Prenatal Genotyping of the RhD Locus to Identify Fetuses at Risk for Hemolytic Disease of the Newborn

Hemolytic disease of the newborn (HDN) can occur when there are fetomaternal incompatibilities within any number of different erythrocyte antigen systems, including the RhD, Cc, Ee, Kidd and Duffy, and Kell antigen systems. In these disorders, maternal antibodies are developed by alloimmunization of the mother to fetal red blood cells during pregnancy when the fetal cells carry an alloantigen inherited from the father. The maternal antibodies result in the destruction of fetal erythrocytes leading to severe hemolytic anemia and hyperbilirubinemia. Permanent neurologic damage can result from HDN, and in extreme cases loss of the fetus or death of the neonate may occur. In subsequent pregnancies, it is important to determine the status of the incompatible allele in the fetus. If the father is heterozygous or homozygous for the allele, the chance of the fetus inheriting the paternal alloallele to which the mother is immunologically sensitized is 50 or 100%, respectively. Fetuses that do not inherit the alloallele will not be at risk for HDN.