TH18- ClariTest® Core Test Information

Testing Methodology

ClariTest® Core is a non-invasive prenatal screen that measures the relative proportion of chromosomes in maternal blood to assess the probability of fetal trisomies 21, 18, and 13, sex chromosome aneuploidies, and if ordered, 22q11.2 deletion syndrome. Evaluation of sex chromosome aneuploidies and 22q11.2 deletion is only available in singleton pregnancies. A directed analysis of cell-free DNA (cfDNA) is performed using Digital Analysis of Selected Regions (DANSR™) with microarray quantitation and Fetal Fraction Optimized Risk of Trisomy Evaluation (FORTE™) analysis. The result incorporates the fetal fraction of cfDNA, maternal age and gestational age.

Limitations of Test

This is a screening test for aneuploidies of chromosomes 21, 18, 13, X and Y and, if ordered, for 22q11.2 microdeletions in singleton pregnancies of at least 10 weeks gestational age. In twin pregnancies of at least 10 weeks gestational age, this test screens for aneuploidies of chromosomes 21, 18, and 13 and for the presence or absence of the Y chromosome, but is not validated to screen for sex chromosome abnormalities. The test evaluates placental DNA in the maternal circulation, which is typically representative of the fetal DNA. This test cannot be used in pregnancies with more than two fetuses, maternal transplant, recent maternal blood transfusion, or induced or spontaneous twin demise, or for the diagnosis of mosaicism, partial chromosome aneuploidy, translocations, maternal aneuploidy, or maternal malignancy. This test does not screen for potential chromosomal or genetic conditions other than those expressly identified in this report. This test does not identify pregnancies at risk for open neural tube defects. A negative test result does not eliminate the possibility of an affected pregnancy with trisomy 21, trisomy 18, trisomy 13, Monosomy X, XXX, XXY, XYY, XXYY, or 22q11.2 microdeletions (see Test Performance Data table). It is not intended nor validated as a sole diagnostic test. Maternal, fetal, and placental mosaicism could lead to discordant results.

Test Performance Data in Singleton Gestations

Disorder N Sensitivity 95% Confidence Interval* Specificity 95% Confidence Interval*
Trisomy 21¹ 23,155 99.3% (418/421) 97.9-99.8 99.96% (22,724/22,734) 99.92-99.98
Trisomy 18¹ 22,399 97.4% (147/151) 93.4-99.0 99.98% (22,243/22,248) 99.95-99.99
Trisomy 13¹ 14,243 93.8% (30/32) 79.9-98.3 99.98% (14,208/14,211) 99.94-99.99
Monosomy X² 1,381 94.3% (82/87) 87.2-97.5 99.8% (1,291/1,294) 99.3-99.9
XXX/XXY/XYY/XXYY²: Sex chromosome aneuploidies will be reported if detected. Limited data of these more rare aneuploidies precludes performance calculations. To date, only XXYY has not been detected at BioReference Laboratories.
Fetal Sex²: Accuracy for fetal sex (male or female) is >99% (95% CI: 99.4-99.9).
*Based on the samples assessed, there is a 95% chance that the true values of sensitivity and specificity lie between the bounds of the confidence interval.
Test performance data displayed in this table are derived from the Roche Ariosa NIPS test, Roche Sequencing Solutions, San Jose, CA.

References:
1. Stokowski R, et al. Prenat Diagn. 2015;35(12):1243-1246.
2. Jones KJ, et al. Ultrasound Obstet Gynecol. 2018;51(2):274-277.

Test Performance Data in Twin Gestations

Study Trisomy 21 Correct Calls Trisomy 18 Correct Calls Trisomy 13 Correct Calls Euploid Correct Calls Fetal Sex Correct Calls
Gil et al¹ 9/10 1/1 181/181
Gil et al² 16/17 9/10 1/2 962/968
Jones et al³ 39/39
Totals: 25/27 9/10 2/3 1,143/1,149 39/39
Limited data precludes performance calculations.
Test performance data displayed in this table are derived from the Roche Ariosa NIPS test, Roche Sequencing Solutions, San Jose, CA.

References:
1. Gil MM, et al. Fetal Diagn Ther. 2014;35:204-211.
2. Gil MM, et al. Ultrasound Obstet Gynecol. 2019;53(6):734-742.
3. Jones KJ, et al. Ultrasound Obstet Gynecol. 2018;51(2):275-276.

Disclaimers

ClariTest® Core is a non-invasive prenatal screen (NIPS) based on cell-free DNA analysis and is considered a screening test, not a diagnostic test. Before making any treatment decisions, all women should discuss the results with their healthcare provider, who can recommend diagnostic testing when appropriate. This test was developed and its performance characteristics were determined by BioReference Laboratories. It has not been cleared by the U.S. Food and Drug Administration. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory has been approved by CLIA 88 and designated as a high complexity laboratory and is qualified to perform this test.

Harmony® is a registered trademark of Roche Molecular Systems, Inc., used under license.