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Fruit of the Womb
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ABO Incompatibility

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Many babies become 'jaundiced' after birth, primarily, as the result of ABO incompatibility. The reader below had a baby who developed severe complications with the same - fortunately a rare event - but gives us reason to discuss this condition as it is now the most common cause of hemolytic disease of the newborn (HDN)....

At Tue Sep 30, 09:21:00 PM 2008, Zoe said…

Dear Dr,

Blood tests taken at the time of the birth of my first baby showed an ABO incompatibility - our pediatrician informed us that my body had released antibodies that had attacked our baby's immune system. As a result he had jaundice for almost 12 weeks and many many tests. I am O+ and my son is A+.

I am currently pregnant with our second child and am concerned after reading articles that state the severity of the condition is greater with subsequent pregnancies, and can result in serious conditions or even fetal death.
Should we be concerned? Are there tests that can be done during the pregnancy to determine if the baby is at risk?
Many many thanks for your help.

• At Wed Oct 08, 10:37:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Zoe:

All people who have O blood types make antibodies against both the A and the B blood group antigens. These antibodies develop very early in life, usually during the first year after birth, probably as the results of similar antigens carried on certain foods and bacteria that normally colonize the gut. Usually these antibodies are of the class of IgM antibodies that are too large to cross the placenta, so that even if you have a baby with A or B blood, the antibodies won't be able to get on the baby's side of the placenta and cause destruction of the baby's red blood cells. You are someone who has antibodies against these blood groups of the IgG class. IgG antibodies readily cross the placenta to the baby, are actively concentrated from your blood to the baby’s side and, indeed, are a major source of protection against many of the things in the environment that could hurt the baby during the first 3-6 months of life before its own immune system has matured.

Unfortunately, the placenta cannot differentiate which IgG antibodies are there to protect the baby and which might hurt, as is also the case in Rh-disease. Your IgG anti-A antibodies can cross the placenta, attach to the baby’s red blood cells, and then mediate destruction of the baby's red blood cells by the baby's own immune system. Not only can that cause fetal anemia (more common in Rh-isoimmunization than with ABO incompatibility) but it can also release large quantities of hemoglobin from the baby’s blood cells. One of the breakdown products of hemoglobin is bilirubin. Bilirubin is metabolized by the liver, but the fetal liver is not efficient at that until after the baby is born. Indeed, high levels of bilirubin can accumulate in the baby before or, more commonly, after birth and if these are not quickly reduced by phototherapy, exchange transfusion, and simple maturation of the liver’s metabolic pathways, this can accumulate in the baby’s brain and cause brain damage (kernicterus).

ABO incompatibility occurs in approximately 15% of all pregnancies. Indeed, since we implemented prophylactic therapy for Rh-disease, ABO incompatibility has become the major cause of hemolytic disease of the newborn (HDN). Fortunately, less than 5% of ABO incompatibility pregnancies result in babies that develop HDN (less than 1% of all pregnancies) and usually the primary manifestation is hyperbilirubinemia rather than anemia. ABO incompatibity can occur in first pregnancies but severity is not necessarily worse in subsequent pregnancies (unlike the situation with Rh-isoimmunization). Black babies are more likely to have severe complications than Caucasians.

The hyperbilirubinemia can often be recognized by a yellow-orange appearance of the baby’s skin and eyes (jaundice). Usually simple phototherapy (bili lights) during the first few days after delivery is sufficient to manage increased bilirubin levels until the baby’s liver adjusts to life outside the womb. Some babies can have a more severe and prolonged course because of the concentration of the antibodies throughout their bodies. However, exchange transfusion is necessary in only about 0.1% of HMD pregnancies related to ABO incompatibility.

If you have another baby with an A blood type, this could happen again, but the recurrence rate is much lower and the outcome much less predictable with ABO incompatibity than with Rh-isoimmunization. You did not tell me whether your baby’s complications were from severe anemia or from hyperbilirubinemia (or both). However, tests that you could consider having done before and during another pregnancy are the following:

1) Check your husband’s blood type to see if he has one (heterozygote) or two (homozygote) doses of the A gene. If he has two, then all your babies with him MUST end up having the A blood type. If he has only one, then half your babies could have O blood types just like you and not be affected by the antibodies at all

2) If your husband is homozygous, then there would be no sense in testing another baby to find out what its blood type is during the pregnancy since it would have to have an A blood type and would therefore be ‘at risk’. But, if he is heterozygous, that testing could be done (by amniocentesis or direct testing of the baby’s blood by percutaneous umbilical cord blood sampling – PUBS) and if the baby has O blood, then you could rest assured and relax the rest of the pregnancy

3) If fetal anemia is a concern, the degree of fetal anemia caused by the antibodies can be monitored by a noninvasive ultrasound procedure called Doppler flow velocimetry (DFV). Using DFV we can measure the velocity of blood (peak systolic velocity – PSV) in a vessel called the middle cerebral artery in the baby's brain. If that blood flow velocity is higher than expected at a given gestational age, this might indicate the baby is developing severe anemia. PUBS could then be done, the degree of anemia determined precisely (as well as the bilirubin levels), and the baby could be transfused with O blood directly by injection in the umbilical vein

4) For your next pregnancy, if you choose to have one, you should get a consultation with a specialist in Maternal-Fetal Medicine. In fact, you might even want to do that BEFORE you think seriously about getting pregnant again.

Hope this helps. Best wishes! Dr T
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