title: Potential role of the placenta in fetal alcohol spectrum disorder.
abstract: BACKGROUND
  Mediators of susceptibility to alcohol-related toxicity in the prenatal environment are relatively unknown. The placenta has been proposed as a potential source of variability in the fetal environment, primarily through its significant metabolic capabilities. Meconium is a toxicological matrix unique to the developing fetus that offers an opportunity to quantify fetal exposure to alcohol through the analysis of fatty acid ethyl esters (FAEE) [nonoxidative ethanol metabolites].
  
  
  OBJECTIVE
  To explore the role of the placenta as a potential source of variability in mediating fetal alcohol exposure via meconium analysis of FAEE, by combining a clinical case report involving human dizygotic twins and a series of guinea pig littermates.
  
  
  METHODS
  Meconium was collected from a pair of dizygotic twins with clinical suspicion of prenatal alcohol exposure and analyzed for FAEE to confirm prenatal alcohol exposure. Meconium was also collected from a series of guinea pig pups prenatally exposed to alcohol at a daily dose of 4 g/kg/day administered to the pregnant dam. FAEE levels were analyzed by gas chromatography with flame ionization detection following liquid-liquid extraction from meconium.
  
  
  RESULTS
  The dizygotic twin pair yielded positive meconium FAEE results (>2.00 nmoL/g) in the female twin (2.21 nmoL/g) and no detectable FAEE in the male twin. A total of 15 meconium samples were collected from 15 pups of five pregnant guinea pig litters. With the exception of one pair of littermates, meconium FAEE concentrations differed substantially within each litter (FAEE expressed in units of nmoL/g): litter 1 (0.996, 4.43, 1.36); litter 2 (5.17, 4.15, 0.00); litter 3 (5.16, 5.27); litter 4 (18.57, 8.26, 7.46); litter 5 (0.00, 4.32, 0.00, 1.27).
  
  
  CONCLUSIONS
  Identical maternal ethanol exposure levels produced differing levels of fetal exposure in a dizygotic human twin pair and a series of guinea pig littermates as evidenced through FAEE meconium analysis. These data indicate that the placenta may have a previously unappreciated role in mediating ethanol-induced fetal injury.
authors.affiliation: Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, Ontario, Canada. joey.gareri@sickkids.ca
authors.forename: Joey
authors.initials: J
authors.lastname: Gareri
authors.forename: James
authors.initials: J
authors.lastname: Brien
authors.forename: James
authors.initials: J
authors.lastname: Reynolds
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D004952:Esters; D000431:Ethanol / Q000633:toxicity*; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000175:diagnosis*; D006168:Guinea Pigs; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D008470:Meconium / Q000737:chemistry / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000502:physiology; D021041:Placental Circulation; D011247:Pregnancy; D014429:Twins, Dizygotic
chemical_list: D015415:Biomarkers; D004952:Esters; D005227:Fatty Acids; D000431:Ethanol