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It is accepted that blood phosphatidylethanol (PEth) concentrations are reliable biomarkers of ethanol (alcohol) exposure. We therefore conducted a preliminary study to test the hypothesis that elevated blood PEth concentrations can help to identifying women with prenatal alcohol exposure who are at higher risk of adverse pregnancy outcomes. The study included 35 first-trimester pregnant women who self-reported alcohol ingestion and had PEth blood concentration ⩾4 nM at recruitment. As a control group, 233 first-trimester pregnant women who self-reported as being either abstainers or light alcohol drinkers and had blood PEth concentrations <4 nM, were also included. All participants were followed up until completion of their pregnancies. Women with prenatal alcohol exposure and PEth concentrations ⩾4 nM had a risk ratio of spontaneous abortions of 3.21 (95%CI 0.93-11.06; P=0.074). Because of the potential implications in the prenatal care of women reporting risky alcohol exposure, the preliminary results from the present study indicate the need for testing the hypothesis in a more definitive approach., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Alcohol exposure has been shown to cause devastating effects on neurobehavioral development in numerous animal and human studies. The alteration of DNA methylation levels in gene-specific promoter regions has been investigated in some studies of human alcoholics. This study was aimed to investigate whether social alcohol consumption during periconceptional period is associated with epigenetic alteration and its generational transmission in the blood cells., Methods: We investigated patterns of alcohol intake in a prospective cohort of 355 pairs of pregnant women and their spouses who reported alcohol intake during the periconceptional period. A subpopulation of 164 families was established for the epigenetic study based on the availability of peripheral blood and cord blood DNA. The relative methylation changes of dopamine transporter (DAT), serotonin transporter (SERT), and methyl CpG binding protein 2 (MeCP2) gene promoters were analyzed using methylation-specific endonuclease digestion followed by quantitative real-time polymerase chain reaction., Results: The relative methylation level of the DAT gene promoter was decreased in the group of mothers reporting above moderate drinking (p = 0.029) and binge drinking (p = 0.037) during pregnancy. The relative methylation level of the DAT promoter was decreased in the group of fathers reporting heavy binge drinking (p = 0.003). The relative methylation levels of the SERT gene promoter were decreased in the group of newborns of light drinking mothers before pregnancy (p = 0.012) and during pregnancy (p = 0.003). The methylation level in the MeCP2 promoter region of babies whose mothers reported above moderate drinking during pregnancy was increased (p = 0.02). In addition, methylation pattern in the DAT promoter region of babies whose fathers reported heavy binge drinking was decreased (p = 0.049)., Conclusions: These findings suggest that periconceptional alcohol intake may cause epigenetic changes in specific locus of parental and newborn genomes as follows: Alcohol consumption decreases the methylation level of the DAT promoter region of the parent themselves, maternal alcohol drinking during the periconceptional period decreases the methylation level of the SERT promoter region of newborns, and maternal alcohol consumption increases the methylation level of the MeCP2 promoter region of newborns., (Copyright © 2015 by the Research Society on Alcoholism.)

Objective: Phosphatidylethanol (PEth) is formed endogenously by the direct action of ethanol, and has a half-life long enough to make it a reliable biomarker of alcohol exposure in early pregnancy. In this study, we aimed to characterize PEth blood concentrations to differentiate different levels of alcohol exposure in pregnant women., Methods: The study consisted of 305 consecutive pregnant women who had been referred to our hospital for antenatal care. Of them, 117 self-reported alcohol ingestion in the first trimester of pregnancy and 188 were abstainers. Total PEth concentration in whole blood was quantified by liquid chromatography-mass spectrometry (LC-MS/MS). Alcohol ingestion was classified according to the United States National Institute on Alcohol Abuse and Alcoholism into light drinkers: ≤ 3 drinks/week, moderate drinkers: 3-7 drinks/week, and heavier drinkers: > 7 drinks/week (a standard drink = 14 g of ethanol)., Results: Participants had quantifiable PEth blood levels 3-4 weeks after the last drink. There were 4.8% abstainers who had positive PEth concentrations; all of them reported a positive history of alcohol consumption before conception. PEth blood concentrations were significantly correlated to drinks per occasion (r = 0.44; P < 0.001) and days drinking per week (r = 0.34; P < 0.001). However, almost 74% of participants with ≤ 3 drinks/week of alcohol, and 46% with 3-7 drinks/week, had PEth blood concentrations below the lower limit of quantification (LLOQ). The area under the curve (AUC) generated by a receiver operation characteristic curve (ROC) analysis increased as the cutoff value of PEth blood concentration increased. However, the cutoff values were below or close to the LLOQ., Conclusions: Our study presents a formal characterization of PEth blood concentrations for screening alcohol ingestion in first-trimester pregnant women. However, caution is recommended for overrepresenting either negative or positive results.

Objective: A reliable biomarker of low alcohol exposure during pregnancy is needed to clarify the controversy on the teratogenicity of low-to-moderate alcohol levels., Methods: Blood samples were obtained from 13 pregnant women who self-reported alcohol ingestion between 2.5 and 20 drinks/week, and from 26 controls. Total lipids were extracted, and phosphatidylethanol (PEth) species 16:0/16:0, 16:0/18:1, and 16:0/18:1 were separated by high-performance liquid chromatography (HPLC) on a reverse-phase phenyl column. These PEth species were quantified by MS/MS using phosphatidylpropanol as internal standard, with electrospray ionization and MRM., Results: PEth species were not detected in women who abstained from alcohol ingestion during pregnancy, whereas PEth-16:0/18:1 was > 5 nmol/L in those with positive alcohol ingestion. PEth species were detected for up to 4 weeks after cessation of exposure., Conclusions: PEth-16:0/18:1 was detected in pregnant women at 4-6 weeks after their last low-to-moderate alcohol ingestion, and therefore appears to be a reliable biomarker of prenatal alcohol exposure to study the teratogenicity of alcohol at these exposure levels.

Objective: This study aimed to assess the pregnancy outcomes of women who reported social intake of low or very low alcohol levels during pregnancy., Methods: Obstetric and foetal outcomes were assessed in a prospective cohort of 1667 pregnant women who reported low or very low alcohol consumption during pregnancy (cases) and 1840 alcohol-abstainer women (controls)., Results: Among cases, alcohol consumption occurred during the first 4.4 (median) weeks of pregnancy, with a median ingestion of 1.0 (0.01-6.0) drinks/week, equivalent to 7.6 (0.09-47.5) g/week. Cigarette smoking was reported approximately four times more often in the exposed group than in the controls (p < 0.001). Pregnancy outcomes were similar between groups. There were 37 (2.4%) babies born with malformations in the exposed group and 41 (2.4%) in the control group (p = 0.9)., Conclusions: Low-to-very low levels of alcohol ingestion during pregnancy do not appear to be associated with adverse maternal or foetal outcomes.

Background Alcohol exposure has been shown to cause devastating effects on neurobehavioral development in numerous animal and human studies. The alteration of DNA methylation levels in gene-specific promoter regions has been investigated in some studies of human alcoholics. This study was aimed to investigate whether social alcohol consumption during periconceptional period is associated with epigenetic alteration and its generational transmission in the blood cells. Methods We investigated patterns of alcohol intake in a prospective cohort of 355 pairs of pregnant women and their spouses who reported alcohol intake during the periconceptional period. A subpopulation of 164 families was established for the epigenetic study based on the availability of peripheral blood and cord blood DNA. The relative methylation changes of dopamine transporter ( DAT) , serotonin transporter ( SERT), and methyl CpG binding protein 2 ( Me CP2) gene promoters were analyzed using methylation-specific endonuclease digestion followed by quantitative real-time polymerase chain reaction. Results The relative methylation level of the DAT gene promoter was decreased in the group of mothers reporting above moderate drinking ( p = 0.029) and binge drinking ( p = 0.037) during pregnancy. The relative methylation level of the DAT promoter was decreased in the group of fathers reporting heavy binge drinking ( p = 0.003). The relative methylation levels of the SERT gene promoter were decreased in the group of newborns of light drinking mothers before pregnancy ( p = 0.012) and during pregnancy ( p = 0.003). The methylation level in the Me CP2 promoter region of babies whose mothers reported above moderate drinking during pregnancy was increased ( p = 0.02). In addition, methylation pattern in the DAT promoter region of babies whose fathers reported heavy binge drinking was decreased ( p = 0.049). Conclusions These findings suggest that periconceptional alcohol intake may cause epigenetic changes in specific locus of parental and newborn genomes as follows: Alcohol consumption decreases the methylation level of the DAT promoter region of the parent themselves, maternal alcohol drinking during the periconceptional period decreases the methylation level of the SERT promoter region of newborns, and maternal alcohol consumption increases the methylation level of the Me CP2 promoter region of newborns. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports the development and validation of an improved assay for quantitation of fatty acid ethyl esters (FAEEs) in human meconium using liquid chromatography/tandem mass spectrometry (LC–MS/MS). FAAEs (ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate, ethyl linolenate, and ethyl arachidonate) and the internal standard (I.S.), ethyl heptadecanoate, were separated by reverse phase HPLC and quantified by MS/MS using electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the positive ionization mode. The absolute recovery of FAEEs varied from 55±10% for 0.33nmol/g (100ng/g) of ethyl linoleate up to 86±8% for 1.55nmol/g (500ng/g) of ethyl miristate. The LODs and LOQs varied from 0.01 to 0.08nmol/g and from 0.02 to 0.27nmol/g, respectively. The assay has been successfully applied to examine the FAEE levels in 81 meconium samples from babies born to mothers reporting alcohol consumption, to varying degrees, during pregnancy. [Copyright &y& Elsevier]