Diagnostic Viability of Umbilical Cord Specimens

描述（由申请人提供）：目前诊断胎儿子宫内药物暴露的“最佳实践”程序是检测新生儿胎粪中药物的存在。胎便很难收集，在美国8-20%的新生儿中，由于某种胎儿窘迫，胎便在出生前被释放到羊水中。虽然药物可能导致胎儿窘迫，但由于缺乏可用的胎粪，这些婴儿不太可能进行药物暴露测试。在第一阶段的资助下，我们研究了在胎儿药物测试中用脐带代替胎粪的可行性。脐带在每个分娩事件中都很容易获得，并且很容易收集。在I期研究中，我们筛选了118个匹配的胎粪/脐带样本，并对安非他明、阿片类药物、可卡因代谢物、大麻素和苯环利定（PCP） （NIDA-5面板）进行了特异性免疫分析。将胎便标本作为常规临床标本报备。制备脐带提取物，筛选相同的药物，并将结果与各自胎粪样品的筛选数据进行比较。通过数据的ROC分析确定脐带筛查试验的截止点。胎便与脐带对安非他明筛查的符合率为96.6%；阿片类药物占94.9%；可卡因代谢物为99.2%；大麻素为90.7%；PCP阴性为100%（未获得PCP阳性样本）。在第一阶段研究中确定了脐带检测的可行性后，我们现在建议将这些研究扩展到第二阶段，以优化和开发脐带提取和分析程序，以进行生产测试。我们将通过药物组特异性免疫分析进行筛选，并通过气相色谱/质谱（GC/MS）进行分析，这是药物测试的金标准，从美国几个分娩地点的不同社会经济和种族人群中获得的1000个潜在药物暴露新生儿的脐带样本进行大样本取样。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截止点。将验证脐带筛选和金标准GC/MS测定，并制定营销计划，将这些测定引入药物检测领域。对脐带标本进行检测将简化新生儿的药物检测，将允许对遭受胎儿窘迫的婴儿进行检测，并将为更多的药物暴露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.