Phosphatidylethanol as an Alcohol Biomarker in Umbilical Cord Tissue

描述（由申请人提供）：酒精引起广泛的胎儿影响，已被指定为“胎儿酒精谱系障碍”（FASD）。患有FASD的儿童可能受益于早期发现，使他们能够接受早期干预并改善其结果。目前确定新生儿是否在子宫内暴露于酒精的客观测试是检测胎粪中的脂肪酸乙酯（FAEE）。虽然这项测试是检测新生儿酒精暴露的“金标准”，但它确实有其局限性。胎粪很难收集，8-20%的新生儿胎粪在子宫内通过，无法进行检测，FAEE检测的灵敏度似乎为70-80%或更低。我们最近证明，在诊断新生儿宫内药物滥用时，可以用脐带组织代替胎粪。脐带在所有出生时都可以立即获得，并且很容易收集。虽然我们无法证明脐带组织中存在FAEE，但我们已经检测到磷脂酰乙醇（PEth），这是另一种直接的酒精生物标志物。文献中涉及18名戒毒患者的一份报告显示，所有18名患者的红细胞均显示出PEth。在这项I期研究中，我们将从200名怀疑在子宫内暴露于酒精的新生儿中收集匹配的胎粪和脐带标本，并比较胎粪中FAEE与匹配脐带样本中PEth的情况。本研究的目的是确定在检测新生儿酒精暴露时，脐带组织中PEth的存在是否等同于或上级于胎粪中FAEE的存在，以及在新生儿滥用药物和酒精检测中用脐带代替胎粪是否可行。每年至少有40，000名婴儿表现出“胎儿酒精谱系障碍”（FASD），美国的成本超过40亿美元。我们发现磷脂酰乙醇，一种直接的酒精生物标志物，可以在脐带组织中发现，这可能提供一个上级的手段来诊断这些新生儿比目前的“金标准”，分析脂肪酸乙酯在胎粪中的存在。在每次分娩时脐带的现成可用性（8-20%的新生儿在子宫内排出胎粪）将有助于识别目前被遗漏的FASD新生儿。

DESCRIPTION (provided by applicant): Alcohol causes a wide range of fetal effects that have been designated "fetal alcohol spectrum disorder" (FASD). Children with FASD may benefit from early detection enabling them to receive early intervention and improve their outcome. The current objective test for determining whether a newborn has been exposed to alcohol in utero is the detection of fatty acid ethyl esters (FAEE) in meconium. While this test is the "gold standard" for detecting neonatal alcohol exposure, it does have its limitations. Meconium is difficult to collect, it is passed in utero in 8-20% of births and is unavailable for testing, and the sensitivity of the FAEE assay appears to be 70-80% or less. We have recently demonstrated that it is possible to substitute umbilical cord tissue for meconium in diagnosing exposure in utero of a neonate to drugs of abuse. Umbilical cord is immediately available in all births and is easy to collect. While we have been unable to demonstrate the presence of FAEE in umbilical cord tissue, we have detected phosphatidylethanol (PEth), another direct alcohol biomarker. One report in the literature involving 18 detoxification patients revealed that all 18 patients exhibited PEth in their erythrocytes. In this Phase I study we will collect matched meconium and umbilical cord specimens from 200 newborns suspected of having been exposed to alcohol in utero and compare the instance of FAEE in meconium to PEth in the matched umbilical cord sample. The goal of this study is to determine whether the presence of PEth in umbilical cord tissue is equivalent or superior to the presence of FAEE in meconium for detecting neonatal alcohol exposure and whether it is feasible to substitute umbilical cord for meconium in both drugs of abuse and alcohol testing of newborns. At least 40,000 babies per year exhibit "fetal alcohol spectrum disorder" (FASD) at a cost to the United States of more than $4 billion dollars. Our finding that phosphatidylethanol, a direct alcohol biomarker, can be found in umbilical cord tissue may provide a superior means to diagnose these newborns than the current "gold standard", assaying for the presence of fatty acid ethyl esters in meconium. The ready availability of umbilical cord at each birthing event (8-20% of newborns pass their meconium in utero) would facilitate the identification of FASD newborns that are currently being missed.