Prenatal diagnosis by rapid aneuploidy detection and karyotyping: a prospective study of the role of ultrasound in 1589 second‐trimester amniocenteses

Abstract

Reliable methods are available for rapid aneuploidy detection (RAD) for the prenatal diagnosis of trisomies 21, 18 and 13. This study examines the potential advantages and limitations of using RAD as a replacement rather than as an adjunct to traditional karyotyping. One thousand five hundred and eighty-nine consecutive pregnancies referred for cytogenetic assessment were offered RAD (FISH or QF-PCR) as an adjunct to traditional karyotyping. The results of these two processes were compared, and the effects of three policies for cytogenetic evaluation were determined: RAD alone, a combination of RAD for all and traditional karyotyping for cases with ultrasound anomalies or a policy of RAD and traditional karyotyping in all cases. RAD was uninformative because of maternal-cell contamination in 37 (2.3%) cases compared to 4 (0.3%) cases of culture failure in traditional karyotyping. RAD and traditional karyotyping results were concordant in 1526 of 1548 (98.6%) cases. All non-mosaic cases of trisomies 21, 18 and 13 and cases of triploidy were correctly identified by RAD, and there were no false-positive diagnoses. The gold standard of a traditional karyotype in each case would have detected all chromosomal abnormalities. A policy of RAD alone would have identified 60 of 73 (82%) clinically important chromosomal abnormalities. The addition of a full karyotype for cases with evidence of ultrasound abnormalities would have improved detection to 95%. A policy offering RAD to all patients, but restricting traditional karyotyping to cases with ultrasound anomalies, would reduce the number of traditional karyotypes requested by 70%, but maintain a 95% detection rate for all clinically important chromosomal abnormalities. Further studies are required to determine whether similar results could be obtained in district general hospital units and to determine whether this approach would be acceptable to health professionals and patients.