Correspondence

Hair Analysis as a Marker for Fetal Exposure to Maternal Smoking

N Engl J Med 1993; 328:66-67January 7, 1993

Article

To the Editor:

Maternal cigarette smoking during pregnancy is associated with fetal risks in the short and long term1,2. Any attempt to understand the effects of maternal smoking on the fetus should include an estimate of the degree of fetal exposure to the constituents of cigarette smoke. To date, no biologic markers have been identified that can assist in such an estimation. We describe the distribution characteristics of nicotine and its metabolite cotinine in maternal and fetal hair.

We studied 10 smoking and 11 nonsmoking mothers (mean ages, 19 and 20 years, respectively) in two hospitals in Toronto. From one to three days after delivery, hair samples were obtained from the mothers and their babies by cutting five to seven shafts of hair near the skull with fine scissors. After being washed with detergent, 2- to 5-mg samples of hair were digested overnight at 50 °C with 0.6 N sodium hydroxide. The nicotine and cotinine content of the extracts was measured by radioimmunoassay3. The sensitivity of the nicotine and cotinine assays was 0.25 and 0.1 ng per milligram of hair, respectively, and the interassay coefficients of variation were less than 10 percent. Our measurements of the hair concentrations of nicotine and cotinine in the mothers agreed with those published by others3,4.

The women who smoked had consumed from 5 to 25 cigarettes per day (mean ±SD, 18 ±8) during pregnancy. Their hair concentrations of nicotine and cotinine were 21 ±18 and 3.7 ±8.8 ng per milligram, respectively; the respective concentrations in the babies' hair were 6.0 ±9.2 and 2.1 ±3.7 ng per milligram. For purposes of statistical analysis, values that were undetectable were assigned a value representing the sensitivity limit of the assay. There was no correlation between the number of cigarettes smoked by the mother and the concentration of nicotine or cotinine in maternal hair. There was a significant correlation between maternal and infant hair concentrations of both nicotine (r = 0.78, P<0.01) and cotinine (r = 0.64, P<0.05). The concentrations of nicotine (but not of cotinine) in the mothers were invariably higher than those in their infants (P<0.01).

In the nonsmoking mothers, the hair concentrations of nicotine and cotinine (0.9 ±0.8 and 0.3 ±0.5 ng per milligram, respectively) were significantly lower than those in the smokers (P<0.001). Similarly, the concentrations of nicotine and cotinine (0.7 ±0.7 and 0.3 ±0.2 ng per milligram) in the hair of the infants of the nonsmokers were significantly lower than those in the infants of the smokers (P<0.001). Four nonsmoking mothers were passively exposed to their spouses' cigarette smoking at home. Their mean hair concentration of nicotine (0.9 ±0.9 ng per milligram) did not differ from that of the other seven nonsmoking mothers (0.9 ±0.9 ng per milligram), but their hair cotinine concentrations (0.6 ±0.7 ng per milligram) were significantly higher (P<0.02). The trend was similar in their infants: the infants of women exposed passively had more cotinine in their hair than the infants of mothers not exposed (0.3 ±0.2 vs. 0.1 ±0.1 ng per milligram; P<0.05), but there were no differences in hair nicotine concentrations.

The positive correlation between maternal exposure to nicotine and cotinine and the accumulation of these compounds in fetal hair suggests that measurements of hair may provide a better estimate of long-term systemic exposure to the toxic constituents of cigarettes and may thereby yield a better prediction of fetal risk.

Julia Klein, M.Sc.
David Chitayat, M.D.
Gideon Koren, M.D.
The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

4 References

1. 1

   The health consequences of smoking: the changing cigarette: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1981:33-61. (DHHS publication no. (PHS) 81-50156.)
   

2. 2

   Rush D, Callahan KR. Exposure to passive cigarette smoking and child development: a critical review. Ann N Y Acad Sci 1989;562:74-100
   CrossRef | Web of Science | Medline

3. 3

   Haley NJ, Hoffmann D. Analysis for nicotine and cotinine in hair to determine cigarette smoker status. Clin Chem 1985;31:1598-1600
   Web of Science | Medline

4. 4

   Ishiyama I, Nagai T, Toshida S. Detection of basic drugs (metamphetamine, antidepressants, and nicotine) from human hair. J Forensic Sci 1983;28:380-385
   Web of Science | Medline

Citing Articles (12)

Citing Articles

1. 1

   Ana Florescu, Roberta Ferrence, Tom Einarson, Peter Selby, Offie Soldin, Gideon Koren. (2009) Methods for Quantification of Exposure to Cigarette Smoking and Environmental Tobacco Smoke: Focus on Developmental Toxicology. Therapeutic Drug Monitoring 31:1, 14-30
   CrossRef

2. 2

   Guillaume Hoizey, Laurence Labat. (2009) Cotinine en pédiatrie et en santé au travail. Annales de Toxicologie Analytique 21:1, 27-35
   CrossRef

3. 3

   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

4. 4

   Ana Florescu, Roberta Ferrence, Thomas R Einarson, Peter Selby, Michael Kramer, Susan Woodruff, Lindsey Grossman, Allison Rankin, Evelyn Jacqz-Aigrain, Gideon Koren. (2007) Reference Values for Hair Cotinine as a Biomarker of Active and Passive Smoking in Women of Reproductive Age, Pregnant Women, Children, and Neonates: Systematic Review and Meta-Analysis. Therapeutic Drug Monitoring 29:4, 437-446
   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

   Constantine I. Vardavas, Manolis N. Tzatzarakis, Aristeidis M. Tsatsakis, Dimitrios Athanasopoulos, Evaggelia Balomenaki, Manolis K. Linardakis, Anthony G. Kafatos. (2006) Biomarkers of passive smoking among Greek preschool children. European Journal of Pediatrics 165:12, 891-896
   CrossRef

7. 7

   Marion Villain, Vincent Cirimele, Pascal Kintz. (2004) Hair analysis in toxicology. Clinical Chemistry and Laboratory Medicine 42:11, 1265-1272
   CrossRef

8. 8

   Sabina Strano-Rossi. (1999) Methods used to detect drug abuse in pregnancy: a brief review. Drug and Alcohol Dependence 53:3, 257-271
   CrossRef

9. 9

   J.P. Goullé, P Kintz. (1996) Un nouveau moyen d'investigation biologique: l'analyse des cheveux. Intérêt en pratique médicale. La Revue de Médecine Interne 17:10, 826-835
   CrossRef

10. 10

    Gideon Koren. (1995) Measurement of drugs in neonatal hair; a window to fetal exposure. Forensic Science International 70:1-3, 77-82
    CrossRef

11. 11

    Bartecchi, Carl E.MacKenzie, Thomas D.Schrier, Robert W.. (1994) The Human Costs of Tobacco Use. New England Journal of Medicine 330:13, 907-912
    Full Text

12. 12

    Gideon Koren. (1993) Cocaine and the human fetus: The concept of teratophilia. Neurotoxicology and Teratology 15:5, 301-304
    CrossRef