The foetus is exposed to multiple xenobiotics through the mother's circulation and this is possibly involved in the development of diseases in later life. Heavy metals and lipophilic genotoxins in umbilical cord blood of newborns may have synergistic effects on mutagenesis in the hypoxanthine-phosphoribosyltransferase (HPRT) reporter gene. Concentrations of zinc (Zn), lead (Pb) and cadmium (Cd) were determined in the peripheral and cord blood of 16 non-smoking and 9 smoking healthy mothers by atomic absorption spectrometry. Lipophilic DNA adducts in lymphocytes were determined in the same subjects by 32P-postlabelling and the HPRT-variant frequency was assessed by the evaluation of 6-thioguanine resistant cells. Although the Cd/Zn ratio was 2.5-fold higher in the blood of smoking women than in non-smoking women (1.0 +/- 0.2 and 0.4 +/- 0.1, respectively, P = 0.007), this difference could not be observed in umbilical cord blood (0.3 +/- 0.1 and 0.3 +/- 0.1, respectively, P = 0.66). Similarly, mean DNA adduct levels were increased in the lymphocytes of smoking women compared with non-smoking controls (0.99 +/- 0.31 adducts/10(8) nt and 0.43 +/- 0.12, respectively, P = 0.009), but were only marginally higher in the neonates of smokers than in their non-smoking counterparts (0.57 +/- 0.29 and 0.24 +/- 0.09, respectively, P = 0.38). Since Cd is known to effectively inhibit DNA repair, we hypothesized that concomitant exposure of neonates to Cd and genotoxic compounds may result in an increased fixation of DNA damage into somatic mutations. Indeed, the number of HPRT-variants per adduct (i.e. the mutagenic efficiency of adducts) correlated positively with the Cd concentrations in cord blood (r = 0.61, P = 0.001). These data suggest a molecular link between DNA damage, inhibition of DNA repair by Cd and in vivo mutagenesis during foetal development. Thus, exposure to heavy metals may enhance the mutagenic potential of DNA-damaging compounds and results in biologically relevant genotoxic effects in neonates.

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In the Netherlands 30% of all women of reproductive age are habitual smokers. One third of these women continue to smoke during pregnancy. Tobacco smoke consists of more than 3600 different compounds. One of its chief pharmacologically active ingredients is nicotine of which 60% is metabolized to cotinine. Cotinine is the best available biochemical marker of nicotine consumption because it is specific for tobacco smoke exposure and it has a relatively long mean t./ 2 of 15 hours. In the present study nicotine and cotinine concentrations were measured in 25 smoking and 25 non-smoking healthy pregnant women. In all 25 non-smoking pregnant women nicotine and cotinine levels were < 10mg/l. Light smokers (< 10 cigarettes/day) were found to have nicotine blood concentrations < 10mg/l and cotinine levels varying between 40 and 99 mg/1. Heavy smokers (^ 10 cigarettes/day) had nicotine concentrations < 10 mg/1, but high cotinine levels varying from 115 to 199 mg/1. Cotinine was also determined in 25 neonates of non-smoking mothers and in 34 neonates of smoking mothers. In 9 of these 34 newborns the relationship between maternal and neonatal cotinine concentrations was investigated. Cotinine levels in neonates born to non-smokers and to women who smoked less than 10 cigarettes/day were below the detection limit of 10 mg/1. Cotinine values in neonates whose mothers smoked ^ 10 cigarettes/day were significantly higher than in those whose mothers smoked < 10 cigarettes/day, but significantly lower than in their mothers. The results of this study confirm that cotinine is more useful than nicotine in discriminating non-smokers, light and heavy smokers. Cotinine concentrations were significantly lower in the neonates than in their mothers, but there was a strong positive linear relationship between maternal and neonatal cotinine concentrations.

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Our objective was to compare the platelet count and platelet indices of smoking and non-smoking women at different stages of normal pregnancy. Study design:In 247 non-smoking and 123 smoking healthy pregnant women the platelet count, the mean platelet volume, the platelet distribution width and the plateletcrit were compared at 0-10, 11-20, 21-30 and 31-40 weeks of pregnancy. Exclusion criteria were a diastolic pressure ^ 90 mmHg, an endocrine disease, a coagulation disorder, acetylsalicylic acid or phenprocoumon use. A women was considered a smoker if she smoked more than 4 cigarettes a day. Non-smokers were defined as women reporting no smoking at all. Blood samples were run on the Sysmex NE-8000.Results: There was no significant difference between the platelet count in the two groups. In the non-smoking group, the platelet count showed a significant decrease with gestational age (287 X 10 9 /1 to 258 X 10 9 /1). This was not the case in the smokers group. The mean platelet volume of the smokers was significantly lower than that of the non-smokers in the last ten weeks of pregnancy (10.4 fl versus 10.7 fl). The platelet distribution width and the plateletcrit did not change under the influence of cigarette smoking. Conclusion:Smoking during pregnancy does not significantly affect platelet count or platelet indices.