Hemolytic disease of the newborn, beyond the Rhesus disease

Hemolytic disease of the fetus and newborn is a consequence of maternal immune response to fetal red blood cells antigens inherited from the father, that the mother does not possess, stimulated by antepartum or intrapartum fetomaternal hemorrhage. As a result, fetal erythrocytes are destroyed, leading to various degrees of anemia and hyperbilirubinemia, with high perinatal morbidity and mortality rates. This review’s purpose is to reveal the importance of the alloantibodies beyond RhD and ABO system, the updated algorithms used in the diagnosis and management of the disease and the importance of RhD universal immune prophylaxis practice. For this purpose, the database from PubMed and UpToDate was searched for literature reviews, case studies, society guidelines and retrospective studies in English regarding hemolytic disease of the fetus and newborn from 2013 to March 2022. Anti D prophylaxis protocols, early diagnosis and proper intrauterine and postpartum treatment help significantly reduce the disease’s burden.