What is the recommended Rhogam (Rho(D) immune globulin) schedule for preventing Rh sensitization during pregnancy?

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Rhogam Schedule for Rh-Negative Pregnant Women

All Rh-negative, unsensitized pregnant women should receive RhIg 300 μg at 28 weeks gestation and again within 72 hours after delivery of an Rh-positive infant, which reduces alloimmunization rates from 1.8% to 0.1-0.2%. 1

Standard Antepartum and Postpartum Protocol

Routine Prophylaxis During Pregnancy

  • Administer RhIg 300 μg (1500 IU) intramuscularly at 28 weeks gestation to all Rh-negative women when fetal blood type is unknown or Rh-positive 1, 2
  • An alternative two-dose regimen of 100-120 μg at both 28 weeks and 34 weeks may be used, though the single 300 μg dose at 28 weeks is standard 3
  • A repeat antepartum dose at 40 weeks is generally not required if the 28-week dose was given on schedule 3

Postpartum Administration

  • Give RhIg 300 μg within 72 hours of delivery if the infant is confirmed Rh-positive 1, 2
  • If RhIg is not given within 72 hours, administer as soon as recognized up to 28 days after delivery 3
  • The postpartum dose may be withheld only if delivery occurs within 3 weeks of the last antenatal dose AND there is no excessive fetomaternal hemorrhage (>15 mL fetal RBCs) 2
  • This two-dose protocol (antepartum plus postpartum) decreases alloimmunization from 13-17% down to 0.1-0.2% 1

Dosing for Pregnancy Complications and Events

First Trimester Events (<12 weeks)

  • For spontaneous or induced abortion, ectopic pregnancy, or threatened abortion before 12 weeks: administer 50 μg (250 IU) within 72 hours 4, 1
  • If the 50 μg dose is unavailable, use the standard 300 μg dose 1, 2
  • Fetal RBCs display Rh antigens from as early as 6 weeks gestation, making sensitization possible even in very early pregnancy 1

Second and Third Trimester Events (≥12 weeks)

  • For miscarriage, abortion, or ectopic pregnancy at or beyond 12 weeks: give 300 μg 2, 3
  • For amniocentesis (at 15-18 weeks or third trimester): administer 300 μg 2, 3
  • For chorionic villus sampling: give 120 μg before 12 weeks or 300 μg after 12 weeks 3
  • For cordocentesis: administer 300 μg 3

Bleeding and Trauma

  • For vaginal or placental bleeding at any gestational age: give RhIg to prevent alloimmunization 1
  • For threatened abortion with heavy bleeding or abdominal pain, especially near 12 weeks: administer RhIg 1
  • For abdominal trauma in second or third trimester: give 300 μg 2
  • Consider RhIg for minor trauma, as 28% of pregnant patients with minor trauma demonstrate fetomaternal hemorrhage 1

Management of Large Fetomaternal Hemorrhage

When to Test for Excess Hemorrhage

  • Consider quantitative testing (modified Kleihauer-Betke or flow cytometry) following events with potential placental trauma: placental abruption, significant abdominal trauma, external cephalic version, placenta previa with bleeding, or cordocentesis 3, 2

Additional Dosing Algorithm

  • Standard 300 μg dose covers up to 15 mL of fetal RBCs (approximately 30 mL whole fetal blood) 2
  • If fetomaternal hemorrhage exceeds 15 mL of fetal RBCs, calculate additional doses: divide the total volume of fetal RBCs by 15 mL to determine number of 300 μg doses needed 2
  • If calculation results in a fraction, round up to the next whole number (e.g., if 1.4, give 2 doses) 2
  • Alternatively, give an additional 10 μg for every 0.5 mL of fetal RBCs beyond the amount covered 3

Administration Guidelines

Route and Timing

  • Administer intramuscularly, preferably in the deltoid muscle of the upper arm or lateral thigh 2
  • Do NOT use the gluteal region due to risk of sciatic nerve injury 2
  • Do NOT inject intravenously or into the neonate 2
  • Optimal timing is within 72 hours of the sensitizing event, though some protection persists if given later 2

Multiple Dose Administration

  • When multiple doses are required, the total volume may be divided and given at different sites simultaneously, or divided over intervals, provided the total is given within 72 hours 2

Essential Screening and Testing

Initial and Follow-up Testing

  • Type and screen all pregnant women (Rh-negative or Rh-positive) at the first prenatal visit and again at 28 weeks 1, 3
  • When paternity is certain, offer Rh testing of the father to Rh-negative women to potentially eliminate unnecessary RhIg administration 3
  • Women with "weak D" (Du-positive) should NOT receive RhIg 3

Postpartum Confirmation

  • Confirm infant's Rh status after delivery before administering postpartum dose 2
  • The infant should have a negative direct antiglobulin test 2

Critical Considerations

Supply Shortages

  • 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

Common Pitfalls to Avoid

  • Do not withhold RhIg based on early gestational age alone - fetal RBCs express Rh antigens from 6 weeks onward 1
  • Do not assume low risk without evidence - while alloimmunization after first-trimester events is uncommon, existing data do not convincingly demonstrate safety of withholding RhIg 4, 1
  • The consequences of alloimmunization are severe (fetal transfusion, hydrops, stillbirth, preterm delivery, hemolytic disease of newborn) and increase with each subsequent pregnancy 4

Informed Consent

  • Obtain verbal or written informed consent prior to administering RhIg, as it is a blood product 3

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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