Evidence Matters

NIPS False Positive Rates and PPVs from a Large Reference Laboratory

BACKGROUND AND PURPOSE:

Petersen et al. (AJOG, 2017) provide the PPV and false positive rates from a large reference laboratory database

This study reviewed 712 confirmatory diagnostic studies performed on patients who have received an abnormal or inconclusive NIPS result including
- Common trisomies (492 cases)
- Sex chromosome aneuploidies (138 cases)
- Microdeletion (52 cases)
- Other large genome-wide copy number abnormalities (4 cases)
- Multiple anomalies (9 cases)
Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples

PPV for trisomies were consistent with previous reports
- Trisomy 13: 45%
- Trisomy 18: 77%
- Trisomy 21: 85%
- Monosomy X (Turner syndrome): 26%
- 47,XXX: 50%
- 47,XXY (Klinefelter syndrome): 86%
PPV for microdeletion syndrome regions
- Cri-du-Chat syndrome (7 cases): 0%
- Prader-Willi/Angelman syndrome (10 cases): 0%
- 1p36 deletion syndrome (7 cases): 14%
- 2 deletion syndrome (28 cases): 21%
Of 4 cases with genome-wide abnormalities, 2 were confirmed

Low PPV (0-21%) and high false positive rates (79-100%) rates for microdeletions likely due to low prevalence of these disorders
Possible causes of NIPS false-positive rates include
- Placental mosaicism
- Vanishing twin syndrome
- Maternal chromosomal abnormalities and neoplastic conditions
While NIPS PPVs compare favorably to PPVs of standard aneuploidy screening, patients must be counseled regarding limitations of NIPS and the importance of confirmatory testing

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