SNP Test Detects Fetal Aneuploidy

By David Douglas

July 15, 2014

NEW YORK (Reuters Health) - The noninvasive prenatal Next-generation Aneuploidy Test (Panorama, Natera) can screen for the majority of live-birth aneuploidies, according to multinational researchers.

Of the currently available noninvasive tests for estimating risks of syndromes including Down, Edwards and Patau, the Natera test is the only one that uses a single nucleotide polymorphism (SNP) -based approach.

In a July 7th online paper in Obstetrics & Gynecology, Dr. Matthew Rabinowitz of Natera Inc, San Carlos, California, and colleagues say they recently reported smaller studies of a SNP-based noninvasive prenatal screen "that used sophisticated informatics, did not require reference chromosomes, and calculated sample-specific accuracies for each tested chromosome."

In the current larger study, the researchers sought to determine the sensitivity and specificity of the approach for detecting trisomies 21, 18, and 13, monosomy X, and fetal sex, in high-risk and low-risk populations.

To do so, they examined maternal blood samples from seven weeks of gestation and beyond. In total, 1051 were within specifications and 518 (49.3%) were low risk. A cell-free DNA result was successfully generated in 966 (91.9%). The overall median maternal age was 30 years and ranged from 18 to 47 years.

Sensitivity and specificity did not differ in low-risk and high-risk populations. Both sensitivity and selectivity for trisomies 21 and 13 were 100%. Sensitivity was also 100% for sex determination. Specificity for trisomy 18 and monosomy X was 99.9%. Corresponding sensitivities were 96.0% and 90.0%.

However, 16% of aneuploid samples did not return a result. Of these, 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. The aneuploidy rate was significantly higher in these samples (odds ratio, 9.2).

This finding, say the investigators, "underscores the importance of redraws for all noninvasive prenatal screening methods, when samples fail to return a result, and for methods where accuracy is decreased at lower fetal fractions."

However, they conclude, "This SNP-based method resulted in improved overall performance over quantitative methods" and "may provide pregnant women, regardless of age, an accurate screen for whole-chromosomal fetal aneuploidies and fetal sex."

Dr. Rabinowitz told Reuters Health by email, "We expect this study, when combined with the growing body of evidence in the scientific literature, will give the medical community added comfort that Panorama is appropriate for use as a front-line screen in low-risk women as well as high-risk women."

Commenting on the findings by email, Dr. Susan Klugman of Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York noted that of the four companies providing noninvasive prenatal screening, "Natera is the only one to use the SNP method to analyze cell free fetal DNA in maternal blood. The sensitivity and specificity of the testing method reported is slightly better than previous studies and half the patients here were considered low risk."

Dr. Klugman, who is Director of Reproductive Genetics, pointed out that her institution was one of 36 centers that supplied study samples.

"It is important to note," she concluded, "that the 'no-call' specimens, or those where a result was not able to be obtained because of low fetal fraction (i.e., not enough cell-free fetal DNA for an appropriate analysis) were more likely to be aneuploid or abnormal. This last point has important clinical correlation as these patients should be encouraged to have invasive testing."

Dr. Rabinowitz is chief executive officer of Natera. A number of authors are employees of or have relationships with the company. The study was supported in part by a grant from the National Institute of Health. The remainder was funded by Natera.


Obstet Gynecol 2014.


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