Analysis of cell‐free <scp>DNA</scp> in maternal blood in screening for fetal aneuploidies: updated meta‐analysis

<jats:title><jats:styled-content style="fixed-case">ABSTRACT</jats:styled-content></jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To review clinical validation or implementation studies of maternal blood cell‐free (cf) <jats:styled-content style="fixed-case">DNA</jats:styled-content> analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Searches of <jats:styled-content style="fixed-case">PubMed</jats:styled-content>, <jats:styled-content style="fixed-case">EMBASE</jats:styled-content> and The Cochrane Library were performed to identify all peer‐reviewed articles on <jats:styled-content style="fixed-case">cfDNA</jats:styled-content> testing in screening for aneuploidies between January 2011, when the first such study was published, and 4 January 2015.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 37 relevant studies were identified and these were used for the meta‐analysis on the performance of <jats:styled-content style="fixed-case">cfDNA</jats:styled-content> testing in screening for aneuploidies. These studies reported <jats:styled-content style="fixed-case">cfDNA</jats:styled-content> results in relation to fetal karyotype from invasive testing or clinical outcome. Weighted pooled detection rates (<jats:styled-content style="fixed-case">DR</jats:styled-content>) and false‐positive rates (<jats:styled-content style="fixed-case">FPR</jats:styled-content>) in singleton pregnancies were 99.2% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 98.5–99.6%) and 0.09% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.05–0.14%), respectively, for trisomy 21, 96.3% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 94.3–97.9%) and 0.13% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.07–0.20) for trisomy 18, 91.0% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 85.0–95.6%) and 0.13% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.05–0.26%) for trisomy 13, 90.3% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 85.7–94.2%) and 0.23% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.14–0.34%) for monosomy X and 93.0% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 85.8–97.8%) and 0.14% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.06–0.24%) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the <jats:styled-content style="fixed-case">DR</jats:styled-content> for trisomy 21 was 93.7% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 83.6–99.2%) and the <jats:styled-content style="fixed-case">FPR</jats:styled-content> was 0.23% (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.00–0.92%).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Screening for trisomy 21 by analysis of <jats:styled-content style="fixed-case">cfDNA</jats:styled-content> in maternal blood is superior to that of all other traditional methods of screening, with higher <jats:styled-content style="fixed-case">DR</jats:styled-content> and lower <jats:styled-content style="fixed-case">FPR</jats:styled-content>. The performance of screening for trisomies 18 and 13 and sex chromosome aneuploidies is considerably worse than that for trisomy 21. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.</jats:p></jats:sec>