Correspondence

Neonatal Hair Analysis as a Biomarker for in Utero Alcohol Exposure

N Engl J Med 2002; 347:2086December 19, 2002

Article

To the Editor:

Alcohol is the most prevalent human teratogen. Fetal alcohol spectrum disorder is estimated to affect up to 1 percent of infants born in North America. The ascertainment of gestational exposure to alcohol is paramount for the diagnosis of the disorder. It is widely recognized that maternal reporting results in underestimates of the prevalence and amount of exposure to alcohol.

Until recently, there have been no objective biologic markers for the detection of long-term in utero exposure to alcohol. Studies in adults have documented that circulating ethanol is transesterified with fatty acids to fatty acid ethyl esters.1 On the basis of this finding, fatty acid ethyl esters (ethyl linoleate, ethyl laurate, and ethyl stearate) have been identified in meconium.2 In infants who were not exposed to alcohol in utero, the concentrations of these compounds in meconium are very low, whereas in infants with in utero alcohol exposure, the concentrations are high, sometimes up to 50 times as high as the values in controls.2 Since meconium is available only during the first two or three days after birth, we have measured fatty acid ethyl esters in neonatal hair, which is available for up to two to three months after birth.3

Four fatty acid ethyl esters — ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate — have been identified in the hair of adults who drink socially or heavily.4 We analyzed hair samples from a woman who admitted that she had drunk alcohol socially and used cocaine throughout pregnancy and from her newborn girl for fatty acid ethyl esters, cocaine, benzoylecgonine, and cocaethylene. The hair samples were analyzed for fatty acid ethyl esters with the use of a recently described method.4 Briefly, samples of approximately 10 mg were extracted overnight with a mixture of n-heptane and dimethyl sulfoxide. The extract was then evaporated, and the residue, after resuspension in phosphate buffer, was reextracted with the use of headspace solid-phase microextraction. The final extract was analyzed by gas chromatography–mass spectrometry.

The hair samples from both the mother and the newborn were highly positive for cocaine, with the use of a method described previously,5 with concentrations of 150 ng per milligram of hair from the mother and 12.9 ng per milligram of hair from the infant. The samples from both the mother and the infant were negative for cocaethylene but were positive for fatty acid ethyl esters, at 2.6 pmol per milligram and 0.4 pmol per milligram, respectively. The limit of detection for this gas chromatographic–mass spectrometric method is 0.25 pmol per milligram of hair when 5 mg of hair is analyzed; the highest yields of fatty acid ethyl ester extraction are obtained with a hair sample of 5 mg.4 In our analyses, we used 5.1 and 6.7 mg of hair from the mother and her infant, respectively.

On the basis of the literature, the fatty acid ethyl ester concentration in the mother's hair corroborates her report of social drinking during pregnancy.4 To the best of our knowledge, this is the first report of use of neonatal hair for the analysis of fatty acid ethyl esters. Our ability to measure fatty acid ethyl esters in the hair of a neonate whose mother was a self-reported social drinker suggests that exposure to larger amounts of alcohol will also be detectable. Large population-based studies are needed to establish a correlation between maternal intake of alcohol and fatty acid ethyl ester concentrations in neonatal hair.

Julia Klein, M.Sc.
Daphne Chan, B.Sc.
Gideon Koren, M.D.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
gkoren@sickkids.ca

5 References

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   Auwarter V, Sporkert F, Hartwig S, Pragst F, Vater H, Diefenbacher A. Fatty acid ethyl esters in hair as markers of alcohol consumption: segmental hair analysis of alcoholics, social drinkers, and teetotalers. Clin Chem 2001;47:2114-2123
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   Klein J, Karaskov T, Koren G. Clinical applications of hair testing for drugs of abuse -- the Canadian experience. Forensic Sci Int 2000;107:281-288
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Citing Articles (9)

Citing Articles

1. 1

   K. Aleksa, J. Liesivuori, G. Koren. (2011) Hair as a biomarker of polybrominated diethyl ethers’ exposure in infants, children and adults. Toxicology Letters
   CrossRef

2. 2

   Isabelle Ouellet-Morin, Ginette Dionne, Sonia J. Lupien, Gina Muckle, Sylvana Côté, Daniel Pérusse, Richard E. Tremblay, Michel Boivin. (2011) Prenatal alcohol exposure and cortisol activity in 19-month-old toddlers: an investigation of the moderating effects of sex and testosterone. Psychopharmacology 214:1, 297-307
   CrossRef

3. 3

   Vivian Kulaga, Fritz Pragst, Gideon Koren. (2009) The fatty acid ethyl esters (FAEE) hair test: emerging technology for the diagnosis of fetal alcohol spectrum disorders (FASD). Annales de Toxicologie Analytique 21:2, 61-65
   CrossRef

4. 4

   Facundo Garcia-Bournissen, Ben Rokach, Tatyana Karaskov, Joey Gareri, Gideon Koren. (2007) Detection of stimulant drugs of abuse in maternal and neonatal hair. Forensic Science, Medicine, and Pathology 3:2, 115-118
   CrossRef

5. 5

   Facundo Garcia-Bournissen, Ben Rokach, Tatyana Karaskov, Gideon Koren. (2007) Cocaine Detection in Maternal and Neonatal Hair: Implications to Fetal Toxicology. Therapeutic Drug Monitoring 29:1, 71-76
   CrossRef

6. 6

   Daniela L. Caprara, Kelly Nash, Rachel Greenbaum, Joanne Rovet, Gideon Koren. (2007) Novel approaches to the diagnosis of fetal alcohol spectrum disorder. Neuroscience & Biobehavioral Reviews 31:2, 254-260
   CrossRef

7. 7

   Daphne Chan, Daniela Caprara, Phillip Blanchette, Julia Klein, Gideon Koren. (2004) Recent developments in meconium and hair testing methods for the confirmation of gestational exposures to alcohol and tobacco smoke. Clinical Biochemistry 37:6, 429-438
   CrossRef

8. 8

   Hua Shan, Ping Zhang. (2004) Viral attacks on the blood supply: the impact of severe acute respiratory syndrome in Beijing. Transfusion 44:4, 467-469
   CrossRef

9. 9

   Nancy Tucker. (2003) BoTox: Ironing Out the Wrinkles in Your Technique. Techniques in Ophthalmology 1:1, 45-50
   CrossRef