The most common type of Rh incompatibility occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery .
Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion.
An Rh-negative woman become alloimmunized to the D antigen present on fetal red blood cells (RBCs) during the first Rh-incompatible pregnancy. The first pregnancy is rarely affected because the number of Rh antibodies produced by the mother during primary immunization is low and the antibodies are usually IgM in nature . IgM can’t cross placental barrier.
When the mother is exposed to D-positive fetal RBCs during a subsequent Rh-incompatible pregnancy, the mother mounts an anamnestic, or secondary, immune response to the fetus’ RBCs. A large number of IgG-class Rh antibodies are produced. The IgG antibodies cross the placenta and make fetal red cells susceptible to destruction. The fetal RBCs are then destroyed by the fetal immune system. Anemia develops in the fetus with a concomitant increase in unconjugated bilirubin. The anemia and unconjugated bilirubin levels can lead to a number of conditions.
Treatment with Rh IgG (RhoGAM)
The current recommendation is that every Rh-negative nonimmunized woman who presents to the ED with antepartum bleeding or potential fetomaternal hemorrhage should receive 300 mcg of Rh IgG IM. For every 30 mL of fetal whole blood exposed to maternal circulation, 300 mcg of Rh IgG should be administered . A lower 50-mcg dose preparation of Rh IgG is available and recommended for Rh-negative females who have termination of pregnancy in the first trimester when fetomaternal hemorrhage is believed to be minimal.
Because of its short half-life, Rh IgG routinely is administered once at 28-32 weeks’ gestation and again within 72 hours after birth to all Rh-negative pregnant females as a part of routine prenatal care.
Other important points:
- Determination of Rh blood type is required in every pregnant female.
- Overall, 16% of Rh-negative women will become sensitized after their first pregnancy if not given Rhogam.
- In a pregnant woman with Rh-negative blood type, the Rosette screening test often is the first test performed. The Rosette test can detect alloimmunization caused by very small amounts of fetomaternal hemorrhage.
- Amniotic bilirubin scan (also known as ΔOD450) is a prenatal testing procedure . Results interpreted using a Liley or Queenan chart (Queenan chart is reported to have higher diagnostic accuracy for identifying severe anemia). The Liley curve is divided into three zones.
A result in Zone I indicates mild or no disease. Fetuses in zone I are usually followed with amniocentesis every 3 weeks.
A result in zone II indicates intermediate disease. Fetuses in low Zone II are usually followed by amniocentesis every 1-2 weeks.
A result above the middle of Zone II may require transfusion or delivery. 
- Obtaining maternal Rh antibody titers can be helpful for future follow-up care of pregnant females who are known to be Rh negative. Maternal serum antibody Rh titer >15 IU/mL indicates high risk of severe fetal anemia. 
- Immediately after the birth of any infant with an Rh-negative mother examine blood from the umbilical cord of the infant for ABO blood group and Rh type, measure hematocrit and hemoglobin levels, perform a serum bilirubin analysis, obtain a blood smear, and perform a direct Coombs test.
- A positive direct Coombs test result confirms the diagnosis of antibody-induced hemolytic anemia, which suggests the presence of ABO or Rh incompatibility. 
Last revised: 05/12/2012