Genotoxic effect of smoking in pregnancy

5 July 2005

Tobacco smoking is known to have a carcinogenic effect on various organs, and maternal smoking during pregnancy is known to have detrimental effects for both the mother and fetus, increasing the risk of intrauterine growth retardation, obstetric complications and other adverse health effects. A new paper in the latest edition of the Journal of the American Medical Association (JAMA) now reports that maternal smoking is also associated with increased chromosomal instability in fetuses. Spanish researchers interviewed 800 pregnant women referred for amniocentesis and prenatal genetic testing for a variety of reasons such as maternal age, previous history of fetal abnormality or spontaneous abortion, or increased risk indicated by standard prenatal screening [de la Chica et al. (2005) JAMA 293, 1212-1222]. Women were asked about their exposure to smoking, other potential mutagens and consumption of alcohol, tea and coffee. They identified 25 women for whom smoking was considered their only significant exposure to a mutagenic agent, along with a matched control group of 25 pregnant non-smokers with no known significant passive exposure to tobacco smoke. All the smoking mothers had at least a 10-year history of smoking and smoked in excess of at least 10 cigarettes per day during pregnancy.

Fetal cells were extracted from amniotic fluid samples and a standard cytogenetic approach (karyotype analysis of at least 25 high-quality metaphase samples per patient) used to identify structural chromosomal abnormalities in the fetal cells. The proportion of fetal cell samples showing chromosomal instability, the frequency and type of chromosomal lesions, and the frequency of structural abnormalities in fetal cells were recorded and used for statistical analysis. The authors note that the mean maternal age was higher (3 years) in the smoking group than the control group, although they suggest that increased maternal age tends to correlate with a higher level of numerical but not structural chromosomal abnormalities

Results showed an approximately 3.5 fold increase in the incidence of structural chromosomal abnormalities (primarily deletions and translocations) in the fetal cells from smokers compared with those from non-smokers, with deletions and translocations accounting for a majority of these changes.The authors also report that abnormalities in a particular chromosomal location (band 11q23) were more frequent in the smokers group, and propose a potential link between this phenomenon and childhood leukaemia, although without any evidence to support this proposal.

This study represents the first direct evidence findings of genotoxic damage to fetal epithelial cells in pregnancies where mothers smoke tobacco, contributing to previous work that has already implicated smoking in pregnancy in mutagenic effects on the fetus, as outlined in an editorial article accompanying the report [DeMarini DM and Preston RJ (2005) JAMA 293, 1264-1265]. These authors point out that the chromosomal abnormalities reported in the study were actually produced by errors of replication in the fetal cells during cell culture after extraction of the original fetal cells, and so cannot necessarily be attributed to the effects of smoking. It will be necessary for further studies to replicate and reinforce the findings of this paper.

Comment: The potential mutagenic effects of maternal smoking on fetal cells is an important public health issue, given the potential immediate and long term health effects for affected fetuses, and one that undoubtedly warrants further investigation. Whether confirmation of the association between tobacco consumption and fetal genotoxicty would influence maternal smoking behaviour any more than existing messages about the dangers to fetal health is not known.

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