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: 10468725
• 负责人: WILLIAM V GOOD
• 金额: $ 60.84万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468725
• 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.

高胆红素血症对高危婴儿视皮质功能的影响 摘要 胆红素的非结合形式可以穿过血脑屏障(BBB)，在血脑屏障中它是一种强有力的神经毒素 新生儿。因此，这种物质的水平受到密切监测，以确保新生儿不会受到 胆红素脑病，一种潜在的破坏性事件。最近，对婴儿神经系统的影响 尚未完全发展的胆红素脑病已被描述(胆红素引起的综合征 神经功能障碍[绑定])。在我们实验室的一项研究中，我们显示出相对较低的总水平 血清/血浆胆红素(TB)会对视皮质功能产生不良影响。因为胆红素是 通常在婴儿出生一周内清除，我们的有害影响在6个月时发现，并在12岁时重复。 几个月的时间可能会令人担忧。这项研究的队列是低风险婴儿；即那些足月、 身体健康，没有已知的溶血性疾病。这一队列中的大多数儿童没有资格接受治疗 他们升高的结核病(光疗或换血)。在随后的黄褐斑的初步研究中 对于早产儿，我们发现对视觉皮质功能的影响比看到的要明显得多。 足月婴儿。有两种类型的新生儿患BIND的风险特别高，而且可能表现出更多 胆红素暴露的显著影响：早产儿有更不成熟的血脑屏障(32-38周 出生时的胎龄)；患有溶血性疾病的婴儿会将大量的胆红素释放到 发行量。我们将使用扫描视觉诱发电位(SVEP)来测量这些婴儿的三种视力 六个月大的时候。游标敏锐度指的是看到线条细微偏移的能力。由于偏移量较小 比视网膜中视锥细胞的间距提供的分辨率更高，对这些偏移的感知需要 相当大的皮质输入。对比敏感度和光栅敏锐度也是视觉的重要方面。三个人都是 伴随着不同的皮质机制。我们将测量视力阈值，传导时间， 阈值以上的变化，以及视觉处理的其他组件，并将这些与胆红素值进行比较 在医院和斯坦福实验室进行了测量。这是一项潜在的非常有意义的研究，可能 影响某些新生儿胆红素的治疗方式。大多数早产儿都有一些 高胆红素血症的程度，所以风险特别高。因为我们不知道胆红素的水平 应在给定的婴儿中进行治疗，在斯坦福大学进行测试，以包括胆红素结合能力、TB和未结合 胆红素可以为更个性化的高胆红素血症治疗铺平道路。潮汐末期 将在医院测量研究中所有婴儿的一氧化碳水平，并与sVEP进行比较 调查结果。这一新方法可能为无创测量胆红素神经毒性铺平道路。