Diagnostic Viability of Umbilical Cord Specimens

脐带标本的诊断活力

• 批准号: 7233260
• 负责人: CHARLES A PLATE
• 金额: $ 37.5万
• 依托单位: U.S. DRUG TESTING LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233260
• 关键词: Agreement; Amniotic Fluid; Amphetamines; Area; Biological Assay; Birth; Birthing Centers; Cannabinoids; Clinical; Cocaine; Data; Data Analyses; Diagnostic; Drug Exposure; Economics; Event; Exhibits; Exposure to; Failure; Feasibility Studies; Fetal Distress; Fetus; Funding; Goals; Gold; Illicit Drugs; Immunoassay; Infant; Marketing; Mass Fragmentography; Meconium; Methods; Metric; National Institute of Drug Abuse; Newborn Infant; Numbers; Opiates; Pattern; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phencyclidine; Population; Preclinical Drug Evaluation; Procedures; Production; Range; Rate; Receiver Operating Characteristics; Recovery; Relative (related person); Reporting; Running; Sampling; Screening procedure; Sensitivity and Specificity; Site; Solid; Solvents; Specimen; Standards of Weights and Measures; Testing; Time; Tissues; Umbilical cord structure; Validation; base; drug exposure in utero; drug testing; fetal; in utero; in utero diagnosis; neonate

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.

描述（由申请人提供）：目前诊断胎儿宫内药物暴露的“最佳实践”程序是测试新生儿胎便中是否存在药物。胎便很难收集，在美国，8-20% 的新生儿由于某种类型的胎儿窘迫，胎便在出生前释放到羊水中。虽然药物可能引起这种胎儿窘迫，但由于缺乏可用于测试的胎便，这些婴儿不太可能接受药物暴露测试。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便的可行性。每次分娩时，脐带都很容易获得，并且很容易收集。在第一阶段研究期间，我们使用针对安非他明、阿片类药物、可卡因代谢物、大麻素和苯环己哌啶 (PCP) 的免疫分析筛选了 118 份匹配的胎便/脐带样本（NIDA-5 小组）。胎便样本作为常规临床样本进行测试和报告。制备脐带提取物，筛选相同的药物，并将结果与​​相应胎便样品的筛选数据进行比较。脐带筛查测试的截止值通过数据的 ROC 分析确定。用于苯丙胺筛查的胎便和脐带之间的一致性为 96.6%；阿片剂为 94.9%；可卡因代谢物的有效率为 99.2%；大麻素为 90.7%；对于 PCP，阴性结果为 100%（未获得 PCP 阳性样本）。在这些第一阶段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展这些研究，以优化和开发用于生产测试的脐带提取和测定程序。我们将通过药物组特异性免疫测定进行筛选，并通过气相色谱/质谱（GC/MS）（药物测试的黄金标准）进行分析，从美国多个出生地的不同社会经济和种族人群中采集可能接触药物的新生儿的大量脐带样本（1000份）。获得的数据将用于建立具有最佳灵敏度和安全性的药物筛选临界值。 特异性。脐带筛查和金标准 GC/MS 检测将得到验证，并将制定营销计划以将这些检测引入药物检测领域。脐带标本的检测将简化新生儿的药物检测，将允许对患有胎儿窘迫的婴儿进行检测，并将为更多接触药物的婴儿提供干预的可能性。