While hemolytic disease of the fetus and newborn (HDFN) is most commonly caused by ABO incompatibility or Rh factor incompatibility, which leads to the formation of anti-D antibodies, other antibodies can also trigger HDFN. After anti-D antibodies, anti-K and anti-c are the most frequent causes of HDFN, and both are known to cause severe presentation of the disease.
What is HDFN?
Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated red blood cell (RBC) disorder that occurs when a baby’s RBCs break down quickly, which is called hemolysis. HDFN is caused by a mismatch between a mother’s and her baby’s blood type (A, B, AB, or O) or Rhesus (Rh) factor (Rh-positive or Rh-negative) during pregnancy. Numerous antibodies to RBC antigens can be linked to HDFN, such as those from the ABO and Rh blood group systems.
Regardless of the cause of HDFN, early detection and timely treatment are essential to positive outcomes. Without treatment, the fetus may experience progressive anemia, hydrops fetalis, heart failure and even death during pregnancy or delivery. In utero, an intrauterine blood transfusion can treat anemia and prolong gestation until the fetus has had time to develop sufficiently. However, preterm delivery is common.
Learn more about HDFN causes and risk factors
Anti-K antibodies
When a pregnant mother is K-negative and the father K-positive, it is likely that their baby will also be K-positive. Maternal antibodies against the Kell blood group antigen on the red blood cells of the fetus can lead to HDFN.
When the pregnant mother produces anti-K antibodies, they attack the fetus’s red blood cell precursors (or erythroblasts), suppressing the production of red blood cells. This leads to severe fetal anemia.
Anti-K antibodies are most commonly found in pregnant women who have a history of red blood cell transfusions. They can therefore be prevented if units of K-negative blood are selected for transfusion in women of child-bearing women. This is policy in some countries, such as the Netherlands, which has subsequently seen a reduction in the risk for anti-K-mediated HDFN.
Anti-c antibodies
First trimester screening can detect the potential for the development of anti-c antibodies or indicate if they already exist.
The Rh antigen c is part of the Rh blood system, one of the most complex human blood groups, with 49 known Rh antigens. The c-antigen is found in around 80% of the U.S. population. Anti-c is the most important Rh antigen after the anti-D antigen.
As with anti-D, anti-c antibodies can occur as a result of hemorrhage, miscarriage, ectopic pregnancy or during a cesarean section. Anti-c antibodies carry a high risk of severe HDFN, not necessarily in first pregnancies, but rather in subsequent pregnancies as the result of exposure in the initial pregnancy.
