Can a patient require RhoGAM (Rho(D) immune globulin) more than once during the same pregnancy?

RhoGAM Administration During Pregnancy: Multiple Doses Are Standard

Yes, patients routinely require RhoGAM more than once during the same pregnancy—the standard protocol includes at least two doses: one at 28 weeks gestation and another within 72 hours after delivery of an Rh-positive infant. 1, 2

Standard Two-Dose Protocol

The American College of Obstetricians and Gynecologists established the two-dose regimen as the gold standard for Rh-negative pregnant women:

• Antepartum dose at 28 weeks gestation to prevent late pregnancy sensitization 1, 2
• Postpartum dose within 72 hours of delivery if the infant is Rh-positive 1, 2

This two-dose approach reduces alloimmunization rates from approximately 1.8% (with postpartum dose alone) down to 0.1-0.2%, representing a 90% further reduction in sensitization risk. 1, 3

Additional Doses for Sensitizing Events

Beyond the routine two doses, Rh-negative women require additional RhoGAM administration for any potentially sensitizing event during pregnancy, including: 1, 4

First Trimester Events (50 μg or 120 μg dose):

• Spontaneous abortion or miscarriage 1, 4
• Induced abortion 1, 4
• Threatened abortion with heavy bleeding 1
• Ectopic pregnancy 4

Second/Third Trimester Events (300 μg dose):

• Vaginal or placental bleeding at any gestational age 1
• Amniocentesis 4
• Chorionic villus sampling after 12 weeks 4
• Cordocentesis 4
• External cephalic version 4
• Abdominal trauma 1, 4
• Placental abruption 4, 5
• Placenta previa with bleeding 4, 5

Critical Timing Considerations

Each sensitizing event requires its own dose of RhoGAM, administered within 72 hours of the event for optimal efficacy. 1, 3 The mechanism of action involves suppressing the maternal immune response to fetal Rh-positive red blood cells, and this protection is event-specific rather than cumulative. 3

• If administration is delayed beyond 72 hours, RhoGAM should still be given up to 28 days post-event, as delayed administration provides some benefit and is preferable to no administration. 1
• The routine 28-week dose does not need to be repeated at 40 weeks if given on schedule. 4

Dose Adjustments for Large Fetomaternal Hemorrhage

For events with significant placental trauma, quantitative testing for fetomaternal hemorrhage should be performed to determine if additional doses are needed. 4

• The standard 300 μg dose covers up to 15 mL of fetal red blood cells (approximately 30 mL of fetal blood). 3, 4
• If fetomaternal hemorrhage exceeds this amount, additional RhoGAM must be given at 10 μg per 0.5 mL of fetal red blood cells. 4
• Events particularly at risk for large hemorrhage include blunt abdominal trauma, placental abruption, and cordocentesis. 4

Physiologic Rationale for Multiple Doses

Fetal red blood cells display Rh antigens from as early as 6 weeks gestation, making maternal sensitization possible at any point in pregnancy. 1, 2 Each exposure to fetal blood represents a distinct sensitization risk that requires its own prophylactic dose. The 28-week dose addresses the increasing fetomaternal hemorrhage that occurs in late pregnancy, while the postpartum dose addresses the substantial blood mixing that occurs during placental separation at delivery. 3

Common Pitfalls to Avoid

• Do not assume the 28-week dose provides coverage for subsequent bleeding events or delivery—each sensitizing event requires its own dose. 1, 4
• Do not withhold RhoGAM for early pregnancy events based on gestational age alone—sensitization can occur from 6 weeks onward. 1, 2
• Do not assume minimal bleeding eliminates risk—even small amounts of fetomaternal hemorrhage can cause sensitization, and bleeding severity does not reliably predict hemorrhage volume. 1
• Verify adequate dosing after placental trauma—failure to recognize large fetomaternal hemorrhage may result in inadequate dosing and subsequent sensitization. 3, 4