Hemolytic Disease of the Fetus and Newborn

(RhD Alloimmunization; Rh Incompatibility; Erythroblastosis Fetalis)

ByAntonette T. Dulay, MD, Main Line Health System
Reviewed/Revised Apr 2024
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Hemolytic disease of the fetus and newborn occurs when a pregnant woman's blood type is Rh-negative and the fetus's blood type is Rh-positive.

  • Hemolytic disease of the fetus and newborn can result in destruction of the fetus’s red blood cells, sometimes causing anemia that can be severe.

  • The fetus of a woman with Rh-negative blood and a man with Rh-positive blood is checked periodically for evidence of anemia.

  • If anemia is suspected, the fetus is given blood transfusions.

  • To prevent problems in the fetus, doctors give injections of Rh antibodies to women with Rh-negative blood at about 28 weeks of pregnancy, after any episode of significant bleeding, after delivery, and after certain procedures.

The fetus of a woman with Rh-negative blood may have Rh-positive blood if the father has Rh-positive blood.

Did You Know...

  • Hemolytic disease of the fetus and newborn does not cause problems in a first pregnancy.

The Rh factor is a molecule on the surface of red blood cells in some people. Blood is Rh-positive if red blood cells have the Rh factor and Rh-negative if they do not. Problems can occur if the fetus’s Rh-positive blood enters the bloodstream of a woman with Rh-negative blood. The woman’s immune system may identify the fetus’s red blood cells as foreign and produce antibodies, called Rh antibodies, to destroy Rh-positive blood cells. The production of these antibodies is called Rh sensitization. (Antibodies are proteins that are produced by immune cells that help defend the body against foreign substances.)

In women with Rh-negative blood, sensitization can occur at any time during pregnancy. However, the most likely time is at delivery. In the pregnancy when sensitization first occurs, the fetus or newborn is not likely to be affected. Once women are sensitized, problems are more likely with each subsequent pregnancy if the fetus’s blood is Rh-positive. In each pregnancy after sensitization, women produce Rh antibodies earlier and in larger amounts.

If Rh antibodies cross the placenta to the fetus, they may destroy some of the fetus’s red blood cells. Such destruction is called hemolytic disease of the fetus (erythroblastosis fetalis) or of the newborn (erythroblastosis neonatorum). If red blood cells are destroyed faster than the fetus can produce new ones, the fetus can develop anemia (have too few red blood cells). Severe anemia can result in the fetus's death.

When red blood cells are destroyed, a yellow pigment called bilirubin is produced. When many red blood cells are destroyed, bilirubin can accumulate within the skin and other tissues. As a result, the newborn's skin and whites of the eyes may appear yellow (called jaundice). In severe cases, the brain may be damaged (called kernicterus).

Usually, hemolytic disease of the fetus and newborn causes no symptoms in pregnant women.

Occasionally, other molecules on the woman's red blood cells are incompatible with those of the fetus. Such incompatibility can cause problems similar to those of hemolytic disease of the fetus and newborn.

Diagnosis of Hemolytic Disease of the Fetus and Newborn

  • Blood tests

  • If the woman's blood contains Rh antibodies, Doppler ultrasonography

At the first visit to a doctor during a pregnancy, all women are screened to determine what their blood type is, whether they have Rh-positive or Rh-negative blood, and whether they have Rh antibodies or other antibodies to red blood cells.

Doctors usually assess the risk of women with Rh-negative blood becoming sensitized to Rh factor and producing Rh antibodies as follows:

  • If the father is available for testing, his blood type is determined.

  • If the father is unavailable for testing or if he was tested and has Rh-positive blood, a blood test called cell-free fetal nucleic acid (DNA) testing can be done to determine whether the fetus has Rh-positive blood. For this test, doctors do a blood test on the mother to detect and test small fragments of the fetus's DNA that are present in the pregnant woman's blood in tiny amounts (usually after 10 to 11 weeks).

If the father has Rh-negative blood, no further testing is needed.

If the father has Rh-positive blood, doctors periodically measure the level of Rh antibodies in the mother's blood. If the level reaches a certain point, the risk of anemia in the fetus is increased. In such cases, Doppler ultrasonography may be done periodically to evaluate blood flow in the fetus’s brain. If it is abnormal, the fetus may have anemia.

Treatment of Hemolytic Disease of the Fetus and Newborn

  • For anemia in the fetus, blood transfusions

  • Sometimes early delivery

If the fetus has Rh-negative blood or if results of tests continue to indicate that the fetus does not have anemia, the pregnancy can continue to term without any treatment.

If anemia is diagnosed in the fetus, the fetus can be given a blood transfusion before birth by a specialist at a center that specializes in high-risk pregnancies. Most often, the transfusion is given through a needle inserted into a vein in the umbilical cord. Usually, additional transfusions are given until 32 to 35 weeks of pregnancy. Exact timing of the transfusions depends on how severe the anemia is and how old the fetus is. Timing of delivery is based on the individual woman's situation.

Before the first transfusion, women are often given corticosteroids if the pregnancy has lasted 23 weeks or longer. Corticosteroids help the fetus's lungs mature and help prevent the common complications that can affect a preterm newborn.

The baby may need additional transfusions after birth. Sometimes no transfusions are needed until after birth.

Prevention of Hemolytic Disease of the Fetus and Newborn

As a precaution, women who have Rh-negative blood are given an injection of Rh antibodies at each of the following times:

  • At 28 weeks of pregnancy (or at both 28 and 34 weeks)

  • Within 72 hours after delivery of a baby who has Rh-positive blood, even after a miscarriage or an abortion

  • After any episode of vaginal bleeding during pregnancy

  • After amniocentesis or chorionic villus sampling

Sometimes, when large amounts of the fetus's blood enters the woman's bloodstream, additional injections are needed.

The antibodies given are called Rho(D) immune globulin. This treatment works by making the woman's immune system less able to recognize the Rh factor on red blood cells from the baby, which may have entered the woman’s bloodstream. Thus, the woman's immune system does not make antibodies to the Rh factor. Such treatment significantly reduces the risk that the fetus's red blood cells will be destroyed in subsequent pregnancies.

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