Noninvasive prenatal screening for aneuploidy: positive predictive values based on cytogenetic findings

We sought to determine the positive predictive value (PPV) of noninvasive prenatal screening (NIPS) for various aneuploidies based on cases referred for follow-up cytogenetic testing. Secondarily, we wanted to determine the false-negative (FN) rate for those cases with a negative NIPS result.

We compared the cytogenetic findings (primarily from chromosome analysis) from 216 cases referred to our laboratories with either a positive or negative NIPS result, and classified NIPS results as true positive, false positive, true negative, or FN. Diagnostic cytogenetic testing was performed on the following tissue types: amniotic fluid (n = 137), chorionic villi (n = 69), neonatal blood (n = 6), and products of conception (n = 4).

The PPV for NIPS were as follows: 93% for trisomy (T)21 (n = 99; 95% confidence interval [CI], 86-97.1%), 58% for T18 (n = 24; 95% CI, 36.6-77.9%), 45% for T13 (n = 11; 95% CI, 16.7-76.6%), 23% for monosomy X (n = 26; 95% CI, 9-43.6%), and 67% for XXY (n = 6; 95% CI, 22.3-95.7%). Of the 26 cases referred for follow-up cytogenetics after a negative NIPS result, 1 (4%) was FN (T13). Two cases of triploidy, a very serious condition but one not claimed to be detectable by the test providers, were among those classified as true negatives.

T21, which has the highest prevalence of all aneuploidies, demonstrated a high true-positive rate, resulting in a high PPV. However, the other aneuploidies, with their lower prevalence, displayed relatively high false-positive rates and, therefore, lower PPV. Patients and physicians must fully understand the limitations of this screening test and the need in many cases to follow up with appropriate diagnostic testing to obtain an accurate diagnosis.