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Red Blood Alloimmunization

Red Blood Alloimmunization
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Red blood cell alloimmunization is a condition that can affect pregnant women in certain circumstances. Understanding why requires a basic knowledge of human physiology.

All human blood shares certain similarities. We all have red blood cells, white blood cells, platelets and plasma, and we all inherit one of four different blood types from our parents:

  • A
  • B
  • AB
  • O

Despite these common characteristics, each person’s blood has certain distinct features passed to us through both parents’ genes. Our red blood cells, for example, have distinct markers called antigens. This combination of markers explains how the body can distinguish red blood cells that belong to us from those that do not. 

One of these markers is a protein called an RhD factor—or Rhesis factor. Some people have the RhD factor; others don’t. This difference is so important that it further divides the four blood types into eight—those that have it, and those that don’t. 

Blood types that have the RhD factor are called positive and blood types that don’t are called negative. No matter what type of blood you have, you are either positive or negative. (This expands the blood types to include: A positive or A negative, B positive or B negative, AB positive or AB negative, and O positive or O negative.) Most people are RhD positive.

The reason these markers are so important to health is that they are linked to our natural immune system, which alerts the body to anything foreign. When the body is exposed to germs or cells that are different from our body's healthy tissues, an antibody is created to fight it. 

This can become a health issue during pregnancy if a mother’s body regards her unborn baby as foreign—which can happen when a baby inherits a blood type from the father that is different from the mother’s. If so, a pregnant woman may produce antibodies against her baby's red blood cells—a maternal condition known as red blood cell alloimmunization, which can occur with RhD and a range of other antigens.

  • Severe anemia
  • Decreased oxygen levels
  • Fluids in the unborn baby (hydrops fetalis)
  • Heart failure 

In some cases, it can even lead to fetal death. Fortunately, the number of fetal deaths due to red blood cell alloimmunization has decreased significantly, due to new detection and treatment options. 

Pregnant women with complications from red blood cell alloimmunization can get expert care from maternal-fetal specialists at Riley at IU Health. Our specialists have the skills, experience and training to guide expectant mothers and their babies from pregnancy to delivery and beyond. This includes any neonatal care that may be needed afterwards. Our Level 4 Neonatal Intensive Care Unit (NICU) is Indiana’s only comprehensive NICU—the state’s highest level of neonatal care. 

Sensitization: The Body’s First Response to an Unfamiliar Antigen

The first time the body encounters an unfamiliar antigen there may be little or no response. This is called sensitization. Women most often become sensitized to a different blood type during a pregnancy or after a blood transfusion. 

Sensitization can also occur naturally or through another cause, such as:

  • Blood transfusion
  • Previous fetal-maternal hemorrhage after an ectopic pregnancy (one outside the uterus) or abortion
  • Procedures such as amniocentesis, chorionic villus sampling, or dilation and curettage (D&C)—a procedure to remove tissue from inside the uterus 
  • Sharing needles

Although the first response may be small, the body may form antibodies to attack more aggressively the next time these foreign antigens are introduced. This can cause problems for later pregnancies because the antibodies are ready and waiting to attack.

An Example of Alloimmunization: What Happens with the D Antigen

If an expectant mother is RhD negative, but the father and the baby are RhD positive, sensitization may occur during her first pregnancy. When her body encounters the RhD antigen again in a later pregnancy, the antibodies she developed earlier may cross the placenta and attack her baby’s red blood cells—a condition known as hemolytic disease or HDFN. 

When this happens, the fetus can become mildly to severely anemic and have a low blood count. This is significant because red blood cells deliver oxygen to nourish the fetus. An unborn child’s heart may work harder and create a situation similar to heart failure in an adult. In serious cases, the fetus may build up fluid—a condition known as hydrops fetalis. Together, these effects can be life-threatening for a fetus

Diagnosis of Red Blood Cell Alloimmunization

All pregnant women have prenatal blood tests  to detect alloimmunization as part of routine prenatal care. If antibodies are detected, an expectant mom may be monitored throughout her pregnancy to check for increased antibody production. Fathers may also be tested to see if they share the same antigens with the fetus. For example, if a mother is RhD negative, a test of the father could show that he is RhD positive, which could result in an RhD positive fetus. 

More extensive testing may be required to monitor the fetus, including ultrasound-guided fetal blood sampling, chorionic villus sampling (CVS) or amniocentesis. Various types of ultrasounds may be performed to check an unborn baby for signs of hydrops (an accumulation of fluids that suggests severe fetal anemia) and to measure fetal blood flow. A Middle Cerebral Artery (MCA) Doppler study, for example, can measure the speed of blood flowing through your baby’s brain starting at about 18 weeks, and it may be repeated every one to two weeks. If blood flows too quickly, severe anemia is more likely. Collectively, these tests can help physicians decide how to approach treatment of an expectant mom and her unborn child.


Treatments

Treatments

If your first pregnancy shows evidence of antibodies, doctors will monitor these levels in your blood. Depending on these results, your pregnancy may progress normally and deliver at full term. The greater the amount of antibody in your blood, the greater chance your baby will have severe anemia. Your physicians will also watch your unborn baby for signs of anemia, especially if this is not the first pregnancy where antibodies are elevated in your blood tests.

Certain medications can prevent expectant mothers from sensitization to some antibodies. Mothers who are known to be RhD negative often receive a medication called RhoGAM in pregnancy to prevent antibody formation. This medication is typically given before delivery or any procedures in pregnancy. This medication is one of the best ways to prevent antibody formation and protect your baby from developing anemia.

If necessary, the fetus can be given blood through a procedure called intrauterine transfusion (IUT)—a blood transfusion to the baby in the womb. IUT is a high-risk procedure reserved for babies that are very sick with severe anemia. This procedure requires specialized experience and should only be performed in major medical centers such as Riley at IU Health. IUT can be repeated several times during pregnancy to treat a baby that has become anemic and prolong pregnancy. The decision to deliver a baby that has received IUT is determined by maternal-fetal specialists based upon the severity of anemia and prognosis. ;

Key Points to Remember

Key Points to Remember

  • When the body is exposed to red blood cells that are different from our body's healthy tissues, an antibody is created.
  • If a pregnant woman’s body produces antibodies against her baby's red blood cells, this condition is known as red blood cell alloimmunization.
  • Red blood cell alloimmunization can lead to problems for the fetus, including severe anemia, decreased oxygen levels, fluid buildup in the fetus (hydrops fetalis) and heart failure.
  • All pregnant women are screened for red blood cell alloimmunization as part of their routine prenatal care.
  • Better detection and treatment for this condition has improved the rate of infant survival.

Support Services & Resources

Support Services & Resources

Visit the following websites for reliable information about red blood cell alloimmunization.

We offer a broad range of supportive services to make life better for families who choose us for their children's care.

Learn More About Riley Support Services

American Academy of Obstetricians and Gynecologists (AAOG)

This professional organization for obstetricians and gynecologists answers frequently asked questions about RhD disease and pregnancy.

Red Blood Alloimmunization Research

Red Blood Alloimmunization Research

Riley at IU Health maternal-fetal specialists conduct research to improve outcomes for mothers and infants. We study pregnancy-related topics, such as medication usage in pregnancy, phenotypes of spontaneous preterm birth and the role of progesterone on uterine contractions. 

Through maternal research, our physicians are learning: 

  • How to identify women who may have early deliveries 
  • How to detect postpartum depression
  • How improve prenatal and infant care
  • How to improve care for high-risk pregnancies 

Departments Treating This Condition

Departments Treating This Condition

  • Comprehensive Hematology Program
  • Maternal-Fetal Medicine
  • Maternity & Newborn Health
  • Neonatology
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Designated as Best Children's Hospitals by U.S. News & World Report, Ranked in 10 Specialties in 2023-24

©2025 Riley Hospital for Children at
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Find adult services at iuhealth.org


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