At what gestational age should the first dose of Rhogam (Rho(D) immune globulin) be administered to an Rh negative mother?

Timing of First Rhogam Dose in Rh Negative Mothers

The first routine dose of Rhogam should be administered at 28 weeks gestation to all Rh-negative, non-sensitized pregnant women when the fetal blood type is unknown or known to be Rh-positive. 1

Standard Prophylaxis Protocol

Routine Antepartum Administration

• Administer 300 μg (1500 IU) of RhIG at 28 weeks gestation as the standard first dose for routine prophylaxis 1, 2
• An alternative two-dose regimen consists of 100-120 μg at 28 weeks followed by another dose at 34 weeks 3
• This antepartum dose must be followed by a postpartum dose (300 μg) within 72 hours of delivery if the infant is Rh-positive 1, 2

Evidence Supporting 28-Week Timing

The American College of Obstetricians and Gynecologists established this protocol based on evidence showing that adding the antenatal dose at 28 weeks reduces alloimmunization rates from 1.8% to 0.1-0.2%, compared to postpartum prophylaxis alone which only reduces rates from 13-17% to 1-2% 1. The 28-week timing provides protection during the third trimester when the risk of fetomaternal hemorrhage increases 2.

Earlier Administration for Specific Events

First Trimester Events (Before 12 Weeks)

• Administer 50 μg (minimum dose) within 72 hours for:
  • Spontaneous or induced abortion 1, 4
  • Threatened abortion with heavy bleeding or abdominal pain 1
  • Miscarriage 5
• If 50 μg is unavailable, use the standard 300 μg dose 1
• This early administration is critical because fetal RBCs display Rh antigens from as early as 6 weeks gestation, making maternal sensitization possible even in very early pregnancy 1, 5

Events at or After 12 Weeks

• Administer 300 μg within 72 hours for:
  • Miscarriage, abortion, or ectopic pregnancy termination at ≥13 weeks 2, 3
  • Amniocentesis (at 15-18 weeks or third trimester) 2, 3
  • Chorionic villus sampling after 12 weeks 3
  • Abdominal trauma in second or third trimester 2
  • Placental or vaginal bleeding at any gestational age 1

Critical Timing Considerations

The 72-Hour Window

• RhIG should ideally be administered within 72 hours of any potentially sensitizing event 1, 2
• However, if the 72-hour window is missed, administer RhIG as soon as recognized, up to 28 days after the event, as some protection may still be afforded 2, 3

Repeat Dosing Requirements

• If a sensitizing event requiring RhIG occurs at 13-18 weeks gestation, another full dose must still be given at 26-28 weeks to maintain protection throughout pregnancy 2
• The half-life of IgG is 23-26 days, so passively acquired anti-D levels must be maintained above the threshold needed to prevent immune response 2
• A repeat antepartum dose at 40 weeks is generally not required if the 28-week dose was given on schedule 3

Common Pitfalls to Avoid

• Do not withhold RhIG based on early gestational age alone - existing data do not convincingly demonstrate the safety of withholding RhIG for first-trimester events, despite some organizations' recommendations based on logistical rather than safety considerations 1
• Do not delay beyond 72 hours when possible - while late administration provides some benefit, optimal protection requires timely administration 2, 3
• Do not forget the postpartum dose - even if antepartum prophylaxis was given, a postpartum dose is still required within 72 hours if the infant is Rh-positive 1, 2
• Consider additional dosing for large fetomaternal hemorrhage - if hemorrhage exceeds 15 mL of fetal RBCs (30 mL whole blood), additional RhIG is required at 10 μg per 0.5 mL of fetal red blood cells 2, 3