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.
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Abbreviations
- AUC:
-
area under the curve
- FAEE:
-
fatty acid ethyl esters
- GD:
-
gestational day
- ROC:
-
receiver operating characteristic
References
Abel EL, Sokol RJ 1991 A revised conservative estimate of the incidence of FAS and its economic impact. Alcohol Clin Exp Res 15: 514–524
Sampson PD, Streissguth AP, Bookstein FL, Little RE, Clarren SK, Dehaene P, Hanson JW, Graham JM 1997 Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology 56: 317–326
Little BB, Snell LM, Rosenfeld CR, Gilstrap LC 3rd, Gant NF 1990 Failure to recognize fetal alcohol syndrome in newborn infants. Am J Dis Child 144: 1142–1146
Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O'Malley K, Young JK 2004 Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr 25: 228–238
Russell M, Martier SS, Sokol RJ, Mudar P, Jacobson S, Jacobson J 1996 Detecting risk drinking during pregnancy: a comparison of four screening questionnaires. Am J Public Health 86: 1435–1439
Stoler JM, Huntington KS, Peterson CM, Peterson KP, Daniel P, Aboagye KK, Lieberman E, Ryan L, Holmes LB 1998 The prenatal detection of significant alcohol exposure with maternal blood markers. J Pediatr 133: 346–352
Walsh RA, Redman S, Adamson L 1996 The accuracy of self-report of smoking status in pregnant women. Addict Behav 21: 675–679
Bearer CF, Gould S, Emerson R, Kinnunen P, Cook CS 1992 Fetal alcohol syndrome and fatty acid ethyl esters. Pediatr Res 31: 492–495
Soderberg BL, Sicinska ET, Blodget E, Cluette-Brown JE, Suter PM, Schuppisser T, Vetter W, Laposata M 1999 Preanalytical variables affecting the quantification of fatty acid ethyl esters in plasma and serum samples. Clin Chem 45: 2183–2190
Caprara DL, Brien JF, Iqbal U, Reynolds JN, Klein J, Koren G 2005 A guinea pig model for the identification of in utero alcohol exposure using fatty acid ethyl esters in neonatal hair. Pediatr Res 58: 1158–1163
Bearer CF, Lee S, Salvator AE, Minnes S, Swick A, Yamashita T, Singer LT 1999 Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure. Alcohol Clin Exp Res 23: 487–493
Bearer CF, Jacobson JL, Jacobson SW, Barr D, Croxford J, Molteno CD, Viljoen DL, Marais AS, Chiodo LM, Cwik AS 2003 Validation of a new biomarker of fetal exposure to alcohol. J Pediatr 143: 463–469
Bearer CF, Santiago LM, O'Riordan MA, Buck K, Lee SC, Singer LT 2005 Fatty acid ethyl esters: quantitative biomarkers for maternal alcohol consumption. J Pediatr 146: 824–830
Moore C, Jones J, Lewis D, Buchi K 2003 Prevalence of fatty acid ethyl esters in meconium specimens. Clin Chem 49: 133–136
Ostrea EM, Hernandez JD, Bielawski DM, Kan JM, Leonardo GM, Abela MB, Church MW, Hannigan JH, Janisse JJ, Ager JW, Sokol RJ 2006 Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?. Alcohol Clin Exp Res 30: 1152–1159
Cudd TA 2005 Animal model systems for the study of alcohol teratology. Exp Biol Med (Maywood) 230: 389–393
Dobbing J, Sands J 1979 Comparative aspects of the brain growth spurt. Early Hum Dev 3: 79–83
Bearer CF 1999 Detection of Teratogen Exposure. U.S. Patent Documents. Case Western Reserve University, Cleveland, OH
Abel EL 1996 Fetal Alcohol Syndrome: From Mechanism to Prevention. CRC Press, Inc, Boca Raton, FL
Klein J, Karaskov T, Koren G 1999 Fatty acid ethyl esters: a novel biologic marker for heavy in utero ethanol exposure: a case report. Ther Drug Monit 21: 644–646
Moore CM, Lewis D 2001 Fatty acid ethyl esters in meconium: biomarkers for the detection of alcohol exposure in neonates. Clin Chim Acta 312: 235–237
Brien JF, Chan D, Green CR, Iqbal U, Gareri J, Kobus SM, McLaughlin BE, Klein J, Rao C, Reynolds JN, Bocking AD, Koren G 2006 Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal guinea pig. Ther Drug Monit 28: 345–350
Kulaga V, Caprara D, Iqbal U, Kapur B, Klein J, Reynolds J, Brien J, Koren G 2006 Fatty acid ethyl esters (FAEE); comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure. Alcohol Alcohol 41: 534–539
Stark KD, Beblo S, Murthy M, Whitty JE, Buda-Abela M, Janisse J, Rockett H, Martier SS, Sokol RJ, Hannigan JH, Salem NJ 2005 Alcohol consumption in pregnant, black women is associated with decreased plasma and erythrocyte docosahexaenoic acid. Alcohol Clin Exp Res 29: 130–140
Horrobin DF 1987 Essential fatty acids, prostaglandins, and alcoholism: an overview. Alcohol Clin Exp Res 11: 2–9
Valles SL, Blanco AM, Pascual M, Guerri C 2004 Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes. Brain Pathol 14: 365–371
Natsuki R, Yamaguchi T 1996 Effects of ethanol on phospholipases in the mouse brain, heart and liver. Biol Pharm Bull 19: 525–529
Refaai MA, Nguyen PN, Steffensen TS, Evans RJ, Cluette-Brown JE, Laposata M 2002 Liver and adipose tissue fatty acid ethyl esters obtained at autopsy are postmortem markers for premortem ethanol intake. Clin Chem 48: 77–83
Chan D, Bar-Oz B, Pellerin B, Paciorek C, Klein J, Kapur B, Farine D, Koren G 2003 Population baseline of meconium fatty acid ethyl esters among infants of nondrinking women in Jerusalem and Toronto. Ther Drug Monit 25: 271–278
Perez-Camino MC, Moreda W, Mateos R, Cert A 2002 Determination of esters of fatty acids with low molecular weight alcohols in olive oils. J Agric Food Chem 50: 4721–4725
Ostrovsky YM, Pronko PS, Shishkin SN, Kolesnikov VB, Volynets SI 1989 An attempt to evaluate diagnostic and prognostic significance of blood endogenous ethanol in alcoholics and their relatives. Alcohol 6: 97–102
Hendrickse W, Stammers JP, Hull D 1985 The transfer of free fatty acids across the human placenta. Br J Obstet Gynaecol 92: 945–952
Elphick MC, Hull D, Broughton PF 1979 The transfer of fatty acids across the sheep placenta. J Dev Physiol 1: 31–45
Jarvis GN, Moore ER, Thiele JH 1997 Formate and ethanol are the major products of glycerol fermentation produced by a Klebsiella planticola strain isolated from red deer. J Appl Microbiol 83: 164–174
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This research is supported by a grant from the National Institute on Alcohol and Alcohol Abuse, R03 AA12618 to CFB.
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Littner, Y., Cudd, T., O'Riordan, M. et al. Elevated Fatty Acid Ethyl Esters in Meconium of Sheep Fetuses Exposed In Utero to Ethanol—A New Animal Model. Pediatr Res 63, 164–168 (2008). https://doi.org/10.1203/PDR.0b013e31815f651e
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DOI: https://doi.org/10.1203/PDR.0b013e31815f651e
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