Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Study Population
2.2. EtG, EtS Determination and Substance Use
3. Discussion
4. Materials and Methods
4.1. Collection of Clinical Data and Biological Samples
4.2. Processing and Analysis of Meconium Samples
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
EtG | ethyl glucuronide |
EtS | ethyl sulfate |
FAEE | fatty acid ethyl ester |
FAS | Fetal Alcohol Syndrome |
FASD | Fetal Alcohol Spectrum Disorder |
IQR | interquartile range |
LC-MS/MS | liquid chromatography—tandem mass spectrometry |
NA | not available |
TPAL | number of term births [T]/number of preterm births [P]/number of abortions [A]/number of living children [L] |
References
- Chaudhuri, J.D. Alcohol and the developing fetus—A review. Med. Sci. Monit. 2000, 6, 1031–1041. [Google Scholar] [PubMed]
- Martínez-Frías, M.L.; Bermejo, E. Frequency and trends of congenital defects in Spain: Usefulness and significance of different frequencies. Med. Clin. 1999, 113, 459–562. [Google Scholar]
- Jones, K.L.; Smith, D.W.; Ulleland, C.N.; Streissguth, P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1973, 1, 1267–1271. [Google Scholar] [CrossRef]
- Bertrand, J.; Floyd, R.L.; Weber, M.K.; O’Connor, M.; Riley, E.P.; Johnson, K.A.; Cohen, D.E. National Task force on FAS/FAE. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Atlanta: Centers for Disease Control and Prevention, 2004. Available online: http://www.cdc.gov/ncbddd/fasd/documents/fas_guidelines_accessible.pdf (accessed on 18 September 2015).
- Goh, Y.I.; Chudley, A.E.; Clarren, S.K.; Koren, G.; Orrbine, E.; Rosales, T.; Rosenbaum, C. Taskforce for development of FASD screening tools. Development of Canadian screening tools for fetal alcohol spectrum disorder. Can. J. Clin. Pharmacol. 2008, 15, e344–e366. [Google Scholar] [PubMed]
- Centers for Disease Control and Prevention-CDC. Fetal Alcohol Spectrum Disorders (FASD), 2013. Available online: http://www.cdc.gov/ncbddd/fasd/index.html (accessed on 18 September 2015).
- Sampson, P.D.; Streissguth, A.P.; Bookstein, F.L.; Little, R.E.; Clarren, S.K.; Dehaene, P.; Hanson, J.W.; Graham, J.M., Jr. Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology 1997, 56, 317–326. [Google Scholar] [CrossRef]
- Government Delgation for the National Plan on Drugs. Spanish DRug Observatory (OED). Informe 2011. Situación y tendencias de los problemas de drogas en España. Madrid; 2011. Available online: http://www.pnsd.msc.es/Categoria2/observa/pdf/oed2011.pdf (accessed on 18 September 2015).
- National Institute on Health. National Institute on Alcohol Abuse and Alcoholism: A Women’s Health Issue. Bethesda, MD; 2005. Available online: http://pubs.niaaa.nih.gov/publications/brochurewomen/women.htm (accessed on 18 September 2015).
- Floyd, R.L.; Sidhu, J.S. Monitoring prenatal alcohol exposure. Am. J. Med. Genet. C Semin. Med. Genet. 2004, 127C, 3–9. [Google Scholar] [CrossRef] [PubMed]
- Wurst, F.M.; Kelso, E.; Weinmann, W.; Pragst, F.; Yegles, M.; Sundstrom Poromaa, I. Measurement of direct ethanol metabolites suggests higher rate of alcohol use among pregnant women than found with the AUDIT—A pilot study in a population-based sample of Swedish women. Am. J. Obstet. Gynecol. 2008, 198, 407.e1–407.e5. [Google Scholar] [CrossRef] [PubMed]
- Morini, L.; Groppi, A.; Marchei, E.; Vagnarelli, F.; Garcia Algar, O.; Zuccaro, P.; Pichini, S. Population baseline of meconium ethyl glucuronide and ethyl sulfate concentrations in newborns of nondrinking women in 2 Mediterranean cohorts. Ther. Drug Monit. 2010, 32, 359–363. [Google Scholar] [CrossRef] [PubMed]
- Gareri, J.; Lynn, H.; Handley, M.; Rao, C.; Koren, G. Prevalence of fetal ethanol exposure in a regional population-based sample by meconium analysis of fatty acid ethyl esters. Ther. Drug Monit. 2008, 30, 239–245. [Google Scholar] [CrossRef] [PubMed]
- Soderberg, B.L.; Salem, R.O.; Best, C.A.; Cluette-Brown, J.E.; Laposata, M. Fatty acid ethyl esters. Ethanol metabolites that reflect ethanol intake. Am. J. Clin. Pathol. 2003, 119, S94–S99. [Google Scholar] [CrossRef] [PubMed]
- Crews, B.; Latyshev, S.; Mikel, C.; Almazan, P.; West, R.; Pesce, A.; West, C. Improved detection of ethyl glucuronide and ethyl sulfate in a pain management population using high-throughput LC-MS/MS. J. Opioid. Manag. 2010, 6, 415–421. [Google Scholar] [CrossRef] [PubMed]
- Crews, B.; West, R.; Gutierrez, R.; Latyshev, S.; Mikel, C.; Almazan, P.; Pesce, A.; West, C.; Rosenthal, M. An improved method of determining ethanol use in a chronic pain population. J. Opioid. Manag. 2011, 7, 27–34. [Google Scholar] [CrossRef] [PubMed]
- Wurst, F.M.; Metzger, J. WHO/ISBRA study on state and trait markers of alcohol use and dependence investigators. The ethanol conjugate ethyl glucuronide is a useful marker of recent alcohol consumption. Alcohol. Clin. Exp. Res. 2002, 26, 1114–1119. [Google Scholar] [CrossRef] [PubMed]
- Wurst, F.M.; Skipper, G.E.; Weinmann, W. Ethyl glucuronide—The direct ethanol metabolite on the threshold from science to routine use. Addiction 2003, 98, 51–61. [Google Scholar] [CrossRef] [PubMed]
- Pichini, S.; Morini, L.; Marchei, E.; Palmi, I.; Rotolo, M.C.; Vagnarelli, F.; Garcia-Algar, O.; Vall, O.; Zuccaro, P. Ethylglucuronide and ethylsulfate in meconium to assess gestational ethanol exposure: Preliminary results in two Mediterranean cohorts. Can. J. Clin. Pharmacol. 2009, 16, e370–e375. [Google Scholar] [PubMed]
- Bearer, C.F.; Jacobson, J.L.; Jacobson, S.W.; Barr, D.; Croxford, J.; Molteno, C.D.; Viljoen, D.L.; Marais, A.S.; Chiodo, L.M.; Cwik, A.S. Validation of a new biomarker of fetal exposure to alcohol. J. Pediatr. 2003, 143, 463–469. [Google Scholar] [CrossRef]
- Pichini, S.; Pacifici, R.; Pellegrini, M.; Marchei, E.; Lozano, J.; Murillo, J.; Vall, O.; García-Algar, O. Development and validation of a high-performance liquid chromatography-mass spectrometry assay for determination of amphetamine, methamphetamine, and methylenedioxy derivatives in meconium. Anal. Chem. 2004, 76, 2124–2132. [Google Scholar] [CrossRef] [PubMed]
- Chan, D.; Bar-Oz, B.; Pellerin, B.; Paciorek, C.; Klein, J.; Kapur, B.; Farine, D.; Koren, G. Population baseline of meconium fatty acid ethyl esters among infants of nondrinking women in Jerusalem and Toronto. Ther. Drug Monit. 2003, 25, 271–278. [Google Scholar] [CrossRef] [PubMed]
- Himes, S.K.; Concheiro, M.; Scheidweiler, K.B.; Huestis, M.A. Validation of a novel method to identify in utero ethanol exposure: Simultaneous meconium extraction of fatty acid ethyl esters, ethyl glucuronide, and ethyl sulfate followed by LC-MS/MS quantification. Anal. Bioanal. Chem. 2014, 406, 1945–1955. [Google Scholar] [CrossRef] [PubMed]
- Morini, L.; Marchei, E.; Vagnarelli, F.; Garcia Algar, O.; Groppi, A.; Mastrobattista, L.; Pichini, S. Ethyl glucuronide and ethyl sulfate in meconium and hair-potential biomarkers of intrauterine exposure to ethanol. Forensic Sci. Int. 2010, 196, 74–77. [Google Scholar] [CrossRef] [PubMed]
- Himes, S.K.; Dukes, K.A.; Tripp, T.; Petersen, J.M.; Raffo, C.; Burd, L.; Odendaal, H.; Elliott, A.J.; Hereld, D.; Signore, C.; et al. Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy. Clin. Chem. 2015, 61, 523–532. [Google Scholar] [CrossRef] [PubMed]
- Lande, R.G.; Marin, B. A comparison of two alcohol biomarkers in clinical practice: Ethyl glucuronide versus ethyl sulfate. J. Addict. Dis. 2013, 32, 288–292. [Google Scholar] [CrossRef] [PubMed]
- Joya, X.; Friguls, B.; Ortigosa, S.; Papaseit, E.; Martínez, S.E.; Manich, A.; Garcia-Algar, O.; Pacifici, R.; Vall, O.; Pichini, S. Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: A review. J. Pharm. Biomed. Anal. 2012, 69, 209–222. [Google Scholar] [CrossRef] [PubMed]
- 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, 725–732. [Google Scholar] [CrossRef] [PubMed]
- Bakdash, A.; Burger, P.; Goecke, T.W.; Fasching, P.A.; Reulbach, U.; Bleich, S.; Hastedt, M.; Rothe, M.; Beckmann, M.W.; Pragst, F.; et al. Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study. Anal. Bioanal. Chem. 2010, 396, 2469–2477. [Google Scholar] [CrossRef] [PubMed]
- Tarcomnicu, I.; van Nuijs, A.L.; Aerts, K.; de Doncker, M.; Covaci, A.; Neels, H. Ethyl glucuronide determination in meconium and hair by hydrophilic interaction liquid chromatography-tandem mass spectrometry. Forensic Sci. Int. 2010, 196, 121–127. [Google Scholar] [CrossRef] [PubMed]
- Ostrea, E.M.; Hernandez, J.D.; Bielawski, D.M.; Kan, J.M.; Leonardo, G.M.; Abela, M.B.; Church, M.W.; Hannigan, J.H.; Janisse, J.J.; Ager, J.W.; et al. Fatty acid ethyl esters in meconium: Are they biomarkers of fetal alcohol exposure and effect? Alcohol. Clin. Exp. Res. 2006, 30, 1152–1159. [Google Scholar] [CrossRef] [PubMed]
- Bearer, C.F.; Santiago, L.M.; O’Riordan, M.A.; Buck, K.; Lee, S.C.; Singer, L.T. Fatty Acid ethyl esters: Quantitative biomarkers for maternal alcohol consumption. J. Pediatr. 2005, 146, 824–830. [Google Scholar] [CrossRef] [PubMed]
- Martínez-Frías, M.L.; Rodríguez-Pinilla, E.; Bermejo, E. Tobacco smoking during pregnancy in Spain: An analysis according to years, autonomous communities and maternal characteristics. Med. Clin. 2005, 124, 86–92. [Google Scholar]
- Paul, L.A.; Grubaugh, A.L.; Frueh, B.C.; Ellis, C.; Egede, L.E. Associations between binge and heavy drinking and health behaviors in a nationally representative sample. Addict. Behav. 2011, 36, 1240–1245. [Google Scholar] [CrossRef] [PubMed]
- Ryu, S.Y.; Crespi, C.M.; Maxwell, A.E. Drinking patterns among korean adults: Results of the 2009 korean community health survey. J. Prev. Med. Public Health 2013, 46, 183–191. [Google Scholar] [CrossRef] [PubMed]
- Murphy, D.J.; Dunney, C.; Mullally, A.; Adnan, N.; Deane, R. Population-based study of smoking behaviour throughout pregnancy and adverse perinatal outcomes. Int. J. Environ. Res. Public Health 2013, 10, 3855–3867. [Google Scholar] [CrossRef] [PubMed]
- Anderson, A.; Hure, A.; Forder, P.; Powers, J.; Kay-Lambkin, F.; Loxton, D. Predictors of antenatal alcohol use among Australian women: A prospective cohort study. BJOG 2013, 120, 1366–1374. [Google Scholar] [CrossRef] [PubMed]
- Ostrea, E.M., Jr.; Knapp, D.K.; Tannenbaum, L.; Ostrea, A.R.; Romero, A.; Salari, V.; Ager, J. Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J. Pediatr. 2001, 138, 344–348. [Google Scholar] [CrossRef] [PubMed]
- Pichini, S.; Puig, C.; Zuccaro, P.; Marchei, E.; Pellegrini, M.; Murillo, J.; Vall, O.; Pacifici, R.; García-Algar, O. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: Preliminary results of the “Meconium Project”. Forensic Sci. Int. 2005, 153, 59–65. [Google Scholar] [CrossRef] [PubMed]
- Friguls, B.; Joya, X.; Garcia-Serra, J.; Gomez-Culebras, M.; Pichini, S.; Martinez, S.; Vall, O.; Garcia-Algar, O. Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island. Addiction 2012, 107, 1471–1479. [Google Scholar] [CrossRef] [PubMed]
- Lange, S.; Shield, K.; Koren, G.; Rehm, J.; Popova, S. A comparison of the prevalence of prenatal alcohol exposure obtained via maternal self-reports versus meconium testing: A systematic literature review and meta-analysis. BMC Pregnancy Childbirth 2014, 14. [Google Scholar] [CrossRef] [PubMed]
- Cheng, D.; Kettinger, L.; Uduhiri, K.; Hurt, L. Alcohol consumption during pregnancy: Prevalence and provider assessment. Obstet. Gynecol. 2011, 117, 212–217. [Google Scholar] [CrossRef] [PubMed]
- Pichini, S.; Marchei, E.; Vagnarelli, F.; Tarani, L.; Raimondi, F.; Maffucci, R.; Sacher, B.; Bisceglia, M.; Rapisardi, G.; Elicio, M.R.; et al. Assessment of prenatal exposure to ethanol by meconium analysis: Results of an Italian multicenter study. Alcohol. Clin. Exp. Res. 2012, 36, 417–424. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Algar, O.; Kulaga, V.; Gareri, J.; Koren, G.; Vall, O.; Zuccaro, P.; Pacifici, R.; Pichini, S. Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther. Drug Monit. 2008, 30, 249–254. [Google Scholar] [CrossRef] [PubMed]
- Departament de Salut de la Generalitat de Catalunya. Protocol de Seguiment de L’embaràs a Catalunya. Barcelona, 2005. Available online: http://www20.gencat.cat/docs/canalsalut/Home Canal Salut/Professionals/Recursos/Protocols_i_recomanacions/17_salut_de_la_mare_i_de_linfant/documents/protocolseguimentembaras.pdf (accessed on 18 September 2015).
Clinical Information of Parturient Women | Markers of Fetal Alcohol Exposure | |||
---|---|---|---|---|
Substance | Structured Questionnaire n (%) | Structured Questionnaire and Chart Review n (%) | EtG n (%) | EtS n (%) |
Alcohol | 3 (6) | 3 (6) | 2 (4.2) | 8 (16.7) |
Tobacco | 7 (12) | 17 (33.3) | NA | NA |
Cannabis, Cocaine and/or Opiates | 2 (3.9) | 3 (6) | NA | NA |
Time (min) | Flow (mL/min) | Phase A: CH3CN 0.1%, Formic Acid % | Phase B: H2O 0.1%, Formic Acid % |
---|---|---|---|
0 | 0.3 | 8 | 92 |
1 | 0.3 | 8 | 92 |
4 | 0.4 | 0 | 100 |
6 | 0.4 | 0 | 100 |
6.5 | 0.3 | 8 | 92 |
8 | 0.3 | 8 | 92 |
Component | Internal Standard | Precursor | Fragment | Dwell Time (msec) | Fragmentor (Volts) | Collision Energy (ev) |
---|---|---|---|---|---|---|
EtG_d5 | IS | 226 | 85 | 250 | 100 | 15 |
EtG_d5 | IS | 226 | 75 | 250 | 100 | 15 |
EtG | ‒ | 221 | 85 | 250 | 100 | 15 |
EtG | ‒ | 221 | 75 | 250 | 100 | 15 |
EtS_d5 | IS | 130 | 98 | 250 | 100 | 15 |
EtS_d5 | IS | 130 | 80 | 250 | 100 | 15 |
EtS | ‒ | 125 | 97 | 250 | 100 | 15 |
EtS | ‒ | 125 | 80 | 250 | 100 | 15 |
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sanvisens, A.; Robert, N.; Hernández, J.M.; Zuluaga, P.; Farré, M.; Coroleu, W.; Serra, M.; Tor, J.; Muga, R. Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium. Int. J. Mol. Sci. 2016, 17, 417. https://doi.org/10.3390/ijms17030417
Sanvisens A, Robert N, Hernández JM, Zuluaga P, Farré M, Coroleu W, Serra M, Tor J, Muga R. Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium. International Journal of Molecular Sciences. 2016; 17(3):417. https://doi.org/10.3390/ijms17030417
Chicago/Turabian StyleSanvisens, Arantza, Neus Robert, José María Hernández, Paola Zuluaga, Magí Farré, Wifredo Coroleu, Montserrat Serra, Jordi Tor, and Robert Muga. 2016. "Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium" International Journal of Molecular Sciences 17, no. 3: 417. https://doi.org/10.3390/ijms17030417