When should Rh‑D immune globulin (RhoGam) be administered to an Rh‑negative pregnant woman?

When to Administer RhoGam (Rh-D Immune Globulin)

All Rh-negative pregnant women without anti-D antibodies should receive RhoGam at 28 weeks gestation and within 72 hours after delivery of an Rh-positive infant, with additional doses required for any potentially sensitizing event throughout pregnancy. 1

Standard Prophylaxis Protocol

Routine Antepartum Administration

• Administer 300 μg RhoGam at 28 weeks gestation to all unsensitized Rh-negative women when fetal blood type is unknown or confirmed Rh-positive 1, 2
• This two-dose protocol (antepartum plus postpartum) reduces alloimmunization rates from 1.8% to 0.1-0.2%, compared to 13-17% without any prophylaxis 1, 2
• Alternative dosing: Two doses of 100-120 μg may be given at 28 and 34 weeks 3

Postpartum Administration

• Give 300 μg RhoGam within 72 hours of delivery if the infant is confirmed Rh-positive 1, 2, 3
• If the 72-hour window is missed, administer as soon as recognized up to 28 days post-delivery, as delayed administration still provides some benefit 1
• Postpartum RhoGam alone (without antepartum dose) reduces alloimmunization from 12-13% to 1-2% 2

Potentially Sensitizing Events Requiring RhoGam

Early Pregnancy Events (Before 12 Weeks)

• Spontaneous or induced abortion: Give minimum 50 μg (or 120 μg if available) within 72 hours 1, 3
• Threatened abortion with heavy bleeding or abdominal pain: Administer RhoGam, especially if near 12 weeks gestation 1
• Ectopic pregnancy: Give minimum 120 μg before 12 weeks 3
• Molar pregnancy: Administer if partial mole possible; may withhold only if complete mole is certain 3

Critical rationale: Fetal red blood cells display D-antigens from as early as 6 weeks gestation, making maternal sensitization physiologically possible even in very early pregnancy 1, 4. Fetomaternal hemorrhage occurs in 48% of threatened abortions, 36% of complete abortions, and 22% of incomplete abortions 1.

Mid-to-Late Pregnancy Events (After 12 Weeks)

• Any abortion or pregnancy loss: Give 300 μg within 72 hours 1, 3
• Amniocentesis: Administer 300 μg 3
• Chorionic villus sampling: Give 120 μg before 12 weeks, 300 μg after 12 weeks 3
• Cordocentesis: Give 300 μg 3
• External cephalic version: Administer 300 μg 3

Bleeding or Trauma Events at Any Gestational Age

• Placental or vaginal bleeding: Give RhoGam to all unsensitized Rh-negative women regardless of gestational age 1
• Abdominal trauma (even minor): Consider administration, as 28% of pregnant patients with minor trauma have fetomaternal hemorrhage 1
• Placental abruption: Administer with consideration for quantitative testing 3
• Placenta previa with bleeding: Give RhoGam with consideration for quantitative testing 3

Dosing Adjustments for Large Fetomaternal Hemorrhage

When to Consider Quantitative Testing

• Perform Kleihauer-Betke or flow cytometry testing following events with potential for significant placental trauma: placental abruption, blunt abdominal trauma, cordocentesis, or placenta previa with bleeding 3

Additional Dosing Algorithm

• Standard 300 μg dose covers up to 15 mL of fetal red blood cells (approximately 30 mL fetal blood) 3
• If fetomaternal hemorrhage exceeds 15 mL of fetal RBCs: Give additional 10 μg RhoGam for every 0.5 mL of fetal red blood cells beyond the standard dose 1, 3
• Alternative: 120 μg dose covers up to 6 mL fetal RBCs; add 10 μg per 0.5 mL beyond this 3

Critical Timing Considerations

The 72-Hour Window

• RhoGam must be administered within 72 hours of exposure for optimal effectiveness in suppressing the maternal immune response 1, 4, 2
• As little as 0.03-0.1 mL of Rh-positive red blood cells can trigger primary alloimmunization 4
• Most sensitization (90%) occurs at delivery, but antepartum exposure increases with gestational age: 7% in first trimester, 16% in second trimester, 29% in third trimester 4

Late Administration

• If beyond 72 hours, still administer up to 28 days post-exposure, as some protection is better than none 1

Special Situations and Caveats

When RhoGam Is NOT Needed

• Women with "weak D" (Du-positive) should NOT receive RhoGam 3
• Women with molecularly defined weak D types 1,2,3,4.0,4.1, or Asian-type DEL (c.1227G>A) do not require RhoGam, as they are unlikely to produce anti-D 5
• If the woman is already sensitized (has detectable anti-D antibodies): RhoGam is ineffective and should not be given 6

Unknown Blood Type Scenarios

• If Rh status is unknown and testing would delay urgent abortion care, counsel the patient but prioritize completing the procedure 1
• If testing is unavailable, administer RhoGam if clinically indicated, as risks of administration are low compared to potential sensitization consequences 1

Paternity Testing Option

• When paternity is certain, offer Rh testing of the baby's father to Rh-negative pregnant women to potentially eliminate unnecessary RhoGam administration 3

Supply Shortage Prioritization

• If RhoGam supply is limited, prioritize postpartum patients and antenatal patients at later gestational ages 1

Common Pitfalls to Avoid

• Do not assume early gestational age eliminates risk: Fetal RBCs with D-antigen are present from 6 weeks onward 1, 4
• Do not withhold RhoGam for "minimal" bleeding: Even small amounts of fetomaternal hemorrhage can cause sensitization, and bleeding severity does not reliably predict hemorrhage volume 1
• Do not forget the antepartum dose: The 1-2% failure rate with postpartum-only prophylaxis is largely due to sensitization occurring during late pregnancy 2
• Do not delay beyond 72 hours when possible: Effectiveness decreases with time, though late administration is still preferable to none 1, 4