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: 8149983
• 负责人: Ludmila Nicole Bakhireva
• 金额: $ 3.63万
• 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 2013-02-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8149983
• 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; 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; Genetic Screening; Genetic screening method; Glucuronides; Goals; Hair; Heel; High Prevalence; Imprisonment; Interview; 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; liquid chromatography mass spectrometry; 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）：由于难以早期鉴定出可能怀孕的孕妇或妇女饮酒的困难，因此对胎儿酒精谱系障碍（FASD）的初级预防（FASD）通常是有问题的。此外，尝试研究与酒精相关的神经发育障碍（ARND）或所谓的“受影响较小的”儿童的尝试，这些儿童被认为占受胎儿饮酒的大部分儿童的大部分，已被确认饮酒的诊断要求所困扰。孕产妇的自我报告是不可靠的，常规的乙醇生物标志物不足以诊断许多孕妇（尤其是中度饮酒者）饮酒。考虑到确认怀孕期间饮酒的困难以及诊断出较少严重的FASD病例，单独或与其他措施结合使用更好的生物标志物的发展将为早期干预措施提供机会，从而减少与胎儿酒精暴露相关的长期不良结果。目前，我们正在对新墨西哥大学附属诊所招募的150名孕妇（中度饮酒者和轻饮酒者/戒酒者）进行ABMRF支持的前瞻性研究，该研究专门针对具有现有或过去的滥用药物史的孕妇。合格的患者参加了诊所训练有素的研究协调员进行的基线访谈。在同一访问中，收集了母体生物样品（血液，尿液和头发）。随访受试者，直到第二次采访和进行标本收集时分娩和分娩为止。这种飙升的应用建议包括在我们已建立的孕妇及其新生儿童中收集的样品中的新型乙醇生物标志物-phosphatidylythanol（Peth）的度量。 Peth将以静脉穿刺收集的孕产妇在入学期间进行的孕产妇进行测量。在新生儿中，Peth将以脚跟 - 果实收集的干血点（DB）或Guthrie卡进行测量，以便在出生时进行常规的基因筛查。鉴于美国95％以上新生儿的DBS样本以及样本收集和处理的低成本，对这种媒体的Peth分析可以提供一种敏感且随​​时可用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-谷氨酰基转肽酶和缺乏碳水化合物缺乏的转铁蛋白），筛选问卷以及其他母亲的其他直接乙醇代谢物（即尿乙基葡萄糖醛酸乙酸酯和硫酸乙酯）和甲基酸酯（即Mecon）（即Mecon）（即Mecon）（即Mecon）。据我们所知，这是第一个研究佩斯在孕妇及其后代的有效性的研究。鉴于Peth在非怀孕人群中的敏感性和特异性高，我们希望这将是生物标志物概况的重要补充，用于检测更中等水平的饮酒和评估母体和胎儿暴露水平。 公共卫生相关性：拟议的研究是估计新颖和有希望的乙醇生物标志物 - 磷脂酰乙醇（Peth）的首次尝试，在母亲和新生儿都进行了评估，以鉴定孕妇中孕妇的产前酒精暴露。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原发性和继发性。

项目成果

A Novel Approach to Prenatal Measurement of the Fetal Frontal Lobe Using Three-Dimensional Sonography.

使用三维超声检查胎儿额叶产前测量的新方法。

• 发表时间: 2017
• 期刊: The Journal of reproductive medicine
• 作者: Brown,SteffenA;Hall,Rebecca;Hund,Lauren;Gutierrez,HildaL;Hurley,Timothy;Holbrook,BradleyD;Bakhireva,LudmilaN
• 通讯作者: Bakhireva,LudmilaN

Fetal Growth Outcomes in a Cohort of Polydrug- and Opioid-Dependent Patients.

多种药物和阿片类药物依赖患者的胎儿生长结果。

• 发表时间: 2016
• 期刊: The Journal of reproductive medicine
• 作者: Garrison,Laura;Leeman,Lawrence;Savich,RenateD;Gutierrez,Hilda;Rayburn,WilliamF;Bakhireva,LudmilaN
• 通讯作者: Bakhireva,LudmilaN