Perinatal outcomes of fetuses with pathogenic copy number variants (pCNVs) and confirmed parental inheritance patterns: A retrospective study at a single institution

Background In prenatal diagnosis, chromosomal microarray(CMA) demonstrates a significantly higher diagnostic yield than conventional karyotyping. Nevertheless, evidence regarding the clinical outcomes of fetuses with pathogenic copy number variants(pCNVs) remains limited, with few studies specifically addressing this outcome. This study aimed to retrospectively evaluate the perinatal outcomes of fetuses with pathogenic copy number variations (pCNVs) with confirmed parental inheritance patterns. Methods From 2019 to 2024, 587 pCNVs were identified, with 91 cases subjected to parental analysis. Maternal information, anomaly scans, and pregnancy complications were documented as part of our comprehensive prenatal assessment. Follow-up data regarding pregnancy outcomes and neonatal health (up to 18 months post-partum) were collected. Results In 91 patients, 25 (27.5%) exhibited inherited pCNVs with a median length of 2.7 ± 3.5 Mb, whereas 66 (72.5%) presented de novo pCNVs with a median length of 5.7 ± 7.2 Mb, indicating a significant difference in length between the two groups ( P =  0.011). Parental inheritance occurred in 34% of pCNVs < 6.2 Mb. Among the 60 de novo cases with follow-up data, 58 (96.7%) opted for termination (TOP). Among the 23 inherited cases, 9 (39.1%) chose TOP. The 14 surviving term fetuses presented no developmental delay or structural anomalies. Conclusion When pCNVs are detected in prenatal diagnosis, parental inheritance information should be provided, especially in cases where the fragment length is less than 6.2 Mb. Parental origin verification has been shown to significantly improve the survival rate of fetuses with pCNVs.