Pathogenesis

Before birth

• Antigen-antibody interaction occurs.
• Antibody coated RBCs are removed from foetal circulation by macrophages of the spleen and liver.
• Results: anaemia
• In response to anaemia, foetal bone marrow and other haematopoietic tissues in the spleen and liver increase the amount of RBCs produced.
• Foetal anemia may range from mild to severe depending on the amount of foetal RBCs destroyed and the capacity of the erythropoiesis to compensate.
• If severe, the foetus may develop hydrops fetalis.
• As RBCs haemolyze, haemoglobin is released and metabolized to indirect bilirubin
• Indirect bilurubin is transported across placenta and conjugated to direct bilirubin in the mother’s liver.
• Conjugated bilirubin is then excreted by the mother and does not cause clinical disease in the fetus.

       After birth

• The rate of RBCs destruction after birth decreases because there is no additional antibody entering the infant’s circulation through placenta.
• After the infant is born, its liver is unable to conjugate bilirubin efficiently because of a deficiency in the enzyme, glucuronyl transferase.
• Result: accumulation of metabolic by products of RBCs destruction can become severe problem for the newborn.
• The unconjugated bilirubin can reach levels toxic to infant’s brain (generally 18mg/dL), cause kernicterus or permanent damage to parts of the brain.