The Diagnosis and Prenatal Management of Non-RHD Alloimmunizations

Red blood cell (RBC) alloimmunization remains a relevant cause of hemolytic disease of the fetus and newborn (HDFN). Although RhD immunization has significantly decreased since the implementation of systematic prophylaxis, it is still the main cause of alloimmunization in pregnancy. Clinically significant non-RhD alloantibodies, particularly those of the Rh (c, C, E), Kell, Kidd, Duffy, and MNS systems, are associated with variable risk of fetal anemia and account for an increasing proportion of alloimmunized pregnancies requiring specialized prenatal care. Most diagnostic algorithms and management protocols are based on evidence derived from RhD alloimmunization. Although these frameworks are often extrapolated to other alloantibodies, important differences exist regarding antibody titration and critical thresholds, the diagnostic accuracy of non-invasive fetal antigen genotyping, and the risk and timing of fetal and neonatal interventions. These differences underscore the need for antibody-specific considerations in the prenatal diagnosis and management of non-RhD alloimmunization. Though advances in non-invasive diagnostic techniques have improved risk stratification and optimized prenatal management, individualized care pathways in alloimmunized pregnancies are needed. This review will focus on the current strategies for prenatal diagnosis and risk assessment in pregnancies complicated by non-RhD red cell alloimmunization.