Hemolytic Disease of the Fetus and Newborn: Modern Practice and Future Investigations.

Red blood cell (RBC) sensitization occurs in some women in response to exposure to paternally derived RBC antigens during pregnancy or to nonself antigens on transfused RBCs during their lifetime. Once sensitized, future pregnancies may be at risk for hemolytic disease of the fetus and newborn. Although great strides have been made over the past few decades in terms of identifying blood group antigens and in predicting fetal anemia through the use of noninvasive monitoring, many questions remain in terms of understanding RBC alloimmunization risk factors, preventative therapies, and treatment strategies. At the present time, there is room for improvement in these areas in both developed and developing countries. Evidence-based, universal guidelines describing recommended RBC antigen matching transfusion strategies for girls or women, before pregnancy or during intrauterine transfusions, would be welcomed. A better understanding of the mechanism(s) of action of Rh immunoglobulin, first introduced more than half of a century ago and one of the most successful immunoprophylaxis therapies in existence today, would also be a large step forward. For example, answers to questions of the role(s) that fetal RBC clearance, antigen masking, antigen modulation, and immune suppression play in the effectiveness of Rh immunoglobulin may help to guide the development of novel preventative therapies during pregnancy for immunization to RhD and non-RhD antigens. Furthermore, a better understanding of the importance of anti-RhD or other alloantibody glycosylation patterns may be beneficial not only in developing such novel immunoprophylaxis therapies but also in predicting the clinical significance of existing maternal alloantibodies. One other area of need includes the development of therapies beyond intrauterine transfusions to mitigate the dangers of maternal alloantibodies to developing fetuses. We challenge physicians, scientists, and funding agencies to prioritize studies of RBC alloimmunization and hemolytic disease of the fetus and newborn and to invest in the children of our future.