D6.2. Evaluation criteria of use case cancers in pregnancy screening

Non-invasive prenatal screening (NIPS) assesses the risk of foetal trisomies 13, 18, and 21 by analysing circulating cell-free DNA (cfDNA) in the maternal bloodstream. At 12 weeks of pregnancy, 5-15% of the cfDNA is derived from the placental trophoblasts, while the larger fraction is maternal. Therefore, NIPS will not only identify CNVs arising from placental chromosomal anomalies but also any maternal chromosomal abnormalities which can be associated with constitutional imbalances or conditions such as maternal mosaicism, uterine myomas, or malignancies.  Several studies have demonstrated the potential of NIPS to detect cfDNA derived from a tumour (circulating tumour DNA, ctDNA) and consequently diagnose incipient maternal malignancies. Occult maternal malignancies during NIPS have been identified in about 1 in 8000 to 10000 pregnancies. However, the estimated occurrence of cancers during pregnancies is 1 in 1000 to 1500.

The lack of guidelines or recommendations on how to deal with those incidental findings often precludes early reporting and consequent treatment during pregnancy.  We recommend the identification of malignancy suspicious NIPS profiles needs to be part of the standard operating procedure (SOP) for the interpretation of the test. In those recommendations we provide both technical criteria when to report potential cancers in pregnancy during NIPS reporting and provide a detailed clinical work-up program, which can guide clinicians and laboratories.  We envision those recommendations to be of widespread use for NIPS laboratories, gynaecologists/obstetricians.  The early reporting will trigger treatments during pregnancy likely resulting in improved outcomes.