Screening for Down syndrome – incidental diagnosis of other aneuploidies

Abstract

Down syndrome screening programmes lead to the prenatal diagnosis of other chromosomal abnormalities, some of which would not be detected by the secondary use of cell-free (cf)DNA testing in screen positives. This study aims to assess the number of these incidental diagnoses. This study is a systematic review of the literature to identify large prospective screening studies that reported diagnoses other than trisomies 21 and 18. There were ten informative prospective studies in which a total of 1,500,999 women were screened, and there were 3689 aneuploidy cases detected in the screen positives. Trisomy 21 was estimated to comprise only 58% of detected aneuploidies, trisomies 21 and 18 comprised 72%, and the common trisomies - 21, 18 and 13 - comprised 76%. Common trisomies and sex chromosome abnormalities, now included in all commercial cfDNA tests, were estimated to comprise 87% of aneuploidies in the Down syndrome screen positives. All these proportions were higher for second trimester protocols compared with those carried out wholly or partly in the first trimester. Secondary use of cfDNA testing will lead to about one-fifth reduction in diagnoses, taking account of both undetectable aneuploidies and false-negatives. This loss might be overcome by contingent cfDNA testing.