A preliminary report suggests that maternal smoking during pregnancy is associated with increased chromosomal abnormalities in fetal cells, according to a study in the March 9 issue of JAMA.

Maternal smoking during pregnancy has many consequences during and after pregnancy, such as infertility, coagulation problems, obstetric complications such as extrauterine pregnancy and placenta previa, and intrauterine growth retardation, according to background information in the article. However, only indirect data have been published on a possible genotoxic (effect of damaging DNA, possibly causing genetic mutation) effect on pregnancy in humans.

Rosa Ana de la Chica, M.Sc., of the Universitat Autnoma de Barcelona, Bellaterra, Spain, and colleagues conducted a study to determine whether maternal smoking has a genotoxic effect on amniotic cells, expressed as an increased chromosomal instability, and analyzed whether any chromosomal regions are especially affected by exposure to tobacco. Fetal amniocytes (cells of fetal origin in the amniotic fluid) were obtained by routine amniocentesis for prenatal diagnosis from 25 controls and 25 women who smoke (10 or more cigarettes/d for 10 or more years). The women were asked to fill out a smoking questionnaire concerning their smoking habits.

The researchers found that when comparing genetic data between smokers and nonsmokers (controls) there were important differences for the proportion of structural chromosomal abnormalities (smokers: 12.1 percent; controls: 3.5 percent) and to a lesser degree for the proportion of metaphases (a phase of cell division) with chromosomal instability (smokers: 10.5 percent; controls: 8.0 percent), and for the proportion of chromosomal lesions (smokers: 15.7 percent; controls: 10.1 percent). Statistical analysis found a certain chromosomal region was most affected by tobacco, and noted that this region has been implicated in hematopoietic (pertaining to the formation of blood or blood cells) malignancies.

"It has been suggested that the increase of chromosomal lesions and structural abnormalities or the very existence of an increased chromosomal instability resulting from the genotoxic effect of tobacco could be indicative of an increased cancer risk and that fragile sites could be responsible for the chromosomal instability observed in cancer cells," the authors write. "Moreover, an increase of chromosomal instability is associated with an increase in the risk of cancer, especially childhood malignancies."

(JAMA. 2005;293:1212-1222. Available post-embargo at jama)

Editor's Note: Financial support for this study was provided by the Comissionat per a Universitats i Recerca.

Editorial: Smoking While Pregnant

In an accompanying editorial, David M. DeMarini, Ph.D., and R. Julian Preston, Ph.D., of the U.S. Environmental Protection Agency, Research Triangle Park, N.C., discuss the findings in the study which examines the affects of smoking while pregnant.

"The findings of de la Chica et al represent the first report of tobacco smoke-associated genotoxic damage in fetal epithelial (membranous cellular tissue) cells from mothers who smoke. As such, these data add to the set of related and indirect data that have implicated tobacco smoke as a transplacental mutagen to the developing fetus."

"Although consistent with previous reports, the study by de la Chica et al contains several limitations that urge caution and suggest that their findings should be viewed as highly preliminary. One limitation is lack of a direct or indirect exposure assessment, such as urinary cotinine measurements of the mother and DNA or protein adduct measurements of both maternal and fetal tissues," they write.

"That so few studies have examined the genotoxic effects of maternal smoking on the fetus reflects the difficulty of such studies in terms of screening and selecting study participants, obtaining fetal cells for analysis, and the limited availability of assays and end points that have been available for use. Although obtaining suitable patients and cells may continue to be problematic, the development of new methods and end points, especially genomic methods, offers hope for progress in this important area of public health. A definitive demonstration of transplacental mutagenesis of fetal epithelial cells by maternal smoking requires further studies that take into account the concerns outlined here. In the meantime, the message to women based on the published literature remains clear: smoking during pregnancy can be hazardous for both the fetus and the mother," the authors conclude.

(JAMA. 2005;293:1264-1265. Available post-embargo at jama)

Contact: Josep Egozcue, M.D.
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