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When to Administer Anti-D Immune Globulin to Prevent Rh D Alloimmunization


Rh D alloimmunization can be prevented with the administration of anti-D immune globulin.  ACOG recommends administration of anti-D immune globulin to unsensitized Rh D-negative women as follows

Level A Recommendation (good and consistent science)

  • 28 weeks (reduces risk from 2% to 0.2%)
  • Within 72 hours of birth, if infant is Rh D positive and patient is not sensitized

Level B Recommendation (limited or inconsistent science)

  • All invasive diagnostic procedures such as CVS and amniocentesis if fetus may be Rh D positive

Level C Recommendation (consensus/expert opinion)

ACOG language in (” “)

  • External cephalic version, regardless of success (“indicated”)
  • Evacuation of suspected molar pregnancy (“reasonable to administer”)
  • First trimester miscarriage
    • Spontaneous (1.5-2% risk – “should be considered”)
    • Instrumentation (4-5% risk – “should be given”)
  • Termination of pregnancy, either medical or surgical (“should be given”)
  • Ectopic pregnancy (“recommended”)
  • Antenatal hemorrhage >20 weeks gestation (“recommended”)
  • Abdominal trauma (“should be administered”)
  • Fetal death in the 2nd or 3rd trimester (“should be administered”)

Note: SMFM recommends “both RhD testing and Rho(D) immune globulin administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals”


All pregnant women are currently tested at the time of the first prenatal visit for ABO blood group and Rh D type and screening for red cell antibodies. The potential volume of fetal–maternal hemorrhage that can cause Rh D alloimmunization is extremely variable and ranges from 0.1 mL to 30 mL.  Data is limited when it comes to many of the potential sensitizing events and therefore some of the recommendations are based on consensus and expert opinion.


  • Multiple consensus guidelines worldwide recommend
    • Patients should undergo repeat Rh D antibody screening before receiving anti-D immune globulin at 28 weeks and postpartum
  • Providers should be alert to any other events in pregnancy that may increase risk for fetal-maternal hemorrhage
  • ACOG advises that for weak D (previously known as Du)

Clinicians are advised to administer Rh D immune globulin to patients with weak D blood type in appropriate clinical situations, by the same rationale as that for Rh D typing blood donors, until further scientific and economic studies are available.

  • Anti-D immune globulin is purified and tested for viral infections, and therefore risk of viral infection is exceedingly low
    • Manufactured without mercury-containing thimerosal since 2001
  • Failures may still occur due to
    • Not administering in 3rd trimester
    • Insufficient dosage or not administering within 72 hours after a known sensitizing pregnancy event or following birth
    • Unrecognized fetal–maternal hemorrhage
  • Note: There is discussion in the CDC recommendations that receipt of antibody-containing blood products such as intravenous immune globulin may interfere with rubella (and MMR) vaccine and seroconversion. However, the CDC states

Previous administration of human anti-Rho(D) immune globulin (RhoGam) does not generally interfere with an immune response to rubella vaccine and is not a contraindication to postpartum vaccination. However, women who have received anti-Rho immune globulin should be serologically tested 6–8 weeks after vaccination to ensure that seroconversion has occurred.

Assessing Fetal-Maternal Hemorrhage Volume

  • Screening
    • Rosette fetal red blood cell assay to detect greater than 2 mL of fetal whole blood in maternal circulation
  • Quantification tests are appropriate if rosette test is positive
    • Kleihauer-Betke (inexpensive, but lacks standardization and precision)
      • Volume of fetal bleed: % fetal cells x maternal blood volume
      • Maternal blood volume: 70 mL/kg x weight (kg) (assume 5,000 mL if maternal information is unknown)
    • Flow cytometry (more accurate, but limited by cost and availability)

Dosing (ACOG)

  • Screen all Rh D-negative women with Rh D-positive infants for fetal-maternal hemorrhage volume
  • Standard 300-microgram dose of anti-D immune globulin covers 30 mL of Rh D-positive fetal whole blood (or 15 mL of fetal red blood cells)
  • Exposures to <30 mL of Rh D-positive fetal whole blood
    • 28 weeks: 300 micrograms
    • After birth (within 72 hours): 300 micrograms
  • Exposures to >30 mL of Rh D-positive fetal whole blood
    • Assess volume of fetal-maternal hemorrhage to guide dosing
    • Can use up to eight full vials at one time
    • IM: Separate sites every 12 hours until the desired dosage has been reached
    • IV: Rh immune globulin is also available


ACOG Practice Bulletin 181: Prevention of Rh D Alloimmunization

ACOG Practice Bulletin 192: Management of Alloimmunization During Pregnancy

CDC: Epidemiology and Prevention of Vaccine-Preventable Diseases – Rubella

SMFM Statement: RhD immune globulin after spontaneous or induced abortion less than 12 weeks of gestation

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