The use of free DNA for fetal RHD genotyping in the Rh negative pregnant patient - the time has come.

Cell-free DNA (cfDNA) to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cfDNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin (RhIG) in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of RhIG were conserved. Recently two U.S. companies have introduced cfDNA assays for RHD as part of their NIPT assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-Ds genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM® has recently announced a national shortage. . Given the current availability of reliable cfDNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S..