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Hemolytic disease of the newborn

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells ( hemolysis). The fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure ( hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts (immature red blood cells) are present in the fetal blood, and so these forms of the disease can be called erythroblastosis fetalis (or erythroblastosis foetalis).

HDFN represents a breach of immune privilege for the fetus or some other form of impairment of the immune tolerance of pregnancy. Various types of HDFN are classified by which alloantigen provokes the response. In order of incidence, the types include ABO, anti-RhD, anti-RhE, anti-Rhc, anti-Rhe, anti-RhC, multiantigen combinations, and anti-Kell.

Hemolytic disease of the newborn (ABO)

In ABO hemolytic disease of the newborn (also known as ABO HDN) maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. For Caucasian populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a very small minority develop symptomatic ABO HDN. The latter typically only occurs in mothers of blood group O, because they can produce enough IgG antibodies to cause hemolysis.

Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A and B.

Hemolytic disease of the newborn (anti-Kell)

Hemolytic disease of the newborn (anti-Kell) is the third most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease and ABO incompatibility. Anti-Kell is becoming relatively more important as prevention of Rh disease is also becoming more effective.

Hemolytic disease of the newborn (anti-Kell) is caused by a mismatch between the Kell antigens of the mother and fetus. About 91% of the population are Kell negative and about 9% are Kell positive. A fraction of a percentage are homozygous for Kell. Therefore, about 4.5% of babies born to a Kell negative mother are Kell positive.

The disease results when maternal antibodies to Kell are transferred to the fetus across the placental barrier, breaching immune privilege. These antibodies can cause severe anemia by interfering with the early proliferation of red blood cells as well as causing alloimmune hemolysis. Very severe disease can occur as early as 20 weeks gestation. Hydrops fetalis can also occur early. The finding of anti-Kell antibodies in an antenatal screening blood test ( indirect Coombs test) is an indication for early referral to a specialist service for assessment, management and treatment.

Hemolytic disease of the newborn (anti-Rhc)

Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN.

It occurs more commonly in women who are Rh D negative.

Hemolytic disease of the newborn (anti-RhE)

Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy.

The anti-RhE antibody is quite common especially in the Rh genotype CDe/CDe; It usually only causes a mild hemolytic disease, but very rarely can cause a severe condition in the newborn. It can occur with other antibodies, usually the anti-Rhc antibody, which can also cause a severe hemolytic disease.