NEW YORK – A new study published Thursday supports the clinical value of BillionToOne's noninvasive prenatal test (NIPT) for detection of fetal RhD status.
Published in Obstetrics and Gynecology, the retrospective cohort study analyzed data from four US healthcare centers that offered BillionToOne's Unity RhD test to non-alloimmunized RhD-negative pregnant individuals as part of regular clinical care. In total, 401 patients who received care between August 2020 and November 2023 were included.
The study's authors wrote that around 15 percent of pregnant individuals in the US are RhD-negative.National guidelines support the use of prophylactic anti-D immunoglobulin (RhIG) in these cases to protect against dangerous reactions if the fetus happens to be RhD-positive.
However, blanket use of this therapy means that the 40 percent of pregnancies in which the fetal and parental RhD status match are receiving treatment they don't actually need.
The American College of Obstetricians and Gynecologists has recognized cell-free DNA (cfDNA) testing to establish fetal RhD status as a reasonable tool for doctors to consider in prioritizing use of RhIG. BillionToOne has been offering its test since 2022 and was joined in the market last year by NIPT competitor Natera.
BillionToOne had previously published data from studies of the test in cohorts of patients that had already been treated with RhIG, but had not yet evaluated its accuracy when used in standard clinical practice.
In the new study, investigators reported that BillionToOne's test was 100 percent concordant with neonatal serology testing performed after birth for the 401 patients who had live births.
There were also 10 pregnant individuals in the study in whom the cfDNA analysis correctly identified a non-RHD gene deletion, including RhDΨ, which occurs in around 25 percent of African American RhD-negative individuals, and hybrid variants in RHD-CE-D.
Although the authors wrote that this reflects a "modest" sample size, it is still notable, as the ability to discriminate these other variants is something BillionToOne has highlighted as a crucial differentiator for its assay — which combines next-generation sequencing combined with the company's quantitative counting template technology — compared to PCR-based tests.
Jennifer Hoskovec, BillionToOne's VP of medical affairs, said in an email that ACOG has recognized the importance of detecting non-RHD deletion variants in an ethnically diverse setting. The company views this ability as crucial to proving the clinical value of this type of NIPT, considering that the potential to return uncertain results lowers the value proposition of testing to guide treatment.
Although the study was not designed to survey clinical decision-making directly, the researchers did also observe that 93 percent of participants with test results indicating an RhD-positive fetus received RhIG, while only 75 percent of those with negative test results got immunoglobulin, suggesting that clinicians were using the test to guide care for their pregnant patients. This also appeared to increase over the course of the cohort's timeline, likely reflecting increased consideration of test results as clinicians became more confident in the assay.
According to the study authors, the UK and several European countries have been using cell-free DNA testing to guide RhIG treatment for more than a decade. But the US has hesitated to embrace those assays because of concerns around their applicability to the more diverse US population.
Some of the previously available assays have primers that are able to predict the presence of a non-RHD gene deletion, which occurs more commonly in individuals of non-European ancestry. However, they can't determine the actual fetal RhD status, and instead report inconclusive results.
BillionToOne's quantitative counting template technology allows more precise quantification of DNA at low concentrations. It also makes it possible to sequence exons that distinguish the RHD gene from the RHCE homolog gene and RhDΨ variant in order to predict the fetal RhD status for both the RHD gene deletion and non-RHD gene deletions.
In their publication, the authors wrote that BillionToOne's approach offers "an optimal test for the demographically diverse US pregnant population." Hoskovec said that when adding this new data to previous publications, the weight of evidence supports a recommendation to offer cfDNA screening for fetal Rh status as an alternative option to prophylactic RhIG for all non-alloimmunized RhD-negative individuals.
She added that BillionToOne continues to see an increase in ordering of the RhD NIPT in the US and has run and reported tests on more than 150,000 patients to date.
Alongside concerns about RhD test applicability in a racially diverse setting, hesitations have also hinged on the fact that prior evaluations have found test-informed RhIG treatment to be economically inferior to a general prophylactic protocol. As such, the study's authors said that future health-economic studies could be beneficial to the field.