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Rhesus (Rh) D blood group incompatibility between a pregnant woman and the fetus can occasionally cause maternal alloimmunization and hemolytic disease of the fetus and of the newborn in subsequent pregnancies. RHD genotyping of fetuses carried by RhD-negative women using fetal DNA obtained invasively through amniocentesis or chorionic villus sampling is an aid to the clinical management of these cases. Technological advances allow for accurate prediction of fetal RHD genotype using cell-free fetal DNA from maternal blood, thus overcoming the invasive procedures. Presently, many laboratories worldwide provide the test as a routine service for immunized women. Mass application of RhD noninvasive prenatal diagnosis for all fetuses carried by RhD-negative women is highly desirable so that unnecessary anti-D administration is avoided.