All about Hemolytic Disease in Newborns

Hemolytic disease in newborns is the result of an incompatibility between the mother's blood and the fetus during pregnancy. Learn more in this article.
All about Hemolytic Disease in Newborns

Last update: 23 August, 2021

Hemolytic disease in newborns (HDN), also called erythroblastosis fetalis, is an autoimmune disease. This condition can be fatal during the baby’s development. With this disease, the mother makes antibodies that pass to the placenta and, by mistake, destroy the fetus’ red blood cells.

As a result of this lack of red blood cells during development, the baby gets anemia before birth. Unfortunately, 50% of babies who develop this disease will not make it, so the prognosis is not positive at all. 

Hemolytic disease in newborns

Hemolytic disease in newborns is an autoimmune condition related to the mother and child’s blood differences. Generally, blood groups belong to the categories A, B, O, and AB. However, there’s another distinction in terms of typology: Rh + and Rh-.

Epidemiological figures

StatPearls demonstrates the development of this disease throughout history. These are some of the highlights:

  • Until the 1970s, hemolytic disease in newborns affected 1% of neonates, with a mortality rate of 50%.
  • Using immunoprophylaxis techniques, this incidence dropped from 1% to 0.5% after 1968. Today, the prevalence is estimated at 1-3 patients per 1000 deliveries. 
  • The majority of the population is Rh+ but in certain ethnic groups the percentages of Rh- patients increase. 15% of white people are Rh-, while in black and Hispanic groups those probabilities are reduced to 5% and 8%, respectively.
  • Native Americans are the group with the lowest percentage of Rh- people. Only 1% of the population has that characteristic. 

The white population is the one most at risk for this condition. That’s because Rh- women have an 85% probability of having children with an Rh+ man. This incompatibility in the Rh factor causes the fetus to suffer from hemolytic disease in newborns. 

blood tests

Hemolytic disease in newborns symptoms

The International Journal of Pharmacotherapy shares the most common symptoms of hemolytic disease in newborns. First, the child will be born with jaundice (yellow skin), epidermal pallor from anemia, hepatosplenomegaly (enlargement of the liver and spleen), and hydrops fetalis in the most severe cases.

Bilirubin is a yellowish pile pigment that synthesizes when red blood cells break down. As these erythrocytes are continuously being destroyed in the patient, unconjugated bilirubin accumulates in the tissues. This causes a concerning yellowish color in the skin. 

Hydrops fetalis is the accumulation of large amounts of fluid in 2 or more areas of the body. These physical deformities at birth are the product of metabolic imbalances caused by the maternal immune attack.

After jaundice, anemia is the clearest clinical sign of this condition. However, you can only see this with a blood test. Either of these conditions is sufficient for confirming hemolytic disease in newborns at the diagnostic level. 

Hemolytic disease in newborns causes

The incompatibility in the Rh factor is the cause that results in the most serious complications. However, it’s not the only cause of this disease. Next, we’ll take a look at some other causes.

Rh incompatibility

Like we’ve mentioned, the incompatibility in the Rh factor of the fetus and the mother is the main cause of HDN. It can result in anemia and fetal death. For this disease to develop, the mother must have Rh- red blood cells and the child must have Rh+, inherited from their father. This is discussed in the MSD Manual. 

Even just 0.1 milliliters of fetal blood inoculation into the maternal bloodstream is enough to start the mother’s alloimmunization process. This means that the maternal immune system recognizes the infant’s blood cells as potential pathogens. As a result, it develops antibodies to fight them.

ABO incompatibility

The incompatibility of the ABo blood group is actually the main cause of this disease. However, most of the cases are mild. Only 1% of cases in this category lead to severe hemolysis (destruction of red blood cells). 

As the National Library of Medicine in the United States indicates, it’s possible for the mother and child to have different and poorly compatible blood groups. In fact, up to 25% of pregnancies do, but only a small percentage (1%) of mothers have antibody populations large enough to cause HDN in the fetus. 

For example, if the mother is blood group O and the child is A or B, it’s possible that the mother will begin to produce anti-A or anti-B antibodies. These antibodies are of the immunoglobulin (IgG) type and can easily cross the placenta. As in the previous case, the incompatibility of the child is inherited from the father. 

Treatment and testing

The most effective way to prevent the alloimmunization of the mother is to perform blood tests on both parents. They should do those blood tests before the fetus begins to experience an immune attack. Generally, alarms will sound when the mother is Rh+ and has antibodies against the Rh- factor.

In addition, if the father is also Rh-, the child won’t be in any danger because they will be Rh- as well. The worst-case scenario is when the mother is Rh-, the father is Rh+, and the maternal immune system has already started to synthesize antibodies to attack the fetus.

In the event that the mother’s maternal immune response has already begun, doctors will use an intraperitoneal blood transfusion to the fetus. According to the Spanish Association of Pediatrics, these transfusions will give the fetus new red blood cells.

If the baby doesn’t respond well to treatment, the next step is usually preterm delivery. The sooner the child leaves the mother’s body, the sooner the antibodies will stop attacking the baby’s red blood cells. However, even outside the mother’s body, the baby may still need regular transfusions.

Once born, the main treatment for jaundice is phototherapy. Light isomerization transforms bilirubin into a compound that the body can easily excrete in urine and feces. It will not need to pass through the liver.


The importance of immunization

An Rh- mother can take steps to prevent Rh+ antibodies from developing.

This requires preparation with special immunoglobulins. The doctor will inject this preparation at 28 weeks of pregnancy and its purpose is to disguise the infant’s erythrocytes. As a result, the maternal immune system won’t recognize them as a threat.


Hemolytic disease in newborns is a very rare disease. It appears in less than 3 cases per 1000 infants.

In addition, not all cases of this condition cause hydrops fetalis, jaundice, anemia, organ failure, and death. In many cases, the incompatibilities caused by the ABO system are much milder and, fortunately, usually end well.

The best treatment for this condition is to strictly follow medical testing during pregnancy. If the doctor suspects the mother will develop an immune response against the fetus, immunization will work to prevent the disease.

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