Haemolytic disease of the fetus and newborn (HDFN)

What is HDFN?

HDFN occurs when pregnant mothers produce IgG antibodies against fetal red cell antigens. These antibodies can cross the placenta and destroy the fetus’ red cells.  

In the most severe cases of HDFN, the fetus may be born with severe anaemia that requires exchange transfusion of red cells, permanent neurological damage due to high bilirubin levels (kernicterus), or even die in utero.

Causes of HDFN

If fetal red cells cross the placenta into the maternal circulation (fetomaternal haemorrhage), antibodies can develop against antigens on the fetus’ red cells that are inherited from the father and are absent in the mother.

Antibody to the RhD antigen is the most frequent cause of moderate to severe HDFN. IgG antibodies against other Rh antigens (including c, e, C, E) and blood group antigens (including Fya and K) occur in about 0.5% of pregnancies.

ABO incompatibility between the mother and fetus are common but usually only causes mild to moderate HDFN.

Routine antenatal screening

The ABO and RhD group of all pregnant women should be determined when they first attend for antenatal care.  

The mother's blood should also be tested for the presence of IgG red cell antibodies, as these may cause HDFN.  

Routine antenatal screening should be performed in accordance with the ANZSBT Guidelines for Transfusion and Immunohaematology Laboratory Practice.

Management of HDFN

Specialist fetal medicine teams should care for pregnancies that are potentially affected by HDFN with facilities for early diagnosis, intrauterine transfusion and support of high-dependency neonates.

The referral should be made before 20 weeks in those women who’ve had a previously severely affected baby, unless there is a new partner who is negative for the relevant antigen.

If antibodies are detected, the antibody titre and/or quantification should be monitored regularly throughout the pregnancy in case they increase, as rising levels are likely to indicate that the fetus is being affected by HDFN.

Management of an affected fetus may include intravenous immunoglobulin for the mother or intrauterine transfusion, early delivery, phototherapy and exchange transfusion for the fetus.

Routine RhD immunoglobulin prophylaxis

Routine RhD immunoglobulin prophylaxis for all RhD negative pregnant women is recommended.

 

Week 28 gestation

Week 34 gestation

Antibody formation occurs during pregnancy in about 1%–1.5% of RhD negative women carrying a RhD positive infant, despite use of postnatal prophylaxis.

The rate of antibody formation can be reduced to 0.2% or less by the administration of RhD immunoglobulin during pregnancy, at 28 weeks and 34 weeks (antenatal prophylaxis), as well as after delivery.

Recommendations for RhD immunoglobulin following a sensitising event

Administration of RhD immunoglobulin to RhD negative women is important after sensitising events and following delivery of a RhD positive baby. This reduces the risk of the RhD negative mother developing an anti-D antibody.

The National Blood Authority (NBA) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) recommends that all RhD negative women who have not developed an anti-D should be offered RhD Immunoglobulin in the following clinical situations:

 

Week 1 to week 12 (first trimester)

  • Chorionic villus sampling
  • miscarriage
  • termination of pregnancy (either medical or surgical), and
  • ectopic pregnancy.

Note: There is insufficient evidence to suggest that a threatened miscarriage before 12 weeks gestation requires RhD immunoglobulin.

  

Beyond week 12 (second & third trimester)

  • obstetric haemorrhage
  • amniocentesis, cordocentesis
  • external cephalic version of breech presentation, whether successful or not, and
  • abdominal trauma, or any other suspected intrauterine bleeding or sensitising event.

 

Delivery of a RhD positive baby

  • RhD immunoglobulin should be administered as soon as possible after the sensitising event or following delivery, ideally within 72 hours for successful prophylaxis.
  • If RhD immunoglobulin has not been administered within 72 hours, a dose offered within 10 days may provide protection.
  • There is some concern that the intramuscular administration of RhD immunoglobulin to RhD negative mothers with a body mass index (BMI) > 30 is associated with an increased risk of lack of effectiveness. Correct administration techniques such as deep intramuscular injection with a long needle into the deltoid may mitigate some of this risk.

Dosage of RhD immunoglobulin for each sensitising event or at delivery*

 

Week 1 to week 12 (first trimester)

 

Beyond week 12 (second & third trimester)

 

Postpartum

  • 625 IU RhD Immunoglobulin-VF Solution for intramuscular injection; more than one dose may be required depending on magnitude of fetomaternal haemorrhage (FMH)

 

Notes:

*The batch number of every vial of RhD immunoglobulin administered must be recorded in the patient's medical history and in accordance with other legal statutory requirements.

**In some circumstances, administration of an intravenous RhD immunoglobulin preparation (Rhophylac) may be warranted. Contact Lifeblood for more information.

Other information

  • To avoid unnecessary use, RhD immunoglobulin should not be given to women with anti-D antibodies.
  • Studies have shown that RhD immunoglobulin 100 IU is sufficient to protect against a fetomaternal haemorrhage (FMH) of 1.0 mL of fetal red cells (2.0 mL whole blood).
    • For example, RhD immunoglobulin 625 IU is sufficient to protect against a FMH of 6 mL of fetal red cells (12 mL of whole blood).
  • Quantify the magnitude of the FMH following a sensitising event (including delivery) to ensure an adequate dose of RhD immunoglobulin is offered, as more than one dose may be required.
  • Tests to assess the volume of FMH include, but are not limited to, the Kleihauer-Betke test and flow cytometry.
  • The majority of fetal bleeds are <6 mL of red blood cells.
    • FMH is less than 0.05 mL in about 50% of cases
    • FMH is greater than 0.5 mL in about 5% of cases
    • FMH is greater than 1 mL in about 3% of cases
    • FMH is 30 mL or greater in up to 0.6% of cases

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