Hong Kong Medical Journal · Oct 22, 2026

Incidental detection of maternal malignancy in non-reportable results from non-invasive prenatal testing: experience in Hong Kong and literature review

By Chan YYY, Xue S, Yu ELM et al.

INTRODUCTION: Non-invasive prenatal testing (NIPT) for fetal aneuploidy occasionally yields non-reportable results due to persistent 'noisy' signals, which may indicate occult maternal malignancy. This study investigated the clinical and genetic implications of non-reportable NIPT results, focusing on multiple chromosomal aberrations associated with maternal malignancy, with the goal of developing standardised management protocols for pregnant women with such suspicious NIPT results. METHODS: From 2020 to 2023, women with persistent non-reportable NIPT results were identified and followed up in Hong Kong. Cancer cases were analysed for clinical history and chromosomal patterns. Incidental cancer detection rates were calculated and compared with literature reports. Tag Z-score chromosomal abnormalities were compared between cancer and non-cancer groups; the corresponding sensitivity and specificity were calculated. RESULTS: Among 84 446 NIPT tests, 151 (0.18%) showed persistent noisy signals. Of 131 patients with follow-up data, five (3.82%) were diagnosed with maternal malignancy; the overall incidental detection rate was 0.006% (5 of 84 446). Although three women delivered healthy babies, most presented with late-stage cancer confirmed by imaging and biopsy. All five cases exhibited ≥3 chromosomal aberrations on repeat NIPT; chromosome 18 was consistently involved. Univariate analysis revealed significant differences in Tag Z-score frequencies for chromosomes 18 (P=0.026) and 21 (P=0.029) between cancer and non-cancer groups. A clinical flowchart was developed to guide management of patients with multiple aberrations. CONCLUSION: Although rare, occult maternal malignancy represents 3.82% of non-reportable NIPT results. This risk should be included in pre-test counselling and may warrant early oncological evaluation. Whole-body magnetic resonance imaging should be considered to facilitate cancer diagnosis.

doi.org/10.12809/hkmj2513970 Open access PubMed 42908122 Biomarkers