Cell‐free fetal DNA analysis in maternal plasma as screening test for trisomies 21, 18 and 13 in twin pregnancy

Objectives To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA (cfDNA) in screening for the three main autosomal fetal trisomies in twin pregnancies. Methods CfDNA testing was offered to 492 patients with twin pregnancies without ultrasound anomalies as a first-line screening test or after serum screening in clinical practice. Data were collected prospectively and a retrospective analysis was performed. CfDNA analysis was performed by massively parallel sequencing. The fetal fraction threshold for test evaluation was 8%. Regression analysis was performed to investigate the effect on the test failure rate of various variables. Performance of the test is also reported. Results The test was performed first line (after first-trimester scan) in 377 patients and following serum screening in 115. 78.8% of pregnancies were dichorionic-diamniotic. The test failed at the first attempt in 12 (2.9%) of 420 pregnancies with available outcomes, and regression analysis demonstrated that only maternal weight was a significant independent predictor of test failure. After redraw, a result was achieved in 10 cases. CfDNA identified all 3 cases of trisomy 21, and the only case of trisomy 18. For trisomy 21, the specificity was 99.8% (95% CI [98.7% - 100.0%]). When considering the spontaneous or ART origin of pregnancies, there were no significant differences in terms of maternal weight or of no-result rate for cfDNA screening in the two groups. Conclusions In twin pregnancies without fetal ultrasound abnormalities, cfDNA had a high success rate and performance. Therefore, in routine practice, cfDNA could be considered as a first- or second-line screening test.