Haemolytic disease of the newborn

Key Information

Appropriate Tests


Maternal alloimmunisation to Rh or other red cell antigens, with development of clinically significant red cell antibodies causing fetal/neonatal haemolysis.

In countries with effective maternal screening and appropriate prophylaxis with Rh(D) immunoglobulin, the prevalence of Rh haemolytic disease of the newborn is greatly reduced; ABO incompatibility is now the most common cause of haemolytic disease in developed countries.

Information on the testing for the presence and type of red cell antibodies is outline below.

Links to guidelines for RhD immunoglobulin administration for RhD negative pregnant women are also provided below.

Maternal screening

See ANZSBT guidelines for blood grouping and antibody screening in the antenatal and perinatal setting.1

Maternal Blood group, Blood group and antibody screen; ABO and RhD blood groups and an antibody screen routinely at first antenatal visit (8-12 weeks).

  • Mother Rh(D) positive - no alloantibodies detected

Repeat Blood group and antibody screen at 26-28 weeks, as dictated by the clinical circumstances and the judgement of the obstetrician.

  • Mother Rh(D) negative - no alloantibodies detected

Repeat Blood group and antibody screen at 28, and 34 weeks. If anti-D prophylaxis is to be given, the blood must be drawn prior to the RhD-IgG being given. If RhD-IgG has already been given an earlier sensitising event, then the antibody screen must still be performed and the date of the prior administration noted on the request form.1  

Links to guidelines for RhD-IgG administration for routine prophylaxis for all RhD negative pregnant women and for administration of RhD-IgG following a sensitising event are provided below.2-4

Feto-maternal haemorrhage testing should also be performed in RhD negative women following potentially sensitising events – see Feto-maternal haemorrhage investigation.

  • Clinically significant alloantibodies detected in maternal serum: see section 4.1 of the Guidelines for Blood Grouping and Antibody Screening1

Repeat Blood group and antibody screen at 4 week intervals until 32 weeks gestation then every 2 weeks until delivery. Further action depends on specificity, titre and quantitation (where appropriate, eg, anti-D, anti-c) of the antibody – refer to guidelines.1

Fetus at risk of anaemia

The risk of Haemolytic Disease of the Newborn (HDN) depends on the cause of alloimmunisation, relevant past history and pregnancy outcomes.

Paternal genotype testing may be indicated

Non-invasive fetal genotyping when available.

For other antigens, invasive testing (CVS or amniocentesis) may be considered if fetal anaemia is a concern or invasive testing is performed for another indications.

Fetal monitoring for anaemia:

Serial ultrasound including middle cerebral artery (MCA) Doppler is now considered standard of care to monitor fetal anaemia. Invasive treatment may be required depending on the results.

These pregnancies require specialist care, including by fetal-maternal specialists, with access to intrauterine transfusions. Delivery should be planned at an institution with facilities for exchange transfusion.

Neonatal haemolysis

Cord blood - Blood group, Direct antiglobulin test, Haemoglobin, Blood film, Bilirubin.

Maternal blood - Blood group and antibody screen; (blood group and testing for alloantibodies).

If initial tests are negative, testing against the paternal red cells may be required.

Monitor neonate bilirubin to determine the need for phototherapy or exchange transfusion. Monitor the neonate’s haemoglobin for anaemia and possible need for transfusion.

  • ABO incompatibility

As above.

Elution study may be required and may confirm anti-A or anti-B. Monitor Haemoglobin levels to determine need for transfusion.

  • Rh incompatibility

Cord blood: Blood group and antibody screen; RhD status, including weak D.

Maternal: Blood group and antibody screen; Rh phenotype. Red cell elution study may be required.

Feto-maternal haemorrhage investigation - Kleihauer or Feto-maternal haemorrhage investigation - flow cytometry of ALL Rh negative females who deliver a Rh positive infant to asses the dose of RhD-IgG required. Also indicated after sensitising event in RhD negative female.


  1. Australian and New Zealand Society of Blood Transfusion and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Guidelines for Blood Grouping & Antibody Screening in the Antenatal & Perinatal Setting. 3rd edition, March 2007.

  2. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. College Statement C-Obs 6: Guidelines for the use of RhD Immunoglobulin (Anti-D) in Obstetrics in Australia, November 2012. 

  3. Australian Red Cross Blood Service. Anti-D prophylaxis. 23 Oct 2014. http://www.transfusion.com.au/disease_therapeutics/fetomaternal/HDN

  4. Royal College of Obstetricians and Gynaecologists.  The management of women with red cell antibodies during pregnancy. Green-top Guideline no. 65, May 2014.


Go Back

Page last updated:

Copyright © 2021 RCPA. All rights reserved.