Diagnostic Viability of Umbilical Cord Specimens

描述(由申请人提供)：目前诊断胎儿宫内药物暴露的“最佳做法”程序是测试新生儿的胎粪中是否存在药物。胎粪很难收集，在美国，8%-20%的新生儿由于某种类型的胎儿窘迫，胎粪在出生前被释放到羊水中。虽然药物可能导致了这种胎儿窘迫，但由于缺乏可供测试的胎粪，这些婴儿不太可能接受药物暴露测试。在第一阶段资助下，我们研究了在胎儿药物测试中用脐带代替胎粪的可行性。脐带在每次出生时都很容易拿到，而且很容易收集。在第一阶段的研究中，我们用苯丙胺、鸦片类药物、可卡因代谢物、大麻素和苯环利定(PCP)的特异性免疫分析法筛选了118个匹配的胎粪/脐带样本(NIDA-5专家组)。对胎粪标本进行检测，并作为常规临床标本报告。制备脐带提取物，对相同的药物进行筛选，并将结果与各自胎粪样本的筛选数据进行比较。脐带筛查试验的临界值通过对数据的ROC分析确定。胎粪与脐带筛查苯丙胺的符合率为96.6%，阿片类药物筛查符合率为94.9%，可卡因代谢物筛查符合率为99.2%，大麻代谢物筛查符合率为90.7%，PCP阴性筛查符合率为100%(未获得PCP阳性样本)。在这些第一阶段的研究中确定了脐带测试的可行性后，我们现在建议在第二阶段扩大这些研究，以优化和开发生产测试的脐带提取和测试程序。我们将通过药物组特异性免疫分析进行筛查，并通过药物测试的黄金标准气相色谱/质谱仪(GC/MS)进行分析，从美国几个分娩地点不同社会经济和种族人群中获得的潜在毒品暴露新生儿的脐带样本进行大样本(1000份)。所获得的数据将用于建立具有最佳灵敏度和特异性的药物筛选界值。脐带筛查和金标准GC/MS分析将得到验证，并将制定营销计划，将这些分析引入药物测试领域。对脐带样本的检测将简化对新生儿的药物测试，允许对遭受胎儿窘迫的婴儿进行测试，并将为更多暴露于药物的婴儿提供干预的可能性。

DESCRIPTION (provided by applicant): The current "best practices" procedure for diagnosing the in utero drug exposure of fetuses is testing the newborn's meconium for the presence of drugs. Meconium is difficult to collect and in 8-20% of births in the U.S. the meconium is released into the amniotic fluid pre-birth due to some type of fetal distress. While drugs may have induced this fetal distress it is unlikely that these infants will be tested for drug exposure due to lack of available meconium for testing. Under Phase I funding we studied the feasibility of substituting umbilical cord for meconium in fetal drug testing. Umbilical cord is readily available at every birth event and is easily collected. During the Phase I study we screened 118 matched meconium/umbilical cord samples with immunoassays specific for amphetamines, opiates, cocaine metabolites, cannabinoids, and phencyclidine (PCP) (NIDA-5 panel). The meconium samples were tested and reported out as routine clinical samples. Umbilical cord extracts were prepared, screened for the same drugs, and the results compared to the screening data for the respective meconium samples. Cutoffs for the umbilical cord screening tests were determined by ROC analyses of the data. Agreement between meconium and umbilical cord for amphetamine screening was 96.6%; for opiates was 94.9%; for cocaine metabolites was 99.2%; for cannabinoids was 90.7%; and for PCP was 100% for negatives (no PCP positive samples were obtained). Having established feasibility of umbilical cord testing in these Phase I studies, we now propose to extend these studies in Phase II to optimize and develop for production testing the umbilical cord extraction and assay procedures. We will screen by drug group-specific immunoassays and analyze by gas chromatography/mass spectrometry (GC/MS), the gold standard in drug testing, a large sampling (1000) of umbilical cord specimens from potentially drug- exposed neonates obtained from various socio-economic and ethnic populations at several birthing sites in the U.S. The data obtained will be used to establish drug screening cutoffs having optimum sensitivity and specificity. The umbilical cord screening and gold standard GC/MS assays will be validated and a marketing plan will be developed to introduce these assays into the drug testing arena. Testing of umbilical cord specimens will simplify drug testing of newborns, will allow testing of those infants suffering fetal distress, and will provide the potential to intervene for a greater population of drug-exposed babies.