• Erythroblastosis fetalis is a disease of the fetus and newborn baby.
• It is characterized by agglutination and phagocytosis of the fetus’s red blood cells (RBCs).
• In most cases, the mother is Rh negative.
• In most cases, the father is Rh positive.
• The baby inherits the Rh-positive antigen from the father.
• The mother becomes exposed to the fetus’s Rh antigen.
• As a result, the mother develops anti-Rh agglutinins.
• The mother’s anti-Rh agglutinins pass through the placenta into the fetus.
• These agglutinins cause agglutination of the fetal RBCs.

Key Concept

• Erythroblastosis fetalis occurs mainly when the mother is Rh negative and the baby is Rh positive.
• The mother produces anti-Rh agglutinins after exposure to the fetal Rh antigen.
• These antibodies cross the placenta and cause agglutination of the fetal RBCs.

Incidence of Erythroblastosis Fetalis

• An Rh-negative mother having her first Rh-positive baby usually does not produce enough anti-Rh agglutinins to cause harm.
• About 3% of second Rh-positive babies show signs of erythroblastosis fetalis.
• About 10% of third Rh-positive babies develop erythroblastosis fetalis.
• The incidence increases progressively with each subsequent Rh-positive pregnancy.

Key Concept

• The first Rh-positive pregnancy is usually not affected because the mother produces few anti-Rh agglutinins.
• The risk of erythroblastosis fetalis increases with each subsequent Rh-positive pregnancy.
• Second Rh-positive baby: 3% affected.
• Third Rh-positive baby: 10% affected.

Effect of Mother’s Antibodies on the Fetus

• After anti-Rh antibodies are formed in the mother, they slowly pass through the placenta into the fetus’s blood.
• In the fetus, these antibodies cause agglutination of the fetal RBCs.
• The agglutinated RBCs are then hemolyzed (destroyed).
• Hemolysis releases hemoglobin into the fetal blood.
• The fetus’s macrophages convert hemoglobin into bilirubin.
• Bilirubin causes the baby’s skin to become yellow (jaundice).
• The anti-Rh antibodies can also attack and damage other body cells.

Key Concept

• Maternal anti-Rh antibodies cross the placenta into the fetus.
• They cause agglutination and hemolysis of fetal RBCs.
• Released hemoglobin is converted into bilirubin, leading to jaundice.
• The antibodies can also damage other fetal body cells.

Clinical Picture of Erythroblastosis

• The jaundiced newborn with erythroblastosis fetalis is usually anemic at birth.
• The mother’s anti-Rh agglutinins continue to circulate in the infant’s blood for 1 to 2 months after birth.
• During this time, these antibodies continue destroying more RBCs.
• The infant’s hematopoietic tissues try to replace the hemolyzed RBCs.
• The liver becomes greatly enlarged and starts producing RBCs.
• The spleen also becomes greatly enlarged and produces RBCs.
• The liver and spleen produce RBCs in the same way they normally do during the middle of gestation.
• Because RBC production is very rapid, many early RBC forms are released into the circulation.
• Many nucleated blastic RBCs are released from the bone marrow into the bloodstream.
• The presence of these nucleated blastic RBCs is why the disease is called erythroblastosis fetalis.
• Severe anemia is usually the main cause of death in erythroblastosis fetalis.
• Some babies who survive severe anemia develop permanent mental impairment.
• Some survivors also develop damage to the motor areas of the brain.
• This damage occurs because bilirubin is deposited in neuronal cells.
• Bilirubin destroys many neuronal cells.
• This condition is called kernicterus.
• Table 36.2 shows the blood typing results with anti-A and anti-B agglutinins:

Red Blood Cell Type	Anti-A	Anti-B
O	−	−
A	+	−
B	−	+
AB	+	+

Key Concept

• Babies with erythroblastosis fetalis are usually anemic and jaundiced at birth.
• Maternal anti-Rh antibodies continue destroying fetal RBCs for 1–2 months after birth.
• The liver, spleen, and bone marrow increase RBC production, releasing nucleated blastic RBCs.
• Severe anemia may cause death, while bilirubin deposition in the brain can cause kernicterus with permanent neurological damage.
• Table 36.2 Blood Typing:
  • O: Anti-A (−), Anti-B (−)
  • A: Anti-A (+), Anti-B (−)
  • B: Anti-A (−), Anti-B (+)
  • AB: Anti-A (+), Anti-B (+)

Treatment of Neonates With Erythroblastosis Fetalis

• One treatment for erythroblastosis fetalis is to replace the neonate’s blood with Rh-negative blood.
• Rh-negative blood is infused over 1.5 hours or more.
• At the same time, the neonate’s own Rh-positive blood is removed.
• This procedure may be repeated several times during the first few weeks of life.
• The main purpose is to keep the bilirubin level low.
• Keeping bilirubin low helps prevent kernicterus.
• The transfused Rh-negative RBCs are gradually replaced by the infant’s own Rh-positive RBCs.
• This replacement takes 6 weeks or more.
• By this time, the maternal anti-Rh agglutinins have been destroyed.

Key Concept

• Exchange transfusion with Rh-negative blood is the treatment for erythroblastosis fetalis.
• The procedure reduces bilirubin levels and helps prevent kernicterus.
• As the infant’s own Rh-positive RBCs gradually replace the transfused cells over 6 weeks or more, the maternal anti-Rh agglutinins are destroyed.

Prevention of Erythroblastosis Fetalis

• The D antigen of the Rh blood group system is the main cause of immunization in an Rh-negative mother carrying an Rh-positive fetus.
• In the 1970s, the incidence of erythroblastosis fetalis was greatly reduced with the development of Rh immunoglobulin (anti-D antibody).
• Rh immunoglobulin (anti-D antibody) is given to the expectant mother starting at 28 to 30 weeks of gestation.
• Anti-D antibody is also given to Rh-negative women who deliver Rh-positive babies.
• This treatment helps prevent sensitization of the mother to the D antigen.
• It greatly reduces the risk of producing large amounts of anti-D antibodies during the second pregnancy.
• The exact mechanism of Rh immunoglobulin is not completely understood.
• One effect of the anti-D antibody is to inhibit antigen-induced B-lymphocyte antibody production in the expectant mother.
• The administered anti-D antibody also binds to D antigen sites on Rh-positive fetal RBCs.
• These fetal RBCs may cross the placenta and enter the mother’s circulation.
• Binding of the anti-D antibody interferes with the mother’s immune response to the D antigen.

Key Concept

• The D antigen is the main cause of erythroblastosis fetalis.
• Rh immunoglobulin (anti-D antibody) is given at 28–30 weeks of gestation and after delivery of an Rh-positive baby to an Rh-negative mother.
• It prevents maternal sensitization to the D antigen.
• Anti-D antibody inhibits B-lymphocyte antibody production and binds to Rh-positive fetal RBCs, reducing the maternal immune response.