Utility of Phosphatidylethanol for Identification of Fetal Alcohol Exposure

描述(由申请人提供)：胎儿酒精谱系障碍(FASD)的初级预防通常是有问题的，因为在孕妇或可能怀孕的妇女中很难及早识别酒精使用情况。此外，研究酒精相关神经发育障碍(ARND)或所谓的“受影响较轻”儿童的尝试，由于需要确认母亲饮酒史的诊断要求而受挫，这些儿童被认为是胎儿酒精影响儿童的绝大多数。母亲的自我报告是不可靠的，传统的酒精生物标志物对许多孕妇，特别是适度饮酒者的饮酒诊断不够敏感。鉴于确认孕期母亲饮酒以及诊断不太严重的FASD病例的困难，单独或与其他措施结合开发更好的生物标记物，将为早期干预创造机会，这些干预可能会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，对象是150名孕妇(适度饮酒者和少量饮酒者/戒酒者)，这些孕妇是从新墨西哥大学附属诊所招募的，专门研究现在或过去有药物滥用史的孕妇。符合条件的患者参加由诊所训练有素的研究协调员进行的基线访谈。在同一次访问中，采集了产妇的生物样本(血液、尿液和头发)。当第二次访谈和标本采集发生时，受试者一直被跟踪到分娩和分娩。这项SOAR应用程序建议在从我们已建立的孕妇及其新生儿队列中收集的样本中包括一种新的乙醇生物标记物-磷脂酰乙醇(PEH)的测量。在参加父母研究时，将通过静脉穿刺术收集储存的母体血液来测量PEH。在新生儿中，将在出生时通过脚后跟穿刺法收集的干血斑(DBS)或格思里卡片中测量PEH，以进行常规基因筛查。考虑到美国95%以上的新生儿可以获得DBS样本，而且样本收集和处理成本较低，这种介质中的PEH分析可以提供一种敏感和容易获得的工具来评估胎儿酒精暴露。PEH的敏感性和特异性将与传统的乙醇生物标志物(伽马谷氨酰转肽酶和碳水化合物缺乏的转铁蛋白)、筛查问卷以及母亲和胎儿的其他直接乙醇代谢物(即尿乙基葡萄糖醛酸乙酯和硫酸乙酯)(即胎粪脂肪酸乙酯)进行比较。据我们所知，这是第一次检查佩斯在孕妇及其后代中的有效性的研究。考虑到PEH在非怀孕人群中的高度敏感性和特异性，我们预计它将成为检测中度饮酒和评估母亲和胎儿暴露水平的生物标志物的重要补充。 公共卫生相关性：这项拟议的研究是第一次尝试评估一种新的、有前景的乙醇生物标记物-磷脂酰乙醇(PEH)的有效性，该标记物在母亲和新生儿中进行了评估，用于识别孕妇产前酒精暴露。生物标志物在临床实践中的应用，无论是单独的还是与其他措施相结合，都可以促进胎儿酒精谱障碍的一级和二级预防。

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.