TL;DR
Hemolytic disease of the newborn (HDN) also known as erythroblastosis fetalis is an allo-immune hemolytic anemia in the fetus or newborn. This is due to a fetal-maternal incompatibility for one of the red cell blood group systems i.e. Rh group causing maternal IgG to cross the placenta and attach to fetal red cells which will be destroyed by the reticuloendothelial system.
Pathophysiology ▾
During a first pregnancy with an Rh-positive fetus, some fetal blood cells can cross the placenta into the mother’s bloodstream. This can cause the mother’s immune system to develop antibodies against the Rh-positive antigen. However, the first pregnancy is uneventful. If the mother becomes pregnant again with another Rh-positive fetus, these antibodies can cross the placenta and attack the fetus’s red blood cells, leading to hemolytic disease of the fetus and newborn (HDFN). This is known as the anamnestic response, where the immune system produces a stronger and faster antibody response in subsequent exposures to the same antigen.
Clinical features ▾
Laboratory investigations of hemolytic disease of the newborn ▾
- Peripheral blood smear: Normochromic normocytic anemia with numerous nucleated red blood cells and occasional spherocytes
- DAT positive
- ↑ serum bilirubin
- ↑ LDH
- ↓ haptoglobin
Treatment and management ▾
For Rh HDN
- Exchange transfusion if necessary
- RhD prophylaxis in RhD negative mothers
ABO HDN
- Mild severity
- May be seen in first pregnancy
- Usually blood group O mothers with blood group A or B infants
- Phototherapy as treatment
*Click ▾ for more information
What is hemolytic disease of the newborn (HDN)?
Hemolytic Disease of the Newborn (HDN), also known as Erythroblastosis Fetalis, is a condition where a fetus’ red blood cells are destroyed by maternal antibodies. This occurs when the mother and baby have incompatible blood types, typically involving the Rh factor or ABO blood group system.
ABO and Rh Blood group systems
| ABO | Rh |
| Most important system in transfusion and organ transplantation medicine. Incompatible transfusion → acute intravascular hemolysis, renal failure and death Gene located in chromosome 9 A & B are co-dominant, O is recessive | Anti RhD can cause hemolytic transfusion reactions Gene located in chromosome 1 Rh positive – gene is present, Rh negative – gene is absent Autosomal recessive inheritance pattern |
How does hemolytic disease of the newborn (HDN) happen?
Hemolytic disease of newborn (erythroblastosis fetalis) most commonly occurs when an Rh-negative mother has an Rh-positive baby. However, it can also occur when the mother and baby have different ABO blood types.
Naturally occurring antibodies occur in the plasma of subjects who lack the corresponding antigen and who have not been transfused or been pregnant. The most important are anti-A and anti-B. They are usually IgM and react optimally at cold temperatures also known as cold antibodies. Immune antibodies develop in response to the introduction of red cells possessing antigens that the subject lacks through transfusion or by transplacental passage during pregnancy. These antibodies are commonly IgG, although some IgM antibodies may also develop usually in the early phase of an immune response. Immune antibodies react optimally at 37oC. Only IgG antibodies are capable of transplacental passage from mother to foetus as IgM is too big. The most important immune antibody is the anti-D. These antibodies can cross the placenta and attack the baby’s red blood cells, causing them to break down.
In hemolytic disease of the newborn (erythroblastosis fetalis), the mother is Rh-negative while the father is Rh-positive. The Rh factor is a protein that is found on the surface of red blood cells. The Rh blood group locus is composed of 2 related structural genes, RhD and RhCE, which encode the membrane proteins that carry the D, Cc and Ee, antigens. The RhD gene may be either present or absent, giving the Rh D+ or Rh D- phenotype, respectively. During the first pregnancy, leakage of D+ fetal red cells across the placenta results in the mother becoming immunised against the D antigen as this antigen is not naturally occurring but is produced after sensitization as the fetus is Rh-positive. However, the amount of anti-D antibody that crosses the placenta into the fetal circulation following the initial exposure is too low to cause hemolysis. During subsequent pregnancies, the mother mounts an anamnestic immunological response to D+ fetal red cells if the fetuses inherit the Rh-positive antigen from the father unless the father is heterozygous for the D antigen and there is a 50% probability that the fetus may be Rh-negative. The IgG alloantibody produced by the mother is small enough to cross through the placenta into the fetal circulation and binds to fetal RBCs that are D+. The IgG-sensitized fetal RBCs are cleared from the circulation by macrophages in the fetal spleen. This leads to anemia and hyperbilirubinemia resulting in hemolytic disease of newborn (erythroblastosis fetalis).
Pathophysiology of hemolytic disease of the newborn (HDN) (erythroblastosis fetalis)
What are the signs and symptoms of hemolytic disease of the newborn (HDN) (erythroblastosis fetalis)?
The severity of hemolytic disease of newborn (erythroblastosis fetalis) can vary from mild to severe. Mild cases of hemolytic disease of newborn (erythroblastosis fetalis) may cause no symptoms, while severe cases can be life-threatening. The severity of hemolytic disease of newborn (erythroblastosis fetalis) depends on the number of antibodies that the mother has produced and the amount of time that the baby has been exposed to the antibodies.
In severe cases of hemolytic disease of newborn (erythroblastosis fetalis), the baby’s red blood cells can be destroyed so quickly that the baby cannot produce new red blood cells fast enough to keep up. This can lead to anemia. In addition to anemia, severe cases of hemolytic disease of newborn (erythroblastosis fetalis) can also cause other complications, such as jaundice, hepatosplenomegaly and edema. Jaundice is a yellowing of the skin and eyes that is caused by the breakdown of red blood cells. Hepatosplenomegaly is an enlargement of the liver and spleen. Edema is swelling of the body caused by fluid retention. In the most severe cases of hemolytic disease of newborn (erythroblastosis fetalis), the baby can develop heart failure or die before birth.
How is hemolytic disease of the newborn (erythroblastosis fetalis) tested?
Hemolytic disease of newborn (erythroblastosis fetalis) is usually diagnosed based on the results of a blood test. The blood test will check the fetus’ blood type, Rh factor and antibody levels. The physician may also request for a complete blood count (CBC) and a bilirubin level.
In laboratory diagnosis, the peripheral blood smear shows normochromic normocytic anemia with the presence of numerous nucleated RBCs and occasional spherocytes. DAT is positive due to the presence of antibodies and there is increased serum bilirubin and LDH with a decrease in haptoglobin level.
How is hemolytic disease of the newborn (erythroblastosis fetalis) treated?
The treatment of hemolytic disease of newborn (erythroblastosis fetalis) depends on the severity of the condition. Mild cases of hemolytic disease of newborn (erythroblastosis fetalis) may not require any treatment. More severe cases of hemolytic disease of newborn (erythroblastosis fetalis) may require phototherapy (light therapy) or blood transfusions.
Phototherapy is a treatment that uses special UV lights to help the baby’s body get rid of bilirubin. Bilirubin is a byproduct of the breakdown of red blood cells. High levels of bilirubin can damage the baby’s brain (kernicterus).
Blood transfusions are a treatment that involves replacing the baby’s blood with blood from a donor. Blood transfusions are necessary if the baby’s anemia is severe or if the baby is developing other complications, such as heart failure. Exchange transfusion can remove circulating bilirubin and antibody-coated RBCs, replacing them with RBCs compatible with maternal serum and providing albumin with new bilirubin binding sites. The process is time consuming and labour intensive but remains the ultimate treatment to prevent kernicterus.
In some cases, hemolytic disease of newborn (erythroblastosis fetalis) can be prevented by giving the mother an injection of Rh immunoglobulin (RhIg) during pregnancy. RhIg is a medication that helps to prevent the mother’s immune system from producing antibodies against the baby’s Rh-positive blood cells.
If a woman is pregnant and Rh-negative, the physician will test the woman’s blood to see if she has been sensitized to Rh-positive blood cells. If she has not been sensitized, she will be given an injection of RhIg at 28 weeks of pregnancy and again after delivery.
Frequently Asked Questions (FAQs)
What happens to mother in erythroblastosis fetalis?
Erythroblastosis fetalis primarily affects the fetus, but it can also have implications for the mother. While the mother’s immune system is responsible for producing the anti-D antibodies that cause the condition, she typically doesn’t experience severe symptoms.
However, the mother’s body may respond to the excessive breakdown of fetal red blood cells by:
- Anemia: In severe cases, the mother’s blood may become anemic due to the loss of red blood cells from the fetus.
- Jaundice: If the mother’s liver cannot process the breakdown products of red blood cells efficiently, she may develop jaundice, characterized by yellowing of the skin and eyes.
- Other complications: In rare cases, severe hemolysis (the breakdown of red blood cells) can lead to complications like kidney failure or liver damage.
It’s important to note that these complications are uncommon and typically occur only in severe cases of erythroblastosis fetalis. Modern prenatal care and preventive measures like Rh immunoglobulin (RhIg) have significantly reduced the risk of severe maternal complications.
What happens if mother is Rh positive and baby is Rh negative?
If a mother is Rh-positive and her baby is Rh-negative, there is no risk of Rh incompatibility.
Rh incompatibility only occurs when the mother is Rh-negative and the baby is Rh-positive. In this case, the mother’s immune system may produce antibodies against the Rh-positive blood cells, which can cross the placenta and harm the baby.
If both mother and baby are Rh-positive or both are Rh-negative, there is no risk of Rh incompatibility.
How long does hemolytic disease of the newborn last?
The duration of hemolytic disease of the newborn (HDN) can vary depending on its severity.
In mild cases, hemolytic disease of the newborn (erythroblastosis fetalis) may resolve within a few days or weeks with supportive care, such as phototherapy to reduce jaundice. However, in more severe cases, hemolytic disease of the newborn (erythroblastosis fetalis) can last for several weeks or even months.
Disclaimer: This article is intended for informational purposes only and is specifically targeted towards medical students. It is not intended to be a substitute for informed professional medical advice, diagnosis, or treatment. While the information presented here is derived from credible medical sources and is believed to be accurate and up-to-date, it is not guaranteed to be complete or error-free. See additional information.
References
- Anemia: Diagnosis and Treatment (Willis, 2016).
- Management of Anemia: A Comprehensive Guide for Clinicians (Provenzano et al., 2018)
- Goldberg S, Hoffman J. Clinical Hematology Made Ridiculously Simple, 1st Edition: An Incredibly Easy Way to Learn for Medical, Nursing, PA Students, and General Practitioners (MedMaster Medical Books). 2021.
