Why is Rhesus D (RhD) immunoglobulin administered in ectopic pregnancy?

Rhesus D Immunoglobulin Administration in Ectopic Pregnancy

Rhesus D immunoglobulin is administered in ectopic pregnancy to prevent maternal sensitization in Rh-negative women, as fetal red blood cells containing the RhD antigen can enter maternal circulation during an ectopic pregnancy, potentially causing alloimmunization that could lead to hemolytic disease of the fetus and newborn in subsequent pregnancies. 1

Mechanism and Rationale

The administration of anti-D immunoglobulin in ectopic pregnancy is based on several key physiological principles:

1. Early RhD antigen development: Fetal red blood cells display RhD antigens from as early as 6 weeks of gestation 1

2. Risk of fetomaternal hemorrhage: During an ectopic pregnancy, particularly with rupture, fetal red blood cells can enter maternal circulation 1

3. Alloimmunization risk: McSweeney et al. reported cases of alloimmunization involving unruptured ectopic pregnancy, demonstrating this is a real clinical concern 1

4. Prevention of future complications: Without prophylaxis, maternal sensitization can lead to hemolytic disease of the fetus and newborn in subsequent pregnancies, causing significant perinatal morbidity and mortality 1

Clinical Evidence and Guidelines

The Society for Maternal-Fetal Medicine (SMFM) recommends RhD testing and RhIg administration for RhD-negative individuals in early pregnancy events, including ectopic pregnancy 1. This recommendation is based on:

• The presence of RhD antigens on fetal RBCs from as early as 6 weeks gestation
• Documented cases of alloimmunization following ectopic pregnancy
• The serious consequences of alloimmunization for future pregnancies
• Limited data that do not convincingly demonstrate the safety of withholding RhIg

The FDA-approved labeling for RhD immune globulin (Rhophylac) specifically indicates its use for "suppression of Rhesus (Rh) Isoimmunization in pregnancy and obstetric conditions in non-sensitized, Rh(D)-negative women with an Rh-incompatible pregnancy," which would include ectopic pregnancy 2.

Administration Protocol

For ectopic pregnancy, the recommended protocol is:

• Timing: Administer within 72 hours of the obstetric complication or procedure 2
• Dose: 300 mcg (1500 IU) intramuscularly or intravenously 2
• Route: Both intramuscular (IM) and intravenous (IV) routes are equally effective 3

Important Clinical Considerations

• Obesity: Recent evidence suggests that obesity (BMI > 35 kg/m²) may be a risk factor for failure of RhIg prophylaxis, potentially requiring dosage adjustments or special attention to administration technique 4

• Timing: Administration within 72 hours of potential exposure to fetal red cells is critical for effectiveness 2

• Documentation: Ensure proper documentation of administration to prevent unnecessary repeat dosing and to inform future pregnancy management

Areas of Uncertainty

While there is strong consensus on administering RhIg for ectopic pregnancy, the French College of Obstetricians and Gynecologists notes that "the literature data are insufficient in quality and quantity to determine if the injection of Rh D immunoglobulin reduces the risk of alloimmunization in the case of an ectopic pregnancy" 5. However, given the potentially severe consequences of alloimmunization and the established safety profile of RhIg, most authorities recommend erring on the side of caution and administering RhIg in cases of ectopic pregnancy.

In conclusion, despite some limitations in the evidence base, the potential benefits of preventing alloimmunization through RhIg administration in ectopic pregnancy outweigh the risks, making it standard practice for Rh-negative women.