Senior Medical Director Natera Carmel, IN, United States
Introduction: RhD immune globulin prophylaxis is standard of care for RhD-negative pregnant people in the US. Internationally, prenatal cell-free DNA screening (cfDNA) for fetal RhD status provides benefits for RhD-negative pregnant people by reducing invasive diagnostic testing and intensity of surveillance for alloimmunized individuals and by reducing blood product use in non-alloimmunized pregnancies. Methods: This prospective clinical validation assessed the performance of prenatal cfDNA for fetal RhD in a large US cohort of RhD-negative pregnant people. Samples were retrospectively identified from individuals who had SNP-based cfDNA for fetal aneuploidy at a commercial laboratory. Maternal and fetal RhD genotype was evaluated through prospective cfDNA analysis. Serological diagnostic confirmation of maternal and newborn RhD status was available for all patients. Investigators were blinded to fetal RhD status. IRB exemption was obtained. Results: Test performance based on over 800 samples from RhD-negative pregnant people will be presented, including sensitivity and specificity for detecting RhD-positive fetal status, making this the largest clinical validation with serological truth of fetal RhD cfDNA in the US to date. Validation will be completed by April 2024. This validation builds on proof-of-concept data generated in 180 RhD-negative pregnant people showing 100% concordance between the cfDNA for fetal RhD and quantitative PCR-based testing.1 (1American Society of Human Genetics meeting, 2023.) Conclusion/Implications: Validation of this test in a large cohort of RhD-negative patients provides data on early and accurate noninvasive prenatal identification of fetal RhD genotype to potentially assist patients and providers in prevention and management of RhD alloimmunization.
