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The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities.Women undergoing routine fetal sonographic examinations were evaluated once for the presence of PLSVC. PLSVC was diagnosed on the basis of the identification of an additional vessel in the left of the pulmonary artery in a three-vessel trachea view. Associated abnormalities, karyotypes, and outcomes were analyzed.A total of 164 (0.7%, 164/25 171) cases of PLSVC were detected and successfully followed-up. The detection rates were 0.5% (81/17 535) and 1.1% (83/7636) in the low-risk and high-risk cases, respectively. The incidence of PLSVC was lower among the chromosomally or clinically normal (0.4%, 110/24 914) compared with chromosomally abnormal fetuses (7.8%, 20/257, p < 0.001). Additional defects were identified in 90% (18/20) of the PLSVC fetuses with chromosomal anomalies, a rate that was higher than those fetuses with chromosomal normal (61.8%, 68/110).Persistent left superior vena cava is more common among chromosomally abnormal than normal fetuses, and PLSVC fetuses with other defects are more highly associated with chromosomal disorders than isolated PLSVC fetuses. Isolated PLSVC is a benign vascular anomaly and may not affect outcomes. © 2014 John Wiley & Sons, Ltd.What's already known about this topic?The incidence of PLSVC in fetal echocardiographic examinations has been reported to be 0.9% in studies conducted in high-risk populations. An association between PLSVC and chromosomal defects has been reported, with 9% of PLSVC fetuses having chromosomal abnormalities. Some authors have advocated karyotyping whenever PLSVC is detected prenatally. However, other authors have noted that most aneuploid fetuses exhibit other defects that may be more directly associated with chromosomal disorders.What does this study add?In this study, we establish the incidence of PLSVC in an unselected low-risk population and confirm from another perspective that the incidence of PLSVC in chromosomally abnormal group was significantly higher (27.5-fold) than in the normal fetuses.