Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

Madeleine J  Swortwood; Sarah H Bartock; Karl B Scheidweiler; Sophie Shaw; Panagiotis Filis; Alex Douglas; Peter J O'Shaughnessy; Ugo Soffientini; Baltasar  Lucendo-Villarin; John P Iredale; David C Hay; Paul A Fowler; Marilyn A Huestis

doi:10.1007/s11419-017-0389-2

Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

Madeleine J Swortwood, Sarah H Bartock, Karl B Scheidweiler, Sophie Shaw, Panagiotis Filis, Alex Douglas, Peter J O'Shaughnessy, Ugo Soffientini, Baltasar Lucendo-Villarin, John P Iredale, David C Hay, Paul A Fowler , Marilyn A Huestis (Corresponding Author)

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Abstract

Purpose
Tobacco and alcohol use during pregnancy is serious public health concerns and result in adverse developmental outcomes. Identifying in utero exposure is often achieved through meconium analysis or via maternal self-report. In this study, we analyzed fetal liver and placenta to examine second trimester alcohol and smoking exposure.

Methods
A validated liquid chromatography–tandem mass spectrometry method for simultaneous analysis of nicotine and its metabolites and alcohol markers (ethyl glucuronide: EtG and ethyl sulfate: EtS) was employed to analyze 193 fetal liver and 48 placenta (n = 47 paired) samples from electively terminated pregnancies.

Results
EtG, EtS, and nicotine markers’ limits of detection were 0.7–20 ng/g in fetal samples. Ninety-eight fetal liver and 23 placenta samples were EtG/EtS-positive, while 137 liver and 25 placenta samples were positive for tobacco exposure. When both alcohol markers were present in samples, EtG/EtS ratios were 1.6–11.1 in 17 livers and 2.5–31.1 in 10 placentas. Median (range) summed tobacco marker concentrations were 422 (1.0–2776) and 154 (1.6–1621) ng/g in livers and placentas, respectively. Median EtG and nicotine marker concentrations were higher in liver than placenta in paired samples. Strong evidence of exposure occurred in 11 and 22 pairs, respectively, when both samples were positive for alcohol and/or tobacco markers.

Conclusions
These paired fetal liver and placenta alcohol and tobacco data provided a unique means for examining the effects of in utero exposure, a critical first step in selecting fetal samples for proteomic and RNA sequencing studies that could provide mechanisms for adverse developmental outcomes.

Original language	English
Pages (from-to)	102-112
Number of pages	11
Journal	Forensic Toxicology
Volume	36
Issue number	1
Early online date	7 Nov 2017
DOIs	https://doi.org/10.1007/s11419-017-0389-2
Publication status	Published - Jan 2018

Bibliographical note

This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org).
The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.

Keywords

ethyl glucuronide
nicotine
fetal liver
placenta
pregnancy
prenatal exposure

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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The final publication is available at link.springer.com via http://dx.doi.org/10.1007/s11419-017-0389-2
Accepted author manuscript, 242 KBLicence: Unspecified

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Cite this

Swortwood, M. J., Bartock, S. H., Scheidweiler, K. B., Shaw, S., Filis, P., Douglas, A., O'Shaughnessy, P. J., Soffientini, U., Lucendo-Villarin, B., Iredale, J. P., Hay, D. C., Fowler , P. A., & Huestis, M. A. (2018). Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta. Forensic Toxicology, 36(1), 102-112. https://doi.org/10.1007/s11419-017-0389-2

Swortwood, MJ, Bartock, SH, Scheidweiler, KB, Shaw, S, Filis, P, Douglas, A, O'Shaughnessy, PJ, Soffientini, U, Lucendo-Villarin, B, Iredale, JP, Hay, DC, Fowler , PA & Huestis, MA 2018, 'Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta', Forensic Toxicology, vol. 36, no. 1, pp. 102-112. https://doi.org/10.1007/s11419-017-0389-2

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title = "Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta",

abstract = "PurposeTobacco and alcohol use during pregnancy is serious public health concerns and result in adverse developmental outcomes. Identifying in utero exposure is often achieved through meconium analysis or via maternal self-report. In this study, we analyzed fetal liver and placenta to examine second trimester alcohol and smoking exposure.MethodsA validated liquid chromatography–tandem mass spectrometry method for simultaneous analysis of nicotine and its metabolites and alcohol markers (ethyl glucuronide: EtG and ethyl sulfate: EtS) was employed to analyze 193 fetal liver and 48 placenta (n = 47 paired) samples from electively terminated pregnancies.ResultsEtG, EtS, and nicotine markers{\textquoteright} limits of detection were 0.7–20 ng/g in fetal samples. Ninety-eight fetal liver and 23 placenta samples were EtG/EtS-positive, while 137 liver and 25 placenta samples were positive for tobacco exposure. When both alcohol markers were present in samples, EtG/EtS ratios were 1.6–11.1 in 17 livers and 2.5–31.1 in 10 placentas. Median (range) summed tobacco marker concentrations were 422 (1.0–2776) and 154 (1.6–1621) ng/g in livers and placentas, respectively. Median EtG and nicotine marker concentrations were higher in liver than placenta in paired samples. Strong evidence of exposure occurred in 11 and 22 pairs, respectively, when both samples were positive for alcohol and/or tobacco markers.ConclusionsThese paired fetal liver and placenta alcohol and tobacco data provided a unique means for examining the effects of in utero exposure, a critical first step in selecting fetal samples for proteomic and RNA sequencing studies that could provide mechanisms for adverse developmental outcomes.",

keywords = "ethyl glucuronide, nicotine, fetal liver, placenta, pregnancy, prenatal exposure",

author = "Swortwood, {Madeleine J} and Bartock, {Sarah H} and Scheidweiler, {Karl B} and Sophie Shaw and Panagiotis Filis and Alex Douglas and O'Shaughnessy, {Peter J} and Ugo Soffientini and Baltasar Lucendo-Villarin and Iredale, {John P} and Hay, {David C} and Fowler, {Paul A} and Huestis, {Marilyn A}",

note = "This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.",

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month = jan,

doi = "10.1007/s11419-017-0389-2",

language = "English",

volume = "36",

pages = "102--112",

journal = "Forensic Toxicology",

issn = "1860-8973",

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T1 - Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

AU - Swortwood, Madeleine J

AU - Bartock, Sarah H

AU - Scheidweiler, Karl B

AU - Shaw, Sophie

AU - Filis, Panagiotis

AU - Douglas, Alex

AU - O'Shaughnessy, Peter J

AU - Soffientini, Ugo

AU - Lucendo-Villarin, Baltasar

AU - Iredale, John P

AU - Hay, David C

AU - Fowler , Paul A

AU - Huestis, Marilyn A

N1 - This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.

PY - 2018/1

Y1 - 2018/1

N2 - PurposeTobacco and alcohol use during pregnancy is serious public health concerns and result in adverse developmental outcomes. Identifying in utero exposure is often achieved through meconium analysis or via maternal self-report. In this study, we analyzed fetal liver and placenta to examine second trimester alcohol and smoking exposure.MethodsA validated liquid chromatography–tandem mass spectrometry method for simultaneous analysis of nicotine and its metabolites and alcohol markers (ethyl glucuronide: EtG and ethyl sulfate: EtS) was employed to analyze 193 fetal liver and 48 placenta (n = 47 paired) samples from electively terminated pregnancies.ResultsEtG, EtS, and nicotine markers’ limits of detection were 0.7–20 ng/g in fetal samples. Ninety-eight fetal liver and 23 placenta samples were EtG/EtS-positive, while 137 liver and 25 placenta samples were positive for tobacco exposure. When both alcohol markers were present in samples, EtG/EtS ratios were 1.6–11.1 in 17 livers and 2.5–31.1 in 10 placentas. Median (range) summed tobacco marker concentrations were 422 (1.0–2776) and 154 (1.6–1621) ng/g in livers and placentas, respectively. Median EtG and nicotine marker concentrations were higher in liver than placenta in paired samples. Strong evidence of exposure occurred in 11 and 22 pairs, respectively, when both samples were positive for alcohol and/or tobacco markers.ConclusionsThese paired fetal liver and placenta alcohol and tobacco data provided a unique means for examining the effects of in utero exposure, a critical first step in selecting fetal samples for proteomic and RNA sequencing studies that could provide mechanisms for adverse developmental outcomes.

AB - PurposeTobacco and alcohol use during pregnancy is serious public health concerns and result in adverse developmental outcomes. Identifying in utero exposure is often achieved through meconium analysis or via maternal self-report. In this study, we analyzed fetal liver and placenta to examine second trimester alcohol and smoking exposure.MethodsA validated liquid chromatography–tandem mass spectrometry method for simultaneous analysis of nicotine and its metabolites and alcohol markers (ethyl glucuronide: EtG and ethyl sulfate: EtS) was employed to analyze 193 fetal liver and 48 placenta (n = 47 paired) samples from electively terminated pregnancies.ResultsEtG, EtS, and nicotine markers’ limits of detection were 0.7–20 ng/g in fetal samples. Ninety-eight fetal liver and 23 placenta samples were EtG/EtS-positive, while 137 liver and 25 placenta samples were positive for tobacco exposure. When both alcohol markers were present in samples, EtG/EtS ratios were 1.6–11.1 in 17 livers and 2.5–31.1 in 10 placentas. Median (range) summed tobacco marker concentrations were 422 (1.0–2776) and 154 (1.6–1621) ng/g in livers and placentas, respectively. Median EtG and nicotine marker concentrations were higher in liver than placenta in paired samples. Strong evidence of exposure occurred in 11 and 22 pairs, respectively, when both samples were positive for alcohol and/or tobacco markers.ConclusionsThese paired fetal liver and placenta alcohol and tobacco data provided a unique means for examining the effects of in utero exposure, a critical first step in selecting fetal samples for proteomic and RNA sequencing studies that could provide mechanisms for adverse developmental outcomes.

KW - ethyl glucuronide

KW - nicotine

KW - fetal liver

KW - placenta

KW - pregnancy

KW - prenatal exposure

U2 - 10.1007/s11419-017-0389-2

DO - 10.1007/s11419-017-0389-2

M3 - Article

SN - 1860-8973

VL - 36

SP - 102

EP - 112

JO - Forensic Toxicology

JF - Forensic Toxicology

IS - 1

ER -

Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

Abstract

Bibliographical note

Keywords

UN SDGs

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