Utility of Phosphatidylethanol for Identification of Fetal Alcohol Exposure

磷脂酰乙醇用于鉴定胎儿酒精暴露的用途

• 批准号: 8063282
• 负责人: Ludmila Nicole Bakhireva
• 金额: $ 3.76万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063282
• 关键词: Adult; Affect; Alcohol consumption; Alcohol-Related Neurodevelopmental Disorder; Alcohol-related birth defects; Alcohols; Beverages; Biological; Biological Markers; Birth; Blood; Blood specimen; Cell membrane; Characteristics; Child; Clinic; Clinical; Cognitive; Congenital Abnormality; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Early identification; Early treatment; Enrollment; Esters; Ethanol; Exposure to; Face; Fatty Acids; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fetus; Foundations; Future; Gamma-glutamyl transferase; General Population; Genetic Screening; Genetic screening method; Glucuronides; Goals; Hair; Heel; High Prevalence; Imprisonment; Interview; Knowledge; Laboratories; Lead; Light; Liquid Chromatography; Measures; Meconium; Medical Research; Mental Health; Methods; Mothers; National Children' s Study; National Institute on Alcohol Abuse and Alcoholism; Neonatal; New Mexico; Newborn Infant; Parents; Patient Self-Report; Patients; Performance; Pilot Projects; Population; Predictive Factor; Pregnancy; Pregnant Women; Prevention; Primary Prevention; Problem behavior; Process; Prospective Studies; Questionnaires; Recommendation; Recording of previous events; Recruitment Activity; Research; Risk; Sampling; Schools; Screening procedure; Secondary Prevention; Sensitivity and Specificity; Sex Behavior; Spottings; Substance abuse problem; Testing; Training; United States; Universities; Urine; Venipunctures; Visit; Whole Blood; Woman; Work; adverse outcome; alcohol exposure; binge drinking; carbohydrate-deficient transferrin; clinical practice; cohort; cost; diethyl sulfate; disability; drinking; drug testing; experience; fetal; follow-up; novel; offspring; phosphatidylethanol; pregnant; prognostic; public health relevance; sample collection; tandem mass spectrometry; tool

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.

描述（由申请人提供）：由于难以及早识别孕妇或可能怀孕的妇女饮酒情况，胎儿酒精谱系障碍 (FASD) 的一级预防常常存在问题。此外，研究酒精相关神经发育障碍（ARND）或所谓“受影响较小”的儿童（被认为占胎儿酒精影响儿童的绝大多数）的尝试因确认诊断要求而受到混淆。母亲有饮酒史。母亲的自我报告不可靠，并且传统的乙醇生物标志物对于许多孕妇（尤其是适度饮酒者）的饮酒诊断不够敏感。鉴于确认母亲在怀孕期间饮酒以及诊断不太严重的胎儿酒精谱系障碍 (FASD) 病例的困难，开发更好的生物标志物，无论是单独使用还是与其他措施结合使用，都将为早期干预创造机会，从而减少相关的长期不良后果。胎儿酒精暴露。我们目前正在进行一项由 ABMRF 支持的前瞻性研究，对象是从新墨西哥大学附属诊所招募的 150 名孕妇（适度饮酒者和轻度饮酒者/戒酒者），专门针对目前或既往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。在同一次就诊时，收集母亲的生物样本（血液、尿液和头发）。对受试者进行随访，直至临产和分娩，此时进行第二次访谈和标本采集。该 SOAR 应用建议在从我们建立的孕妇及其新生儿队列中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。 PEth 将在入组母研究时通过静脉穿刺收集的母体血液库中进行测量。对于新生儿，将通过干血斑 (DBS) 或通过足跟采血收集的 Guthrie 卡来测量 PEth，以进行出生时的常规遗传筛查。鉴于美国超过 95% 的新生儿可以获取 DBS 样本，并且样本采集和处理的成本较低，因此对这种介质中的 PEth 进行分析可以提供一种灵敏且易于使用的工具来评估胎儿酒精暴露情况。 PEth 的敏感性和特异性将与传统乙醇生物标志物（γ 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（即尿液乙基葡萄糖醛酸和硫酸乙酯）和胎儿（即，胎粪脂肪酸乙酯）。据我们所知，这是第一项检验 PEth 对孕妇及其后代有效性的研究。鉴于 PEth 在非妊娠人群中的高敏感性和特异性，我们预计它将成为生物标志物谱的重要补充，用于检测适度饮酒水平并评估母体和胎儿的暴露水平。 公共健康相关性：拟议的研究是首次尝试评估一种新型且有前景的乙醇生物标志物 - 磷脂酰乙醇 (PEth) 的有效性，该标志物在母亲和新生儿中进行评估，以识别孕妇的产前酒精暴露情况。生物标志物在临床实践中的应用，无论是单独使用还是与其他措施结合使用，都可以促进胎儿酒精谱系障碍的一级和二级预防。