What are the Australian guidelines for anti‑D (Rho(D) immune globulin) prophylaxis in Rh‑negative pregnant women, including dosing schedule and indications?

Australian Anti-D Prophylaxis Guidelines for Rh-Negative Pregnant Women

Standard Prophylaxis Protocol

All RhD-negative pregnant women should receive anti-D immunoglobulin at 28 weeks gestation and within 72 hours after delivery of an RhD-positive infant, using either a single-dose or two-dose regimen. 1

Antenatal Dosing Options

• Single-dose regimen: 300 μg (1500 IU) at 28 weeks gestation 2
• Two-dose regimen: 100-120 μg at 28 weeks AND 34 weeks gestation (120 μg being the lowest currently available dose in Australia) 2
• Both regimens reduce alloimmunization rates from approximately 1.8% to 0.1-0.2% 1

Postpartum Administration

• Dose: 300 μg IM or IV within 72 hours of delivery if infant is RhD-positive 2
• Alternative: 120 μg IM or IV may be used, with testing for fetomaternal hemorrhage (FMH) >6 mL of fetal red blood cells 2
• Late administration: 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

Potentially Sensitizing Events Requiring Anti-D

First Trimester (<12 weeks)

• Spontaneous or induced abortion: Minimum 120 μg (50 μg acceptable if available, though 120 μg is the lowest dose currently available in Australia) 1, 2
• Ectopic pregnancy: Minimum 120 μg before 12 weeks 2
• Threatened abortion with heavy bleeding or abdominal pain: Administer anti-D, as 48% of threatened abortions involve fetomaternal hemorrhage 1
• Molar pregnancy: Give anti-D unless complete mole is confirmed (withhold if certain of complete mole) 2

Critical caveat: Fetal RBCs display D-antigens from as early as 6 weeks gestation, making sensitization physiologically possible even in very early pregnancy. 3 Australian audit data shows only 78% of women receive anti-D when recommended for potentially sensitizing events, indicating significant room for practice improvement. 4

After 12 Weeks Gestation

• Miscarriage or abortion: 300 μg 2
• Ectopic pregnancy: 300 μg 2
• Amniocentesis: 300 μg 2
• Chorionic villus sampling: 300 μg 2
• Cordocentesis: 300 μg 2
• External cephalic version: 300 μg with FMH quantification 2

High-Risk Events Requiring FMH Quantification

For events with substantial placental trauma risk, administer 300 μg anti-D immediately AND perform quantitative FMH testing: 2

• Placental abruption
• Blunt abdominal trauma (28% of pregnant patients with minor trauma have FMH) 1
• Placenta previa with bleeding
• Cordocentesis

Additional dosing: If FMH exceeds 15 mL of fetal red blood cells (30 mL fetal blood), give additional 10 μg anti-D per 0.5 mL of fetal red blood cells. 2 Australian data shows poor compliance with supplemental dosing guidelines, with only 11.5% of cases receiving appropriate additional doses. 5

Screening and Testing Requirements

Initial and Follow-up Testing

• First prenatal visit: Blood type and antibody screen (indirect antiglobulin test) for ALL pregnant women 2
• 28 weeks gestation: Repeat antibody screen 2
• Paternal testing: When paternity is certain, offer RhD testing of the father to eliminate unnecessary anti-D administration 2

Special Populations

• Women with "weak D" (Du-positive): Do NOT give anti-D 2
• Cell-free fetal DNA testing: Can determine fetal RHD status with 97.2% sensitivity and 96.8% specificity, or >99% accuracy after 11 weeks gestation, allowing targeted prophylaxis 1

Route of Administration

Both intramuscular and intravenous routes are equally effective. 6 The choice depends on available preparations, dose requirements, and patient preference. Mean anti-D IgG concentrations differ between routes only up to seven days post-administration, but are equivalent from two to three weeks onward. 6

Critical Pitfalls to Avoid

• Do not withhold anti-D based on early gestational age alone: Fetal RBCs with D-antigen are present from 6 weeks onward, and fetomaternal hemorrhage occurs in 7% of first trimester pregnancies 3
• Do not assume minimal bleeding eliminates risk: Bleeding severity does not reliably predict hemorrhage volume, and as little as 0.03-0.1 mL of fetal blood can trigger alloimmunization 3
• Do not skip the 28-week dose: Australian audit data shows only 76% of eligible women receive anti-D at the appropriate time and dose 4
• Do not forget consent documentation: Only 62% of Australian cases had documented consent, which is legally required 4
• Do not skip FMH quantification after high-risk events: Australian data shows a 4% alloimmunization rate following large-volume FMH despite prophylaxis, partly due to inadequate supplemental dosing 5

Effectiveness Data

• Postpartum anti-D alone: Reduces alloimmunization from 13-17% to 1-2% 1
• Adding antenatal dose at 28 weeks: Further reduces alloimmunization from 1.8% to 0.1-0.2% 1
• Most sensitization occurs at delivery: Approximately 90% of fetomaternal hemorrhage and alloimmunization events occur during delivery itself 3, 7