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To assess the risk of the association of single umbilical artery and aneuploidies.In a general unselected obstetric population of 12,672 singleton pregnant women from January 1998 to December 2002, we detected 61 fetuses (prevalence, 0.48%) with single umbilical artery (SUA) on prenatal ultrasound at 16 to 23 menstrual weeks.Among the 61 fetuses with 2-vessel cord, 39 (64%) had SUA as an isolated finding, and 22 (36%) had additional findings, either minor or major. One (2.56%) of the 39 fetuses with SUA as an isolated finding had aneuploidy (trisomy 21 at maternal age of 32 years), whereas 5 (41.6%) of the 12 fetuses with SUA concomitant with major anomalies were aneuploid. None of the 10 fetuses with SUA and minor anomalies had aneuploidy. Among the 12,611 women with 3-vessel cord, we instead found 8 cases of trisomy 21 (0.06%), 1 case of translocation 14-21 (0.007%), 5 cases of trisomy 18 (0.04%), 1 case of trisomy 13 (0.007%), 1 case of 47,XXX (0.007%), and 2 cases of monosomy X (0.01%).In an unselected population, second trimester sonographic detection of SUA and major fetal anomalies indicate increased risk for fetal aneuploidy. However, even if this study is based on a large population, the only 1 case of trisomy 21 among the fetuses with SUA as an isolated finding is not sufficient to draw a conclusion, and larger studies are needed to confirm or infirm this single case.