• Clinical science

Hemolytic disease of the fetus and newborn


Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by the destruction of fetal red blood cells (RBC) and anemia. It is commonly caused by a Rhesus (Rh) and ABO incompatibility between the mother and fetus, although other blood incompatibilities also exist. In Rhesus incompatibility, maternal IgG antibodies form after maternal exposure to fetal Rh-positive blood during birth or pregnancy-related complications (e.g., fetomaternal hemorrhage). The initial pregnancy is not affected; however, consecutive pregnancies are at risk of fetal hemolysis and, in severe cases, intrauterine hydrops fetalis. ABO incompatibility, on the other hand, may lead to fetal hemolysis in the first pregnancy because of preexisting antibodies in the mother from infancy and usually has a milder disease course. Newborn infants may present with pallor, jaundice, and hepatosplenomegaly. Diagnosis of HDFN involves clinical and laboratory assessment for evidence of antibody-mediated hemolysis (e.g., Coombs test). Prenatal imaging may be considered to exclude hydrops fetalis. Treatment includes iron supplementation and, in the case of severe jaundice, phototherapy. In rare cases, extremely low hemoglobin (Hb) levels require transfusion of red cell concentrates. Since Rh incompatibility may be fatal, anti-D immunoglobulin prophylaxis is administered to Rh-negative pregnant women. ABO incompatibility, on the other hand, rarely presents with complications and does not require immunoglobulin prophylaxis.


HDFN is characterized by destruction of the fetal erythrocytes by maternal antibodies due to blood group incompatibility.




ABO incompatibility

  • Highest risk: mother, blood group O; child, blood group A or B
  • Maternal antibodies (anti-A and/or anti-B) against non-self antigens of the ABO system are present even if sensitization has not occurred; , therefore fetal hemolysis may occur during the first pregnancy

Rhesus incompatibility


Clinical features



ABO incompatibility usually has a significantly milder course of disease than Rhesus incompability!

Anemia may conceal cyanosis!



The diagnosis of HDFN requires evidence of hemolysis in the presence of a fetomaternal blood incompatibility. These parameters can be determined during the prenatal period after suggestive screening tests or postnatal period.

Prenatal diagnosis

  • Imaging
    • Ultrasound: to determine hydrops fetalis
    • Doppler sonography of fetal blood vessels → increased flow rate indicates fetal anemia

Postnatal diagnosis


Differential diagnoses

ABO vs. Rhesus incompatibility

ABO incompatibility

Rh incompatibility

  • Frequent
  • Rare
Disease during the first pregnancy
  • Frequent
  • Rare

Clinical findings

  • Generally normal to mild; may be asymptomatic
  • Mild to severe

Coombs test (direct or indirect)

  • Weak positive or negative
  • Positive
  • Present
  • Rare


The differential diagnoses listed here are not exhaustive.





Anti-D immunoglobulin (RhoGAM)


last updated 01/23/2020
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