Neonatal Jaundice and Vision Loss

新生儿黄疸和视力丧失

• 批准号: 8066603
• 负责人: WILLIAM V GOOD
• 金额: $ 23.03万
• 依托单位: SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066603
• 关键词: Affect; Age-Months; Albumins; Bilirubin; Binding; Biological Assay; Blindness; Blood - brain barrier anatomy; Blood Transfusion; California; Caring; Categories; Child; Child health care; Contrast Sensitivity; Data; Dose; Future; Goals; Graph; Guidelines; Hyperbilirubinemia; Icterus; Infant; Kernicterus; Lead; Learning; Life; Logistic Regressions; Measurable; Measurement; Measures; Medical center; Neonatal Jaundice; Nervous System Trauma; Neurologic; Newborn Infant; Normal Range; Nurseries; Pediatrics; Phototherapy; Pilot Projects; Prospective Studies; Qualifying; Receiver Operating Characteristics; Recruitment Activity; Relative (related person); Research; Sample Size; Sampling; Serum; Severities; Signal Transduction; Testing; Time; Vision; Visual; Visual Acuity; Visual evoked cortical potential; Visual system structure; cohort; early childhood; high risk; improved; infancy; neurotoxic; novel strategies; public health relevance; response; standard of care; total measurement Bilirubin; vision development

DESCRIPTION (provided by applicant): Neonatal jaundice caused by hyperbilirubinemia affects more than 50% of all newborn children. Significantly elevated levels of bilirubin are neurotoxic and can cause a permanent neurological condition called kernicterus. Evidence that lower levels of bilirubin may lead to subtle neurological injury exists, but despite extensive research on the subject, it has not been possible to precisely define a "safe" level of hyperbilirubinemia for some infants; i.e., a level that does not require phototherapy or blood transfusion. Whether subtle neurological effects are transient is also an open question for many bilirubin-associated conditions. One reason for difficulty determining safe levels of serum bilirubin is that many concurrent conditions are known to affect bilirubin's ability to cross the blood brain barrier. Another problem is that traditional measurements of serum bilirubin evaluate free and albumin-bound bilirubin levels together. It is only free bilirubin that can cross the blood brain barrier. In this study we will measure free and total bilirubin in a cohort of full term, healthy infants with neonatal jaundice. Results will be compared with steady state VEP measurements of threshold and response amplitudes for contrast, grating, and vernier acuity. Tests will be performed longitudinally at 6 and 12 months of age to learn whether any effects are transient, worsen, or remain the same. Control infants with low levels of serum bilirubin will also be examined. Preliminary data from our lab indicates that signal responses are diminished in infants with neonatal jaundice, and that in the case of vernier acuity, thresholds worsen with increasing total serum bilirubin levels. These effects persist to at least 9 months of age, even though jaundice dissipates in the first few weeks of life. Total and free bilirubin will be compared to VEP findings to learn which is more accurate for predicting VEP changes. If findings from this study suggest a deleterious effect of bilirubin on the visual system, then this could lead to additional studies that could have a significant impact on the care of newborn children. Findings of no effect will also be significant and offer additional evidence that current management guidelines can't be improved. Determining which bilirubin measurement is most accurate could also influence future care of newborn infants. PUBLIC HEALTH RELEVANCE: Neonatal jaundice, caused by elevated bilirubin levels, affects more than 50% of full term infants; yet precise guidelines for its treatment are debated. Using a new approach to measure the type of bilirubin that can cause neurological damage, and an assay that quantitates vision later in infancy, we will explore whether neonatal jaundice has an enduring negative effect on the visual system. If we find a detrimental effect, this will lead to further studies, and could have an enormous impact on the health of children. If no effect is found, this, too, is important and offers reassurance that current guidelines for management of jaundice are correct.

描述(申请人提供)：由高胆红素血症引起的新生儿黄疸影响超过50%的新生儿。显著升高的胆红素水平是神经毒性的，可能会导致一种名为核黄斑的永久性神经疾病。有证据表明，较低的胆红素水平可能会导致轻微的神经损伤，但尽管对这一主题进行了广泛的研究，仍不可能准确地定义某些婴儿的高胆红素血症的“安全”水平，即不需要光疗或输血的水平。对于许多胆红素相关的疾病来说，细微的神经影响是否是暂时的也是一个悬而未决的问题。很难确定血清胆红素安全水平的一个原因是，已知许多同时存在的情况会影响胆红素通过血脑屏障的能力。另一个问题是，传统的血清胆红素测量方法是同时评估游离胆红素和白蛋白结合胆红素水平。只有游离胆红素才能通过血脑屏障。在这项研究中，我们将测量一组患有新生儿黄疸的足月健康婴儿的游离胆红素和总胆红素。结果将与稳态VEP的对比度、光栅度和游标敏感度的阈值和反应幅度的测量结果进行比较。将在6个月和12个月大时进行纵向测试，以了解是否有任何影响是暂时的、恶化的或保持不变的。血清胆红素水平低的对照婴儿也将接受检查。我们实验室的初步数据显示，患有新生儿黄疸的婴儿的信号反应减弱，而在游标视力的情况下，阈值随着血清总胆红素水平的增加而恶化。这些影响至少持续到9个月大，即使黄疸在生命的最初几周就消失了。总胆红素和游离胆红素将与VEP结果进行比较，以了解哪个更准确地预测VEP的变化。如果这项研究的结果表明胆红素对视觉系统有有害影响，那么这可能会导致更多的研究，可能会对新生儿的护理产生重大影响。没有效果的结果也将是重要的，并提供了更多证据，表明当前的管理指南无法改进。确定哪种胆红素测量最准确也可能影响未来对新生儿的护理。 与公共卫生相关：由胆红素水平升高引起的新生儿黄疸影响了超过50%的足月儿；然而，对其治疗的准确指南仍存在争议。使用一种新的方法来测量可能导致神经损伤的胆红素的类型，以及一种在婴儿后期量化视力的分析方法，我们将探索新生儿黄疸是否对视觉系统有持久的负面影响。如果我们发现了有害的影响，这将导致进一步的研究，并可能对儿童的健康产生巨大影响。如果没有发现效果，这一点也很重要，并保证目前的黄疸管理指南是正确的。