiperoxia/complicaciones , Retinopatía de la Prematuridad/patología , Factor Estimulante de Colonias de Granulocitos , Animales Recién Nacidos
6.
Am J Pathol ; 193(11): 1776-1788, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36822266

RESUMEN

Retinopathy of prematurity (ROP), a blinding condition affecting preterm infants, is an interruption of retinal vascular maturation that is incomplete when born preterm. Although ROP demonstrates delayed onset following preterm birth, representing a window for therapeutic intervention, there are no curative or preventative measures available for this condition. The in utero environment, including placental function, is increasingly recognized for contributions to preterm infant disease risk. The current study identified a protective association between acute placental inflammation and preterm infant ROP development using logistic regression, with the most significant association found for infants without gestational exposure to maternal preeclampsia and those with earlier preterm birth. Expression analysis of proteins with described ROP risk associations demonstrated significantly decreased placental high temperature requirement A serine peptidase-1 (HTRA-1) and fatty acid binding protein 4 protein expression in infants with acute placental inflammation compared with those without. Within the postnatal peripheral circulation, HTRA-1 and vascular endothelial growth factor-A demonstrated inverse longitudinal trends for infants born in the presence of, compared with absence of, acute placental inflammation. An agnostic approach, including whole transcriptome and differential methylation placental analysis, further identify novel mediators and pathways that may underly protection. Taken together, these data build on emerging literature showing a protective association between acute placental inflammation and ROP development and identify novel mechanisms that may inform postnatal risk associations in preterm infants.


Asunto(s)
Nacimiento Prematuro , Retinopatía de la Prematuridad , Lactante , Recién Nacido , Humanos , Femenino , Embarazo , Recien Nacido Prematuro , Factor A de Crecimiento Endotelial Vascular , Placenta , Edad Gestacional , Inflamación , Factores de Riesgo
7.
Microvasc Res ; 152: 104626, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37963514

RESUMEN

Retinopathy of prematurity (ROP), a retinal disease that can occur in premature infants, can lead to severe visual impairment. In this study, we examined the preventive and therapeutic effects of mammalian target of rapamycin complex 1 (mTORC1) inhibition on abnormal retinal blood vessels in a rat model of ROP. To induce ROP-like vascular abnormalities, rats were subcutaneously treated with KRN633, an inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinase, on postnatal day 7 (P7) and P8. KRN633-treated (ROP) rats were treated subcutaneously with the mTORC1 inhibitor rapamycin according to preventive and therapeutic protocols, i.e., from P11 to P13 (P11-P13) and from P14 to P20 (P14-P20), respectively. To compare with the effects of VEGF inhibition, KRN633 was administered according to similar protocols. Changes in retinal vasculature, phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTORC1 activity, and the proliferative status of vascular cells were evaluated at P14 and P21 using immunohistochemistry. Rapamycin treatment from P11 to P13 prevented increases in arteriolar tortuosity, capillary density, and the number of proliferating vascular cells, and eliminated pS6 immunoreactivity in ROP rats. KRN633 treatment at P11 and P12 (P11/P12) also prevented the appearance of ROP-like retinal blood vessels. Rapamycin treatment from P14 to P20 failed to attenuate arteriolar tortuosity but prevented increases in capillary density and proliferating vascular cell number at the vascular front, but not at the central zone. KRN633 treatment from P14 to P20 significantly reduced abnormalities in the retinal vasculature; however, the effects were inferior to those of KRN633 treatment on P11/P12. These results suggest that activation of the mTORC1 pathway in proliferating endothelial cells contributes to the appearance and progression of ROP-like retinal blood vessels. Therefore, inhibition of mTORC1 may be a promising approach for selectively targeting abnormal retinal blood vessels in ROP.


Asunto(s)
Compuestos de Fenilurea , Quinazolinas , Retinopatía de la Prematuridad , Animales , Ratas , Animales Recién Nacidos , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/farmacología , Vasos Retinianos , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/prevención & control , Sirolimus/farmacología , Sirolimus/metabolismo , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
8.
Exp Eye Res ; 239: 109773, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38171476

RESUMEN

The retinopathy of prematurity (ROP) can cause serious clinical consequences and, fortunately, it is remediable while the time window for treatment is relatively narrow. Therefore, it is urgent to screen all premature infants and diagnose ROP degree timely, which has become a large workload for pediatric ophthalmologists. We developed a retinal image-free procedure using small amount of blood samples based on the plasma Raman spectrum with the machine learning model to automatically classify ROP cases before medical intervention was performed. Statistical differences in infrared Raman spectra of plasma samples were found among the control, mild (ZIIIS1), moderate (ZIIIS2 & ZIIS1), and advanced (ZIIS2) ROP groups. With the different wave points of Raman spectra as the inputs, the outputs of our support vector machine showed that the area under the curves in the receiver operating characteristic (AUC) were 0.763 for the pair comparisons of the control with the mild groups, 0.821 between moderate and advanced groups (ZIIS2), while more than 90% in comparisons of the other four pairs: control vs. moderate (0.981), control vs. advanced (0.963), mild vs. moderate (0.936), and mild vs. advanced (0.953), respectively. Our study could advance principally the ROP diagnosis in two dimensions: the moderate ROPs have been classified remarkably from the mild ones, which leaves more time for the medical treatments, and the procedure of Raman spectrum with a machine learning model based on blood samples can be conveniently promoted to those hospitals lacking of the pediatric ophthalmologists with experience in reading retinal images.


Asunto(s)
Retinopatía de la Prematuridad , Telemedicina , Recién Nacido , Lactante , Humanos , Niño , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/terapia , Sensibilidad y Especificidad , Telemedicina/métodos , Algoritmos , Aprendizaje Automático , Edad Gestacional
9.
Exp Eye Res ; 239: 109750, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38097102

RESUMEN

Retinopathy of prematurity (ROP) is the leading cause of blindness in children, but there is no safe and effective treatment available. Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor for IL-1 may affect ROP progression. This study aimed to investigate the role of IL1R2 in ROP. A microglial cell model was established under hypoxia conditions and co-cultured with choroidal endothelial cells, while an oxygen-induced retinopathy (OIR) model was also established. Microglial activation and IL1R2 levels in retinal tissues were analyzed using immunofluorescence assay. Endothelial cell migration was evaluated by Transwell assay and scratch test, angiogenesis was assessed using ELISA and tube formation assay, and proliferation was evaluated by EdU assay. The HIF1α/PFKFB3 pathway was analyzed by western blot. We observed that IL1R2 expression was predicted to be upregulated in ROP and was increased in hypoxia-treated BV2 cells. Additionally, IL1R2 levels were upregulated in the retinal tissues of OIR mice and correlated with microglial activation. In vitro experiments, we found that hypoxia promoted endothelial cell migration, angiogenesis, proliferation, and activated the HIF1α/PFKFB3 pathway, which were rescued by IL1R2 knockdown. Moreover, NHWD-870 (a HIF1α/PFKFB3 pathway inhibitor) suppressed endothelial cell migration, angiogenesis, and proliferation induced by IL1R2 overexpression. In conclusion, IL1R2 facilitates the migration, angiogenesis, and proliferation of choroidal endothelial cells by activating the HIF1α/PFKFB3 pathway to regulate ROP progression.


Asunto(s)
Neovascularización Retiniana , Retinopatía de la Prematuridad , Animales , Humanos , Ratones , Angiogénesis , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Hipoxia/metabolismo , Ratones Endogámicos C57BL , Oxígeno/metabolismo , Fosfofructoquinasa-2/efectos adversos , Fosfofructoquinasa-2/metabolismo , Receptores Tipo II de Interleucina-1/metabolismo , Retina/metabolismo , Neovascularización Retiniana/metabolismo , Retinopatía de la Prematuridad/metabolismo
10.
Pediatr Res ; 95(7): 1868-1874, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38402317

RESUMEN

BACKGROUND: Retinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation. METHODS: Prospective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models. RESULTS: We included 224 infants born at median (IQR) 29.6 (27.1-30.8) weeks gestation and birth weight of 1160 (860-1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659-1564) pmol/L and 348 (300-382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210-502) pmol/L and 196 (156-268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score. CONCLUSIONS: MR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future. IMPACT: Plasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II. Both biomarkers have the potential to improve early prediction of retinopathy of prematurity. Vasoactive peptides might allow to reduce the proportion of screened infants substantially.


Asunto(s)
Factor Natriurético Atrial , Biomarcadores , Endotelina-1 , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/sangre , Retinopatía de la Prematuridad/diagnóstico , Recién Nacido , Biomarcadores/sangre , Estudios Prospectivos , Factor Natriurético Atrial/sangre , Femenino , Masculino , Endotelina-1/sangre , Recien Nacido Prematuro/sangre , Edad Gestacional , Fragmentos de Péptidos/sangre , Modelos Logísticos , Precursores de Proteínas/sangre
11.
Curr Opin Ophthalmol ; 35(3): 252-259, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38205941

RESUMEN

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.


Asunto(s)
Retinopatía de la Prematuridad , Recién Nacido , Humanos , Niño , Retinopatía de la Prematuridad/diagnóstico , Tomografía de Coherencia Óptica/métodos , Retina , Oftalmoscopía/métodos , Técnicas de Diagnóstico Oftalmológico
12.
Eur J Pediatr ; 183(2): 827-834, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38030929

RESUMEN

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness in preterm infants. The incidence of ROP varies widely across countries, with rates as high as 30% in some regions. This study investigated the incidence, risk factors, treatment, and mortality of ROP patients in Germany. Data were extracted from the German Federal Statistical Office (Destatis) diagnosis-related group (DRG) and Institute for the Remuneration System in Hospitals (InEK) databases. Patients with a secondary diagnosis of ROP (ICD-10 code H35.1) in the first 28 days of life were included. Data were extracted for patients admitted between January 1, 2019 and December 31, 2019. The diagnoses and procedures were determined using the German version of the International Classification of Diseases (ICD-10-GM) and the German procedure coding system (OPS). The codes 5-154.xx, 5-155.xx, 8-020.xx, 5-156.9, 6-003.(c&d), 6-007.(2&8) were utilised to denote different ocular treatments. Patient Clinical Complexity Levels were extracted and used to compare ROP with non-ROP patients. A total of 1326 patients with ROP were identified. The incidence of ROP is estimated to be 17.04 per 10,000 live births. The incidence was highest in infants with birth weights less than 500 g and decreased with increasing birth weight. The most common risk factors for ROP were low birth weight, male sex, and prematurity. Of the infants with ROP, 7.2% required ocular treatment. The most common treatment was intraocular injections, followed by photocoagulation. No surgical treatment was required for any of the infants during the study period. The mortality rate for infants with ROP was 60.33 per 10,000. This is higher than the overall neonatal death rate of 24.2 per 10,000. CONCLUSIONS: This study found that the incidence of ROP in Germany is similar to that in other developed countries. The study also found that the mortality rate for infants with ROP is higher than the overall neonatal death rate. These findings highlight the importance of early detection and treatment of ROP in preterm infants. WHAT IS KNOWN: • ROP is a severe eye condition often affecting preterm infants. • Previous data are limited in scope and generalizability. WHAT IS NEW: • Based on a national database, our study found ROP incidence to be 17.04 per 10,000 new births, higher in males (17.71) than in females (16.34). • 7.2% of ROP cases required ocular treatment, inversely correlated with birth weight. • High rates of multimorbidity such as neonatal jaundice (84.69%), respiratory distress syndrome (80.84%), and apnea (78.88%) were observed.


Asunto(s)
Muerte Perinatal , Retinopatía de la Prematuridad , Lactante , Femenino , Recién Nacido , Humanos , Masculino , Recien Nacido Prematuro , Peso al Nacer , Estudios de Cohortes , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/terapia , Incidencia , Edad Gestacional , Factores de Riesgo
13.
Eur J Pediatr ; 183(4): 1891-1900, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38319404

RESUMEN

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.


Asunto(s)
Enfermedades del Recién Nacido , Retinopatía de la Prematuridad , Recién Nacido , Masculino , Lactante , Femenino , Humanos , Niño , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/epidemiología , Países en Desarrollo , Recien Nacido Extremadamente Prematuro , Prevalencia , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Edad Gestacional
14.
Eur J Pediatr ; 183(6): 2671-2682, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38509232

RESUMEN

To describe the variability in carotenoid content of human milk (HM) in mothers of very to extremely low birth weight preterm infants throughout lactation and to explore the relationship between lutein in HM and the occurrence of retinopathy of prematurity (ROP) in preterm infants. We recruited healthy mothers along with their preterm infants that were born at gestational age 24 + 2 to 29 + 6 weeks or with a birth weight under 1500 g and were exclusively breastfed HM. Each participant provided up to 7 HM samples (2-10 ml) on day 0-3 and once a week until 6 weeks. Additionally, when possible, a blood sample was collected from the infant at week 6. Concentrations of the major carotenoids (lutein, zeaxanthin, beta-carotene, and lycopene) in all HM and blood samples were assessed and compared. Thirty-nine mother-infant dyads were included and 184 HM samples and 21 plasma samples were provided. Mean lutein, zeaxanthin, beta-carotene, and lycopene concentration decreased as lactation progressed, being at their highest in colostrum samples (156.9 vs. 66.9 vs. 363.9 vs. 426.8 ng/ml, respectively). Lycopene (41%) and beta-carotene (36%) were the predominant carotenoids in colostrum and up to 2 weeks post-delivery. Inversely, the proportion of lutein and zeaxanthin increased with lactation duration to account for 45% of the carotenoids in mature HM. Lutein accounted for 58% of the carotenoids in infant plasma and only 28% in HM. Lutein content of transition and mature HM did not differ between mothers of ROP and non-ROP infants.Conclusion Carotenoid content of HM was dynamic and varied between mothers and as lactation progressed. Infant plasma displayed a distinct distribution of carotenoids from HM.


Asunto(s)
Carotenoides , Leche Humana , Humanos , Leche Humana/química , Femenino , Carotenoides/análisis , Carotenoides/sangre , Recién Nacido , Adulto , Estudios Longitudinales , Retinopatía de la Prematuridad/sangre , Recien Nacido Prematuro , Masculino , Lactancia/metabolismo , Calostro/química , Lactancia Materna , Luteína/análisis , Luteína/sangre
15.
Med Sci Monit ; 30: e943486, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613144

RESUMEN

BACKGROUND Retinopathy of prematurity (ROP), originally described as retrolental fibroplasia, represents an abnormal growth of blood vessels in the premature retina that can occur in response to oxygen therapy. The association between ROP and invasive mechanical ventilation has been widely studied in the literature; however, the relationships between different types of ventilation and ROP have not been as well documented. This study aimed to compare the association of ROP incidence with mechanical ventilation (MV), nasal continuous positive airway pressure (nCPAP), and high-flow nasal cannula (HFNC) therapies in 130 pre-term infants with gestational ages <32 weeks. MATERIAL AND METHODS The study includes 130 premature newborns, out of which 54 underwent MV therapy, either alone or in combination with nCPAP or HFNC therapy, 63 underwent nCPAP therapy, either alone or in combination with MV or HFNC therapy, and 23 underwent HFNC therapy, either alone or in combination with MV or nCPAP therapy. The relationships between ROP and the 3 types of ventilation were analyzed by univariate followed by multivariate logistic regression. RESULTS When adjusting for covariates, only nCPAP and birth weight were significantly associated with ROP, the former being a strong risk factor, with an adjusted odds ratio (AOR) of 7.264 (95% CI, 2.622-20.120; P<0.001), and the latter being a weak protective factor, with an AOR of 0.998 (95% CI, 0.996-0.999; P<0.05). CONCLUSIONS The results showed nCPAP was a strong ROP risk factor, birth weight was a weak ROP protective factor, and MV and HFNC were not significantly associated with increased ROP risk.


Asunto(s)
4-Butirolactona/análogos & derivados , Respiración Artificial , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Respiración Artificial/efectos adversos , Presión de las Vías Aéreas Positiva Contínua , Retinopatía de la Prematuridad/terapia , Peso al Nacer , Cánula
16.
Retina ; 44(2): 295-305, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37903446

RESUMEN

PURPOSE: To investigate recent trends in the cumulative incidence and treatment patterns of retinopathy of prematurity (ROP) in Japan. METHODS: A retrospective multicenter cohort was conducted from 2011 to 2020 using the Diagnosis Procedure Combination inpatient database. Preterm newborns with birth weight <2,500 g were categorized by birth weight. The cumulative incidence of ROP, treatment patterns, and association between treatment and birth weight were investigated. RESULTS: A total of 82,683 preterm infants were identified, of whom 9,335 (11.3%) were diagnosed with ROP. The cumulative incidence of ROP increased by 15% in those with birth weight <500 g over the study period. Among the ROP infants, 20.2% received treatment, including laser photocoagulation (94.8%), intravitreal injection (3.8%), or both (1.8%). The proportion receiving laser photocoagulation decreased followed by an increase in intravitreal injection. This shift in intervention pattern was most conspicuous for those with birth weight 750 to 1,249 g. The risk ratio of receiving laser and intravitreal injection for those weighing <500 g was 24.7 (95% confidence interval, 10.5-58.2) and 28.4 (5.8-138.1), respectively, as compared with infants weighing >1,500 g. CONCLUSION: The cumulative incidence of ROP increased in infants with birth weight <500 g. A shift from laser photocoagulation to intravitreal injection was observed in the more recent years.


Asunto(s)
Recien Nacido Prematuro , Retinopatía de la Prematuridad , Humanos , Recién Nacido , Peso al Nacer , Edad Gestacional , Incidencia , Japón/epidemiología , Coagulación con Láser , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos
17.
Retina ; 44(4): 652-658, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38064668

RESUMEN

PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.


Asunto(s)
Astigmatismo , Miopía , Errores de Refracción , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Astigmatismo/terapia , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos , Factores de Crecimiento Endotelial , Resultado del Tratamiento , Coagulación con Láser
18.
Retina ; 44(2): 306-315, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37824817

RESUMEN

PURPOSE: To identify structural markers of active retinopathy of prematurity (ROP) in foveal and parafoveal retinal layers using hand-held optical coherence tomography. METHODS: Hand-held optical coherence tomography images (n = 278) were acquired from a prospective mixed cross-sectional longitudinal observational study of 87 participants (23-36 weeks gestational age; n = 30 with ROP, n = 57 without ROP) between 31 and 44 weeks postmenstrual age excluding treated ROP and features of cystoid macular edema. Six retinal layer thicknesses from the fovea to the parafovea were analyzed at five locations up to 1,000 µ m, temporally and nasally. RESULTS: The mean outer retinal thickness during active ROP increased at the fovea and parafovea from postmenstrual age 33 weeks to 39 weeks ( P < 0.001), whereas the parafoveal inner nuclear layer and retinal nerve fiber layer reduced ( P < 0.001). Outer retinal thickness at the fovea from 33 weeks to 39 weeks postmenstrual age was consistently thicker in infants with ROP across all levels of prematurity (gestational age). CONCLUSION: Increased foveal and parafoveal outer retina measured using hand-held optical coherence tomography shows potential as a marker for ROP screening.


Asunto(s)
Recien Nacido Prematuro , Retinopatía de la Prematuridad , Humanos , Recién Nacido , Estudios Transversales , Edad Gestacional , Estudios Prospectivos , Retina/diagnóstico por imagen , Retinopatía de la Prematuridad/diagnóstico , Tomografía de Coherencia Óptica/métodos , Estudios Observacionales como Asunto
19.
Retina ; 44(6): 1073-1082, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38346099

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis , Edad Gestacional , Inyecciones Intravítreas , Coagulación con Láser , Retinopatía de la Prematuridad , Factor A de Crecimiento Endotelial Vascular , Humanos , Retinopatía de la Prematuridad/cirugía , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/terapia , Retinopatía de la Prematuridad/diagnóstico , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Estudios Retrospectivos , Femenino , Masculino , India/epidemiología , Recién Nacido , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Prospectivos , Coagulación con Láser/métodos , Estudios de Seguimiento , Vitrectomía/métodos , Resultado del Tratamiento , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Peso al Nacer , Lactante , Agudeza Visual
20.
Retina ; 44(2): 288-294, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948737

RESUMEN

PURPOSE: Exudative retinal detachment (ERD) may result from laser photocoagulation for retinopathy of prematurity. Although risk factors have been hypothesized from case reports, comparative studies have not been reported. We sought to evaluate risk factors for ERD following laser, comparing affected and unaffected infants. METHODS: Retrospective cohort study of infants undergoing retinopathy of prematurity laser at the Children's Hospital of Philadelphia over 6 years. All received near-confluent laser of avascular retina. Demographic, medical, and procedural risk factors for ERD were evaluated in univariate analysis because of the rarity of ERD. RESULTS: Among 149 lasered infants, 6 infants (4%, 95% confidence interval [CI] 1.5%-8.6%) developed ERD. Race was a significant risk factor ( P = 0.01). Among 71 African American or Hispanic infants, 6 (8.5%, 95% CI 3.2%-17.5%) developed ERD. Among 78 non-African American or Hispanic infants, 0 (0%, 95% CI 0%-4.6%) developed ERD. There were no significant differences in the other studied factors. CONCLUSION: Exudative retinal detachment was uncommon (4%) following retinopathy of prematurity laser. Despite so few cases, darker pigmented race with likely increased pigmented fundi was significantly associated with an increased ERD risk. Further study may reveal whether increased choroidal pigment causes greater laser tissue damage or makes it difficult to discern the ora, resulting in inadvertent lasering of the ciliary body, leading to ERD.


Asunto(s)
Desprendimiento de Retina , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Niño , Humanos , Desprendimiento de Retina/epidemiología , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/cirugía , Incidencia , Estudios Retrospectivos , Coagulación con Láser/efectos adversos , Factores de Riesgo , Edad Gestacional
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