ABO Incompatibility in Newborns

testing blood from the newborn for ABO incompatibility

ABO incompatibility and Rh incompatibility are frequently heard diagnostic terms in normal newborn nurseries. Parents often get confused regarding those terms as sometimes these conditions cause severe problems for newborns, and other times babies will be unaffected. 

In this article, I will focus on ABO incompatibility, its definition, physiology, clinical significance for babies, and available treatments. I will dedicate another post to the topic of Rh incompatibility.

Definitions and statistics regarding ABO incompatibility

ABO incompatibility

ABO incompatibility exists when the mother has blood type “O,” and her baby has blood type “A,” “B,” or “AB.” 

Hemolysis due to ABO incompatibility:

For ABO incompatibility to be clinically relevant, it has to lead to hemolysis. Hemolysis is defined as the destruction of red blood cells. It can occur physiologically or due to pathologic causes such as ABO incompatibility or other reasons. 

Hemolysis due to ABO incompatibility in the newborn is present when the following conditions are met: 

  • Mother has blood type O 
  • Baby has blood type A, B or AB
  • Mother has antibodies against the baby’s blood type antigen (anti-A or anti-B) of IgG subclass. Only IgG subclass can pass through the placenta to the baby
  • Maternal antibodies are present in the baby’s circulation
  • Maternal antibodies react with the baby’s red blood cells causing their destruction (hemolysis)

How common is ABO incompatibility?

ABO incompatibility occurs in 15% of pregnancies, but it does not cause clinically significant hemolysis in all cases. In fact, only 4% of ABO incompatibilities result in hemolysis, which constitutes about 0.6% of all pregnancies. Interestingly, this condition occurs more frequently among African-American babies. 

Even though the overall numbers of affected babies are not high, this condition always has to be taken seriously. Retrospective studies of babies with bilirubin induced encephalopathy (severe brain damage) showed that babies with ABO incompatibility constituted a significant portion of them.

ABO blood type explained

ABO blood groups system relies on the presence of antigen A or antigen B. Antigens are unique proteins residing on the cell wall and facilitating communication between cells. They are like a name. Each cell will have multiple antigens for various purposes. 

People with blood type A will have antigen A. People with blood type B will have antigen B. People with blood type AB will have both antigens. Finally, a person with blood type O will not have any of those two types of antigens at all (Source)

In addition to an antigen, we also produce antibodies. Antibodies are small peptides or proteins produced for the purpose of defending us from foreign cells, tissues, and microbes. Since our body does not like to exposure to foreign cells and tissues, we do produce antibodies against antigens that we don’t own. 

People with different blood types in the ABO system will have and will produce if needed antibodies against antigens that are not present in their bodies. For example, people with type A will have anti-B antibodies, people with type B will have anti-A antibodies and so on ( see Table 1).

Table 1

ABO Blood TypeAntigen-AAntigen-BAnti-AAnti-B

In the case of neonatal ABO incompatibility, a mother with blood type O will have antibodies against A and B antigens. If those antibodies reach the baby’s system, they can destroy baby’s red cells in cases where there are antigens A or B on those cells (baby with blood type A, B, AB).

What happens in ABO incompatibility? 

If ABO incompatibility exists, there are two possible clinical scenarios:

  • Baby is unaffected 
  • Baby is clinically affected 

The baby would be unaffected if maternal antibodies did not cross the placenta, or they are in too low concentration to react with its red blood cells. One should remember that many other cells in our body have A and B antigens. Therefore, a small number of maternal antibodies will get scattered and will not affect adversely the baby’s red blood cells. 

Whenever a sufficient amount of maternal antibodies reached the baby’s circulation, they will be reacting with the baby’s red cells causing their hemolysis (destruction). Hemolysis is likely to cause anemia and pathologic jaundice. 

A sudden increase in the rate of hemolysis will lead to anemia because the baby’s bone marrow will not be able to produce enough new red cells to compensate for such rapid destruction of red cells. Depending on the amount of hemolysis, the baby may not have any anemia at all, have only mild one, or may develop severe anemia requiring supplementary blood transfusion.

An increase in the rate of hemolysis will contribute to the rise of bilirubin levels. Thus it will create pathologic jaundice. Again, depending on the rate of hemolysis, jaundice disease may be insignificant, mild, or quite severe. (I invite you to read my comprehensive article on the topic of Jaundice). 

Specific parameters such as cord blood bilirubin level, reticulocyte count, and drop in hemoglobin over time will be indicators of clinically significant ABO incompatibility and rapid hemolytic process in the baby. I will explain more about those tests in the next section.

How do we evaluate babies with ABO incompatibility?

We will use various tests in the evaluation of ABO incompatibility:

  • Mother’s blood type
  • Baby’s blood type
  • DAT test – also known as Coombs test
  • CBC – complete blood count
  • Reticulocyte count
  • Bilirubin levels

Most institutions implemented testing the baby’s cord blood (blood drawn from the clamped umbilical cord right after delivery) or the baby’s blood for blood type, DAT, and initial bilirubin levels whenever the mother has blood type O. 

Knowing that the baby has blood type A, B, or AB gives us only information about the possibility of increased hemolysis in the baby. 

DAT test (Coombs test), if positive, proves that maternal antibodies against the baby’s erythrocytes (red cells) are present in the baby’s circulation. It tells us that we have to be more serious, now there is a higher possibility for anemia and jaundice in the baby, and we have to keep monitoring this newborn very closely.

CBC – complete blood count will provide us with information about the number of blood cells in a baby and, most importantly, hemoglobin level.  A low number of erythrocytes and low hemoglobin levels or dropping levels over time are indicators of anemia, in this case, anemia due to hemolysis. In ABO incompatibility, babies usually don’t have significant anemia at birth. However, they can become anemic over time, even 2-3 weeks after discharge home. 

It is not unusual for babies with ABO incompatibility to require a blood transfusion after discharge home. 

The reticulocyte count is an indicator of how vigorously bone marrow is working to compensate for an increase in hemolysis. Reticulocytes are the new red blood cells that did not lose their nucleus yet, as it is common for mature red blood cells to do. The reticulocyte count is reported as a percentage of the total number of red blood cells. 

In newborns, normal reticulocyte is below 5%. Significantly elevated reticulocyte count above 10% will be an indicator of significant hemolysis and a new production of red blood cells. 

Bilirubin levels need to be done early in each baby with ABO incompatibility, particularly in those with DAT test positive and elevated reticulocyte counts. Bilirubin helps us assess the severity of jaundice. In some babies with ABO incompatibility jaundice progresses very rapidly and may reach dangerous levels for the baby’s brain. Therefore, frequent surveillance of bilirubin levels is essential. More about the dangerous effects of bilirubin in my article here.

Treatment of newborns with ABO incompatibility

If a baby is not significantly affected, we do not need to use any treatment. However, for those babies who are clinically affected, we have several treatment options that we would use in a step-up fashion.

Treatment options for ABO incompatibility:

  • Hydration and proper nutrition
  • Phototherapy
  • IV IgG infusion
  • Double volume exchange blood transfusion
  • Supplementary blood transfusion

Proper hydration and nutrition will ensure that food will not stay in the bowel loops for too long, and the baby has regular bowel movements. These two actions will prevent unnecessary reabsorption of already excreted bilirubin from bowel loops back into the baby’s circulation. 

Typically, circulating bilirubin is transformed in the liver and then excreted into the intestines with bile. Some of the excreted bilirubin may get reabsorbed. More of that bilirubin gets reabsorbed if the food is not moving fast in a downward (caudal) direction. 

Phototherapy is a therapy that uses particular types of light that are capable of transforming bilirubin in the skin into water-soluble bilirubin that can be easily excreted from the body.  You can read much more about this mode of therapy in my article here. Usually, it is very effective.  If light therapy is started early, in most cases, the baby will not need any other treatments to resolve its jaundice due to ABO incompatibility (Source). 

IV IgG infusion – this medication can be given to a baby with bilirubin levels close to exchange transfusion. It is not clear how IgG works in immune hemolytic conditions. Still, we suspect that it can block antigen sites on red cells, thus making them unavailable to anti-A or anti-B maternal antibodies. As a result, the rate of hemolysis and production of new bilirubin drop quickly. 

Double volume exchange blood transfusion – is necessary whenever bilirubin levels are so high that they are likely to cause neurological damage. The goal of double-volume exchange transfusion is to remove both bilirubin and maternal antibodies from the baby’s circulation.  In rare cases, extremely high bilirubin levels may lead to severe acute encephalopathy, chronic neurological abnormalities, and even death.  

Supplementary blood transfusion – In some babies, bone marrow is not able to compensate for hemolysis. A baby may become anemic within a few days or later, after 2-3 weeks. Maternal antibodies may stay active in the baby’s circulations for weeks, and during that time, the destruction of red cells will continue. It is rare, but some babies who developed severe and symptomatic anemia will need a blood transfusion. 

The prognosis for babies with ABO incompatibility

Only a fraction of all babies who have ABO incompatibility setup will have severe hyperbilirubinemia (jaundice). With proper surveillance of these babies and phototherapy started promptly, very few will require IV IgG infusion or double exchange transfusion. 

If babies with ABO incompatibility are followed closely, and aggressive treatment protocol is implemented, none of these babies should ever develop severe neurological complications. 

Other conditions causing anemia and jaundice due to hemolysis

Other conditions that ABO incompatibility may lead to increased hemolysis and its consequences:

  • Rh incompatibility (Read my article)
  • Minor blood groups incompatibilities (Duffy, MNS, P, and other)
  • Many enzymatic defects (for example G6PD)
  • Red cells wall defects (spherocytosis, elliptocytosis)
  • Infections

Differences between ABO and Rh incompatibilities

Blood type incompatibility in the ABO system has some similarities and differences when compared to Rh incompatibility. Let’s look at both in the table below:

FeaturesABO – systemRh – system
Affects fetusrarelymore often
Severitymildermore severe
Presence of clinical features at birthusually notyes
Affects 1-st pregnancyyesrarely
Treatments usedphototherapy
exchange transfusion
supplementary transfusion
exchange transfusion
supplementary transfusion


This article is only for general information purposes. It should not be viewed as any medical advice. There is a chance that the information here may be inaccurate. It would be best if you always discussed all health-related matters with your doctor before making any decisions that may affect your health or the health of your family members. 


Dr.Wisniewski is a board-certified pediatrician and neonatologist with over 20 years of clinical experience in the USA. He authored the book: "Babies Born Early - A guide for Parents of Babies Born Before 32 Weeks" Dr.Wisniewski loves educating parents on various health conditions affecting their newborn babies and children.

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