Introduction

The fetus has a special immunological relationship with the mother that prevents rejection despite it being an allogeneic tissue [1–4]. If fetal blood cells enter the maternal circulation, the peaceful coexistence may be disrupted. The clinical problem of maternal antibody-mediated fetal red-blood-cell (RBC) destruction was a powerful stimulus to the acquisition of knowledge of the RBC antigen systems [5]. The triumphs of Landsteiner, Wiener, Levine, Darrow, Diamond, Chown, Liley, Clarke, Freda, Bowman and many others were among the great accomplishments of twentieth-century medicine [6]. Additionally, the assessment and management of hemolytic disease of the newborn (HDN) was a stimulus to progress in perinatal care in the second half of the twentieth century, including advances in fetal monitoring, in utero intervention, Cesarian section, neonatal resuscitation, and neonatal intensive care [7, 8]. A study of the interactions of RBC antigens with the maternal immune system and the fetal response to anemia can provide tremendous insight into systems of fundamental importance to neonatal health and disease.

The term “hemolytic disease of the newborn” was chosen to replace the term “erythroblastosis fetalis” when the mechanism of fetal anemia and neonatal jaundice was determined [9]. It was intended to name the maternal antibody-mediated fetal hemolytic disease, which, in these investigators' subjects, was the dominant etiology of fetal hemolysis and is a major cause of HDN worldwide. RhD continues to be the most commonly identified antigenic stimulus to HDN [10]. RhD-negative mothers give birth to RhD-positive fetuses in about 9% of European-ancestry pregnancies.