Noninvasive detection of fetal trisomy 21 a step closer

In the latest step toward making noninvasive detection of fetal trisomy 21 a reality, researchers in California evaluated a multiplexed, massively parallel shotgun sequencing (MPSS) assay, which uses circulating cell-free fetal (ccff) DNA in the plasma of pregnant women, to identify women carrying a trisomy 21 fetus.

Researchers obtained 480 plasma samples from pregnant women at high risk for fetal trisomy 21. Of 449 samples eligible for inclusion, 410 were euploid and 39 were trisomy 21. The MPSS assay correctly identified all 39 of the trisomy 21 samples. Of the euploid samples, the assay incorrectly classified 1 as being trisomy 21 when it was not (false positive). As a result, the method had 100% sensitivity (95% confidence interval [CI], 89%-100%) and 99.7% specificity (95% CI, 98.5%-99.9%).

The authors of the feasibility study caution that the number of samples analyzed was relatively limited and that the sample cohort may not span the entire spectrum of cases presenting in clinical practice. Future clinical validation studies with larger numbers of trisomy 21 samples are needed to assess the true sensitivity of the method. The authors believe that the test has the potential to make a substantial impact on clinical practice for the ever-increasing number of pregnant women who are candidates for invasive testing for fetal chromosome abnormalities.

Ehrich M, Deciu C, Zwiefelhofer T, et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol. 2011;204(3):205.e1-205.e11.