Rhesus incompatibility and fetal anaemia

Definition

• In rhesus incompatibility a Rh(D)-negative pregnant woman carrying a Rh-positive fetus forms antibodies against the D antigen on fetal red cells; in later pregnancies these cross the placenta and cause haemolysis in a Rh-positive fetus.
• The result is haemolytic disease of the fetus and newborn (formerly erythroblastosis fetalis).

Aetiopathogenesis

Aetiology and pathogenesis

• Fetal red cells enter the maternal circulation throughout pregnancy, most at birth or termination of pregnancy; larger fetomaternal haemorrhages occur, for example, after trauma, and the larger the haemorrhage, the more antibodies are formed.
• Other routes of sensitisation are needles contaminated with Rh-positive blood and inadvertent transfusion of Rh-positive blood.
• No complications develop in the sensitising pregnancy; subsequent pregnancies are affected.
• Other blood group systems such as Kell, Duffy, Kidd or Cc and Ee can also cause haemolytic disease; anti-Kell antibodies additionally suppress red cell production in the bone marrow directly.

Clinical features

Clinical features and complications

• In the fetus, haemolysis causes anaemia, hypoalbuminaemia, possibly high-output heart failure and fetal death; immature red cells (erythroblasts) are released into the circulation, and in severe cases hydrops fetalis develops.
• In the neonate, haemolysis raises indirect bilirubin with jaundice up to kernicterus; the pregnant woman herself usually remains asymptomatic.

Diagnosis

• At the first antenatal visit all women are tested for blood group, Rh type and an antibody screen; if relevant antibodies are present, the father's blood group and zygosity and serial titres are determined, with a laboratory-specific critical titre usually between 1:8 and 1:32.
• Fetal Rh status can be determined non-invasively from cell-free fetal DNA in maternal blood (RHD gene).
• An elevated middle cerebral artery flow velocity for gestational age indicates fetal anaemia; fetal haemoglobin is determined by umbilical cord blood sampling.

Keep learning in the app

Further reading (selection)

1. StatPearls: Hemolytic Disease of the Fetus and Newborn (NCBI Bookshelf)
2. MSD Manual Professional Edition: Hemolytic Disease of the Fetus and Neonate

Cross-references