Incidental Findings of Copy Number Variants by SNP-Based Noninvasive Prenatal Testing: Implications for Maternal Health

Somatic abnormalities involving chromosome 21, 18, and 13 are found in cancers and are detectable in circulating cfDNA. Previous publications have suggested increased risks of maternal neoplasm when multiple aneuploidies are detected on non-SNP-based NIPTs with normal fetal karyotypes. SNP-based NIPT distinguishes maternal/fetal cfDNA, allowing for CNV origin identification. This study reviewed maternal/fetal outcome SNP-based NIPT data to determine if multiple maternal copy number variants (CNVs) can predict increased risk of maternal neoplasms. Fetal/maternal outcomes were retrospectively collected for SNP-based NIPT cases accessioned from 7/1/2017 to 3/30/2021. Cases reported as unspecified atypical findings with data suggesting multiple maternal CNVs were included. Of 2,004,428 cases with results, 38 (0.002%) had unspecified atypical results with internal data consistent with maternal CNVs. Fetal/maternal health outcomes were obtained in 26/38 (68.4%) cases. A malignancy was diagnosed before, during, or after delivery in 14/26 cases. Positive predictive values (PPVs) for maternal neoplasm ranged from 39% (15/38 all cases) to 58% (15/26 known outcomes). One case of leiomyoma (1/26, 3.8%), and one case of lymphadenopathy (1/26, 3.8%) were observed. Fetal triploidy without reported maternal health issues was seen in 2 cases (2/26; 7.7%). 8/26 (30.8%) cases had no reported fetal/maternal health issues, including one with a family history of a BRCA mutation with patient mutation status unknown. (Table 1) SNP-based NIPT can incidentally identify maternal neoplasm presence/recurrence. When maternal CNVs are identified on SNP-based NIPT, our data suggests an increased risk of maternal neoplasm with PPVs ranging from 39-59%. Neoplasms in this cohort could be underdiagnosed due to limited follow-up time post NIPT (2-48 months). Reporting this incidental finding allows for better informed maternal clinical management, with possible earlier neoplasm detection.