Function of the Rh Factor and Rationale for RhIg Administration
The Rh factor (specifically the RhD antigen) is a protein on red blood cell membranes that serves as a critical structural component of the erythrocyte membrane and may play a physiologic role in ammonia transport, while RhIg is administered to Rh-negative pregnant women to prevent maternal immune system sensitization against fetal Rh-positive red blood cells, thereby preventing hemolytic disease of the fetus and newborn in current and future pregnancies. 1, 2
Biological Function of the Rh Factor
The Rh proteins form a core complex that is essential to erythrocyte membrane integrity and structure. 2 These proteins belong to an ancient family of membrane proteins involved in ammonia transport, suggesting they may participate in the sequestration of blood ammonia. 2 When Rh antigens are normal, they lend stability to the red blood cell membrane structure, but their absence results in decreased red cell survival. 3
The RhD antigen specifically is an integral part of the red blood cell membrane and represents the most clinically significant blood group antigen after the ABO antigens. 3 Fetal red blood cells display RhD antigens from as early as 6 weeks of gestation, making this antigen present throughout pregnancy. 1, 4
Why RhIg is Administered to Rh-Negative Pregnant Women
The Core Problem: Maternal Sensitization
When an Rh-negative mother carries an Rh-positive fetus, fetal red blood cells can enter maternal circulation and trigger an immune response, causing the mother to produce anti-D antibodies that can attack fetal red blood cells in the current or subsequent pregnancies, leading to hemolytic disease of the fetus and newborn. 1, 4
The sensitization process occurs because:
- As little as 0.03-0.1 mL of Rh-positive red blood cells can trigger primary alloimmunization in susceptible individuals 4
- Fetomaternal hemorrhage increases with gestational age: 7% in first trimester, 16% in second trimester, and 29% in third trimester 4
- Approximately 90% of fetomaternal hemorrhage and alloimmunization events occur during delivery itself 4
- Without prophylaxis, 13-17% of Rh-negative mothers develop anti-D antibodies after delivering an Rh-positive infant 1
Devastating Consequences of Alloimmunization
RhD alloimmunization leads to severe fetal and neonatal outcomes including hemolytic disease of the fetus/newborn, need for fetal transfusion, fetal hydrops, stillbirth, and preterm delivery. 1 Once a woman is sensitized, these antibodies persist and pose risks in all subsequent Rh-positive pregnancies. 1
How RhIg Prevents Sensitization
RhIg works by suppressing the maternal immune response to fetal RhD-positive red blood cells, though the complete mechanism is not fully understood. 1 The immunoglobulin must be administered within 72 hours of exposure for optimal effectiveness. 1, 4
Evidence-Based Effectiveness
The two-dose RhIg protocol has proven remarkably effective:
- Postpartum RhIg alone decreases alloimmunization from 13-17% to 1-2% 1
- Adding the antenatal dose at 28 weeks further reduces alloimmunization from 1.8% to 0.1-0.2% 1
Standard Administration Protocol
The American College of Obstetricians and Gynecologists recommends that Rh-negative pregnant women receive:
- Routine antenatal dose: 300 μg RhIg at 28 weeks gestation 1
- Postpartum dose: 300 μg RhIg within 72 hours after delivery of an Rh-positive infant 1
- Additional doses: RhIg for any potentially sensitizing events including bleeding, trauma, miscarriage, or invasive procedures 1
Special Considerations for Early Pregnancy
A critical pitfall to avoid is assuming early gestational age eliminates risk. Since fetal RBCs with D-antigen are present from 6 weeks onward, maternal sensitization is physiologically possible even in very early pregnancy. 1, 4 For bleeding events or pregnancy loss before 12 weeks gestation, a minimum dose of 50 μg RhIg within 72 hours is adequate, though the standard 300 μg dose should be used if the lower dose is unavailable. 1
Priority Populations
Prevention of RhD alloimmunization should be particularly considered for RhD-negative children (especially girls) and women of childbearing age, as the consequences affect future reproductive capacity. 5, 1