Chromosomal abnormalities in isolated persistent left superior vena cava: A systematic review and meta-analysis

Persistent left superior vena cava (PLSVC) is the most common systemic venous anomaly detected prenatally, yet the risk of chromosomal abnormalities in truly isolated cases remains uncertain. This systematic review and meta-analysis aimed to determine the rate of chromosomal anomalies in fetuses with isolated PLSVC by including only fetuses who underwent chromosomal analysis. A systematic search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed from January 2000 through March 2026. Studies reporting chromosomal data for fetuses with sonographically confirmed isolated PLSVC were eligible. Isolated PLSVC was defined as PLSVC in the absence of intracardiac or extracardiac structural anomalies, irrespective of the presence of the right superior vena cava. Only isolated fetuses with prenatal or postnatal chromosomal analysis were included; untested fetuses were not assumed to be chromosomally normal. The pooled proportion was calculated as the total number of events divided by the total number of genetically assessed isolated fetuses, with 95% confidence intervals (CIs) calculated using the Wilson score method. Twelve studies were included, comprising 892 isolated PLSVC fetuses, of whom 302 underwent genetic testing. Eight chromosomal anomalies were identified, yielding a pooled chromosomal anomaly rate of 2.6% (95% CI: 1.3-5.1%). In the leave-one-out sensitivity analysis, the pooled rate ranged from 1.3% to 4.8%. The risk of chromosomal abnormalities in isolated PLSVC is low but not negligible. Because genetic testing was performed more often in higher-risk pregnancies, this estimate probably overestimates the background risk. The available evidence does not support a universal recommendation for invasive prenatal diagnosis based solely on an isolated PLSVC; decision-making should be individualized based on maternal age, serum screening or cell-free DNA results, nuchal translucency, detailed fetal anatomical assessment, and patient preference.