Rh antibodies are IgG immunoglobulins and, as such, are capable of crossing the placenta (chiefly IgG subclasses 1 and 3). Rh antigens are well-developed early in fetal life. Therefore, the antibodies can coat the red cells of the developing fetus and cause them to be removed prematurely from circulation. If undetected/untreated, this can result in the fetus's death or severe, life-threatening complications at birth - clinically termed hemolytic disease of the fetus and newborn (HDFN).
Until the advent of Rh immune globulin treatment in 1968, anti-D was the most frequent cause of HDFN. Given that D is the most antigenic of the Rh antigens, providing Rh-negative blood to Rh-negative females of child-bearing age (generally considered to be below age 50) requires strict adherence along with the provision of maternal Rh immune globulin treatment as antenatal and postnatal prevention.
Other antigens of the Rh system (C, E, c) are also potent immunogens, and antibodies directed against these antigens have been implicated in moderate to severe cases of HDFN. Anti-E and anti-c have been documented in cases of severe HDFN that required intervention and treatment. However, there is no immune globulin currently marketed to prevent maternal production of antibodies to other Rh antigens.
