Description

A hemolytic anemia in newborns due to the destruction of fetal and newborn RBCs by maternal antibodies passively transferred across the placenta; primarily related to ABO blood group or RhD incompatibility

Epidemiology

• ABO incompatibility
  • Occurs in 12% of first pregnancies
  • Only 10–20% become significantly jaundiced, requiring phototherapy.
• Rh incompatibility
  • Incidence of Rh hemolytic disease: 6–7/1,000 live births
  • Prevalence of RhD positive (RhD+) fetus in RhD negative (Rh−) mother: 15%
  • RhD(−) status in 15% of white, 7–8% of black and Hispanic, and 2% of Asian persons
  • 48–55% are heterozygous (Dd)
  • 35–45% are homozygous (DD)
  • Of all Rh-sensitized pregnancies:
    • 9% require intrauterine transfusion.
    • 10% are delivered early and require newborn exchange transfusion.
    • 31% require treatment after a full-term delivery.
    • 50% require no treatment.

Risk Factors

• Type O mother pregnant with either type A, B, or AB fetus
• RhD(−) mother becomes pregnant with an RhD(+) fetus; D-antigen is inherited from the father.
• Omitted or failed RhIG (anti-D) prophylaxis
• Only a fraction of women at risk develop antibodies.

General Prevention

• Rh incompatibility: RhIG is given to an RhD(−) woman after any exposure to RhD(+) blood.
  • RhIG is also known by trade names RhoGAM and HyperRHO.
  • Given at 28 weeks, 34 weeks (prophylaxis), and within 72 hours of birth, or following, for example, amniocentesis, abortion, antepartum bleeds
• No prophylaxis for HDN caused by other blood group incompatibilities.

Pathophysiology

• Isoimmunization—general principles:
  • Passage of fetal RBCs into maternal circulation occurs as a result of asymptomatic transplacental hemorrhage.
  • Initial sensitization of mother from fetomaternal hemorrhage can occur with placental abruption, abortion, ectopic pregnancy, or procedures (CVS, amniocentesis, or cordocentesis).
  • Exposure triggers maternal immune response (anti-D antibodies).
  • Maternal IgG antibodies (Ab) cross the placenta and bind to fetal RBCs. Coated RBCs are then destroyed in the reticuloendothelial system, primarily the spleen.
  • Isoimmunization may lead to hyperbilirubinemia, severe anemia, and potentially hydrops.
  • Extramedullary hematopoiesis in the fetal liver and spleen is a response to severe fetal anemia, leading to hepatosplenomegaly.
• ABO isoimmunization
  • Occurs in type O mothers with a type A or B fetus; clinically a milder hemolysis compared to Rh incompatibility and rarely requires intervention
  • 1% of type O mothers have high titers of IgG Ab against both A and B that cross the placenta and cause HDN.
  • Hemolysis due to anti-A is more common.
  • Hemolysis due to anti-B can be more severe and may require exchange transfusion in the newborn.
• Rh isoimmunization
  • Passage of RhD(+) fetal RBCs which cross the placenta into the circulation of an Rh(−) mother
  • RhD(−) state is the absence of D antigens on RBCs.
  • Decreased risk of RhD sensitization of mother if fetus is also ABO incompatible
  • Rh isoimmunization rarely occurs in first pregnancy.

Etiology

• Fetomaternal hemorrhage, usually asymptomatic, with maternal immune response to foreign fetal RBC antigens
• Most common systems involved: ABO blood group antigens, with mild HDN, and RhD antigens, with more severe HDN
• 1% of cases involve other RBC antigens, such as Kell, Kidd, Duffy, or MNS blood groups.