Neonatal Jaundice and Vision Loss

描述（由申请人提供）：由高胆红素血症引起的新生儿黄疸影响超过50%的新生儿。胆红素水平的显著升高是神经毒性的，并可能导致永久性的神经系统疾病，称为核黄疸。有证据表明，较低水平的胆红素可能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，但对于一些婴儿来说，精确定义高胆红素血症的“安全”水平是不可能的；也就是说，不需要光疗或输血的水平。对于许多胆红素相关疾病来说，微妙的神经系统影响是否只是短暂的也是一个悬而未决的问题。难以确定血清胆红素安全水平的一个原因是，已知许多同时发生的情况会影响胆红素穿过血脑屏障的能力。另一个问题是，传统的血清胆红素测量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穿过血脑屏障。在这项研究中，我们将在一组患有新生儿黄疸的足月健康婴儿中测量游离胆红素和总胆红素。结果将与稳态VEP测量的对比度、光栅和游标灵敏度的阈值和响应幅度进行比较。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、恶化的还是保持不变的。血清胆红素水平低的对照婴儿也将被检查。我们实验室的初步数据表明，新生儿黄疸婴儿的信号反应减弱，而在游标敏锐度的情况下，阈值随着血清总胆红素水平的升高而恶化。这些影响至少会持续到9个月大，即使黄疸在出生后的最初几周就消失了。将总胆红素和游离胆红素与VEP结果进行比较，以了解哪种方法更准确地预测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，这可能会对新生儿的护理产生重大影响。没有效果的发现也很重要，并提供了现有管理指南无法改进的额外证据。确定哪种胆红素测量最准确也可能影响新生儿未来的护理。

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.