2%) than women with a maximum-risk

GDC-0449 molecular weight score (19/198, 9.6%, P < .001). For the 36 cases that experienced spontaneous abortion and did not obtain karyotype confirmation, 33 (91.7%) had a maximum-risk score. All 22 patients who elected to terminate the pregnancy without confirmation had a maximal-risk score. Based only on cases with cytogenetic diagnosis (Table 4), the PPV was 90.9% for trisomy 21 and 82.9% for all 4 cytogenetic abnormalities combined (Table 5). A theoretical PPV was also calculated under the 2 boundary conditions that all unconfirmed high-risk cases were either FP or TP (Table 5). This provided a range for the PPV of 60-94% for trisomy 21 and 52-89% for all abnormalities combined. Among women without ICD-9-coded indications, 63 women aged <35 years received high-risk calls, of which 39 (60.9%) had diagnostic testing and 34 were TP, a PPV of 87.2% (95% CI, 72.6–95.7%). Of 176 women ≥35 years with high-risk calls, 105 Anti-diabetic Compound Library research buy (59.7%) had confirmatory karyotyping and 87 were TP, a PPV of 82.9% (95% CI, 74.3–89.5%). This report of initial clinical

experience with this SNP-based NIPT in >31,000 pregnancies demonstrates that performance in clinical settings is consistent with validation studies.2, 3, 4 and 5 Using only cases confirmed through chromosome analysis or clinical evaluation at birth, the PPV in this mixed low- and high-risk population is 90.9% for trisomy 21 and 82.9% for all 4 aneuploidies, which is far better than current screening methods. Even under the highly conservative assumption that all unconfirmed high-risk cases are incorrect, this test still offers improved clinical performance over traditional screening. The main advantage of this study is the robust information it provides on clinical application of NIPT, which can contribute to, and improve, both test performance and counseling of patients. Fetal fraction, the main variable that affects redraw rates, is positively correlated with gestational age and negatively

correlated with maternal weight, agreeing with previous studies.30, 31, 32 and 33 There are 2 main clinical implications from these findings. First, adequate dating will lower the need for redraw, particularly at early gestational ages. Second, inclusion of a paternal blood sample significantly lowers redraw rates and should be offered from to patients, particularly those >200 lb. Importantly, cases with extremely low fetal fraction, which typically do not resolve with redraw, may have an increased risk for fetal aneuploidy.2 This is likely particularly important for maternal triploidy, which is associated with smaller placentas and lower fetal fractions,2 and 5 and trisomy 13 and trisomy 18 pregnancies. In addition to determining the most likely ploidy state of a fetus, the NATUS algorithm also generates a chromosome-specific risk score, which is a measure of the probability of nonmosaic fetal aneuploidy.