MATERNAL SMOKING DURING PREGNANCY: FIRST EVIDENCE OF TRANSPLACENTAL TRANSFER OF TOBACCO-SPECIFIC CARCINOGENS TO THE FETUS

G.-M. Lackmann¹. U. Salzberger², U. Töllner², S. S. Hecht³

¹Dept. of Pediatrics, Heinrich Heine University Düsseldorf, ²Dept. of Pediatrics, Städtisches Klinikum Fulda, both in Germany, and University of Minnesota Cancer Center, Minneapolis, USA

OBJECTIVE: Cigarette smoking during pregnancy can result in fetal exposure to transplacental carcinogens, but little information is available on fetal uptake of such compounds.

METHODS: We analyzed first urine samples of newborns whose mothers did or did not smoke during pregnancy for the presence of metabolites of the tobacco-specific carcinogen 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK), i.e. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). Gas chromatography and nitrosamine-selective detection, with confirmation by mass spectrometry, were used in the analyses, which were performed without knowledge of the origin of the urine samples.

RESULTS: NNAL-Gluc was detected in 71% of 31 urine samples of mothers who smoked; NNAL was detected in four of these 31 samples. Neither compound was detected in the 17 urine samples from newborns of mothers who did not smoke. The arithmetic mean level of NNAL plus NNAL-Gluc in the 27 newborns of smokers for which both analytes were quantified was 0.14 (95% confidence interval [Cl] = 0.083-0.200) pmol/mL). The levels of NNAL plus NNAL-Gluc in the urine from these babies were statistically significantly higher than those in the urine from newborns of nonsmoking mothers (geometric means = 0.062 [95% Cl = 0.035-0.110] and 0.010 [considered as not detected; no Cl], respectively; two-sided p<0.001). NNAL plus NNAL-Gluc levels in the 18 positive urine samples in which both analytes were quantified ranged from 0.045 to 0.4 pmol/mL, with an arithmetic mean level of 0.20 (95% Cl = 0.14-0.26) pmol/mL, about 5% to 10% of the levels of these compounds detected in the urine from adult smokers.

CONCLUSIONS: Two metabolites of the tobacco-specific transplacental carcinogen NNK can be detected in the urine from newborns of mothers who smoked cigarettes during pregnancy. Prenatal uptake of toxicologically relevant amounts of transplacental carcinogens is expected to have serious adverse sequelae on the fetus.