Management of Rh Negative Pregnancy
All Rh-negative pregnant women should receive RhD immune globulin (RhIg) at 28 weeks gestation and within 72 hours after delivery of an Rh-positive infant, which reduces alloimmunization rates from 12-13% to 0.1-0.2% with the two-dose protocol. 1, 2, 3
Standard Prophylaxis Protocol
Routine Antenatal and Postpartum Administration
- Administer RhIg 300 μg at 28 weeks gestation to all unsensitized Rh-negative women when fetal blood type is unknown or known to be Rh-positive 1, 2, 4
- Administer RhIg 300 μg within 72 hours after delivery if the infant is Rh-positive 1, 2, 3
- If RhIg is not given within 72 hours, administer as soon as recognized up to 28 days post-delivery, as delayed administration still provides benefit 1, 4
- The two-dose protocol (antenatal + postpartum) is the gold standard, reducing alloimmunization from approximately 1.8% (with postpartum dose alone) to 0.1-0.2% 1, 2
Initial Prenatal Testing
- Type and screen all pregnant women at the first prenatal visit and again at 28 weeks with an indirect antiglobulin test 4
- Consider paternal Rh testing when paternity is certain to eliminate unnecessary RhIg administration if the father is Rh-negative 4
- Women with "weak D" (Du-positive) should NOT receive RhIg 4
RhIg Administration for Pregnancy Complications
First Trimester Events (Before 12 Weeks)
- Administer 50 μg RhIg within 72 hours for spontaneous abortion, induced abortion, threatened abortion with heavy bleeding/abdominal pain, or ectopic pregnancy 1, 3, 4, 5
- If 50 μg dose is unavailable, use the standard 300 μg dose 1
- Critical pitfall to avoid: Do not withhold RhIg based on early gestational age alone—fetal RBCs display D antigen from as early as 6 weeks gestation, making maternal sensitization possible even in very early pregnancy 1, 2
- Fetomaternal hemorrhage occurs in 48% of threatened abortions, 36% of complete abortions, and 22% of incomplete abortions 1
Second and Third Trimester Events (After 12 Weeks)
- Administer 300 μg RhIg within 72 hours for spontaneous or induced abortion, ectopic pregnancy, intrauterine fetal death, or molar pregnancy (unless complete mole is certain) 3, 4, 5
- For invasive procedures: amniocentesis, chorionic villus sampling (CVS), cordocentesis, or external cephalic version, administer 300 μg RhIg 4, 5
- For CVS specifically: 120 μg before 12 weeks, 300 μg after 12 weeks 4
Placental Trauma and Bleeding Events
- Administer RhIg for any placental or vaginal bleeding at any gestational age to prevent alloimmunization 1
- For events with significant placental trauma (placental abruption, blunt abdominal trauma, placenta previa with bleeding), administer 300 μg RhIg AND consider quantitative testing for fetomaternal hemorrhage 1, 4, 5
- Critical consideration: 28% of pregnant patients with minor trauma have fetomaternal hemorrhage 1
- If fetomaternal hemorrhage exceeds 15 mL of fetal RBCs (approximately 30 mL of whole fetal blood), administer additional RhIg at 10 μg per 0.5 mL of fetal RBCs 4, 5
Special Clinical Scenarios
Unknown Blood Type
- If blood type is unknown and testing is unavailable or would delay care (particularly for abortion), counsel the patient on risks but prioritize completing the procedure 1
- Administer RhIg if clinically indicated, as the risks of administration are minimal compared to potential sensitization consequences 1, 2
Determining Need for Postpartum RhIg
- Cell-free fetal DNA testing from maternal plasma can determine fetal RHD status with 97.2% sensitivity and 96.8% specificity, or exceeding 99% accuracy when performed after 11 weeks gestation 1
- This allows for targeted antenatal RhIg administration only when the fetus is Rh-positive 1
Repeat Antepartum Dosing
- A repeat antepartum dose at 40 weeks is generally not required if the initial dose was given at 28 weeks or later 4
Critical Timing and Dosing Summary
| Clinical Scenario | Timing | Dose |
|---|---|---|
| Routine antenatal prophylaxis | 28 weeks gestation | 300 μg |
| Postpartum (Rh+ infant) | Within 72 hours of delivery | 300 μg |
| First trimester events (<12 weeks) | Within 72 hours | 50 μg (or 300 μg if unavailable) |
| Second/third trimester events (≥12 weeks) | Within 72 hours | 300 μg |
| Invasive procedures | Within 72 hours | 300 μg |
| Large fetomaternal hemorrhage | As soon as identified | Additional 10 μg per 0.5 mL fetal RBCs |
Common Pitfalls to Avoid
- Do not assume early gestational age eliminates risk—fetal RBCs with D-antigen are present from 6 weeks onward 1, 2
- Do not withhold RhIg for "minimal" bleeding—even small amounts of fetomaternal hemorrhage can cause sensitization, and bleeding severity does not reliably predict hemorrhage volume 1
- Do not miss the 72-hour window without attempting late administration—RhIg given up to 28 days post-event still provides some benefit 1, 4
- Do not forget the postpartum dose if antenatal RhIg was given—both doses are essential for optimal protection 1, 2, 3
- Verify the infant's blood type before withholding postpartum RhIg—if unknown, assume Rh-positive and administer 3
Product Shortage Considerations
- During RhIg shortages, prioritize postpartum patients and antenatal patients at later gestational ages 1
- If the typically used brand is unavailable, an equivalent RhIg product may be substituted 1
Informed Consent
- Verbal or written informed consent must be obtained prior to administration of RhIg, as it is a blood product 4