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Haemolytic Disease of the Newborn

Haemolytic disease of the newborn (HDN), also known as erythroblastosis fetalis, is an alloimmune condition occurring when the mother's IgG antibodies cross the placenta and attack foetal red blood cells. This can lead to reticulocytosis, anaemia, and in severe cases, heart failure (hydrops fetalis).

The condition arises from a breach of immune privilege or impairment of immune tolerance during pregnancy. Various alloantigens can provoke HDN, with anti-RhD being the most common cause, followed by anti-RhE, anti-RhC, and anti-Rhc.

Newborn infant with Rhesus disease, a type of haemolytic disease of the newborn, suffering from hydrops fetalis (oedema caused by heart failure). The infant did not survive.
Newborn infant with Rhesus disease, a type of haemolytic disease of the newborn, suffering from hydrops fetalis (oedema caused by heart failure). The infant did not survive.

Signs and Symptoms

Clinical signs of HDN include a positive direct Coombs test, elevated cord bilirubin levels, and haemolytic anaemia. Jaundice develops within 24 hours after birth due to elevated bilirubin levels. Severe neonatal jaundice increases the risk of kernicterus, a form of brain damage.

Other complications can include hepatosplenomegaly, inspissated bile syndrome, greenish staining of the teeth, and haemolytic anaemia. Additional symptoms may present as high bilirubin at birth, cerebral palsy, neutropenia, thrombocytopenia, and late-onset anaemia.


HDN occurs when the mother’s immune system produces IgG antibodies against foetal red blood cell antigens, often due to foetal-maternal haemorrhage, blood transfusions, or ABO incompatibility. The antibodies cross the placenta into the foetal bloodstream, leading to the destruction of foetal red blood cells. Sensitisation can occur from exposure to as little as 0.1 mL of foetal blood.

Sensitisation is most commonly related to Rh and Kell antigens. In ABO incompatibility, type O mothers are more prone to making IgG anti-A and anti-B antibodies which can cross the placenta.

Serological Types

HDN is classified by the type of antigens involved. The main types include:

  • ABO HDN: Generally mild and caused by anti-A and anti-B antibodies.
  • Rhesus D HDN: The most common and preventable severe form, reduced significantly by Rho-D immunoglobulin.
  • Rhesus c HDN: Can range from mild to severe.
  • Anti-Kell HDN: Primarily caused by anti-K1 antibodies, often severe.


Diagnosis relies on maternal and neonatal history and laboratory findings. Tests include:

  • For the newborn: Biochemistry for jaundice, complete blood count (CBC), reticulocyte count, peripheral blood smear, and direct Coombs test.
  • For the mother: Indirect Coombs test.
  • Rarely, for the father: Erythrocyte antigen status.


For Rhesus incompatibility, Rho(D) immunoglobulin is administered to prevent sensitisation. Other measures include IVIG and plasmapheresis during early pregnancy, and intrauterine transfusions (IUT), steroids, phenobarbital, and early delivery in mid-to-late pregnancy. Rho(D) immunoglobulin significantly reduces the risk of isoimmunisation when administered at 28 weeks of pregnancy, at 34 weeks, and within 48 hours after delivery.

After Birth Testing

Erythroblastosis Fetalis - a severe form of haemolytic disease of the newborn.
Erythroblastosis Fetalis - a severe form of haemolytic disease of the newborn.

Post-birth tests include the direct Coombs test, haemoglobin levels, reticulocyte count, neutrophil and thrombocyte counts, and bilirubin levels. Ferritin levels are also checked due to potential iron overload. Newborn screening tests may be affected by prior transfusions, necessitating retesting.


Treatment varies with severity and includes temperature stabilisation, phototherapy, transfusion, exchange transfusion, sodium bicarbonate for acidosis correction, and assisted ventilation. Phototherapy is recommended for high bilirubin levels. IVIG can reduce the need for exchange transfusions and shorten phototherapy duration. Exchange transfusion is used when bilirubin levels are critically high.

In conclusion, HDN is a complex condition requiring prompt diagnosis and treatment to mitigate severe complications and improve outcomes for affected neonates.

Self-assessment MCQs (single best answer)

What is the primary cause of haemolytic disease of the newborn (HDN)?

Which test is used to confirm the presence of antibodies on the surface of red blood cells in a newborn with HDN?

Which antigen is most commonly associated with the most severe form of HDN?

Which of the following is a complication of severe neonatal jaundice in HDN?

What is the purpose of administering Rho(D) immunoglobulin to a pregnant woman?

Which of the following is a preventive measure for HDN due to Rh incompatibility?

What is the first-line treatment for high bilirubin levels in a newborn with HDN?

Which population is more prone to making IgG anti-A and anti-B antibodies that can cross the placenta?

Which of the following is not a serological type of HDN?

What is the primary indication for an exchange transfusion in a newborn with HDN?


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