Maternal blood testing of DNA more effectively screens for Down syndrome in early pregnancy than standard screening methods that include ultrasound, according to an article published April 1 in the New England Journal of Medicine.
In a large study that followed nearly 16,000 pregnant women from 35 centers in six countries, a research team led by Dr. Mary Norton of the University of California, San Francisco found that cell-free DNA (cfDNA) testing for trisomy 21 detected all 38 fetuses with Down syndrome. In comparison, the standard screening combination of measuring biochemical analytes and ultrasound-based nuchal translucency identified only 30 of 38 (78.9%) cases.
Cell-free DNA testing also had only nine false positives (0.06% false-positive rate), compared with 854 false positives (5.4% false-positive rate) from standard screening. Cell-free DNA testing yielded an 80.9% positive predictive value, compared with 3.4% for standard screening. Both differences were also statistically significant (p < 0.001).
The researchers noted that the cfDNA testing technique was also better for detecting two other less common chromosomal abnormalities: trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome).
"Although these data support the use of cfDNA testing in women regardless of age or risk status, further cost utility studies are warranted," the authors wrote. "As emphasized by professional societies, the use of cfDNA testing and other genetic tests requires an explanation of the limitations and benefits of prenatal test choices to the patient."
Some caution is also indicated, as standard screening can identify risk for a broad array of abnormalities that can't be identified on cfDNA testing, according to the researchers. Furthermore, the team noted that there were a surprisingly high number of aneuploidies found in the 488 pregnant women whose plasma samples were disqualified due to factors such as an inadequate or immeasurable quantity of fetal DNA, assay failure, or high sequencing variance. Chromosomal defects were found in 2.7% of these fetuses, a markedly higher rate than the 0.4% prevalence in the overall group.
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&dpr=2&fit=crop&h=167&q=70&w=250)
