Maternal Plasma DNA Testing

In October 2011, the Sequenom Center for Molecular Medicine (SCMM) became the first laboratory in the United States to offer next-generation sequencing of circulating cell-free (ccf) DNA testing for Down syndrome (trisomy 21). This commercial launch followed the publication of an external clinical validation study demonstrating that testing could identify 98.6% of fetuses with Down syndrome (209/212) with a 0.2% false-positive rate (FPR) (Palomaki et al., 2011). In a later publication derived from that same high-risk cohort, 100% cases of trisomy 18 interpreted (59/59) were detected (FPR=0.28%) as were 91.7% (11/12) cases of trisomy 13 (FPR=0.97%) (Palomaki et al., 2012). Less than 1% of samples failed testing, including both case and control samples.

This level of performance is much better compared with the existing serum screening tests, offering the potential to reduce the number of invasive procedures (chorionic villus sampling [CVS] or amniocentesis) among high-risk women substantially, while maintaining detection of these common trisomies. The American Congress of Obstetricians and Gynecologists has recommended that women, regardless of age, be offered prenatal assessment for aneuploidy by screening or invasive prenatal diagnosis (ACOG, 2007). However, ccfDNA testing is currently recommended as a secondary screening test in women already identified at increased risk of aneuploidy (ACOG, 2012). Our prenatal diagnostic center planned on routinely offering ccfDNA testing to high-risk women receiving genetic counseling and sought to document implementation issues and women’s decision-making encountered in the early introduction of this technology.

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