When any fetal blood group factor inherited from the father is not possessed by the mother, antepartumor intrapartum fetal–maternal bleeding may stim-ulate an immune reaction in the mother. Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies is called isoimmuniza-tion. It can lead to various degrees of transplacental passage ofthese antibodies into the fetal circulation, causing an anti-body response sufficient to destroy fetal red cells.Althoughearly exposures to maternal antigens during pregnancy may occur in the same pregnancy, isoimmunization more commonly occurs in a subsequent pregnancy. The bind-ing of maternal antibodies to fetal red blood cells leads to hemolytic disease in the fetus or newborn, characterizedby hemolysis, bilirubin release, and anemia. The sever-ity of the illness encountered by the fetus or newborn is determined by a number of factors, including the degree of immune response elicited (i.e., how much antibody is pro-duced), how strongly the antibody binds the antigen, the gestational age at which the diagnosis is made, and the abil-ity of the fetus to replenish the destroyed red cells to main-tain a hematocrit sufficient for growth and development (Table 19.1).