The safety of RhIG in the prevention of haemolytic disease of the newborn

Abstract

Overview Haemolytic disease of the newborn (HDN), erythroblastosis fetalis, is an immune reaction caused by an incompatibility between the blood types of the mother and fetus. Haemolytic disease of the newborn was first described in 1609 by a midwife in France, after the birth of twins, one of whom was stillborn and hydropic and the other who was jaundiced and died of kernicterus (Levine 1941). This syndrome was named erythroblastosis fetalis by Diamond and colleagues in 1932, who hypothesised a relationship between stillbirth with erythroblastosis in the tissues, fetal hydrops, congenital anaemia, and icterus gravis, all due to a single pathophysiologic process (Diamond 1932; Brantley 2002). Rhesus (Rh) antibodies were discovered by Karl Landsteiner in 1940, who had also discovered and described ABO blood antibodies earlier, for which he won a Nobel Prize (Avent and Reid 2000; Nobel Prize [Internet] 2006). In 1941, the primary cause of HDN was determined to be a difference in the D antigen (a member of the Rh system) between mother and fetus. This occurs when the mother does not express the D antigen while the fetus is positive (Levine 1941). Originally, similar blood antibody-blood incompatibility was isolated on Rhesus monkey red cells, the human analogue (D antigen) was shown to be present in nearly 85% of humans. Since then, other blood antigens have also been shown to cause HDN, including Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), MNSs (M, N, S, and s), and many others; however, Rh incompatibility is still the most common clinically significant factor (Avent and Reid 2000). Today, pregnancy is still associated with a rate of D incompatibility (RhD-negative mother with a RhD-positive fetus) of approximately 10% in Caucasians; however, the rate of haemolytic disease in the newborn has been substantially reduced, but not completely eliminated. Through education, improvements in screening, and better access to care, it is the hope that the number of cases of HDN decreases even further.