Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis.

OBJECTIVE: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis in screening for aneuploidies and to explore the potential use of this method in clinical practice. METHODS: Searches of PubMed and MEDLINE were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between 2011, when the first such study was published, and 20 December 2013. RESULTS: Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.0% (95% CI 98.2­99.6) and 0.08% (95% CI0.03­0.14), respectively, for trisomy 21; 96.8% (95% CI 94.5­98.4) and 0.15% (95% CI 0.08­0.25) for trisomy 18; 92.1% (95% CI 85.9­96.7) and 0.20% (95% CI 0.04­0.46) for trisomy 13; 88.6% (95% CI 83.0­93.1) and 0.12% (95% CI 0.05­0.24) for monosomy X, and 93.8% (95% CI 85.9­98.7) and 0.12% (95% CI 0.02­0.28) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR was 94.4% (95% 74.2­99.0) and the FPR was 0% (95% CI 0.00­1.84) for trisomy 21. CONCLUSION: An analysis of cfDNA in maternal blood provides effective screening for trisomies.

Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies.

OBJECTIVE: To explore the feasibility of routine maternal blood cell-free (cf) DNA testing in screening for trisomies 21, 18 and 13 at 10 weeks' gestation. METHOD: In this prospective study, women attending The Fetal Medicine Centre in London, UK, between October 2012 and April 2013, with singleton pregnancy and live fetus with CRL 32-45 mm, were screened for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks and the combined test at 12 weeks. RESULTS: cfDNA testing was performed in 1005 singleton pregnancies with a median maternal age of 37 (range, 20-49) years. Risks for trisomies were provided for 957 (95.2%) cases and in 98.0% these were available within 14 days from sampling. In 48 (4.8%) cases no result was provided due to problems with delivery to the laboratory, low fetal fraction or assay failure. Repeat sampling was performed in 40 cases and a result obtained in 27 (67.5%) of these. In 11 cases the risk score for trisomy 21 and in five cases that for trisomy 18 was > 99%, in one the risk for trisomy 13 was 34% and in 968 the risk for each of the three trisomies was < 0.01%. The suspected trisomies were confirmed by karyotyping after chorionic villus sampling (CVS), except in one case of trisomy 18 in which the karyotype was normal. On the basis of the maternal age distribution of the study population, the expected and observed numbers for each of the three trisomies were similar. Both cfDNA and combined testing detected all trisomies, but the estimated false-positive rates (FPR) were 0.1% and 3.4%, respectively. CONCLUSION: Routine screening for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks is feasible and has a lower FPR than does combined testing, but abnormal results require confirmation by CVS.