ETHYLGLUCURONIDE AND ETHYLSULFATE IN MECONIUM TO ASSESS GESTATIONAL ETHANOL EXPOSURE: PRELIMINARY RESULTS IN TWO MEDITERRANEAN COHORTS
Main Article Content
Keywords
Meconium, ethylglucuronide, ethylsulfate, FAEEs, gestational ethanol consumption
Abstract
Background
In recent years, fatty acid ethyl esters (FAEEs) in meconium emerged as reliable, direct biological markers for establishing gestational ethanol exposure. Among the minor nonoxidative products of ethanol metabolism, there are ethyl glucuronide (EtG) and ethyl sulfate (EtS).
Objectives
The aim of the study was to analyse meconium specimens from two different Mediterranean cohorts to check for the presence of EtG and EtS, and to investigate the eventual correlation between meconium FAEEs and these two metabolites and their possible application as direct biomarkers of gestational ethanol exposure.
Methods
FAEEs, EtG and EtS were quantified by liquid chromatography tandem mass spectrometry in meconium samples obtained from the Neonatal Intensive Care Unit of Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (N= 96) and from the Pediatric Service of the Hospital del Mar in Barcelona, Spain (N=81).
Results
EtG was present in more than 80% meconium samples while EtS only in 50% specimens Although the samples from Spain and Italy originated from similar socio-demographic cohort, EtG values in the Barcelona samples (median value: 101.5 ng/g) were statistically higher than those from Reggio Emilia ones (median value: 15.6 ng/g). In the Barcelona cohort, EtG values could differentiate between samples with FAEEs below and those equal or above 2 nmol/g - the cut-off used to differentiate heavy maternal ethanol consumption during pregnancy from occasional or no use.
Conclusion
For the first time the presence of EtG and EtS in meconium has been proven, with EtG concentration likely to discriminate heavy maternal ethanol consumption during pregnancy disclosed by FAEEs concentration in this matrix. Further investigations are needed to verify the use of these two ethanol metabolites as alternative biomarkers of chronic in utero exposure to ethanol.
References
2. Bearer CF, Jacobson JL, Jacobson SW, Barr D, Croxford J, Molteno CD, Viljoen D, Marais AS, Chiodo LM, Cwik AS. Validation of a new biomarker of fetal exposure to ethanol. J Pediatr. 2003; 143: 463-469.
3. Moore C, Jones J, Lewis D, Buchi K. Prevalence of fatty acid ethyl esters in meconium specimens. Clin. Chem 2003; 49: 133-136.
4. Ostrea EM, Hernandez JD, Bielawski DM, Kan JM, Leonardo GM, Abela MB, Church MW, Hannigan JH, Vanisse JJ, Ager JW, Sokol RJ. Fatty acid ethyl esters in meconium: are they biomarkers of fetal ethanol exposure and effect? Ethanol Clin. Exp. Res 2006; 30:1152-1159.
5. Pichini S, Pellegrini M, Gareri J, Koren J, García-Algar O, Vall O, Pacifici R, Zuccaro P, Marchei E. Alarming Prevalence of Fetal Ethanol Exposure in a Mediterranean City. Ther Drug Monit 2008; 30: 249-254.
6. Burd L, Roberts D, Olson M, et al. Ethanol and the placenta: a review. J Matern Fetal Neonatal Med 2007; 20: 361-375.
7. Politi L, Leone F, Morini L, Polettini A. Bioanalytical procedures for determination of conjugates or fatty acid esters of ethanol as markers of ethanol consumption: a review.Anal Biochem 2007; 368: 1-16.
8. Helander A, Beck O. Ethyl sulfate: a metabolite of ethanol in humans and potential biomarker of acute alcohol intake. J Anal Toxicol 2005; 29: 270-4.
9. Politi L, Morini L, Groppi A, Poloni V, Pozzi F, Polettini A. Direct determination of the ethanol metabolites ethyl glucuronide and ethyl sulfate in urine by liquid chromatography/electrospray tandem mass spectrometry. Rapid Commun Mass Spectrom 2005; 19:321-1331.
10. Schmitt G, Aderjan R, Keller T, Wu M. Ethyl glucuronide: an unusual ethanol metabolite in humans. Synthesis, analytical data and determination in serum and urine. J Anal Toxicol 1995; 19: 91-4.
11. Halter CC, Dresen S, Auwaerter V, Wurst FM, Weinmann W. Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake. Int J Legal Med 2008; 122: 123-8.
12. Høiseth G, Morini L, Polettini A, Christophersen A, Mørland J. Blood kinetics of ethyl glucuronide and ethyl sulphate in heavy drinkers during alcohol detoxification, Forensic Sci Int 2009, (Article in press).
13. Dahl H, Stephanson N, Beck O, Helander A. Comparison of urinary excretion characteristics of etanol and ethyl glucuronide. J Anal Toxicol 2002; 26: 201-4.
14. Helander A, Beck O. Mass spectrometric identification of ethyl sulfate as an ethanol metabolite in humans. Clin Chem 2004; 50: 936- 7.
15. Politi L, Morini L, Leone F, Polettini A. Ethyl glucuronide in hair: Is it a reliable marker of chronic high levels of ethanol consumption? Addiction 2006; 101: 1408–1412.
16. Pichini S, Altieri I, Zuccaro P, Pacifici R. Meconium as a matrix. Clin Pharmacokinet 1996; 31: 81.
17. Bar-Oz B, Klein J, Karaskov T, Koren G. Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse. Arch Dis Child Fetal Neonatal Ed (2003); 88:F98-F100.
18. Morini L, Marchei E, Pellegrini M, Groppi A, Stramesi C, Vagnarelli F, Garcia-Algar O, Pacifici R, Pichini S. Liquid chromatography with tandem mass spectrometric detection for the measurement of ethyl glucuronide and ethyl sulfate in meconium: new biomarkers of gestational ethanol exposure? Ther Drug Monit 2008; 30:725-32.
19. http://www.pnsd.msc.es/Categoria2/publica/pdf/ oed-2004.pdf (Accessed April 2009).
20. http://www.istat.it/salastampa/comunicati/non_c alendario/20080417_00/testointegrale20080417. pdf (Accessed April 2009).
21. Pichini S, Pellegrini M, Gareri J, Koren J, Garcia-Algar O, Vall O, Vagnarelli F, Zuccaro P, Marchei E. Liquid chromatography-tandem mass spectrometry for fatty acid ethyl esters in meconium: a assessment of prenatal exposure to alcohol in two European cohorts. J Pharm Biomed Anal 2008; 48: 927-933.
22. Chan D, Klein J, Karaskov T, Koren G. Fetal exposure to alcohol as evidenced by fatty acid ethyl esters in meconium in the absence of maternal drinking history in pregnancy. Ther Drug Monit.2004; 26:474-481.
23. Pragst F, Yegles M. Determination of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in hair: a promising way for retrospective detection of ethanol abuse during pregnancy? Ther Drug Monit 2008; 30: 255-263.
24. Cook JD. Biochemical markers of ethanol use in pregnant women: review. Clin Biochem 2003; 36: 9-19.
25. Rosano TG, Lin J. Ethyl glucuronide excretion in humans following oral administration of and dermal exposure to ethanol. J Anal Toxicol 2008; 32: 594-600.