Newborn Phosphatidylethanol Screening to Detect Fetal Alcohol Exposure in Uruguay

 描述(由申请人提供)：在美国，产前酒精暴露是导致出生缺陷的主要可预防原因，导致一系列神经、行为和身体异常，统称为胎儿酒精谱系障碍(FASD)。FASD的早期诊断是有效干预和治疗的关键，特别是对于3岁以下的儿童，他们可能受益于早期神经可塑性，并减少长期不良反应。我们研究计划的长期目标是为支持新生儿产前酒精暴露的常规筛查提供科学依据。这项国际U01赠款提案的主要目的是在一个怀孕期间大量饮酒普遍的国家(乌拉圭)，研究母亲饮酒与新生儿新生儿磷脂酰乙醇(PEH)水平之间的关系。我们之前在乌拉圭蒙得维的亚的公共卫生保健医院的研究表明，怀孕期间酒精使用率高(60%)，新生儿的酒精水平高(79%)。佩斯是一种新的生物标志物，可以检测过去30天内的间歇性重度饮酒(3次或更多饮酒)。这项检测在检测最近饮酒方面是100%特异的，没有已知的假阳性。这项拟议的设计是一项横断面研究，将包括1500名18岁及以上的妇女及其新生儿。在乌拉圭蒙得维的亚两家选定的公立医疗保健医院中选择一家接受产科护理的女性将被招募参加这项研究。将使用菲尔·梅博士和威尔斯奈克博士开发的经过验证的衡量标准来评估孕妇的酒精使用情况。在美国和其他国家，面试日程已经成为评估母亲饮酒和胎儿酒精暴露的标准标准。孕妇酒精生物标志物分析将包括在分娩时获得的头发和指甲中的乙基葡萄糖醛酸(EtG)和血液中的乙基葡萄糖醛酸(EtG)。采集新生儿脐带血和常规48小时足跟棒血，以评估新生儿的PEP水平。通过收集新生儿出生时和出生后48小时的心跳指数，我们可以评估新生儿的心跳动力学，以确定测定新生儿心跳指数的最佳时间。通过比较新生儿PEH水平与母亲自我报告的酒精使用和酒精生物标志物，这项创新性的研究将提供关于PEH作为产前酒精暴露的新生儿生物标志物的敏感性和特异性的新信息。这项研究的发现可能会对公共卫生和政策产生巨大的影响，如果peth被证明是一个高度敏感和特定的危险产前酒精暴露的指标。干血斑卡中的PEH分析将是第一个在普遍可用的新生儿血液样本中确定产前酒精暴露的测试。未来的工作也可能帮助我们将新生儿的PEH水平与儿童长期的行为、学习和发育缺陷联系起来，并有助于FASD儿童的早期诊断。

 DESCRIPTION (provided by applicant): Prenatal alcohol exposure is the leading preventable cause of birth defects in the United States, producing an array of neurological, behavioral and physical abnormalities collectively known as Fetal Alcohol Spectrum Disorders (FASD). Early diagnosis of FASD is the key to effective interventions and treatments, particularly for children under the age of 3 who may benefit from early neuroplasticity and reduce the long-term adverse effects. The long-term goal of our research program is to provide the science to support routine newborn screening for prenatal alcohol exposure. The primary aim of this international U01 grant proposal is to examine the association between maternal alcohol use and newborn phosphatidylethanol (PEth) levels in their newborn children, in a country (Uruguay) where significant alcohol use is common during pregnancy. Our previous work in public health care hospitals in Montevideo, Uruguay documented high rates of alcohol use during pregnancy (60%) and PEth levels in newborns (79%). PEth is a new biomarker that detects episodic heavy drinking (3 or more drinks) in the last 30 days. The test is 100% specific in detecting recent alcohol use with no known false positives. This proposed design is a cross-sectional study that will include1500 women 18 years and older and their newborns. Women who are admitted to one of two selected public health care hospitals in Montevideo, Uruguay for obstetrical care will be recruited to participate in the study. Maternal alcohol use will be assessed using a validated measure developed by Drs. Phil May and Wilsnack. The interview schedule has become the standard measure to assess maternal alcohol use and fetal alcohol exposure in the US and other countries. Maternal alcohol biomarker assays will include ethylglucuronide (EtG) in hair and nails and PEth in blood obtained at the time of delivery. Newborn umbilical cord and routine 48 hour heel stick blood will be collected to assess newborn PEth levels. By collecting newborn PEth levels at birth and 48 hours later we can assess the PEth kinetics to determine the optimum time to measure newborn PEth levels. By comparing newborn Peth levels with maternal self-reported alcohol use and alcohol biomarkers this innovative study will provide new information on the sensitivity and specificity of PEth as a newborn biomarker of prenatal alcohol exposure. The findings from this study could have enormous public health and policy implications, should PEth prove to be a highly sensitive and specific indicator of risky prenatal alcohol exposure. Analysis of PEth in dried blood spot cards would be the first assay to identify prenatal alcohol exposure in a universally available sample of newborn blood. Future work may also help us correlate newborn PEth levels with long-term behavioral, learning and developmental deficits in children and assist in early diagnosis of children with FASD.