Hemolytic disease of the newborn (ABO)
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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.
- 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 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.
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.
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.
The antibodies in ABO HDN cause anemia due to destruction of fetal red blood cells and jaundice due to the rise in blood levels of bilirubin a by-product of hemoglobin break down. If the anemia is severe, it can be treated with a blood transfusion, however this is rarely needed. On the other hand, neonates have underdeveloped livers that are unable to process large amounts of bilirubin and a poorly developed blood-brain barrier that is unable to block bilirubin from entering the brain. This can result in kernicterus if left unchecked. If the bilirubin level is sufficiently high as to cause worry, it can be lowered via phototherapy in the first instance or an exchange transfusion if severely elevated.
- Wang, M, Hays T, Ambruso, DR, Silliman CC, Dickey WC. Hemolytic Disease of the Newborn Caused by a High Titer Anti-Group B IgG From a Group A Mother. Pediatric Blood & Cancer 2005;45(6): 861-862
- Jeon H, Calhoun B, Pothiawala M, Herschel M, Baron BW. Significant ABO Hemolytic Disease of the Newborn in a Group B Infant with a Group A2 Mother. Immunohematology 2000; 16(3):105-8.
- Haque KM, Rahman M. An Unusual Case of ABO-Haemolytic Disease of the Newborn. Bangladesh Medical Research Council Bulletin 2000; 26(2): 61-4.