A study published in the Journal of the American Medical Association analysed the results of prenatal maternal blood tests where a high chance of fetal chromosomal abnormality had been indicated, but where no fetal abnormality in fact existed.
Out of 125,426 prenatal tests conducted between 2012 and 2014, about three percent (3,757) screened positively for one or more aneuploidies. Of these, only 39 women showed a multiple aneuploidy pattern that matched cancer cases that had already been reported, and in 16 of these the fetus turned out not to have the abnormalities detected in the NIPT.
Seven out of these 16 women were later diagnosed with cancer, leading the researchers to estimate that 20—44 percent of cases in which the mother's blood sample does not 'match' the fetal karyotype will be because of the mother's previously undiagnosed cancer. The study also revealed three cases in which a single abnormality result occurred and maternal cancer was later diagnosed.
The results were obtained from Illumina's NIPT test (sold under the name Verifi), which screens for the presence of whole-chromosome aneuploidy for chromosomes 13, 18 and 21. It can also test for sex chromosome aneuploidy by considering sequencing counts for chromosomes X and Y.
In common with other NIPT screenings, the Illumina test uses the discovery that cell-free fetal DNA can be detected in maternal plasma, but can be separately analysed to provide information on the fetus.
While Illumina is adamant that its test is a fetal screening tool and not a diagnostic test, the results were published after rival company Sequenom revealed earlier in the year that its prenatal blood test had detected potential cancer in at least 40 expectant mothers since its launch three years ago. Sequenom is developing a related cancer test (see BioNews 793).
The potential detection of cancer as a secondary finding gives rise to a number of ethical issues about false positives, over-diagnosis and how women and clinicians should be expected to deal with their results (see BioNews 797).
Professor Diana Bianchi, lead author of the study and executive director at the Tufts Medical Centre, comments that 'until further studies are done to assess the clinical implications of discordant NIPT and fetal karyotype results, it is not clear what, if any, follow-up clinical evaluation is appropriate'.
Dr Roberto Romero of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Professor Maurice Mahoney of Yale University School of Medicine agree. In an editorial accompanying the study, they comment that 'at this time, there is insufficient evidence about the benefits, risks, and costs of reporting the incidental findings'.
They also note 'given that it is likely that NIPT will increase in the coming years, an active dialogue among stakeholders needs to take place to provide informed advice to potentially affected pregnant women and to guide their care'.