Littner Yoav, Cudd Timothy A, O'Riordan Mary A, Cwik Andrew, Bearer Cynthia F
Department of Pediatrics, Case Western Reserve University and Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA.
Pediatr Res. 2008 Feb;63(2):164-8. doi: 10.1203/PDR.0b013e31815f651e.
Specific fatty acid ethyl esters (FAEE) in meconium of newborns have been shown to correlate with maternal ethanol exposure. An animal model is needed to assess the validity of this biomarker. We hypothesized that the pregnant/fetal sheep is a feasible animal model for validating FAEE as a biomarker of prenatal ethanol exposure. Nine pregnant ewes were treated during the third trimester with different i.v. ethanol doses. The control group consisted of 14 pregnant ewes exposed to similar volumes of saline. On gestational d 133, the fetuses were delivered and meconium samples removed. FAEEs were quantified by gas chromatography-flame ionization detection. FAEEs were found in both control and ethanol exposed fetuses. Ethyl oleate, ethyl linoleate, and ethyl arachidonate levels were significantly higher in the ethanol-exposed sheep. Ethyl oleate was the FAEE that correlated most strongly with alcohol ingestion during pregnancy and had the greatest area under the curve (0.94). Using a cut-off value of 131 ng/g ethyl oleate dry weight, sensitivity was 89% and specificity was 100%. In conclusion, pregnant ewes are a feasible model for validating biomarkers of prenatal ethanol exposure. Ethyl oleate, ethyl linoleate, and ethyl arachidonate may be useful biomarkers of prenatal alcohol exposure.
新生儿胎粪中的特定脂肪酸乙酯(FAEE)已被证明与母体乙醇暴露有关。需要一种动物模型来评估这种生物标志物的有效性。我们假设妊娠/胎儿绵羊是验证FAEE作为产前乙醇暴露生物标志物的可行动物模型。9只妊娠母羊在妊娠晚期接受不同静脉注射乙醇剂量治疗。对照组由14只暴露于相似体积生理盐水的妊娠母羊组成。在妊娠第133天,取出胎儿并采集胎粪样本。通过气相色谱-火焰离子化检测对FAEE进行定量。在对照组和乙醇暴露组的胎儿中均发现了FAEE。乙醇暴露组绵羊的油酸乙酯、亚油酸乙酯和花生四烯酸乙酯水平显著更高。油酸乙酯是与孕期酒精摄入量相关性最强且曲线下面积最大(0.94)的FAEE。使用131 ng/g油酸乙酯干重的临界值,敏感性为89%,特异性为100%。总之,妊娠母羊是验证产前乙醇暴露生物标志物的可行模型。油酸乙酯、亚油酸乙酯和花生四烯酸乙酯可能是产前酒精暴露的有用生物标志物。