Skip to main content
Premium Trial:

Request an Annual Quote

Study Assesses Natera's DiGeorge Syndrome NIPT Screening Test in More Than 20,000 Cases

NEW YORK (GenomeWeb) – Analyzing results from more than 20,000 clinical samples, researchers at Natera and their collaborators have found that noninvasive prenatal screening for DiGeorge syndrome, also known as 22q11.2 deletion syndrome, classified almost 0.5 percent of cases as high risk, among them at least 11 true cases but also at least 50 false positives.

"We found that 22q11.2 deletions are relatively common in the referral population, and that many can be identified using this screening test," the researchers, led by Natera Chief Medical Officer Susan Gross, wrote in a study published online in Ultrasound in Obstretrics & Gynecology this week.

Natera's screening test flagged 95 cases as high risk for a fetal 22q11.2 deletion. Of those for which confirmatory diagnostic results were available, 18 percent turned out to be true positives and 82 percent false positives.

The company's Panorama NIPT, which relies on targeted sequencing and SNP analysis, screens not only for trisomies and sex chromosome abnormalities but also for five microdeletion syndromes, among them DiGeorge syndrome, which affects about 1 in 2,000 newborns.

For their retrospective study, which aimed to assess the clinical performance of the 22q11.2 microdeletion test, the scientists analyzed results from maternal blood samples Natera received for testing during a six-month period in 2014.

After excluding more than 1,000 samples for quality control and other reasons, almost 21,000 samples underwent DiGeorge syndrome testing using Natera's assay, which covers 87 percent of all 22q11.2 microdeletions and had an average turnaround time of about eight days.

Of these cases, 97 were classified as high risk, 19,140 as low risk, and 1,539 as average or unchanged risk for a fetal 22q11.2 microdeletion.     

Two of the high-risk cases had a suspected maternal 22q11.2 microdeletion, which was confirmed in one case. For 61 of the remaining 95 cases, results from confirmatory diagnostic testing — prenatal invasive testing, postnatal testing, or testing after miscarriage — were available. Of those, 11 cases, or 18 percent, were confirmed as true positives, and 50, or 82 percent, as false positives, translating to a positive predictive value of 18 percent for the microdeletion test.

Depending on whether the 34 high-risk cases for which no confirmatory diagnostic results were available were all true positives or all false positives, the true PPV of the test could range from 11.6 to 47.4 percent, the authors calculated.

By performing a second round of reflex testing with higher depth sequencing on 89 of the 95 high-risk samples, they were also able to lower the number of false positives and raise the PPV of the test to 42.3 percent.

For 77 of the high-risk cases, ultrasound data were available, which showed anomalies for nine of the 11 true positive cases, and for nine of the 50 false positives.

The researchers were unable to calculate the negative predictive value of the test because they had no follow-up date on the low-risk cases, but they did not receive any reports of false-negative cases from doctors.

Based on their results, they calculated the prevalence of DiGeorge syndrome in their study population to be about 1 in 1,000, which is higher than the prevalence found in live births but comparable to rates from other types of prenatal testing.

Women receiving a high-risk result from Natera's test, the authors wrote, should always undergo confirmatory diagnostic testing. Finding out about a fetal 22q11.2 microdeletion early can have a number of benefits, they pointed out, such as preparing for calcium treatment at birth and identifying cardiac defects early.

"The decision to add 22q11.2 deletion screening as an adjunct to existing NIPT needs to balance the medical benefits of early diagnosis of 22q11.2 deletions against efficacy of the test, the prevalence in the referral group, … additional clinical service considerations, and cost," they concluded. "The data on clinical experience presented in this study may be helpful in this assessment."