Cell-Free DNA Screening Results by Stage of Maternal Malignancy.

Background: Cell-free DNA screening is increasingly used for fetal aneuploidy screening. Maternal malignancy is associated with abnormal cell-free DNA results; however, the impact of tumor staging and origin on cell-free DNA results remains unclear.

Objective: To characterize the types and stages of malignancies resulting in abnormal cell-free DNA screening results.

Study design: This is a single center, retrospective review of cases with a known, suspected, or incidentally diagnosed malignancy during pregnancy from 2015-2023 queried using ICD9/10 codes for malignancy. We extracted maternal medical history, cancer history, aneuploidy screening results and fetal outcomes. We used Fishers exact and Wilcoxon rank sum tests to determine associations between cfDNA screening results and (1) demographic factors, (2) cancer characteristics, and (3) fetal outcomes.

Results: We identified 97 cases of malignancy in pregnancy. Thirty-three patients had no aneuploidy screening. Twenty-two underwent first trimester screening and 4 underwent quad screening, all with low-risk results. Among the 38 patients who had cell-free DNA screening, 21.1% (8/38) were hematologic and 78.9% (30/38) were solid tumors. The most common locations were breast (11/38), blood (8/38), and gastrointestinal (5/38). Overall, 31.6% (12/38) of patients had abnormal cell-free DNA results. The fraction of stage 0, I, II, III, and IV solid cancers with abnormal cell-free DNA results was 0/4 (0%), 0/5 (0%), 2/6 (33.3%), 1/4 (25%), and 7/11 (63.6%), respectively. Metastasized status was significantly different between groups: 47.6% (10/21) of patients with stage II-IV solid cancers had abnormal cell-free DNA results, compared to 0% (0/9) of patients with stage 0-I solid cancers (p=0.013). No fetuses had a confirmed aneuploidy.

Conclusions: Our data suggest that early stage, solid tumors are less likely to impact cell-free DNA screening results than metastatic tumors. Larger cohorts are needed to further characterize the association between tumor type/stage and cell-free DNA result. Ultimately, cell-free DNA screening may be more likely to incidentally diagnose certain types of maternal malignancy than others.