Noninvasive DNA test: highly specific for fetal aneuploidy

Results from an international multicenter study suggest that a new plasma-based DNA test detects nearly all cases of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome), in addition to Down syndrome, with low false-positive rates.

The MaterniT21 test, developed by the Sequenom Center for Molecular Medicine, uses circulating cell-free DNA fragments isolated from maternal plasma and determines the fetal fraction using a published method relying on differentially methylated markers.

Maternal plasma samples were gathered at 27 prenatal diagnostic centers from women at high risk for fetal aneuploidy who were undergoing diagnostic testing in the late first and early second trimester. Results from the blinded testing of 212 pregnancies with trisomy 21 and their 1,484 matched controls already appeared in Genetics in Medicine.

"The study provides strong evidence that secondary screening using maternal plasma samples from high-risk pregnancies will simultaneously identify nearly all cases of trisomy 18 and 13," the authors write.

Interpretation of the massively parallel shotgun-sequencing (MPSS) test was possible in 99.1% of samples for the 3 aneuploidies, yielding an overall detection rate of 98.9%. The 3 false-negatives involved 2 Down syndrome pregnancies and 1 trisomy 13 pregnancy. Full clinical interpretation was not possible for 17 pregnancies, even after testing twice.

The manufacturer is in discussion with the US Food and Drug Administration to determine necessary preclinical and clinical studies required to support a premarket approval application for an in vitro diagnostic device for trisomy 21.

Palomaki GE, Deciu C, Kloza EM, et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med. February 2, 2012, [Epub ahead of print.]