Erythroblastosis Fetalis

Erythroblastosis fetalis is a rare pregnancy complication that occurs when a pregnant person’s immune system attacks the fetus’s red blood cells. It can happen if you have Rh-negative blood and the fetus has Rh-positive blood. Your provider will give you medicines to prevent the condition if you and the fetus have this blood type incompatibility.


What is erythroblastosis fetalis?

Erythroblastosis fetalis is a rare pregnancy complication that can occur if you’re pregnant with a fetus that has a different blood type, which may be incompatible with yours. Blood type differences don’t always cause problems — unless you have Rh-negative blood and the fetus has Rh-positive blood. If this is the case and you’ve been exposed to Rh-positive blood before (either through another pregnancy or a transfusion), your immune system could attack the fetus’s red blood cells. This could cause dangerously low levels of red blood cells (anemia) in the fetus. Severe anemia can be life-threatening without treatment.

Fortunately, healthcare providers test your blood type as part of routine prenatal care early in pregnancy. If you have Rh-negative blood type, your provider will give you medication to prevent the attack.

Other names for erythroblastosis fetalis include alloimmune hemolytic disease of the newborn (HDN) and hemolytic disease of the fetus and newborn (HFDN).


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Symptoms and Causes

What are the symptoms of erythroblastosis fetalis?

Babies born with erythroblastosis fetalis may show signs of anemia that range from mild to severe. They may also develop jaundice (usually within 24 hours of birth). Symptoms include:

  • Yellowing of the eyes and skin.
  • Pale skin.
  • Lethargy (slow movement).
  • Rapid heartbeat (tachycardia).
  • Lack of appetite.

In severe cases, a fetus or newborn may show signs of a potentially life-threatening condition called hydrops fetalis. Signs and symptoms include:

  • Swelling.
  • Fluid buildup in a fetus or newborn’s abdomen and between essential organs, like their heart or lungs.

What are the causes of erythroblastosis fetalis?

Erythroblastosis fetalis happens when a pregnant person’s immune system attacks the fetus’s red blood cells.

Red blood cells contain unique markers called antigens. Antigens are like name tags that let your immune system know where your red blood cells belong. Your immune system won’t attack if it recognizes an antigen.

The causes of erythroblastosis fetalis depend on the blood type difference between you and the fetus. Blood type refers to these antigens made on the surface of the red blood cells. The most common blood types are classified based on the Rh factor and the ABO antigens.

  • Rh factor: Positive (+) or negative (-) blood.
  • ABO: A, B, AB or O blood.

If you’re pregnant and your immune system doesn’t recognize the antigens in the fetus’s red blood cells, it’ll make antibodies to attack those blood cells. The response is similar to how your body fights actual threats like germs that make you sick. For this to happen, the fetus’s blood needs to come into contact with your own. This often doesn’t happen until delivery. However, there’s a risk of blood exposure during a/an:

Once your body makes the antibodies, it remembers. If it comes into contact with red blood cells with the antigen in a future pregnancy, it’ll attack and destroy those cells (hemolysis).

Rh incompatibility

The most serious and well-known form of erythroblastosis fetalis happens when you’re Rh-negative, and the fetus is Rh-positive. When this happens, your immune system attacks the Rh-positive blood cells. To put it into perspective, only about 15% of people in the U.S have Rh-negative blood. It’s much more common for both biological parents and the fetus to be Rh-positive.

Typically, Rh incompatibility doesn’t cause problems during a first pregnancy. Even if you’re Rh-negative and the fetus is Rh-positive, it’s unlikely your blood will come into enough contact during pregnancy to trigger your body to make antibodies. During delivery, though, your blood will contact the fetus’s blood. Unless you’ve taken a medication to prevent your immune system from attacking, your body may make antibodies against the Rh-positive red blood cells.

If you get pregnant again and this fetus also has Rh-positive blood, these antibodies will attack the fetus’s red blood cells.

Uncommon blood type incompatibilities

Your immune system may attack the fetus’s red blood cells if there’s an incompatibility with a less common red blood cell antigen. This would happen if the fetus has one of these uncommon antigens and you don’t. If you were exposed to the antigen from a prior pregnancy or a transfusion, you could’ve developed antibodies to this red blood cell antigen. Some of these antigens include:

  • Colton.
  • Duffy.
  • Diego.
  • Ee.
  • Gerbich.
  • H.
  • Kell.
  • Kidd.
  • Lutheran.
  • MNS.
  • P.
  • Xg.

Blood work from early in pregnancy will identify if you make antibodies against any of these less common red blood cell types.

How common is erythroblastosis fetalis?

Approximately 276 per 100,000 live births worldwide involve pregnancy complications related to Rh-blood type incompatibility. Researchers estimate that without treatment, there’s about a 50% chance that the fetus will die or experience severe health issues.

But blood type testing and medicines can prevent the worst outcomes. In parts of the world with easy access to prenatal care, only 2.5 per 100,000 births involve problems related to Rh-blood type incompatibility.


Diagnosis and Tests

How is erythroblastosis fetalis diagnosed?

Pregnant people are screened for blood type and the presence of any antibodies as part of routine prenatal care in the United States. If you’re pregnant and have Rh-negative blood, your provider will screen for antibodies to Rh-positive blood. If you don’t have the antibodies, they’ll give you medicine to prevent your immune system from making them.

If you test positive for the antibodies, this means there’s a risk your immune system will attack the fetus’s red blood cells if they’re Rh-positive. Your provider may need to screen your antibodies every few weeks. Additional tests for anemia and even fetal transfusions can be required if the antibodies are at a concerning level. You may need to deliver the baby early if they’re at risk of being born with severe anemia.

Once the baby’s born, your provider can determine their blood type. This can confirm that their anemia results from a blood type incompatibility.

Other tests include:

  • Complete blood count (CBC): This test can show how low your baby’s red blood cells are. Lower levels mean more severe anemia.
  • Peripheral blood smear (PBS): This test examines a blood sample through a microscope. It can show if low levels are likely because of hemolysis (red blood cells being destroyed prematurely).
  • Bilirubin test: This test checks bilirubin levels. Bilirubin is a byproduct of red blood cell destruction. High levels of bilirubin signal hyperbilirubinemia, which may suggest red blood cell destruction.
  • Direct antiglobulin test (DAT): This test shows if antibodies are present on the fetus’s red blood cells. This means the maternal immune system attacked the fetal cells.

Management and Treatment

How is it treated?

Treatments depend on whether you’re pregnant or if you’ve already delivered your baby.

During pregnancy

If you have antibodies that could place the fetus at risk of erythroblastosis fetalis, your provider will monitor your antibody levels every few weeks. If the antibodies reach a high enough level, extra ultrasound monitoring of the fetus for anemia may be required. If the anemia is severe, the fetus may need blood transfusions.

After delivery

Healthcare providers treat newborns with erythroblastosis fetalis by treating the anemia and hyperbilirubinemia. Treatment options include:

  • Phototherapy: Phototherapy uses light to treat hyperbilirubinemia. It converts the bilirubin to substances that can easily pass through your baby’s system.
  • Blood transfusion: Your baby may need blood transfusions after they’re born so they have enough red blood cells.
  • Erythropoiesis stimulating agents (ESA). These treatments may be an option to treat anemia that’s not severe enough to require a blood transfusion. Your baby may need to take these alongside iron supplements to encourage their body to make healthy red blood cells.

In severe cases, your baby may need supportive care, like a breathing machine (ventilator) and IV fluids.



Can this be prevented?

Erythroblastosis fetalis is highly preventable with prenatal care that includes blood type testing and preventive medication. If you’re Rh-negative, taking Rh immune globulin (RhIg or RhoGAM®) can prevent your body from making antibodies against Rh-positive blood. You’ll need to take it 28 weeks into pregnancy and 72 hours after a pregnancy ends, and in the event of any significant pregnancy-related bleeding (including in the first trimester).

It only works if you take it before your blood becomes exposed to Rh-positive blood.

Outlook / Prognosis

What happens to babies with erythroblastosis fetalis?

Outcomes depend on how severe your baby’s symptoms are. Severe anemia and hyperbilirubinemia can be fatal without treatment.

But babies who receive proper treatment can survive erythroblastosis fetalis. They may need blood transfusions during pregnancy and/or after delivery to replace their red blood cells. Your provider may need to monitor them several months afterward to ensure there are no issues.

Living With

What questions should I ask my healthcare provider?

Questions to ask include:

  • What’s my blood type? Do I have any concerning antibodies?
  • Should I be concerned about erythroblastosis fetalis?
  • Will I need additional monitoring or more frequent checkups?
  • Will I need to take Rh immune globulin?
  • When should I reach out to schedule an appointment or seek emergency care?

Additional Common Questions

What happens if the mother is Rh-positive and the baby is Rh-negative?

This isn’t a concerning blood type incompatibility. An Rh-negative fetus doesn’t have an Rh-antigen that the mother’s immune system may attack. There shouldn’t be an issue unless there’s a different type of incompatibility, like a rare blood type.

A note from Cleveland Clinic

The idea that your immune system is capable of attacking the fetus you’re carrying may seem terrifying. The good news is that these types of dangerous blood incompatibilities are uncommon. Also, healthcare providers take great pains to prevent problems from occurring. Blood type testing is a routine part of prenatal care. And monitoring and treating blood type incompatibilities that could put your baby at risk are an established part of obstetric care. Your provider will work with you every step of the way to keep you and the fetus safe.

Medically Reviewed

Last reviewed on 03/12/2024.

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