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）的一级预防往往是有问题的，因为难以早期识别孕妇或可能怀孕的妇女使用酒精。此外，试图研究酒精相关的神经发育障碍（ARND）或所谓的“受影响较小”的儿童，这被认为是构成绝大多数的胎儿酒精影响的儿童，已被混淆的诊断要求，确认母亲的饮酒史。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，特别是适度饮酒者的饮酒诊断不够敏感。鉴于确认孕妇在怀孕期间饮酒以及诊断不太严重的FASD病例的困难，单独或与其他措施相结合，开发更好的生物标志物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，研究对象是从新墨西哥大学附属诊所招募的150名孕妇（中度饮酒者和轻度饮酒者/戒酒者），这些诊所专门针对有药物滥用史或既往药物滥用史的孕妇。符合条件的患者参加由训练有素的研究协调员在诊所进行的基线访谈。在同一次访视时，采集母体生物样本（血液、尿液和毛发）。随访受试者，直至分娩和分娩，此时进行第二次访谈并收集标本。该SOAR申请建议在从我们建立的孕妇及其新生儿队列收集的样本中纳入一种新型乙醇生物标志物-磷脂酰乙醇（PEth）的测量。将在入组母研究时通过静脉穿刺采集的库存母体血液中测量PEth。在新生儿中，将在出生时通过足跟穿刺收集的干血斑（DBS）或古特里卡中测量PEth，用于常规遗传筛查。考虑到美国95%以上新生儿的DBS样本可用性以及样本采集和处理的低成本，该培养基中的PEth分析可以提供一种敏感且易于获得的工具来评估胎儿酒精暴露。PEth的灵敏度和特异性将与传统的乙醇生物标志物（γ谷氨酰转肽酶和碳水化合物缺乏型转铁蛋白）、筛查问卷和母亲的其他直接乙醇代谢产物（即，尿乙基葡糖苷酸和硫酸乙酯）和胎儿（即，胎粪脂肪酸乙酯）。据我们所知，这是第一项研究，以检查有效性的PEth在孕妇和他们的后代。考虑到PEth在非妊娠人群中的高灵敏度和特异性，我们预计它将成为生物标志物谱的重要补充，用于检测更适度的饮酒水平并评估母体和胎儿的暴露水平。 公共卫生相关性：这项研究是首次尝试评估一种新的和有前途的乙醇生物标志物-磷脂酰乙醇（PEth）的有效性，在母亲和新生儿中进行评估，用于识别孕妇产前酒精暴露。生物标志物在临床实践中的效用，无论是单独或与其他措施相结合，可以促进胎儿酒精谱系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.