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 tiny minority develop symptomatic ABO HDN^[1]. The latter only occurs in mothers of blood group O because they can produce enough IgG antibodies to cause hemolysis.

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Causes

• Environmental exposure

Anti-A and anti-B antibodies are usually IgM and do not pass through the placenta, but some mothers "naturally" have IgG anti-A or IgG anti-B antibodies, which can pass through the placenta. Exposure to A-antigens and B-antigens, which are both widespread in nature, usually leads to the production of IgM anti-A and IgM anti-B antibodies but occasionally IgG antibodies are produced.

• Fetal-maternal transfusion

Some mothers may be sensitized by fetal-maternal transfusion of ABO incompatible red blood and produce immune IgG antibodies against the antigen they do not have and their baby does. For example, when a mother of genotype OO (blood group O) carries a fetus of genotype AO (blood group A) she may produce IgG anti-A antibodies. The father will either have blood group A, with genotype AA or AO, or more rarely, have blood group AB, with genotype AB.

• Blood transfusion

It would be very very rare for ABO sensitization to be caused by therapeutic blood transfusion as a great deal of effort and checking is done to ensure that blood is ABO compatible between the recipient and the donor.

Moderating factors

In about a third of all ABO incompatible pregnancies maternal IgG anti-A or IgG anti-B antibodies pass through the placenta to the fetal circulation leading to a weakly positive direct Coombs test for the neonate's blood. However, ABO HDN is generally mild and short-lived and only occasionally severe because:

• IgG anti-A (or IgG anti-B) antibodies that enter the fetal circulation from the mother find A (or B) antigens on many different fetal cell types, leaving fewer antibodies available for binding onto fetal red blood cells.
• Fetal RBC surface A and B antigens are not fully developed during gestation and so there are a smaller number of antigenic sites on fetal RBCs.

Diagnosis

Routine antenatal antibody screening blood tests (indirect Coombs test) do not screen for ABO HDN. If IgG anti-A or IgG anti-B antibodies are found in the pregnant woman's blood, they are not reported with the test results, because they do not correlate well with ABO HDN. Diagnosis is usually made by investigation of a newborn baby who has developed jaundice during the first day of life.

Treatment

Neonatal jaundice caused by ABO HDN is usually successfully treated with phototherapy, unless the ABO HDN is uncommonly severe. Treatment of moderate or severe HDN caused by ABO antibodies is similar to that for Rh disease.

References

• Mollison PL, Engelfriet CP and Contreras M. Blood Transfusion in Clinical Medicine. 1997. 10th edition. Blackwell Science, Oxford, UK.

[1] www.obgyn.net/english/pubs/features/presentations/panda13/ABO-Rh.ppt

See also

• Coombs test
• Hemolytic anemia
• Hematology