Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants

高胆红素血症对高危儿视皮层功能的影响 摘要 未结合的胆红素可以穿过血脑屏障（BBB），在那里它是一种强效的神经毒素， 新生儿因此，密切监测这种物质的水平，以确保新生儿不会受到 胆红素脑病，一个潜在的毁灭性事件。最近，对婴儿神经系统的影响 未达到完全胆红素脑病的症状（胆红素诱导的综合征 神经功能障碍[BIND]）。在我们实验室的一项研究中，我们表明，相对较低水平的总 血清/血浆胆红素（TB）将对视皮层功能产生不期望的影响。由于胆红素是 通常在一周内的婴儿中清除，我们的发现在6个月时有害作用，并在12岁时重复 这几个月可能令人担忧。这项研究的队列是低风险婴儿;即，那些足月的， 健康，没有已知的溶血性疾病。该队列中的大多数儿童没有资格接受治疗， 他们的结核病升高（光疗或交换输血）。在随后对黄疸的初步研究中， 我们发现，对早产儿的视皮层功能的影响比我们看到的要明显得多。 在足月婴儿中。两种类型的新生儿BIND的风险特别高，并且可能显示出更多 胆红素暴露的显著影响：早产儿，BBB更不成熟（32-38周 出生时的胎龄）;和婴儿谁有溶血性疾病将释放大量的胆红素， 流通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个月大的时候游标敏锐度是指能够看到线条的细微偏移。由于偏移量较小， 比由视网膜中的视锥细胞的间隔提供的分辨率更高，对这些偏移的感知需要 相当多的皮层输入对比敏感度和光栅敏锐度也是视觉的重要方面。三个都是 由不同的皮层机制控制我们会测量敏锐度阈值，传导时间， 阈上变化和视觉处理的其他组成部分，并将其与胆红素值进行比较 在医院和斯坦福大学的实验室里测量。这是一项潜在的非常重要的研究， 影响胆红素在某些新生儿中的治疗方式。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 在斯坦福大学进行的测试，包括胆红素结合能力、结核病和未结合的 胆红素可以为更个性化的高胆红素血症管理方法铺平道路。潮气末 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。这种新方法可以为胆红素神经毒性的非侵入性测量铺平道路。

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.