FATTY ACID ETHYL ESTERS IN SHEEP MECONIUM

怀孕期间大量饮酒是导致胎儿酒精综合症的原因，这是已知的导致智力迟钝的主要原因。即使在怀孕期间适度饮酒也会导致一系列更微妙的影响，这些影响取决于乙醇的剂量和暴露时的胎龄。据估计，1%的新生儿受到产前乙醇暴露的影响。识别这些酒精暴露的新生儿是困难的。目前还没有实验室工具来识别它们。怀孕期间低至中度饮酒（每周1-14杯）的生物标志物将是重大的进步。初步研究表明，胎粪中的脂肪酸乙酯（乙醇的长寿命非氧化代谢物）可能起到这一作用。该提案旨在通过实现以下三个具体目标来解决胎粪中的脂肪酸乙酯是妊娠期间暴露于低至中度母体乙醇使用的有用生物标志物的假设：1）确定分母以标准化受试者之间的脂肪酸乙酯的量。2)测定体内脂肪酸乙酯的半数。3)使用3个变量，即胎粪内的位置、数量和脂肪酸部分，可以确定暴露时的数量和胎龄。这些研究将使用酒精相关神经发育障碍的绵羊模型。这些研究将为研究该生物标志物在人群中的效用提供初步数据。

Heavy drinking during pregnancy is the cause of fetal alcohol syndrome, the leading known cause of mental retardation. Even moderate drinking during pregnancy can result in a spectrum of more subtle effects which are determined by both the dose of ethanol and the gestational age at the time of exposure. It is estimated that 1% of all newborns are affected by prenatal ethanol exposure. Identifying these alcohol exposed newborns is difficult. Currently there is no laboratory tool for their identification. A biological marker for low to moderate alcohol use (1-14 drinks/week) during pregnancy would be significant step forward. Preliminary research has shown that fatty acid ethyl esters, long lived non-oxidative metabolites of ethanol, in meconium may serve such a purpose. This proposal seeks to address the hypothesis that fatty acid ethyl esters in meconium are useful biological markers for exposure to low to moderate maternal ethanol use during pregnancy, by achieving the following three specific aims: 1) Determine a denominator to normalize the quantify of fatty acid ethyl esters between subjects. 2) Determining the half of fatty acid ethyl esters in vivo. 3) Using 3 variables, location within the meconium, the quantity and the fatty acid moiety, the quantity and gestational age at exposure can be determined. These studies will use a sheep model of alcohol related neurodevelopmental disorder. These studies will provide preliminary data to study the utility of this biomarker in a human population.