title: Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?
abstract: BACKGROUND
  Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect.
  
  
  METHODS
  Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use.
  
  
  RESULTS
  A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p = 0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001).
  
  
  CONCLUSIONS
  We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.
authors.affiliation: Department of Pediatrics, Hutzel Women's Hospital and the Mott Center for Human Growth and Development, Detroit, Michigan 48201, USA. eostrea@med.wayne.edu
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ostrea
authors.forename: Joel D
authors.initials: JD
authors.lastname: Hernandez
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Bielawski
authors.forename: Jack M
authors.initials: JM
authors.lastname: Kan
authors.forename: Gregorio M
authors.initials: GM
authors.lastname: Leonardo
authors.forename: Michelle Buda
authors.initials: MB
authors.lastname: Abela
authors.forename: Michael W
authors.initials: MW
authors.lastname: Church
authors.forename: John H
authors.initials: JH
authors.lastname: Hannigan
authors.forename: James J
authors.initials: JJ
authors.lastname: Janisse
authors.forename: Joel W
authors.initials: JW
authors.lastname: Ager
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sokol
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004952:Esters / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D008470:Meconium / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D001095:Arachidonic Acids; D015415:Biomarkers; D004952:Esters; D005227:Fatty Acids; D000431:Ethanol; C035723:ethyl arachidonate