cfDNA testing predicts aneuploidy in low-risk pregnancies

Massively parallel sequencing of maternal cell-free DNA (cfDNA testing) has been shown better at predicting fetal aneuploidies than standard screening in a new study among a general obstetric population. Published in The New England Journal of Medicine, the report by the CARE Study group was funded by Illumina.

Twenty-one centers in the United States were included in the research, which was performed on 1914 women (mean age 29.6 years) with singleton pregnancies who were undergoing standard aneuploidy screening with serum biochemical assays with or without nuchal translucency measurement. cfDNA testing was performed in blinded fashion to determine the chromosome dosage for each sample.

The primary end point was a comparison of the false-positive rates for detection of fetal trisomies 21 and 18 with use of standard screening and cfDNA testing. The reference standard was birth outcomes or karyotypes.

cfDNA testing was associated with significantly lower false-positive rates than standard screening  for trisomies 21 and 18 (0.3% vs 3.6%, P<0.001 and 0.2% vs 0.6%, P=0.003, respectively). With cfDNA testing, all cases of aneuploidy were detected (5 trisomy 21, 2 trisomy 18, 1 trisomy 13), for a negative predictive value of 100%. Positive predictive values for cfDNA testing versus standard screening were 45.5% vs 4.2% for trisomy 21 and 40.0% vs 8.3% for trisomy 18.

cfDNA testing previously has been proven to accurately detect fetal autosomal aneuploidy in high-risk pregnant women. This study, the authors said, sheds new light on false-positive rates and positive predictive values for the technology in detection of trisomies 21 and 18 in women with low-risk pregnancies.