Maternal Malignancies Identified Through Non-invasive Prenatal Testing: A Systematic Review and Meta-Analysis.

OBJECTIVE: Non-invasive prenatal testing (NIPT) may incidentally reveal chromosomal abnormalities of maternal origin. Although specific chromosomal aberrations have been associated with maternal malignancy, reported risks vary widely. This meta-analysis aimed to quantify the magnitude and consistency of these associations. METHODS: A systematic review and meta-analysis of observational studies reporting maternal malignancy among pregnant individuals with abnormal NIPT results was conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Risk of bias was assessed using the ROBINS-I tool. RESULTS: Six studies met the inclusion criteria. Multiple chromosomal aberrations (MCA), although representing a minority of abnormal NIPT findings, accounted for a substantial proportion of confirmed maternal malignancies. MCA were strongly associated with cancer (OR 239.98; 95% CI 80.16-718.44; I 2 = 0%). In studies that further characterized genomic patterns, complex gain-loss profiles were also associated with increased risk (OR 188.64; 95% CI 34.17-1041.51; I 2 = 9.5%). Heterogeneity was low across analyses. CONCLUSION: Multiple chromosomal aberrations and complex gain-loss patterns on NIPT were strongly associated with maternal malignancy. These findings support the use of structured diagnostic pathways and targeted clinical evaluation when high-risk genomic patterns are identified.