Accuracy and Clinical Value of Maternal Incidental Findings During Noninvasive Prenatal Testing for Fetal Aneuploidies

Genome-wide shotgun sequencing of cell-free (cf) DNA from the serum of pregnant women can identify chromosomal imbalances in an unborn fetus. Although initially developed to screen for fetal trisomies 21, 18, and 13, several studies have now demonstrated that genome-wide analysis can also detect other fetal aneuploidies, segmental imbalances, and even submicroscopic copy-number variations (CNVs). Because genome-wide cfDNA sequencing interrogates maternal as well as fetal DNA, maternal genetic variation can be detected as well. However, current analyses do not include an interpretation of maternal copy number variants. In this study, results from 9882 women undergoing cfDNA screening were analyzed to interpret the incidence of different types of CNVs. As expected based on prior population-based studies, 10% of nonrecurrent (unique) and 0.4% of susceptibility CNVs (for genomic disorders) were identified. Results from 5 of these were returned to the women, as they were felt to represent actionable conditions, including a deletion in the RUNX1 gene, and 4 cases of chromosomal rearrangements of potential significance to offspring. Analyzing sequencing data from the maternal cfDNA when performing prenatal cfDNA screening can be helpful to overall pregnancy management. The presence of such variants in maternal serum should be reported if clinically relevant. The identification and reporting of such CNVs, however, raise potential counseling dilemmas that warrant consideration.