Novel non-invasive approach for predicting retinopathy of prematurity in premature neonates

预测早产儿视网膜病变的新型非侵入性方法

• 批准号: 10665438
• 负责人: Isabelle G De Plaen
• 金额: $ 19.38万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665438
• 关键词: Adult; Affect; Age; Antibodies; Antibody Therapy; Area; Artificial Intelligence; Birth; Birth Weight; Blindness; Blood Vessels; Blood capillaries; Bronchopulmonary Dysplasia; Chicago; Child; Childhood; Clinical; Connective Tissue Diseases; Control Groups; Data; Development; Diagnosis; Engineering; Extremely Low Birth Weight Infant; Eye; Fingers; Future; Gestational Age; Growth; Hypoxia; Image; Impairment; Infant; Injections; Interdisciplinary Study; International; Intervention; Lasers; Length; Life; Lung; Medical; Methods; Microcirculatory Bed; Microscopic Angioscopy; Microvascular Dysfunction; Monitor; Morbidity - disease rate; Nail plate; Necrotizing Enterocolitis; Neonatal; Neonatology; Non-Invasive Detection; Ophthalmology; Organ; Pathogenicity; Patient-Focused Outcomes; Pediatric Hospitals; Play; Premature Infant; Prevalence; Process; Production; Prospective cohort; Protocols documentation; Public Health; Pulmonary Hypertension; ROC Curve; Research; Resolution; Retina; Retinal Detachment; Retinopathy of Prematurity; Role; Schools; Software Tools; Structure; Techniques; Testing; Time; Universities; VEGFA gene; Vascular Endothelial Growth Factors; Vascular System; Very Low Birth Weight Infant; angiogenesis; capillary bed; contrast enhanced; density; design; improved; improved outcome; indexing; interest; mortality; neonate; novel; novel therapeutic intervention; ophthalmic examination; postnatal; premature; preservation; preterm newborn; prevent; retina blood vessel structure; skeletal; targeted treatment; tool

ABSTRACT: Maldevelopment of the microvasculature in premature neonates plays a major role in complications of prematurity with life-long consequences such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and pulmonary hypertension (PHTN) complicating bronchopulmonary dysplasia (BPD), which are major causes of morbidity and mortality in premature infants. Unfortunately, there is no non-invasive method established to assess and monitor systemic microvascular development in premature babies to predict which infant will develop these complications. Nailfold capillaroscopy is a non-invasive technique useful in adults and children with connective tissue diseases to predict relapses, but not currently used in premature neonates to assess capillary development. Our preliminary data suggest that, in very-low-birthweight (VLBW) infants, nailbed capillary network density parameters (e.g. capillary skeletal length per area and branch points per area) significantly decrease during the first month of life. Our data also suggest that babies who ultimately developed ROP had a higher capillary density in the first few weeks after birth compared to those who do not. In this proposal, we will test the hypothesis that nailfold capillaroscopy can non-invasively detect capillary development impairment in premature infants and predict development of ROP requiring medical intervention. Therefore, we will address the following specific aims: 1) Identify the longitudinal developmental changes of nailfold capillaries in premature infants; 2) define capillary nailfold parameters that most reliably predict moderate to severe ROP development in VLBW infants. We have established a multi-disciplinary research team which includes the Northwestern University (NU) Imaging Core, the NU school of engineering and the departments of Ophthalmology and Neonatology at Ann & Robert H. Lurie Children’s Hospital of Chicago. If successful, the scientific premise of this project would include: 1) To non-invasively identify infants with vascular growth impairment which could benefit from novel therapeutic interventions aimed at preventing microvascular complications of prematurity, including ROP, thus improving patient outcomes; 2) To monitor the systemic effect of therapies targeting the microvasculature e.g. anti-VEGF antibodies. For this proof-of-principle study, we will focus on prediction of moderate to severe ROP as its diagnosis is directly based on the extent of retinal capillary maldevelopment. However, we plan in the future to expand our study to other microvascular beds that are less accessible to exam and to determine whether abnormal nailfold capillary development is able to predict other complications of prematurity e.g. NEC, BPD-related PHTN.

摘要： 早产儿微血管发育不良在早产儿的并发症中起着重要作用。 具有终身后果的早产，如早产儿视网膜病变（ROP）、坏死性小肠结肠炎 (NEC)和肺动脉高压（PHTN）合并支气管肺发育不良（BPD），这是主要的 早产儿发病和死亡的原因。不幸的是，没有非侵入性的方法 建立评估和监测早产儿全身微血管发育，以预测 婴儿会出现这些并发症。甲襞毛细血管镜检查是一种对成人有用的非侵入性技术， 儿童结缔组织疾病，以预测复发，但目前尚未用于早产儿， 评估毛细血管发育。我们的初步数据表明，在极低出生体重（VLBW）婴儿中， 甲床毛细血管网络密度参数（例如，单位面积的毛细血管骨架长度和单位面积的分支点） 在出生后的第一个月，体重明显下降。我们的数据还表明， 与未发生ROP的人相比，发生ROP的人在出生后的最初几周内具有更高的毛细血管密度。 在这个建议中，我们将测试甲襞毛细血管镜检查可以非侵入性地检测毛细血管的假设， 早产儿的发育障碍，并预测需要医疗干预的ROP的发展。 因此，我们将致力于以下具体目标：1）确定甲襞的纵向发展变化 早产儿毛细血管; 2）定义毛细血管甲襞参数，最可靠地预测中度至中度 极低出生体重婴儿发生严重ROP。我们建立了一个多学科的研究团队， 包括西北大学（NU）成像核心，工程和部门的NU学院 眼科和新生儿在安和罗伯特H。芝加哥卢瑞儿童医院。如果成功， 该项目的科学前提包括：1）非侵入性地识别具有血管生长的婴儿 可能受益于旨在预防微血管损伤的新型治疗干预措施 早产儿并发症，包括ROP，从而改善患者结局; 2）监测全身效应 靶向微血管系统的治疗，例如抗VEGF抗体。对于这项原理验证研究，我们将 重点是预测中度至重度ROP，因为其诊断直接基于视网膜毛细血管的程度 发育不良然而，我们计划在未来将我们的研究扩展到其他微血管床， 可用于检查，并确定异常甲襞毛细血管发育是否能够预测其他 早产并发症，例如NEC、BPD相关PHTN。