(187) Cell-Free DNA Screening Results by Stage of Maternal Malignancy

Objective: Cell-free DNA (cfDNA) screening is increasingly used for non-invasive fetal aneuploidy screening. Maternal malignancy is associated with abnormal or non-reportable cfDNA screening results but the impact of tumor staging and origin on cfDNA screening remains unclear. Our objective was to characterize the types and stages of malignancies that result in atypical cfDNA results.

Study Design: We present a single center, retrospective review of cases with a known, suspected, or incidentally diagnosed malignancy during pregnancy who underwent cfDNA fetal aneuploidy screening between 2015-2023. We queried patients using ICD9/10 codes for malignancy. We excluded patients who did not have a confirmed malignancy during pregnancy or within 2 years post-partum, and those who did not undergo cfDNA testing. We extracted maternal history, cancer type/stage, cfDNA results, and fetal outcomes from the medical record. We used Fisher’s exact test to analyze categorical variables.

Results: 97 cases of malignancy in pregnancy were identified, of which 37 patients underwent cfDNA screening. Eleven patients (30%) had abnormal or non-reportable cfDNA results: 2/8 (25%) patients with blood cancers and 9/29 (31%) patients with solid tumors. Overall, the fraction of stage 0, I, II, III, and IV solid cancers with abnormal cfDNA screening results was 0/3 (0%), 0/5 (0%), 2/6 (33%), 1/4 (25%), and 6/11 (50%), respectively. Pregnant patients with stage 2-4 cancers were more likely to have an abnormal cfDNA result than those with stage 0-1 cancers (p=0.03). No fetuses had a confirmed cytogenetic abnormality.

Conclusion: Our data suggest that early stage, solid tumors are not reliably detected by prenatal cfDNA screening, while metastatic tumors are more likely to result in atypical cfDNA results. Larger patient cohorts are needed to further characterize the association of different tumor types and the pattern of cfDNA results. Ultimately, cfDNA may be more likely to incidentally diagnose certain types of maternal malignancy than others.