Bilirubin-induced Auditory Neuropathy in Preterms

胆红素诱发的早产儿听觉神经病变

• 批准号: 6672243
• 负责人: SANJIV B AMIN
• 金额: $ 19.33万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6672243
• 关键词: acidosis; acoustic nerve; albumins; bilirubin; blood brain barrier; clinical research; cochlea; ear disorder diagnosis; hemolysis; human subject; hyperbilirubinemia; hypoxia; jaundice; kernicterus; nerve injury; neurotoxicology; otoacoustic emission; patient oriented research; pediatrics; premature infant human; septicemia

DESCRIPTION (provided by applicant): The goal of the research plan for this K23 award is to establish the incidence and determinants of bilirubin-induced auditory neuropathy (AN) in high-risk premature infants with hyperbilirubinemia. AN was first reported in 1996. It is functionally defined by an absent or abnormal auditory brainstem response (ABR) and a normal otoacoustic emission (OAE) response. The OAE reflects cochlear function and is the current standard of care in many Neonatal Intensive Care Units (NICU) for hearing screening. Infants with retrocochlear, bilirubin-induced AN are being missed by OAE measures. Bilirubin has specific predilection for the auditory neural pathway, but relatively little is known regarding the prevalence and determinants of AN in high-risk premature infants with hyperbilirubinemia. According to current theory, unbound bilirubin (UB) can cross the intact blood-brain barrier and cause neuronal damage. However, the diagnostic utility of UB levels has not been established nor are these levels routinely measured in NICU infants. We will use OAE, ABR, and laboratory tests for bilirubin-albumin binding variables, including UB, to examine whether the risk of bilirubin-induced AN in premature infants is: 1) increased in infants who, early on, demonstrate abnormal changes in ABR in association with hyperbilirubinemia; 2) more closely associated with UB levels than with estimates of total serum bilirubin or the bilirubin:albumin molar ratio; and 3) increased in the presence of clinical risk factors such as asphyxia, sepsis, hypoxia, acidosis, and hemolysis. Ultimately, these findings will reveal the magnitude of jaundice-related morbidity in premature infants, the usefulness of UB as a predictor of bilirubin-induced AN, and the role of clinical risk factors in bilirubin-induced AN. New knowledge of UB levels that place infants at risk for AN will be important for: 1) developing interventional trials to prevent bilirubin-induced AN and 2) identifying those at-risk infants who need evaluation for AN. n the training component of this award the candidate will acquire and refine basic skills for conducting high-quality patient-oriented research. Namely, he will gain intimate knowledge of epidemiology and biostatistics and experience with advanced clinical and laboratory methods. An outstanding set of mentors and consultants at the University of Maryland and the University of Pennsylvania offer the candidate a rich and vibrant research and training environment in which to advance his career goals and this promising and important new line of research.

描述（由申请人提供）：本K23奖的研究计划的目标是确定高胆红素血症高危早产儿中胆红素诱导的听神经病（AN）的发病率和决定因素。AN于1996年首次报道。其功能定义为听觉脑干反应（ABR）缺失或异常以及耳声发射（OAE）反应正常。OAE反映耳蜗功能，是许多新生儿重症监护室（NICU）听力筛查的当前护理标准。OAE测量遗漏了耳蜗后、胆红素诱导的AN婴儿。胆红素对听觉神经通路有特殊的偏好，但对高胆红素血症高危早产儿AN的患病率和决定因素知之甚少。根据目前的理论，未结合胆红素（UB）可以穿过完整的血脑屏障并引起神经元损伤。然而，UB水平的诊断效用尚未建立，也不是这些水平在NICU婴儿常规测量。我们将使用OAE、ABR和胆红素-白蛋白结合变量（包括UB）的实验室检查，以检查早产儿中胆红素诱导AN的风险是否：1）在早期表现出与高胆红素血症相关的ABR异常变化的婴儿中增加; 2）与UB水平的关系比与血清总胆红素或胆红素：白蛋白摩尔比的估计值更密切;和3）在存在临床危险因素如窒息、败血症、缺氧、酸中毒和溶血时增加。最终，这些研究结果将揭示早产儿黄疸相关发病率的程度，UB作为胆红素诱导的AN的预测因子的有用性，以及临床危险因素在胆红素诱导的AN中的作用。关于UB水平使婴儿处于AN风险的新知识对于以下方面将是重要的：1）开发干预性试验以预防UB诱导的AN和2）识别需要评估AN的风险婴儿。 在该奖项的培训部分，候选人将获得和完善进行高质量的以患者为导向的研究的基本技能。也就是说，他将获得流行病学和生物统计学的深入知识，以及先进的临床和实验室方法的经验。马里兰州和宾夕法尼亚大学的一组优秀的导师和顾问为候选人提供了一个丰富而充满活力的研究和培训环境，以推进他的职业目标和这一有前途的重要新研究方向。