Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: A single-center retrospective analysis of over 85,000 pregnancies

“…Ji et al. also reported a PPV of 75%, yet this was only achieved by combining the analysis of NIPT cfDNA data and serum protein levels [4] . Similarly as previously reported, hematological malignancies were most frequently identified, followed by detection of breast cancers [ 5 , 7 , 8 ].…”

“…Because fetal cfDNA fractions exist in a high background of maternal cfDNA, NIPT can also detect maternal chromosomal abnormalities, like those resulting from maternal mosaicisms or malignancies [3] . Indeed, various reports have shown that NIPT detection of tumor-derived cfDNA (ctDNA) in pregnant women with an occult malignancy was causing the aberrant cfDNA signal thereby disturbing the interpretation of fetal trisomies [4] , [5] , [6] , [7] , [8] , [9] . As the use of NIPT is increasingly expanding to low-risk pregnancies - in some countries it is offered as a first-tier test to all pregnant women - and its scope is being broadened beyond aneuploidy screening, more aberrant results, caused by a malignancy, are expected to emerge.…”

“…No prospective large-scale evaluation of incidental cancer detection following routine NIPT has been published, and existing retrospective reports often present scarce details on the identified genomic aberrations and clinical follow-up [ 4 , 5 ]. We here propose a retrospective analysis of a large series of over 85.000 NIPT tests performed in University Hospitals Leuven, between November 2013 and March 2020, in which women with a NIPT that was suggestive for an underlying malignancy were offered multidisciplinary follow-up investigations.…”

Pregnant women with confirmed neoplasms should not have noninvasive prenatal testing

“…Since the introduction of NIPT in prenatal diagnostics, incidental findings of an occult maternal malignancy following a “false‐positive” NIPT test have been reported repeatedly. Common cancer types encountered in pregnancy (such as breast cancer, lymphoma, and leukemia) and also other cancers (like ovarian cancer, multiple myeloma, digestive cancers, malignant melanoma, or sarcomas) and benign tumors (uterine leiomyomas) have been accidentally identified upon aberrant NIPT testing (previous work and unpublished results). From these cases, it is now appreciated that the presence of tumor‐derived cfDNA can skew the NIPT profile and confound its interpretation.…”

Noninvasive prenatal testing detected acute myeloid leukemia in paucisymptomatic pregnant patient

“…Diagnosis of an acquired malignancy during pregnancy can be difficult since some of the symptoms related to cancer, like fatigue or nausea, are very similar to those of pregnancy 2 . For several types of cancer, it was already shown that NIPT is able to detect cancer‐related genetic aberrations in the presymptomatic stage 2,3 . This holds the promise of accelerating the diagnosis of maternal malignancy and improving long‐term maternal and neonatal outcomes 1,2 …”