Noninvasive DNA test is highly specific for fetal aneuploidy

February 9, 2012

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.

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 of fetal aneuploidy who were undergoing diagnostic testing in the late first and early second trimesters. Results from the blinded testing of 212 pregnancies with trisomy 21 and their 1,484 matched controls already appeared in Genetics in Medicine. Simultaneous with that study, the authors tested 62 trisomy 18 and 12 trisomy 13 blinded samples, along with samples from controls. They calculated a detection rate of 100% for trisomy 18 and 91.7% for trisomy 13. Corresponding false-positive rates were 0.28 and 0.97, respectively. The results were published online February 2 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.

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