A limited body of data over the past 35 years has suggested that autoimmunity may be responsible for some cases of aneuploidy. The role of diabetes mellitus in the etiology of chromosomal anomalies has been infrequently studied. This study was designed to compare the prevalence of chromosome abnormalities among the offspring of women with gestational diabetes and the offspring of women without it. The authors used data from 7,332 women who underwent amniocentesis in a prospective study of pregnancy outcome (1984-1988) and examined the prevalence of autosomal and sex chromosome defects associated with gestational diabetes. Among the offspring of 231 women with gestational diabetes, the crude prevalence of chromosomal defects was twice as high as that seen in the offspring of 7,101 women without gestational diabetes. These anomalies were predominantly numeric sex chromosome defects. After adjusting for potential confounding by maternal age, body mass index, education, and first-trimester exposures in multiple logistic regression analysis, the authors found that women with gestational diabetes were 7.7 times as likely (95% confidence interval: 2.8, 21.1) to have an infant with a numeric sex chromosome defect as those without gestational diabetes. These results support the theory that some women who develop gestational diabetes may have underlying biochemical changes that induce nondisjunction and the development of chromosomal defects.