What is the recommended administration protocol for Anti-D (Rho(D) immune globulin) injection in Rh-negative mothers?

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Anti-D Injection Protocol for Rh-Negative Mothers

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, with additional doses required for specific pregnancy complications to prevent RhD alloimmunization. 1

Standard Prophylaxis Protocol

  • A two-dose protocol is recommended for Rh-negative pregnant women: 300 μg RhIg at 28 weeks gestation and within 72 hours after delivery of an Rh-positive infant 1
  • This protocol reduces the rate of RhD alloimmunization from approximately 1.8% to between 0.1% and 0.2% 1
  • If paternity is certain, testing the baby's father for Rh status may eliminate unnecessary administration of RhIg 2
  • Women with "weak D" (Du-positive) should not receive anti-D 2

Dosing for Pregnancy Complications

First Trimester Events (<12 weeks gestation)

  • For spontaneous or induced abortion, ectopic pregnancy, or chorionic villus sampling: 50 μg RhIg within 72 hours 3, 1, 4
  • If the 50 μg dose is unavailable, use the standard 300 μg dose 1

Second and Third Trimester Events (>12 weeks gestation)

  • For amniocentesis, cordocentesis, other invasive procedures, spontaneous or induced abortion, intrauterine fetal death, external cephalic version attempts, abdominal trauma, or obstetric hemorrhage: 100-300 μg RhIg 1, 4

Administration Timing and Route

  • RhIg should be administered as soon as possible after a sensitizing event, ideally within 72 hours 1, 2
  • If not given within 72 hours, RhIg should still be administered up to 28 days after the event, though effectiveness may be reduced 2
  • Both intramuscular (IM) and intravenous (IV) administration routes are equally effective 5
  • Anti-D IgG concentrations differ between IV and IM routes up to 7 days post-administration but become similar after 2-3 weeks 5

Special Considerations

Fetomaternal Hemorrhage (FMH)

  • For events with potential placental trauma (abruption, blunt abdominal trauma, placenta previa with bleeding), quantitative testing for FMH should be considered 1, 2
  • If FMH exceeds the amount covered by the standard dose, additional RhIg should be given at 10 μg per 0.5 mL of fetal red blood cells 4, 6

First Trimester Abortion or Miscarriage

  • Despite some guidelines suggesting RhIg may not be necessary before 12 weeks, the Society for Maternal-Fetal Medicine recommends offering RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks gestation 3, 1
  • This recommendation is based on the fact that fetal RBCs display red cell antigens from as early as 6 weeks of gestation, making maternal sensitization possible even in early pregnancy 3, 1

Clinical Impact and Rationale

  • Prevention of RhD alloimmunization is essential given its potential to cause hemolytic disease of the fetus and newborn in subsequent pregnancies 1, 7
  • Without prophylaxis, approximately 13-17% of Rh-negative women delivering Rh-positive infants would develop anti-D antibodies 1
  • The risks associated with RhIg administration are low compared to the potential benefits of preventing alloimmunization 1

Common Pitfalls to Avoid

  • Failing to recognize that fetal RBCs display red cell antigens from as early as 6 weeks gestation, making maternal sensitization possible in early pregnancy 1
  • Not administering RhIg for first trimester pregnancy losses or terminations due to misconceptions about risk 3
  • Delaying administration beyond 72 hours, which may reduce effectiveness 2
  • Not considering additional doses for significant fetomaternal hemorrhage 2, 4

References

Guideline

Management Guidelines for Rh Negative Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Prevention of Rh alloimmunization.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2003

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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