Neonatal Hyperbilirubinemia

Hemolytic Disease of the Newborn (HDN)

• Hyperbilirubinemia becomes apparent only in the delivered newborn because the placenta effectively metabolizes bilirubin.
• Hemolysis associated with ABO incompatibility exclusively occurs in type-O mothers with fetuses who have type A or type B blood.

Pathogenesis of ABO Incompatibility

• It has rarely been documented in type-A mothers with type-B infants with a high titer of anti-B IgG.
• In mothers with type A or type B, naturally occurring antibodies are of the IgM class and do not cross the placenta.
• 1% of type-O mothers have a high titer of the antibodies of IgG class against both A and B, which cross the placenta and cause hemolysis in the fetus.
• The reason for the low incidence of alloimmunization in ABO incompatibility is that ABO antigen is widely expressed in other tissues but less expressed on the surface of fetal RBC.

Epidemiology of ABO Incompatibility

• The incidence is 45 per 10,000 live births.
• The prevalence is 6-7 per 1000 live births.
• It is rare in Nigeria, probably because of the presence of an RhD pseudogene in Africans.

Comparison of Rh and ABO Incompatibility

• Stillborn/hydrops are frequent in Rh incompatibility and rare in ABO incompatibility.
• Severe anemia is frequent in Rh incompatibility and rare in ABO incompatibility.
• Jaundice is moderate to severe and frequent in Rh incompatibility, but mild in ABO incompatibility.
• Late anemia is frequent in Rh incompatibility and rare in ABO incompatibility.

Clinical Features of HDN

• Anemia
• Jaundice
• Hepatosplenomegaly
• Kernicterus
• Late anemia, caused by:
  • Erythropoietin suppression
  • Continued cell lysis by maternal antibodies

Laboratory Features of HDN

• FBC:
  • Increased nucleated RBCs
  • Reticulocytosis
  • Polychromasia
  • Anisocytosis
  • Spherocytes
  • Cell fragmentation
• Coombs test:
  • Direct
  • Indirect
• Imaging studies:
  • Ultrasonography
  • Doppler (MCA blood flow velocity) for detection of fetal anemia
• Rh grouping and genotyping
• Kleihauer-Betke test
• Optical density measurement

Management of HDN

• Intrauterine blood transfusion:
  • Intraperitoneal transfusion
  • Intravenous transfusion
• Phototherapy
• Intravenous immunoglobulin (IVIG)
• Exchange blood transfusion

Prevention of HDN

• Rh immunoglobulin at 28 weeks and within 72 hours of delivery
• Also administer RhIG to unsensitized Rh-negative women

Pathogenesis of Rh Incompatibility

• After the initial exposure to a foreign antigen, B-lymphocyte clones that recognize the RBC antigen are established.
• The maternal immune system initially produces antibodies of the IgM isotype that do not cross the placenta.
• Later, produces antibodies of the IgG isotype that traverse the placental barrier.
• Predominant antibody subclass appears to be IgG1 in one-third of individuals, whereas a combination of IgG1 and IgG3 subclasses are found in the remaining individuals.
• The ABO-incompatible RBCs are rapidly destroyed in the maternal circulation, reducing the likelihood of exposure to the immune system.
• The degree of Rh sensitization of the mother is directly related to the amount of fetomaternal hemorrhage.