Noninvasive prenatal screening for fetal aneuploidies

Fetuses with trisomy 21, or Down syndrome, can be identified in the first or second trimester of pregnancy using a combination of serum markers in maternal serum and ultrasound findings. The sensitivity and specificity of these modalities are quite good, being in the range of 95%. Recently, several groups have begun to exploit the power of massively parallel sequencing (MPS) to identify prenatal aneuploidies in cell-free fetal DNA that is found in the maternal circulation. Although court rulings regarding the patent positions surrounding this technology have led to other entities being able to offer this form of testing, including academic institutions, four major companies were originally founded with prenatal detection of fetal chromosome abnormalities as their primary focus and most testing in the United States is performed through these companies. The sensitivity and specificity of detection for Down syndrome using MPS are markedly superior to serum and ultrasound markers, being greater than 99%. However, it is important to stress to women seeking testing that the specificity of the MPS approach, while very high, is not perfect. This is a screening test and positive results need confirmation with invasive testing (amniocentesis). In this chapter, we review the techniques that each of these major, currently active U.S. companies are using for noninvasive prenatal screening.