Diagnostic performance of quantitative fluorescence PCR analysis in high-risk pregnancies after combined first-trimester screening

INTRODUCTION: We aimed to determine the diagnostic efficiency of quantitative fluorescence polymerase chain reaction (QF-PCR) in a clinical setting where most of the analyses are performed on chorion villus samples from high-risk pregnancies as determined by combined first-trimester screening. METHODS: A retrospective study on QF-PCR data from all pregnancies in the Central and North Denmark Regions over a four-year period (n = 2,550) with invasive prenatal testing carried out due to a high risk of carrying a foetus with Down's syndrome. Results of QF-PCR were compared with those obtained by karyotyping. Other supplementary data were obtained from the Danish Foetal Medicine Database and the Danish Cytogenetic Central Register. RESULTS: QF-PCR for common aneuploidies is fast, has a low failure rate, and is associated with high positive and negative predictive values (PPV, NPV) (> 99.8%) for all analysed abnormal karyotypes except for mosaicism for trisomy 13 (PPV 20%) and sex chromosome mosaic cases (PPV = 40%; NPV = 99.7%)). In 25 (1%) cases, clinically significant chromosome abnormalities other than chromosomes 13, 18, 21, X, and Y were identified by karyotyping. CONCLUSION: QF-PCR is a rapid and accurate diagnostic method to detect common aneuploidies in high-risk pregnancies. However, the rapid test cannot stand alone as several clinically significant abnormal karyotypes would be overlooked.