Clinical Validation of a Prenatal Cell-Free DNA Screening Test for Fetal RHD in a Large U.S. Cohort.
Publication/Presentation Date
2-1-2025
Abstract
OBJECTIVE: To present a large U.S. clinical validation of a next-generation sequencing-based, noninvasive prenatal cell-free DNA test for fetal RHD .
METHODS: This clinical validation study assessed the performance of a commercially available, next-generation sequencing-based cell-free DNA test for fetal RHD status. Samples that passed quality metrics were included if the patient had a previously reported cell-free DNA result for fetal aneuploidy, maternal RhD-negative serology, newborn RhD serology, and maternal RHD deletion or RHD-CE-D hybrid(r's) genotype. Dizygotic twin pregnancies were excluded. Maternal and fetal RHD genotypes were evaluated with prospective cell-free DNA next-generation sequencing analysis. At the time of analysis, investigators were blinded to fetal RhD status.
RESULTS: The cohort consisted of 655 pregnant patients with serologic results for RhD antigen. Patient demographics included a representative distribution of race and ethnicities in the RhD-negative U.S. population (74.0% White, 13.7% Hispanic, 7.0% Black, and 2.1% Asian). Cell-free DNA fetal RHD was not reported in two cases. There were zero false-negative cases; 356 of 356 fetuses were correctly identified as fetal RhD positive (sensitivity 100%, 95% CI, 98.9-100%). Of the 297 RhD-negative fetuses, 295 were correctly identified as RhD negative (specificity 99.3%, 95% CI, 97.6-99.8%). Of the fetuses with a negative RhD phenotype, the cell-free DNA test accurately identified three with the fetal RHD pseudogene ( RHDΨ) genotype.
CONCLUSION: Validation of this test in this large U.S. cohort of RhD-negative patients provides data on early and accurate noninvasive prenatal identification of fetal RHD genotype at 9 weeks of gestation or more. This test has the potential to assist patients and clinicians in the prevention and management of RhD alloimmunization.
Volume
145
Issue
2
First Page
211
Last Page
216
ISSN
1873-233X
Published In/Presented At
Gilstrop Thompson, M., Xu, W., Moore, B., Wang, T., Sun, N., Pewar, H., Avent, N. D., Vernaza, A., Acosta, F., Saben, J. L., Souter, V., Parmar, S., Sengupta, U., Altug, Y., EmBree, J., Cantos, C., Kotwaliwale, C., Babiarz, J., Zimmermann, B., Swenerton, R., … Meltzer, J. T. (2025). Clinical Validation of a Prenatal Cell-Free DNA Screening Test for Fetal RHD in a Large U.S. Cohort. Obstetrics and gynecology, 145(2), 211–216. https://doi.org/10.1097/AOG.0000000000005794
Disciplines
Medicine and Health Sciences
PubMedID
39591628
Department(s)
Department of Obstetrics and Gynecology
Document Type
Article