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 pooled rate of chromosomal anomalies in fetuses with isolated PLSVC and no associated structural anomalies, with particular attention to extractable denominators for genetic testing. A systematic search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed from January 2000 through March 2026. Studies reporting data on chromosomal anomalies in fetuses with sonographically confirmed, isolated PLSVC were eligible. Isolated PLSVC was defined as bilateral superior vena cava without intracardiac or extracardiac structural anomalies. When a study reported a larger isolated clinical cohort but conducted chromosomal testing only in an extractable subgroup, the genetically assessed isolated subgroup was used as the denominator for the primary chromosomal analysis. Proportions were pooled using the Freeman-Tukey double arcsine transformation and a random-effects DerSimonian-Laird model. Thirteen studies encompassing 699 genetically assessed isolated PLSVC fetuses were included in the quantitative synthesis. Thirteen chromosomal anomalies were identified, yielding a pooled chromosomal anomaly rate of 2.2% (95% confidence interval: 0.9-4.1%) with low heterogeneity (I²=29.0%, p=0.15). Sensitivity analyses demonstrated the robustness of the findings. Although the risk of chromosomal abnormalities in sonographically isolated PLSVC is low, it is not negligible. Therefore, isolated PLSVC should not be considered an indication for routine invasive prenatal diagnosis, and clinical decision-making should be individualized based on maternal age, serum screening or cell-free DNA results, nuchal translucency findings, detailed fetal anatomical assessment, and patient preference.