ABSTRACT
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.
Subject(s)
Esters/metabolism , Ethanol/toxicity , Fatty Acids/metabolism , Maternal Exposure , Meconium/metabolism , Animals , Area Under Curve , Disease Models, Animal , Female , Fetal Alcohol Spectrum Disorders/metabolism , Oleic Acids/chemistry , Pregnancy , Pregnancy, Animal , Sheep , Sheep, DomesticABSTRACT
OBJECTIVE: To test the sensitivity and specificity of fatty acid ethyl esters (FAEEs) extracted from meconium to identify alcohol-using pregnant women with a sensitive and specific methodology, gas chromatography-tandem mass spectroscopy (GC/MS/MS). Study design Twenty-seven samples of meconium were obtained from infants from the mixed race community in Cape Town, South Africa, who were enrolled in a longitudinal neurobehavioral study. Maternal alcohol use was reported prospectively during pregnancy. FAEEs were isolated from meconium and quantitated by GC/MS/MS. RESULTS: Ethyl oleate was the FAEE that correlated most strongly with maternal self-reported drinking, especially with the average ounces of absolute alcohol ingested per drinking day. Ethyl oleate was most strongly related to drinking in the second and third trimesters (Pearson r=.55 and.40, respectively). At a threshold of 1.5 average ounces of absolute alcohol ingested per drinking day, the area under the receiving operator characteristic curve was.92 (95% confidence interval, 0.74-0.97). Using a cut-off value of 32 ng/g, sensitivity was 84.2% and specificity was 83.3%. CONCLUSIONS: Ethyl oleate concentration in meconium assayed by GC/MS/MS provides a highly sensitive and specific indicator of maternal alcohol use during pregnancy.
