Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants

高胆红素血症对高危婴儿视觉皮质功能的影响

• 批准号: 9803368
• 负责人: WILLIAM V GOOD
• 金额: $ 70.43万
• 依托单位: SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9803368
• 关键词: Affect; Age; Age-Months; Bilirubin; Binding; Birth; Blood - brain barrier anatomy; Blood Circulation; Brain; Carbon Monoxide; Child; Cohort Studies; Contrast Sensitivity; Cytolysis; Data; Detection; Disease; Ensure; Erythrocytes; Event; Exclusion Criteria; Functional disorder; Gestational Age; Goals; Hemolysis; Hospitals; Hour; Human; Hyperbilirubinemia; Icterus; Infant; Kernicterus; Laboratories; Learning; Measurement; Measures; Mediating; Monitor; Neonatal Jaundice; Nervous system structure; Neurologic; Neurologic Dysfunctions; Neurotoxins; Perception; Phototherapy; Plasma; Pregnancy; Premature Infant; Production; Research; Resolution; Retina; Retinal Cone; Rh Disease; Risk; Serum Albumin; Syndrome; System; Testing; Time; Toxic effect; Transfusion; Vision; Visual evoked cortical potential; Visual system structure; cohort; expectation; experience; falls; high risk; high risk infant; inclusion criteria; neonate; neurotoxicity; novel strategies; personalized approach; postnatal period; public health relevance; response

Effects of hyperbilirubunemia on visuocortical functioning in high-risk infants Abstract Bilirubin in its unconjugated version can cross the blood-brain barrier (BBB), where it is a potent neurotoxin in neonates. Levels of this substance are therefore closely monitored to ensure the neonate is not subject to bilirubin encephalopathy, a potentially devastating event. Recently, effects on an infant's neurological system that fall short of full-blown bilirubin encephalopathy have been described (syndromes of bilirubin-induced neurologic dysfunction [BIND]). In a study from our laboratory, we showed that relatively low levels of total serum/plasma bilirubin (TB) will produce undesired effects on visuocortical functioning. Since bilirubin is usually cleared in infants within week of age, our findings of deleterious effects at 6 months and repeated at 12 months are potentially alarming. The cohort for this study was low-risk infants; i.e., those who were full-term, healthy, and had no known hemolytic disease. Most of the children in this cohort did not qualify for therapy for their elevated TB (phototherapy or exchange transfusion). In a subsequent preliminary study of jaundiced preterm infants, we found that the effect on visuocortical functioning is much more pronounced than that seen in full term infants. Two types of neonates are at particularly high-risk for BIND, and could show more significant effects from bilirubin exposure: preterm infants, who have a more immature BBB (32–38 wks gestational age at birth); and infants who have hemolytic disease will release larger quantities of bilirubin into circulation. We will use the sweep visual evoked potential (sVEP) to measure 3 types of vision in these infants at 6 months of age. Vernier acuity refers to the ability to see fine offsets of lines. Since the offsets are smaller than the resolution afforded by the spacing of cone cells in the retina, the perception of these offsets requires considerable cortical input. Contrast sensitivity and grating acuity are also important aspects of vision. All 3 are subserved by different cortical mechanisms. We will measure acuity thresholds, conduction time, suprathreshold changes, and other components of vision processing and compare these to bilirubin values measured in the hospital and in the Stanford laboratory. This is a potentially highly significant study and could affect the manner in which bilirubin is treated in certain neonates. The majority of premature infants have some degree of hyperbilirubinemia, so the stakes are especially high. Since we don't know the level at which bilirubin should be treated in a given infant, tests at Stanford, to include bilirubin binding capacity, TB, and unbound bilirubin could pave the way to a more individualized approach to hyperbilirubinemia management. End-tidal carbon monoxide levels will be measured for all infants in the study at the hospital and compared to sVEP findings. This novel approach could pave the way to a noninvasive measure of bilirubin neurotoxicity.

高弹性血症对高危婴儿视觉皮质功能的影响 抽象的 胆红素在其未结合的版本中可以穿越血脑屏障（BBB），在该障碍物中，它是潜在的神经毒素 新生儿。因此，对此主题的水平进行密切监测，以确保新生儿不受 胆红素脑病，这是一个潜在的毁灭性事件。最近，对婴儿神经系统的影响 已经描述了那个成熟的胆红素脑病（胆红素诱导的综合症） 神经功能障碍[BIND]）。在我们实验室的一项研究中，我们表明总的总水平相对较低 血清/血浆胆红素（TB）将对视觉皮层功能产生未线子的影响。因为胆红素是 通常在一周内的婴儿中清除，我们在6个月时对有害影响的发现，在12岁时重复 月可能令人震惊。这项研究的队列是低风险婴儿。即，那些完整的人， 健康，没有已知的溶血疾病。该队列中的大多数孩子都没有资格接受治疗 它们升高的结核病（光疗或交换输血）。在随后的Janned初步研究中 早产儿，我们发现对视觉皮层功能的影响比看到的要明显得多 在完整的婴儿中。两种类型的新生儿特别高风险，可以显示更多 胆红素暴露的显着影响：早产儿，患有更不成熟的BBB（32-38周 出生时的胎龄）；患有溶血性疾病的婴儿将释放更多的胆红素 循环。我们将使用扫描视觉诱发电位（SVEP）来测量这些婴儿的3种视力 在6个月大。 vernier敏锐度是指看到线条偏移的能力。由于偏移较小 比视网膜中锥形细胞间距所提供的分辨率，这些偏移的感知需要 大量皮质输入。对比敏感性和光栅敏锐度也是视觉的重要方面。所有3个都是 通过不同的皮质机制供应。我们将测量敏锐度阈值，传导时间， 上方的变化以及视力处理的其他组成部分，并将其与胆红素值进行比较 在医院和斯坦福实验室中进行测量。这是一项潜在的重要研究，可以 影响胆红素在某些新生儿的处理方式。大多数早产婴儿有一些 高胆红素血症的程度，因此赌注特别高。因为我们不知道哪个胆红素的水平 应在给定的婴儿中进行治疗，在斯坦福的测试中，以包括胆红素结合能力，结核病和未结合 胆红素可以为高胆红素管理的更个性化的方法铺平道路。末端 一氧化碳水平将在医院研究中的所有婴儿中测量，并与SVEP进行比较 发现。这种新颖的方法可以为胆红素神经毒性的无创测量铺平道路。