Utility of Phosphatidylethanol for Identification of Fetal Alcohol Exposure

描述（由申请人提供）：由于孕妇或可能怀孕的妇女难以早期识别酒精使用，胎儿酒精谱系障碍（FASD）的初级预防通常是有问题的。此外，研究酒精相关神经发育障碍（ARND）或所谓的“受影响较小”儿童（被认为占胎儿酒精影响儿童的绝大多数）的尝试，由于确认母亲饮酒史的诊断要求而受到困扰。母亲的自我报告是不可靠的，传统的乙醇生物标志物对许多孕妇的饮酒诊断不够敏感，尤其是适度饮酒者。鉴于确认孕妇孕期饮酒的困难，以及诊断不太严重的FASD病例的困难，开发更好的生物标志物，无论是单独的还是与其他措施相结合，都将为早期干预创造机会，从而减少与胎儿酒精暴露相关的长期不良后果。我们目前正在进行一项由abmrf支持的前瞻性研究，从新墨西哥大学附属诊所招募了150名孕妇（中度饮酒者和轻度饮酒者/戒酒者），该诊所致力于治疗有药物滥用史或既往史的孕妇。符合条件的患者参加由临床训练有素的研究协调员进行的基线访谈。在同一次访问中，收集母亲的生物样本（血液、尿液和头发）。对受试者进行随访，直到分娩时进行第二次访谈和标本采集。该SOAR应用程序建议在我们已建立的孕妇及其新生儿队列中收集的样品中包括一种新型乙醇生物标志物-磷脂酰乙醇（PEth）的测量。在加入父母研究时，将在静脉穿刺采集的母体血液中测量PEth。在新生儿中，PEth将在干血斑（DBS）或格思里卡（Guthrie cards）中进行测量，用于出生时的常规遗传筛查。鉴于美国95%以上的新生儿可获得DBS样本，且样本采集和处理成本较低，对这种培养基中的PEth的分析可提供一种敏感且易于获得的工具来评估胎儿酒精暴露。PEth的敏感性和特异性将与传统的乙醇生物标志物（γ谷氨酰转肽酶和缺乏碳水化合物的转铁蛋白）、筛选问卷以及母体（即尿葡萄糖醛酸乙酯和硫酸乙酯）和胎儿（即胎粪脂肪酸乙酯）的其他直接乙醇代谢物进行比较。据我们所知，这是第一次对孕妇及其后代进行有效性检验的研究。鉴于PEth在非怀孕人群中的高敏感性和特异性，我们预计它将成为检测更适度饮酒水平和评估母体和胎儿暴露水平的生物标志物谱的重要补充。

DESCRIPTION (provided by applicant): Primary prevention of Fetal Alcohol Spectrum Disorders (FASD) is often problematic due to difficulties of early identification of alcohol use among pregnant women or women who might become pregnant. In addition, attempts to study Alcohol-related Neurodevelopmental Disorder (ARND) or the so-called "lesser affected" children, which are thought to make up a large majority of fetal alcohol-affected children, has been confounded by the diagnostic requirement of confirming a maternal history of drinking. Maternal self-report is unreliable and conventional ethanol biomarkers are not sensitive enough for a diagnosis of drinking in many pregnant women, especially moderate drinkers. Given the difficulties of confirming maternal drinking during pregnancy, as well as diagnosing less severe cases of FASD, the development of better biomarkers, either alone or in combination with other measures, would create opportunities for earlier interventions that may reduce long-term adverse outcomes associated with fetal alcohol exposure. We are currently conducting a ABMRF-supported prospective study of 150 pregnant women (moderate drinkers and light drinkers/abstainers) recruited from the University of New Mexico-affiliated clinic dedicated to pregnant women with a present or past history of substance abuse. Eligible patients participate in a baseline interview conducted by a trained study coordinator at the clinic. At the same visit, maternal biological samples (blood, urine, and hair) are collected. Subjects are followed up until labor and delivery when the second interview and collection of specimens take place. This SOAR application proposes to include the measure of a novel ethanol biomarker - phosphatidylethanol (PEth) in samples collected from our established cohort of pregnant women and their newborn children. PEth will be measured in banked maternal blood collected by venipuncture at the enrollment into the parent study. In newborns, PEth will be measured in dried blood spots (DBS) or Guthrie cards collected by heel-prick for routine genetic screening at birth. The analysis of PEth in this media could provide a sensitive and readily available tool to assess fetal alcohol exposure, given the availability of DBS samples from over 95% of newborns in the United States and the low cost of sample collection and processing. The sensitivity and specificity of PEth will be compared to traditional ethanol biomarkers (gamma glutamyltranspeptidase and carbohydrate-deficient transferrin), screening questionnaires, and other direct ethanol metabolites of the mother (i.e., urine ethyl glucuronide and ethyl sulfate) and the fetus (i.e., meconium fatty acid ethyl esters). To our knowledge this is the first study to examine validity of PEth in pregnant women and their offspring. Given the high sensitivity and specificity of PEth in non-pregnant populations, we expect that it will be an important addition to the biomarker profile for detecting more moderate levels of drinking and evaluating both maternal and fetal levels of exposure. PUBLIC HEALTH RELEVANCE: The proposed study is a first attempt to estimate validity of a novel and promising ethanol biomarker - Phosphatidylethanol (PEth), assessed both in the mother and newborn, for identification of prenatal alcohol exposure among pregnant women. The utility of biomarkers in the clinical practice, either alone or in combination with other measures, can facilitate primary and secondary prevention of Fetal Alcohol Spectrum Disorder.