Objective: To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA for detection of the three main autosomal fetal trisomies in the setting of ultrasonographically identified fetal anomalies.
Methods: Nine hundred patients at risk for fetal aneuploidy with or without ultrasonography anomalies and who underwent invasive procedures were included in the study. Cell-free DNA analysis was performed by massive parallel sequencing during a multicenter, noninterventional, prospective study and the results were compared with a fetal karyotype.
Results: Among all 900 pregnancies, cell-free DNA identified 76 of 76 (100%) fetal Down syndrome, 22 of 25 (88%) trisomy 18, and 12 of 12 (100%) trisomy 13. In those with a normal ultrasonogram and normal cell-free DNA analysis, karyotype identified 2 of 483 (0.4%) additional aneuploidies other than trisomies 13, 18, and 21. In those with an abnormal ultrasonogram and a normal cell-free DNA analysis, there were 23 of 290 (7.9%) additional pathogenic karyotypes. These additional aneuploidies included sex chromosome abnormalities and triploidy. The rates of additional aneuploidies not identifiable by standard cell-free DNA screening in the two groups is significantly different at P<.01.
Conclusion: In women with fetal abnormalities by ultrasonography, the rate of pathogenic chromosome abnormalities missed by cell-free DNA was 8%. Noninvasive prenatal testing should not be offered to women with fetal abnormalities because a negative result is falsely reassuring.
Level of evidence: III.