QNatal^® Advanced

The QNatal Advanced test is performed on cell-free DNA (cfDNA) isolated from maternal blood. This cfDNA contains both maternal DNA and fetal DNA derived from apoptotic placental cells (trophoblasts). Once isolated, the cfDNA is sequenced using massively parallel shotgun sequencing (MPSS); this is followed by quantitative bioinformatics analysis. In this way, the fetal copy number of chromosomes 21, 18, 13, X, Y, as well as select microdeletion regions, are calculated.

QNatal Advanced screens for the most common autosomal fetal abnormalities: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). It can also screen for abnormalities of the sex chromosomes. These include Turner syndrome (monosomy X) and Klinefelter syndrome (XXY) as well as XXX and XYY syndromes. In addition, if elected, QNatal Advanced can screen for microdeletions that are too small to be detected by standard cytogenetic analysis. These include microdeletions of chromosomes 1p (1p36 syndrome), 4p (Wolf-Hirschhorn syndrome), 5p (Cri-du-chat syndrome), 8q (Langer-Giedion syndrome), 11q (Jacobsen syndrome), 15q (Prader-Willi/Angelman syndromes), and 22q (DiGeorge syndrome).  

Yes, if elected, the QNatal Advanced test can screen for fetal sex based on the presence or absence of cell-free DNA from the Y chromosome. However, if the patient does not wish to know the fetal sex, the healthcare provider can opt out of having it reported.

No. Like all noninvasive cell-free DNA prenatal screening tests, the QNatal Advanced test does not provide a diagnostic result.^* If the QNatal Advanced test yields a result of positive for increased risk, the patient should receive genetic counseling and further diagnostic testing and procedures, when clinically indicated.

Pregnancy management decisions should not be based on the results of a cell-free DNA test alone. 

The QNatal Advanced test does not detect copy number abnormalities of chromosomes other than 21, 18, 13, X, or Y, or abnormalities involving only a portion of a chromosome outside the microdeletion regions of interest. Additionally, like other noninvasive cell-free DNA prenatal screening tests, the QNatal Advanced test cannot identify nonsyndromic congenital anomalies (ie, birth defects). For example, it cannot detect a neural tube defect or a ventral wall defect.

This test can be used for all pregnant women. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) recommend that all women should be offered the option of aneuploidy screening (ie, screening for the trisomies and sex chromosome abnormalities) or diagnostic testing, regardless of maternal age.¹ The American College of Medical Genetics and Genomics (ACMG) states that noninvasive prenatal cell-free DNA screening is “the most effective screening test” for trisomies 13, 18, and 21 “in singleton and twin gestations.”²

A published clinical study³ examined the performance of the QNatal Advanced test in a population of pregnant women that included both those at average and those at high risk. The results demonstrated strong analytical sensitivity and specificity for trisomy 21, 18, and 13. The positive predictive value (PPV) was 98.1% for trisomy 21, 88.2% for trisomy 18, 59.3% for trisomy 13, 69.0% for sex-chromosome aneuploidies (ie, 45,X; 47,XXY; 47,XXX; and 47,XYY in the aggregate), and 75.0% for microdeletions (ie, 22q; 5p; 1p36; 15q; 11q; 8q; and 4p in the aggregate).* 

Testing should not be performed prior to 10 weeks gestational age.

Yes, the QNatal Advanced test can be performed on specimens from twin gestations.⁴

Noninvasive cell-free DNA-based prenatal screening tests have been shown to be very reliable in validation/verification^3,4 and real-world studies.²

False-positive and false-negative results do occur; causes include, but are not limited to, confined placental mosaicism, co-twin demise/vanishing twin, fetal mosaicism, maternal mosaicism, possible fibroids, and maternal malignancy.

Results are typically reported within 7 days after specimens are received in the laboratory. Results are sent to the ordering healthcare provider’s office or to the electronic medical record (EMR).

The report includes a “negative” or “positive” result for trisomy 21, 18, and 13.  All positive results for trisomies include age-adjusted positive predictive value (PPV). Sex-chromosome abnormalities and microdeletion syndromes are reported as “increased risk” (unless microdeletion testing has been opted out). Fetal sex is reported as well, if not opted out.

Some specimens do not contain enough fetal cell-free DNA (fetal fraction). If this happens, test results cannot be obtained, interpreted, or reported. Low fetal fraction can be due to several factors, including, but not limited to, maternal obesity. The test can be repeated using newly collected maternal blood specimens. If no result is obtained on the second specimen, consideration of a diagnostic test may be appropriate.

No specific follow-up is needed when the test is negative.* However, if ultrasound examination of the fetus reveals anomalies, then further fetal studies might be indicated.

Implications of a positive or increased risk result should be discussed by the healthcare provider with the patient. Diagnostic confirmation using amniocentesis or chorionic villus sampling should be offered.¹