Red blood cell alloimmunization and pregnancy: Diagnosis and management

Red blood cell alloimmunization in pregnancy is a major cause of hemolytic disease of the fetus and neonate (HDFN), which can lead to fetal anemia, hydrops fetalis, and perinatal morbidity and mortality. The implementation of routine RhD prophylaxis has significantly reduced the incidence of RhD alloimmunization, especially in high-income countries. Management relies on maternal antibody screening, fetal antigen determination, and Doppler ultrasonography, with the middle cerebral artery peak systolic velocity being the gold standard for identifying fetuses at high risk of moderate-to-severe anemia that may benefit from intrauterine transfusion. Management depends on alloantibody type and titer, which usually correlate to the severity of fetal anemia. In cases of moderate-to-severe fetal anemia the primary treatment consists of intrauterine transfusion, which is an invasive procedure associated with an increased risk of fetal demise, particularly when performed prior to 20 weeks of gestation. Alternative therapeutic approaches, including intravenous immunoglobulin and plasmapheresis have been reported to delay or reduce the need for intrauterine transfusions, whilst the use of the neonatal Fc receptor inhibitor nipocalimab is currently under investigation. Despite significant advances, HDFN remains a global health concern, particularly in low-resource settings where access to RhD prophylaxis, non-invasive screening, and intrauterine transfusion is limited. A multidisciplinary management involving obstetrician, neonatologist, hematologist, and transfusion specialist is essential for optimizing outcomes. In this review, we provide an overview of the pathophysiology, diagnosis, management, and treatment options for red blood cell alloimmunization and HDFN.