QF-PCR-based prenatal detection of common aneuploidies in the Czech population: Five years of experience

Abstract

We present the results from the largest clinical application of QF-PCR for antenatal rapid aneuploidy detection (RAD) in routine prenatal diagnosis in the Czech Republic. QF-PCR was performed in addition to karyotyping (dual testing) in two settings: the first was a single multiplex reaction testing only trisomy 21 and amelogenin X/Y alleles in the second trimester screened positive cases (T21 test), and the second setting consisted of two multiplexes (2M test) for common aneuploidies (13, 18, 21, X and Y) in cases with other RAD indications such as ultrasound findings, late booking or maternal anxiety. Dual testing was performed in 6349/12,778 (49.7%) of prenatal samples using either T21 or 2M test between 2002 and 2007. The clinical acceptability of our dual testing policy, methodological efficiency of RAD and residual risks of other chromosomal aberrations (CHAs) were evaluated. QF-PCR detected 92% (175/190) of significant CHAs. The 2M test identified 93.5% and the T21 test identified 87.5% of the significant CHAs with complete specificity. The residual risk of significant CHA was 1/231 in the 2M test and 1/565 in the T21 test. If RAD for all common aneuploidies is used as the sole prenatal diagnosis method, the odds of missing a CHA of any type are 1:90 and the odds of missing significant CHA with no ultrasound findings are 1:1513. If prenatal karyotyping were used as an additional procedure to RAD in cases only with ultrasound findings, 186/190 (97.8%) of the significant CHAs would be detected when 15.7% cases were karyotyped, according to our data. We consider RAD directed towards trisomy 21 alone (our T21 test) as an economically and clinically acceptable part of second trimester screening for Down syndrome. Both RAD tests allow fast alleviation of maternal anxiety with low residual risk when the test results are negative, and allow fast decision making if the results are positive. However, replacement of dual testing with only the RAD procedure in specific indications accepted in some countries (Great Britain) remains in the Czech Republic a theme for debate.