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Study Shows Natera's NIPT Can ID Unrecognized Twins, Fetal Triploidy; May Lower False Positive Rate

NEW YORK (GenomeWeb) — Natera's SNP-based non-invasive prenatal Panorama test can detect unrecognized twin pregnancies, including vanishing twins, and fetal triploidy in women undergoing routine prenatal screening, according to a recent study by researchers at Natera and a collaborator at Brigham and Women's Hospital in Boston. The ability to identify vanishing twins and triploid pregnancies could lower the rate of false-positive results from NIPT, prevent incorrect calls on fetal sex, and help with clinical management of triploid pregnancies, Natera said.

The study, published online this month in the American Journal of Obstetrics and Gynecology, gauged the ability of Natera's test to identify fetal triploidy, unrecognized twins, and vanished twins — where one twins dies in utero — in almost 31,000 samples the company received for testing. In 130 or 0.42 percent of cases, the test identified additional fetal haplotypes, which indicate one of the three conditions is present. For 76 of those, confirmation data from ultrasound and karyotyping showed that most cases were either viable or vanishing twin pregnancies, while a small number were triploids.

Susan Gross, chief medical officer for Natera and the senior author of the paper, said that being able to identify vanishing twin and triploid pregnancies with NIPT is "clinically important," and noted that previous publications showed that unidentified vanishing twins caused up to 15 percent of false positive NIPT results, leading to unnecessary invasive procedures. This is because chromosomal abnormalities are common in vanished twins, and leftovers from their DNA in the mother's blood can erroneously indicate that the viable fetus is affected.

In addition, unidentified vanishing twins can result in the incorrect prediction of fetal sex if the fetus is female but there is leftover DNA from a male vanished twin present in the mother's blood.

Triploid pregnancies, on the other hand, where the fetus carries three instead of two copies of each chromosome, result in severe fetal abnormalities and an elevated risk for spontaneous abortion, preeclampsia, excessive postdelivery bleeding, molar placentas, and choriocarcinoma. Early detection can help with clinical management of the mother.

For their study, the researchers included all samples received by Natera for commercial NIPT testing between March and November of 2013, a total of 30,795, which were analyzed in its CLIA laboratory in San Carlos, Calif.

Natera's test studies 19,488 SNPs in circulating free DNA from the mother's blood, using PCR amplification and next-generation sequencing followed by analysis with its Next-generation Aneuploidy Test Using SNPs, or NATUS, algorithm.

The algorithm is able to identify additional fetal haplotypes, which indicate either fetal triploidy or the presence of an undetected twin pregnancy, but cannot distinguish between the two at this time because the allele distributions look very similar.

Other NIPT approaches, which are used by other commercial providers and rely on counting methods to determine fetal chromosome copy number, are unable to determine fetal haplotype and, thus, triploidy or vanishing twins, according to the authors.

Natera reported all cases where they identified an additional fetal haplotype and recommended follow-up counseling and testing.

Unrecognized twin pregnancies were confirmed by ultrasound, both those with a viable twin and those with a vanished twin where a second empty sac or a second sac with a dead fetus was present.

Triploid pregnancies were confirmed by karyotyping, either by invasive testing or by testing the remains of a spontaneous abortion.

In total, NIPT testing indicated additional fetal haplotypes in 130 cases, of which 76 had follow-up testing by either karyotype or ultrasound. Of those, 37, or 48.7 percent, turned out to be viable twins; 32, or 42.1 percent, were vanishing twins; four, or 5.3 percent, were triploid pregnancies; and 3, or 3.9 percent, were non-triploid pregnancies that lacked evidence of co-twin demise.

According to the authors, this is the first report showing clinical outcomes for cases where NIPT indicated additional fetal haplotypes in a larger general screening population.