Evaluation of a New Method of Bilirubin Screening for Biliary Atresia

项目总结 NIDDK的一个重要目标是更早地发现患有胆道闭锁(BA)的婴儿，因为在治疗之前 30-45天的生命与避免需要肝移植的最佳机会相关。然而，早些时候 确诊是困难的，因为婴儿通常在出生后的头几周表现出无症状。一种解决方案 这个问题是通过血清结合胆红素测定来筛查新生儿，而新生儿出生时结合胆红素水平会升高。 然而，这种方法需要单独的抽血和个别的产科医院来解释和 随访异常结果。另一种可能的解决方案是用干血斑(DBS)卡对新生儿进行筛查 作为现有国家新生儿筛查计划的一部分，已经从所有婴儿身上收集了这些数据。这 应用程序的长期、广泛的目标是评估一种近似共轭的新方法 DBS卡中的胆红素水平可能会与国家新生儿筛查方案相结合。在目标1中， 我们将通过首先建立一个复制分析方法的实验系统来改进新方法 国家实验室的工作流程。有了这个系统，新方法的参数将会得到优化。在目标2中，我们 将使用之前收集并存储在 德克萨斯州卫生服务部。健康新生儿的DBS卡将被分析，以确定 新方法的阳性率。此外，还将分析患有BA的新生儿的DBS卡，以确定是否 该方法对BA的检测与血清结合胆红素检测一样敏感。这项研究的结果应该是 确定新方法是否可以用于将BA筛查纳入当前新生儿状态 筛查方案。这一发现将有助于指导未来前瞻性筛查的最佳方法 实施研究，最终目标是在生命的头几周确定BA并减少BA 儿科肝移植负担沉重。

PROJECT SUMMARY An important goal of the NIDDK is to identify infants with biliary atresia (BA) earlier, because treatment before 30-45 days of life correlates with the best chances of avoiding need for liver transplantation. However, early identification is difficult, because infants often appear asymptomatic in the first weeks of life. One solution to this problem is screening newborns with serum conjugated bilirubin measurements, which are elevated at birth in BA; however, this method requires a separate blood draw and individual birth hospitals to interpret and follow-up abnormal results. Another possible solution is to screen newborns with dried blood spot (DBS) cards which are already collected from all infants as part of existing state newborn screening programs. This application’s long, broad-term objective is to assess whether a new method which approximates conjugated bilirubin levels from DBS cards can potentially be integrated with state newborn screening protocols. In Aim 1, we will improve the new method by first establishing an experimental system that replicates the analytical workflow of state laboratories. With this system, the new method’s parameters will be optimized. In Aim 2, we will test the new method using newborn DBS cards which were previously collected and are stored at the Texas State Department of Health Services. DBS cards from healthy newborns will be analyzed, to determine the new method’s positive rate. In addition, DBS cards from newborns with BA will be analyzed, to determine if the method is as sensitive for BA as serum conjugated bilirubin testing. Results from this study should determine whether the new method can be used to incorporate BA screening into current state newborn screening protocols. The findings will help guide the best approach for future prospective screening implementation studies, with the ultimate goal of identifying BA in the first weeks of life and reducing BA’s significant pediatric liver transplantation burden.