Erythroblastosis fetalis, also known as hemolytic disease of the fetus and newborn (HDFN), is a type of anemia in which the red blood cells of a fetus are destroyed in a maternal immune reaction resulting from a blood group incompatibility between the fetus and its mother. The condition is caused by the destruction of neonatal red blood cells by maternal immunoglobulin G (IgG) antibodies, which form when fetal erythrocytes expressing certain red blood cell antigens that are not expressed in the mother cross the placenta and gain access to maternal blood. Erythroblastosis fetalis classically results from Rho(D) incompatibility, which may develop when a woman with Rh-negative blood is impregnated by a man with Rh-positive blood and conceives a fetus. Other fetomaternal incompatibilities that can cause erythroblastosis fetalis involve the Kell, Duffy, Kidd, MNSs, Lutheran, Diego, Xg, P, Ee, and Cc antigen systems, as well as other antigens.

Symptoms of erythroblastosis fetalis range from mild to severe, and may include anemia, jaundice, and an enlarged liver and spleen. In its mildest form, the disease manifests only as slight anemia with no other complications; in its most extreme form, the fetus dies in utero. Hydrops fetalis, which is characterized by extreme edema and congestive heart failure, is the most severe form of the disease in newborns. Treatment includes blood transfusion, IV fluids, immunoglobin, and addressing any breathing difficulties. Giving a pregnant woman Rh immunoglobin can also help prevent the condition by blocking Rh sensitization.