Rhesus (Rh) D blood group incompatibility between the pregnant woman and her fetus is a significant problem due to the possibility of maternal alloimmunization and consequent hemolytic disease of the newborn. The RhD-negative blood group is found in 15% of whites, 3–5% of black Africans, and is rare in Asians. Advances in both our understanding of the RHD locus and its variants, as well as technical improvements in the extraction and amplification of cell-free fetal DNA in maternal plasma, have led to incorporation of noninvasive diagnosis of RHD genotype into routine prenatal care in the United Kingdom, France, and the Netherlands. In this commentary we examine the experience to date with large-scale clinical trials performed in the European Union, describe approaches to reduce false-positive and false-negative results, and review ongoing research to standardize assays and reduce costs using automated assays. False-negative cases are mainly due to either a lack of fetal DNA in the maternal sample due to early gestation or insensitive methods. False-positive cases are due to genotypic variants observed in individuals of African ancestry. Noninvasive prenatal diagnosis of fetal Rhesus D genotype is sensitive and accurate and has been widely validated in Europe. The United States should begin to undertake clinical trials to bring this technology to patient care as soon as possible.
Noninvasive prenatal diagnosis of fetal Rhesus D is sensitive, accurate, and being incorporated into routine clinical care in the European Union.
From the 1Division of Genetics, Department of Pediatrics, Tufts-New England Medical Center, Boston, Massachusetts; 2Center for Research in Biomedicine, University of the West of England, Bristol, United Kingdom; 3Molecular Biology Laboratory, Prenatal Diagnosis Center, American Hospital of Paris, Neuilly, France; and 4Experimental Immunohematology, Sanquin Research at CLB, Amsterdam, the Netherlands.
See related editorial on page 682.
Corresponding author: Diana W. Bianchi, MD, Department of Pediatrics, Division of Genetics, Box 394, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111; e-mail: firstname.lastname@example.org.
Supported by a grant from the National Institutes of Health (NIH R01 HD42053).