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The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues.

Background: Meconium fatty acid ethyl esters (FAEE) constitute a biomarker of heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal sheep following daily, relatively moderate-dose ethanol exposure in late gestation, and to evaluate their utility in identifying fetal organ-system injury., Methods: Pregnant ewes received ethanol (0.75 g/kg; n = 14) or saline (n = 8) via 1-h i.v. infusion daily during the third trimester equivalent, while additional pregnant sheep served as untreated controls (n = 6). The daily ethanol regimen produced similar maximal maternal and fetal plasma ethanol concentrations of 0.11-0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and meconium was collected and analyzed for FAEE (ethyl palmitate, stearate, linoleate, and oleate)., Results: Meconium total FAEE concentration was significantly higher in ethanol-exposed fetuses compared with controls, and a positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and specificity for detecting fetal ethanol exposure. When the studied animals (ethanol-exposed and controls) were classified according to meconium FAEE concentration, FAEE-positive and FAEE-negative groups frequently differed with respect to previously examined pathological endpoints, including nephron endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin gene expression in cerebral vessels. Furthermore, in all studied animals as a group (ethanol-exposed and controls combined), meconium FAEE concentration was correlated with many of these pathological endpoints in fetal organs., Conclusions: We conclude that, in fetal sheep, meconium FAEE could serve as a biomarker of daily ethanol exposure in late gestation and could identify fetuses with subtle ethanol-induced toxic effects in various organs. This study illustrates the potential for using meconium FAEE to identify neonates at risk for dysfunction of major organs following in-utero ethanol exposure that does not result in overt physical signs of ethanol teratogenicity.

Background: Meconium analysis for fatty acid ethyl esters (FAEEs) is a validated method for identifying heavy prenatal ethanol (EtOH) exposure. This study investigated whether delayed sample collection can result in false-positive test results for FAEEs because of collection of samples potentially contaminated with postnatally produced stool., Methods: Serial excretions were prospectively collected from neonates born to nondrinking mothers to capture the transition from meconium to postnatal stool. These were analyzed for FAEEs using headspace-solid phase microextraction and gas chromatography-mass spectrometry. Experiments involving incubation of samples with glucose or EtOH were performed to explore a potential mechanism of FAEE elevation., Results: A total of 136 samples were collected from 30 neonates during their first few days of life (median of 4 samples/baby over a mean period of 68.5 hours postpartum). Although the first-collected meconium sample tested negative for FAEEs in all babies, later samples tested above the 2 nmol/g positive cutoff in 19 of 30 babies. Median time to appearance of FAEE-positive samples was 59.2 hours postpartum. In vitro experiments demonstrated that FAEE levels can be further increased in late samples (likely containing postnatal stool) after incubation with glucose, and that FAEEs are readily formed in meconium in the presence of EtOH., Conclusions: Collection of samples excreted later in the postpartum period can lead to false-positive test results for FAEEs, which could be because of contamination with dietary components of postnatally produced stool and EtOH-producing microorganisms. Clinically, it is critical to collect the earliest possible excretion for determination of FAEEs to ensure that the FAEE content is representative of in utero EtOH exposure., (Copyright © 2012 by the Research Society on Alcoholism.)

Fatty acid ethyl esters (FAEEs) in meconium are validated biomarkers of heavy fetal alcohol exposure that may potentially be used clinically for identifying children at risk for alcohol-related disabilities. However, until now, FAEEs have been largely used anonymously in epidemiological studies, and by child protection authorities in need for verification of heavy alcohol use in pregnancy. Here we describe the first case of a neonate identified as part of a research study on a pilot neonatal screening program for prenatal alcohol exposure. The neonate's meconium tested high for FAEEs (52 nmol/g; positive cut-off ≥ 2 nmol/g), which prompted active follow-up of the infant's development, identifying early neurocognitive problems and allowing initiation of a remedial program.