Diagnostic accuracy of the BACs-on-BeadsTM assay versus karyotyping for prenatal detection of chromosomal abnormalities: a retrospective consecutive case series

Objective To evaluate the diagnostic performance of the BACs-on-Beads(TM) (BoBs(TM)) assay for prenatal detection of chromosomal abnormalities. Design Retrospective study. Setting Tertiary prenatal diagnosis centre. Population Women referred for prenatal diagnosis. Methods We retrieved 2153 archived DNA samples collected between January 2010 and August 2011 for the BoBs(TM) assay. These samples had previously been tested by quantitative fluorescence polymerase chain reaction (QF-PCR) and karyotyping. In the BoBs(TM) assay a sample was defined as normal disomic when the ratio of the fluorescence intensities in a chromosome locus lay within the threshold (mean ratio +/- 2SD), and as deleted or duplicated when the ratio was below the lower threshold (0.6-0.8) or above the upper threshold (1.3-1.4), respectively. The BoBs(TM) results were further validated by microarray and compared in a blinded manner with the original QF-PCR and karyotyping results. Main outcome measures Concordance of any numerical, structural, and submicroscopic chromosomal abnormalities between the methods. Results BACs-on-Beads(TM) was similar to karyotyping and QF-PCR in detecting trisomy 13, trisomy 18, trisomy 21, and sex chromosomal aneuploidies, and superior to QF-PCR in detecting major structural abnormalities (53.3 versus 13.3%) and mosaicism (28.6 versus 0%) involving chromosomal abnormalities other than the common aneuploidies. BoBs(TM) detected six microdeletion syndromes missed by karyotyping and QF-PCR; however, BoBs(TM) missed two cases of triploidy identified by QF-PCR. Therefore, the sensitivity of BoBs(TM) is 96.7% (95% CI 92.6-98.7%), and its specificity is 100% (95% CI 99.8-100%). Conclusions BACs-on-Beads(TM) can replace QF-PCR for triaging in prenatal diagnosis, and gives a better diagnostic yield than current rapid aneuploidy tests.