Beyond Hemolysis and Transfusion: The Untold Story of Blood Groups in Neonatal Disease

Blood, as a genetically determined phenotypic characteristic of red blood cells (RBCs), has traditionally been associated with transfusion safety and prevention of hemolytic reactions. However, recent data suggest that the ABO system may influence the predisposition to and the course of various pathological conditions, with potential implications for the development of comorbidities and clinical management of patients. Blood group antigens are expressed on RBCs, platelets, epithelial cells, and endothelial cells, and are involved in fundamental biological functions, such as cell recognition, intercellular adhesion, regulation of hemostasis, and immune response. Many epidemiological studies in adult populations demonstrate an association between specific blood groups of the ABO system and the Rh factor, and a differential risk of cardiovascular, metabolic, and infectious diseases, as well as the development of malignancies; however, in neonates, relevant studies are limited, and the impact of blood group on morbidity during the perinatal period remains unclear. The purpose of this narrative review is to investigate the association between neonatal blood group and the occurrence and severity of critical neonatal comorbidities, through an evaluation of the available clinical and epidemiological evidence, and to clarify the suspected pathogenetic mechanisms, with the aim of supporting future research efforts and improving the clinical care of this vulnerable population.