What will be the role of first-trimester ultrasound if cell-free DNA screening for aneuploidy becomes routine?

Abstract

Until recently, most developed countries either hadadopted the first-trimester combined test as the standardapproach to antenatal screening for Down syndromeor were in the process of doing so. Some had evenintroduced sequential protocols such as the contingenttest, which builds on the combined-test markers andoffers second-trimester serum markers and/or furtherultrasound examination to a large subgroup of women,selected according to their estimated risk. Others haveextended the combined test by incorporating routinelysimultaneous determination of additional ultrasoundmarkers. However, the situation has changed radicallywith the introduction of non-invasive prenatal testingusing maternal plasma cell-free (cf) DNA.Inresponsetotheencouragingpublishedresultsofearlystudies, professional bodies cautiously recommended theuse of cfDNA only as a secondary test in those patientsalready regarded as being at high risk. This approachrestricted testing to women with positive conventionalscreening tests and, in some localities, to women withadvanced maternal age, a family history of aneuploidyor ultrasound markers of aneuploidy. Since then, furtherconfirmatory studies have been published, particularlyin unselected populations, and now there can be nodoubt that primary cfDNA screening could achieve vastlysuperiorperformanceforthedetectionofDownsyndromecompared with any of the conventional protocols orsecondary cfDNA screening. However, this approachis currently impractical in most public-health settingsbecause of the high cost of cfDNA testing and the factthat, in many localities, the tests are available only byshipping samples to commercial laboratories in the USAand China.To overcome the problem of cost, a compromisehas been suggested: the contingent cfDNA test