Hemolytic disease of the fetus and newborn

Last updated: April 13, 2022

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Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by the destruction of fetal red blood cells (RBC) and subsequent anemia. It is commonly caused by a Rhesus (Rh) or ABO incompatibility between the mother and fetus, although other blood incompatibilities (e.g., Kell blood group incompatibility) and other conditions not caused by red cell alloimmunization (e.g., congenital heart defects) can also cause HDFN. In Rh 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, subsequent 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, and it usually has a milder course of disease. Newborns 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 used 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 a condition characterized by blood group incompatibility between the mother and fetus that leads to the destruction of fetal erythrocytes by maternal antibodies.


ABO incompatibility

Rh incompatibility


Nonimmune hydrops fetalis [4]



ABO incompatibility usually has a significantly milder course of disease than Rh incompatibility.

Anemia may conceal cyanosis.

The diagnosis of HDFN requires evidence of hemolysis in the presence of fetomaternal blood incompatibility.

Prenatal diagnosis

Postnatal diagnosis

ABO vs. Rh incompatibility

ABO incompatibility

Rh incompatibility

  • Common
  • Rare
Disease during the first pregnancy
  • Common
  • Rare

Clinical symptoms

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

Coombs test (direct or indirect)

  • Weak positive or negative
  • Positive
  • Present
  • Rare

Differential diagnoses of petechiae in newborns

Neonatal alloimmune thrombocytopenia


The differential diagnoses listed here are not exhaustive.



Anti-D immunoglobulin (RhoGAM)


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