Newborn Phosphatidylethanol Screening to Detect Fetal Alcohol Exposure in Uruguay

 描述（由申请人提供）：产前酒精暴露是美国出生缺陷的主要可预防原因，产生一系列神经，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，他们可能从早期神经可塑性中受益，并减少长期不良影响。 我们研究计划的长期目标是提供科学支持产前酒精暴露的常规新生儿筛查。这项国际U01赠款提案的主要目的是研究母亲饮酒与新生儿磷脂酰乙醇（PEth）水平之间的关联，在一个国家（乌拉圭），怀孕期间大量饮酒是常见的。我们之前在乌拉圭蒙得维的亚的公共卫生保健医院的工作记录了怀孕期间饮酒的高比率（60%）和新生儿的PEth水平（79%）。PEth是一种新的生物标志物，可以检测过去30天内的间歇性大量饮酒（3杯或更多）。该测试在检测最近的酒精使用方面具有100%的特异性，没有已知的假阳性。 这项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。将招募在乌拉圭蒙得维的亚两家选定的公共卫生保健医院之一接受产科护理的妇女参加本研究。将使用Phil May和Wilsnack博士开发的经验证的措施评估产妇饮酒情况。在美国和其他国家，访谈时间表已成为评估母亲饮酒和胎儿酒精暴露的标准措施。母体酒精生物标志物测定将包括分娩时获得的头发和指甲中的乙基葡糖苷酸（EtG）和血液中的PEth。将采集新生儿脐带血和常规48小时足跟采血，以评估新生儿PEth水平。通过收集出生时和48小时后的新生儿PEth水平，我们可以评估PEth动力学，以确定测量新生儿PEth水平的最佳时间。通过将新生儿Peth水平与母亲自我报告的酒精使用和酒精生物标志物进行比较，这项创新研究将提供关于Peth作为产前酒精暴露的新生儿生物标志物的灵敏度和特异性的新信息。 这项研究的结果可能具有巨大的公共卫生和政策意义，如果PEth被证明是产前酒精暴露风险的高度敏感和具体指标。分析干血斑卡中的PEth将是第一个在普遍可用的新生儿血液样本中识别产前酒精暴露的检测方法。未来的工作还可能帮助我们将新生儿PEth水平与儿童的长期行为，学习和发育缺陷相关联，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.