We read with interest the article by Meck et al and were pleased to see an emphasis on the importance of positive predictive value (PPV). PPVs are more valuable to clinicians than detection rates. When the detection rate is close to 100% (as in the case for trisomy 21), it may provide a misleading view on noninvasive prenatal testing (NIPT) and suggest that it is actually a diagnostic test.

However, several of the key findings presented in this study had been reported previously, but not referenced. High PPV for trisomy 21 and lower PPVs for trisomies 13 and monosomy X were reported by Dar et al. Likewise, the finding that twins can lead to false-positive calls has been discussed previously by Curnow et al. Although the inability to determine additional haplotypes might lead to an increase in false-positive calls with quantitative NIPT methods, this limitation is eliminated when the SNP-based method is used.

Meck et al assume that the use of chorionic villus sampling (CVS) is sufficiently accurate for the confirmation of NIPT results. We advise caution when CVS is used after NIPT. The diagnostic accuracy of CVS was established mostly on the basis of studies of women of advanced maternal age who were at risk for nonmosaic aneuploidy arising from meiotic nondisjunction. NIPT identifies women with aneuploid cells in the placenta that have arisen from both meiotic error and mitotic error. Mitotic errors often result in mosaicism. Therefore, placental mosaicism may be much more common in women with positive NIPT results. The presence of confined placental mosaicism accounted for at least 3.6% of high-risk calls in the study by Dar et al. In 2 cases for which CVS appeared to confirm a high-risk call, further follow-up evaluation revealed that the fetus was actually normal. Others have reported similar findings. Therefore, we believe that, at this time, an abnormal CVS result should not be considered fully diagnostic. NIPT-positive, CVS-positive cases need confirmation through amniocentesis or ultrasound scans to prevent termination of a normal pregnancy.