Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA

Our NIPT validation in high risk pts for DS, T18, T13, SCAs, and fetal sex • Overall, there were 137 pregnancies with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13.  • Trisomy 21: sensitivity was 100%, specificity >99%, False positive rate 0.1%, PPV of 97.9%.  • 3 false negatives T18 and 2 false negatives T13 • No false positive tests for trisomies 18 or 13 (positive predictive value, 100%).  • Fetal sex prediction showed sensitivity and specificity performance > 99% • The SCAs are few in absolute number in this prospective data set. Sensitivity was 100.0% (15 of 15) for all of the SCAs taken together. There were 11 false positive results for 45, X (0.3%). There were 2 false positive results for 47, XXY, 3 false positive results for 47, XXX, and none for 47, XYY. • The overall positive predictive valueof the SCAs was 48.4% and the negative predictive value was 100% (although the small number of sex chromosome aneuploidies detected in our population of high-risk patients precluded definitive conclusions. We showed high sensitivity (100%) but variable results in terms of positive predictive value. This was especially true for 45, X, in which maternal mosaicism may be a contributor to discordant non-invasive MPS results.