Phosphatidylethanol as an Alcohol Biomarker in Neonatal Blood Spots

磷脂酰乙醇作为新生儿血斑中的酒精生物标志物

• 批准号: 7536245
• 负责人: CHARLES A PLATE
• 金额: $ 15.73万
• 依托单位: U.S. DRUG TESTING LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536245
• 关键词: Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Behavioral; Biological Assay; Biological Markers; Birth; Blood; Blood specimen; Caring; Catalysis; Cell membrane; Cellular Membrane; Centers for Disease Control and Prevention (U.S.); Child; Congenital Abnormality; Coupled; Data; Detection; Early Diagnosis; Erythrocytes; Esters; Fatty Acids; Female of child bearing age; Fetal alcohol effects; Fetus; General Population; Genetic Screening; Goals; Gold; Government; Heel; Incidence; Liquid Chromatography; Liquid substance; Measures; Meconium; Medical; Membrane; Neonatal; Newborn Infant; Noise; Numbers; Organic solvent product; Pathologic; Patient Self-Report; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phospholipase D; Phospholipids; Pregnant Women; Prevalence; Procedures; Reporting; Risk; Sampling; Savings; Screening procedure; Services; Signal Transduction; Spottings; Standards of Weights and Measures; Surveys; System; Testing; United States; Uruguay; Validation; alcohol exposure; binge drinking; cost; cost effective; design; drinking; fetal; improved; mass spectrometer; microbial alkaline proteinase inhibitor; neonate; phosphatidylethanol; relating to nervous system; response; solvent extraction; tandem mass spectrometry

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.

描述（由申请人提供）：现在人们普遍认识到，孕妇频繁和/或酗酒会使胎儿有很高的出生缺陷风险。此外，在育龄妇女中酗酒的流行似乎正在增加。虽然目前还无法治愈胎儿酒精引起的神经损伤，但对这些儿童的早期诊断和适当的护理和治疗可以改善他们的长期前景。目前鉴别酒精暴露新生儿的金标准是检测胎便中的脂肪酸乙酯（FAEE）。然而，该试验也有局限性，其中包括8-20%的新生儿缺乏胎便样本，以及FAEE胎便试验的灵敏度相对较低（<70%）。此外，对于已经饮酒的孕妇来说，没有好的标识符，自我报告被认为是不可靠的。一项具有成本效益的筛选试验，将以高灵敏度（>90%）识别重度酒精暴露的新生儿，可能会为患有酒精引起的出生缺陷的大龄儿童节省数亿美元的医疗、行为、监护和司法服务费用。一种相对较新的特异性酒精生物标志物，磷脂酰乙醇（PEth），已被证明存在于重度饮酒者的红细胞中，灵敏度接近100%。PEth是一种病理性膜磷脂，由磷脂酶D在酒精存在下形成。本一期项目的目标是确定在新生儿血斑中检测PEth的可行性，并将血斑中PEth的发生率和水平与连续200个新生儿的胎粪样本中FAEE的发生率和水平进行比较。如果血斑/PEth试验等同于或优于胎粪/FAEE试验，我们将建立一种具有成本效益的普通人群新生儿酒精暴露试验的可行性，该试验可能与目前使用的综合遗传筛查试验相结合。设计和验证这种耦合酒精暴露试验将是II期研究的主要目标。