Neonatal Jaundice and Vision Loss

描述（由申请人提供）：高胆红素血症引起的新生儿黄疸影响超过50%的新生儿。胆红素水平显著升高具有神经毒性，可导致称为核黄疸的永久性神经系统疾病。有证据表明，较低水平的胆红素可能会导致轻微的神经损伤，但尽管对该主题进行了广泛的研究，但仍无法精确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。微妙的神经影响是否是短暂的，也是许多胆红素相关疾病的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并发症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，我们将测量一组足月健康新生儿黄疸的游离胆红素和总胆红素。结果将与对比度、光栅和游标敏锐度的阈值和响应幅度的稳态VEP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，以了解任何影响是否是短暂的，恶化或保持不变。还将检查血清胆红素水平低的对照婴儿。我们实验室的初步数据表明，新生儿黄疸的婴儿信号反应减弱，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。这些影响持续到至少9个月大，即使黄疸在出生后的前几周内消失。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，那么这可能会导致对新生儿护理产生重大影响的其他研究。没有效果的发现也将是重要的，并提供额外的证据表明，目前的管理方针不能得到改善。确定哪种胆红素测量最准确也可能影响新生儿的未来护理。 公共卫生相关性：由胆红素水平升高引起的新生儿黄疸影响了50%以上的足月婴儿;但其治疗的确切指南仍存在争议。使用一种新的方法来测量可能导致神经损伤的胆红素类型，以及一种在婴儿期后期定量视力的测定方法，我们将探讨新生儿黄疸是否对视觉系统有持久的负面影响。如果我们发现有害影响，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，这也很重要，并保证目前的黄疸管理指南是正确的。

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.