Anti-D Immunoglobulin in Pregnancy
BSH Guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn. Last reviewed: Aug 2023.
Background and Implication
Rhesus D and Sensitisation Process
The Rh D antigen is a protein found on the surface of red blood cells. Individuals who express this antigen are Rh D positive; those who do not are Rh D negative.
When a D-negative woman carries a D-positive fetus, fetal red cells can leak into the maternal circulation (called fetomaternal haemorrhage). Fetomaternal haemorrhage can occur spontaneously during pregnancy or delivery, but is also triggered by a number of clinical events (see the indications section below).
If fetomaternal haemorrhage happens, the maternal immune system may recognise the fetal D antigen as foreign and mount an immune response → producing anti-D IgG antibodies. This process is called sensitisation (Rh D alloimmunisation)
The purpose of anti-D immunoglobulin is to prevent this sensitisation from occurring in the first place.
Why does this only affect RhD-negative women?
- RhD-positive women already express the D antigen and will not produce antibodies against it, as their immune system recognises it as self
- Fetomaternal haemorrhage still happens, but it just won’t result in the sensitisation process (i.e. production of anti-D IgG antibodies)
How can a RhD-negative woman carry a RhD-positive baby?
- The RhD gene is inherited from both parents and follows autosomal dominant inheritance
- The D allele is dominant over the d allele
- Therefore, individuals with at least one dominant D allele (DD or Dd) are RhD positive, while those with two recessive d alleles (dd) are RhD negative
- A RhD-negative mother is homozygous recessive (dd); if the father carries at least one D allele (DD or Dd), the fetus may inherit the D allele and be RhD positive
Haemolytic Disease of the Fetus and Newborn (HDN)
The main implication is that if a previously sensitised Rhesus D-negative mother carries a Rhesus D-positive baby → HDN
- Maternal IgG anti-D antibodies formed from the previous sensitising event will cross the placenta and attack fetal RBCs
- This causes
- Fetal anaemia
- Hydrops fetalis
- Neonatal jaundice
HDN does NOT typically affect the first pregnancy as sensitisation usually occurs during delivery of the first D-positive infant.
It is subsequent pregnancies that are at risk. This is why prevention, rather than treatment, is the priority.
Indications
| Gestational age | Indications for anti-D prophylaxis |
|---|---|
| <12 weeks | ONLY indicated for the following potentially sensitising events:
|
| 12 weeks and onwards | ANY potentially sensitising events:
|
Anti-D prophylaxis is specifically intended only for Rhesus D-negative pregnant women who do not have immune anti-D (i.e. non-sensitised). Therefore, before giving anti-D prophylaxis, one must verify that the woman is:
- Rhesus D negative on blood group typing, and
- Does NOT have immune anti-D antibodies on antibody screen
If a woman has already been sensitised and formed her own immune anti-D antibodies (suggested by the presence of immune anti-D antibodies), she should NOT receive anti-D prophylaxis.
The entire purpose of giving prophylactic anti-D immunoglobulin is to prevent the woman’s immune system from becoming sensitised to the D antigen
IMPORTANT disclaimer on guideline conflict:
BSH 2014 recommends anti-D following therapeutic termination at any gestation and ectopic pregnancy regardless of method. However, a BSH addendum (March 2020) noted: “The more recent NICE guidances (below) should be referred to in relation to ectopic pregnancy and also abortion care pending an update the BSH guidelines. The National Institute for Health and Care Excellence (NICE) have issued two guidelines referencing anti-D prophylaxis.”
NICE ng140 and 126 recommended that:
- Termination of pregnancy <12 weeks does NOT need anti-D prophylaxis regardless of Rhesus status
- For ectopic pregnancy and miscarriage, anti-D prophylaxis is only necessary if surgically managed
Where NICE guidance (NG126, NG140) conflicts with BCSH 2014, NICE takes precedence in line with the BSH 2020 addendum.
Anti-D Prophylaxis
Anti-D prophylaixs invovles administrating anti-D immunoglobulin to prevent sensitisation
- It should be ASAP and always within 72 hours of a sensitising event.
- The precise mechanism by which anti-D immunoglobulin prevents alloimmunisation is unknown (possible mechanisms likely involve rapid clearance of anti-D-coated D-positive RBCs by macrophages and down-regulation of antigen-specific B cells)
Dosage:
- Fixed doses are recommended depending on gestational age
- If the sensitising event happened at ≥20 weeks, fetomaternal haemorrhage should be assessed using the Klehauer test or flow cytometry
- Anti-D dose should be increased if a large fetomaternal haemorrhage is detected
Routine Antenatal Anti-D Prophylaxis
All Rhesus D-negative, non-sensitised pregnant women should be offered routine antenatal anti-D prophylaxis
2 established dosing regimens are available (both equally effective):
- Two-dose regimen: 1st dose given at 28 weeks and 2nd given at 34 weeks
- Single-dose regimen: one larger dose is given at 28-30 weeks
Routine antenatal anti-D prophylaxis is a separate entity from anti-D given for potentially sensitising events.
It should be administered regardless of, and in addition to, any anti-D immunoglobulin that a woman may have already received for a sensitising event earlier in the same pregnancy.
Postpartum Prophylaxis
Following delivery, for all Rhesus D-negative, previously non-sensitised women with a Rhesus D-positive baby (confirmed via cord blood or heel prick sample) → administer maternal anti-D immunoglobulin