The Use of Anti-D Immunoglobulin for Rh D Prophylaxis

RCOG has retired this as a standalone Green-top guideline. Routine antenatal anti-D prophylaxis is now covered within NICE NG201 Antenatal Care. Retained here as the clinical detail on anti-D dosing and indications below remains accurate and exam-relevant.

Key Recommendations

• All RhD-negative pregnant women should be offered routine antenatal anti-D prophylaxis (RAADP)
• Anti-D should be given within 72 hours of any potentially sensitising event
• Kleihauer test should be performed after any potentially sensitising event from 20 weeks gestation
• Anti-D is a blood product — women must give informed consent

Sensitising Events Requiring Anti-D

First Trimester (before 12 weeks)

• Ectopic pregnancy (all management types)
• Molar pregnancy
• Therapeutic termination of pregnancy
• Miscarriage with surgical or medical intervention (NOT required for threatened miscarriage <12 weeks with no intervention and bleeding has stopped)
• Chorionic villus sampling (CVS)

Second and Third Trimester (12 weeks onwards)

• Amniocentesis and any invasive prenatal procedure
• Antepartum haemorrhage (APH)
• External cephalic version (ECV) — successful or failed
• Abdominal trauma
• Intrauterine death
• Any in-utero therapeutic intervention (e.g. intrauterine transfusion)
• Delivery — vaginal or caesarean

Dose and Timing

• Minimum dose: 250 IU before 20 weeks, 500 IU from 20 weeks onwards
• Must be given within 72 hours of the sensitising event
• If more than 72 hours have elapsed, anti-D may still offer partial protection up to 10 days
• RAADP: single dose of 1500 IU at 28 weeks gestation, OR two doses of 500 IU at 28 and 34 weeks

Routine Antenatal Anti-D Prophylaxis (RAADP)

• Offered to all RhD-negative women who have not already been sensitised
• Single-dose regimen (1500 IU at 28 weeks) is as effective as two-dose (500 IU at 28 and 34 weeks)
• RAADP does not replace event-driven anti-D — additional doses needed for sensitising events
• Check antibody screen at booking; if anti-D antibodies already present, RAADP is not indicated (already sensitised)

Kleihauer Test

• Performed on maternal blood to detect fetal red cells (acid elution test)
• Quantifies fetal-maternal haemorrhage (FMH) to guide additional anti-D dosing
• Indicated after all potentially sensitising events from 20 weeks onwards
• Large FMH (>4ml fetal red cells): additional anti-D required (500 IU per 4ml FMH)
• Follow-up Kleihauer at 48 hours after large FMH to confirm clearance

Management Algorithm

1. Determine maternal blood group at booking
2. If RhD-negative: offer RAADP at 28 weeks (or 28 + 34 weeks)
3. At each sensitising event: give anti-D within 72 hours + Kleihauer (if ≥20 weeks)
4. After delivery: determine neonatal blood group from cord blood
5. If neonate is RhD-positive: give anti-D within 72 hours + Kleihauer
6. If neonate is RhD-negative: no postnatal anti-D required

Important Facts for MRCOG

• Anti-D must be given within 72 hours but can provide partial protection up to 10 days
• Threatened miscarriage <12 weeks without intervention does NOT require anti-D
• Kleihauer test is required from 20 weeks (not in first trimester)
• Standard dose: 250 IU before 20 weeks, 500 IU from 20 weeks
• RAADP: 1500 IU single dose at 28 weeks is the preferred regimen
• Anti-D does NOT prevent sensitisation if antibodies are already present
• Cell-free fetal DNA (cffDNA) testing can determine fetal RhD status from maternal blood from 11+2 weeks — increasingly used to target RAADP only to those carrying RhD-positive fetuses

Common Exam Pitfalls

• Forgetting anti-D for ECV (both attempted and successful)
• Not offering anti-D for ectopic pregnancy
• Giving anti-D to an already-sensitised woman (check antibody status first)
• Omitting Kleihauer test after sensitising events in 2nd/3rd trimester

Source: RCOG Green-top Guideline No. 22 (Archived) (2011 (reviewed 2021, RCOG archived thereafter))

Read the original on rcog.org.uk

Clinically reviewed by NHS obstetricians and gynaecologists · Source last updated 2011 (reviewed 2021, RCOG archived thereafter)

MRCOG AI is an independent educational tool. It is not affiliated with, endorsed by, or connected to the Royal College of Obstetricians and Gynaecologists (RCOG).