Hemolytic Disease of the Newborn

Hemolytic Disease of the Newborn is a topic covered in the Select 5-Minute Pediatrics Topics.

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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


  • 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.


  • 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.


  • 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.

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