Gareri Joey, Lynn Hazel, Handley Maureen, Rao Chitra, Koren Gideon
Motherisk Program, Hospital for Sick Children, Toronto, Ontario, Canada.
Ther Drug Monit. 2008 Apr;30(2):239-45. doi: 10.1097/FTD.0b013e318167cfe5.
Challenges in identifying children exposed prenatally to ethanol necessitate the development of a biomarker for neonates at risk for fetal alcohol spectrum disorder. Meconium fatty acid ethyl esters (FAEE), products of nonoxidative ethanol metabolism, have been established as a novel biomarker of fetal ethanol exposure. We present the first application of this biomarker to a population-based sample in Canada. Six-hundred eighty-two meconium specimens were anonymously collected in the region of Grey Bruce, Ontario, Canada. Meconium FAEE were extracted by liquid-liquid and solid-phase extraction and analyzed by gas chromatography with flame-ionization detection confirmed by gas chromatography with mass spectrometry. We measured ethyl palmitate (E16:0), ethyl palmitoleate (E16:1), ethyl stearate (E18:0), ethyl oleate (E18:1), ethyl linoleate (E18:2), ethyl linolenate (E18:3), and ethyl arachidonate (E20:4). Seventeen of 682 meconium samples tested positive for significant prenatal ethanol exposure (>2.0 nmol/g). FAEE analysis detected fivefold more ethanol-exposed pregnancies than standard postpartum questionnaires in this population (2.5% versus 0.5%) (P < 0.001). The prevalence of ethanol-exposed pregnancies was consistent with Centers for Disease Control and Prevention estimates of "frequent" prenatal drinking and previously published estimates of fetal alcohol spectrum disorder disease prevalence in the general North American population. The FAEE concentrations of negative (95% confidence interval, 0.38-0.49 nmol/g) versus positive (95% confidence interval, 7.74-151.28 nmol/g) samples were distinct, further demonstrating the specificity of this biomarker in determining significant prenatal ethanol exposure. Meconium FAEE analysis demonstrates a fivefold increase in sensitivity over currently used methods of self-report-based screening in Ontario for the detection of ethanol-exposed pregnancies in a clinical setting.
识别产前暴露于乙醇的儿童面临诸多挑战，因此有必要开发一种用于筛查有胎儿酒精谱系障碍风险的新生儿的生物标志物。胎粪脂肪酸乙酯（FAEE）是乙醇非氧化代谢的产物，已被确立为胎儿乙醇暴露的一种新型生物标志物。我们首次将这种生物标志物应用于加拿大一个基于人群的样本。在加拿大安大略省格雷布鲁斯地区匿名收集了682份胎粪样本。通过液-液萃取和固相萃取法提取胎粪中的FAEE，并采用火焰离子化检测气相色谱法进行分析，同时通过质谱气相色谱法进行确认。我们测定了棕榈酸乙酯（E16:0）、棕榈油酸乙酯（E16:1）、硬脂酸乙酯（E18:0）、油酸乙酯（E18:1）、亚油酸乙酯（E18:2）、亚麻酸乙酯（E18:3）和花生四烯酸乙酯（E20:4）。在682份胎粪样本中，有17份检测出产前乙醇暴露显著阳性（>2.0 nmol/g）。在该人群中，FAEE分析检测出的乙醇暴露妊娠数比标准产后问卷调查多五倍（2.5%对0.5%）（P<0.001）。乙醇暴露妊娠的患病率与美国疾病控制与预防中心对“频繁”产前饮酒的估计以及此前公布的北美普通人群胎儿酒精谱系障碍疾病患病率估计一致。阴性样本（95%置信区间，0.38 - 0.49 nmol/g）与阳性样本（95%置信区间，7.74 - 151.28 nmol/g）的FAEE浓度明显不同，这进一步证明了该生物标志物在确定产前乙醇暴露显著情况时的特异性。胎粪FAEE分析表明，在临床环境中，其检测乙醇暴露妊娠的灵敏度比安大略省目前基于自我报告的筛查方法高出五倍。
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