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.

抽象的： 早产儿的微血管发育不良在并发症中起着重要作用 造成终生后果的早产，例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）并发支气管肺发育不良（BPD），这是主要的 不幸的是，没有非侵入性方法。 旨在评估和监测早产儿的全身微血管发育，以预测哪些 甲襞毛细血管镜检查是一种适用于成人和婴儿的非侵入性技术。 患有结缔组织疾病的儿童可以预测复发，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， 钉床毛细血管网络密度参数（例如每个区域的毛细血管骨架长度和每个分支点） 我们的数据还表明，婴儿最终的面积）会在出生后第一个月显着减少。 与未患 ROP 的人相比，患 ROP 的人在出生后最初几周内毛细血管密度更高。 在本提案中，我们将测试甲襞毛细血管镜检查可以无创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，我们将解决以下具体目标：1）识别甲襞的纵向发育变化 早产儿的毛细血管；2) 定义最可靠地预测中度至中度的毛细血管甲襞参数。 VLBW 婴儿严重 ROP 的发展我们已经建立了一个多学科研究团队。 包括西北大学 (NU) 影像中心、西北大学工程学院和 芝加哥 Ann & Robert H. Lurie 儿童医院的眼科和新生儿科 如果成功， 该项目的科学前提包括：1）非侵入性地识别婴儿的血管生长情况 可能受益于旨在预防微血管的新型治疗干预措施的损伤 早产儿并发症，包括 ROP，从而改善患者预后 2) 监测全身效果； 针对微血管系统的疗法，例如抗 VEGF 抗体，我们将进行这项原理验证研究。 重点关注中度至重度 ROP 的预测，因为其诊断直接基于视网膜毛细血管的范围 然而，我们计划将来将我们的研究扩展到其他较少的微血管床。 可进行检查并确定异常的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 相关的 PHTN。