Phosphatidylethanol as an Alcohol Biomarker in Neonatal Blood Spots

描述(由申请人提供)：现在公认的是，孕妇经常和/或酗酒会使其胎儿处于出生缺陷的高风险中。此外，育龄妇女酗酒的流行率似乎正在上升。虽然目前还没有治愈胎儿酒精所致神经损伤的方法，但对这些儿童进行早期诊断和适当的护理和治疗可以改善他们的长期前景。目前识别酒精暴露新生儿的金标准是检测胎粪中的脂肪酸乙酯(FAEE)。然而，这种检测也有局限性，其中包括8-20%的新生儿缺乏胎粪样本，以及FAEE胎粪检测的敏感性相对较低(70%)。此外，对于一直饮酒的孕妇来说，没有好的识别方法，自我报告也被认为是不可靠的。一种成本效益高的筛查方法将识别高度敏感的重度酒精暴露新生儿(&gt；90%)，可能会为患有酒精导致出生缺陷的大龄儿童节省数亿美元的医疗、行为、监护和司法服务。一种相对较新的特定酒精生物标志物磷脂酰乙醇酯(PEH)已被证明存在于酗酒者的红细胞中，其敏感度接近100%。PEH是一种由磷脂酶D在乙醇存在下形成的病理性膜磷脂。该第一阶段项目的目标是确定检测新生儿血点中的PEH的可行性，并将血点中的PEH的发生率和水平与200名连续新生儿的匹配胎粪样本中的FAEE的发生率和水平进行比较。如果血斑/PEH检测等同于或优于胎粪/FAEE检测，我们将确定开发一种具有成本效益的、普通人群新生儿酒精暴露检测的可行性，该检测可能与目前使用的全面基因筛查检测相结合。第二阶段研究的主要目标将是设计和验证这种耦合酒精暴露试验。

DESCRIPTION (provided by applicant): It is now well recognized that frequent and/or binge drinking of alcohol by a pregnant woman puts her fetus at high risk for birth defects. Moreover, the prevalence of binge drinking in women of childbearing-age seems to be increasing. While there is presently no cure for fetal alcohol-induced neural damage, early diagnosis and appropriate care and treatment of these children can improve their long-term outlook. The current gold standard for identifying alcohol-exposed neonates is the detection of fatty acid ethyl esters (FAEE) in their meconium. There are limitations of this test, however, and these include the lack of a meconium sample in 8-20% of births and the relatively low sensitivity (<70%) of the FAEE meconium test. In addition, there are no good identifiers for a pregnant woman who has been drinking and self-reporting is not considered reliable. A cost-effective screening assay that would identify heavily alcohol-exposed neonates with high sensitivity (>90%) could potentially result in the savings of hundreds of millions of dollars in costs associated with medical, behavioral, custodial, and judicial services for older children suffering from alcohol-induced birth defects. A relatively new specific alcohol biomarker, phosphatidylethanol (PEth), has been shown to be present in red cells of heavy drinkers with a sensitivity approaching 100%. PEth is a pathologic membrane phospholipid formed by phospholipase D in the presence of alcohol. The goal of this Phase I project is to determine the feasibility of detecting PEth in blood spots taken from neonates and comparing the incidence and level of PEth in the blood spot to the incidence and level of FAEE present in a matching meconium sample from 200 consecutive newborns. If the blood spot/PEth assay is equivalent or superior to the meconium/FAEE assay, we will have established the feasibility of developing a cost- effective, general population neonate alcohol exposure assay that could potentially be coupled to comprehensive genetic screening assays currently in use. Design and validation of such a coupled alcohol exposure assay would be the primary goal of a Phase II study.