Context Tobacco increases the risk of systemic diseases, and it has adverse effects on pregnancy. However, only indirect data have been published on a possible genotoxic effect on pregnancy in humans. Objectives To determine whether maternal smoking has a genotoxic effect on amniotic cells, expressed as an increased chromosomal instability, and to analyze whether any chromosomal regions are especially affected by exposure to tobacco. Design, Setting, and Patients In this prospective study, amniocytes were obtained by routine amniocentesis for prenatal diagnosis from 25 controls and 25 women who smoke (Ն10 cigarettes/d for Ն10 years), who were asked to fill out a smoking questionnaire concerning their smoking habits. Chromosomal instability was analyzed in blinded fashion by 2 independent observers in routine chromosome spreads. Breakpoints implicated in chromosomal abnormalities were identified by G-banding. Main Outcome Measures Association between maternal smoking and increased chromosomal instability in amniotic fluid cells, expressed as chromosomal lesions (gaps and breaks) and structural chromosomal abnormalities. Results Comparison of cytogenetic data between smokers and nonsmokers (controls) showed important differences for the proportion of structural chromosomal abnormalities (smokers: 12.1% [96/793]; controls: 3.5% [26/752]; P=.002) and to a lesser degree for the proportion of metaphases with chromosomal instability (smok

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