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Hemolytic Disease of the Fetus and Newborn

(Rh Incompatibility; Erythroblastosis Fetalis or Neonatorum)


Antonette T. Dulay

, MD, Main Line Health System

Reviewed/Revised Oct 2022

Rh incompatibility occurs when a pregnant woman has Rh-negative blood and the fetus has Rh-positive blood.

  • Rh incompatibility can result in destruction of the fetus’s red blood cells, sometimes causing anemia that can be severe.

  • The fetus of a women 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.

Pregnancy complications, such as Rh incompatibility, are problems that occur only during pregnancy. They may affect the woman, the fetus, or both and may occur at different times during the pregnancy. However, most pregnancy complications can be effectively treated.

The fetus of a woman with Rh-negative blood may have Rh-positive blood if the father has Rh-positive blood. The percentage of people who have Rh-negative blood is small and varies by ethnicity:

  • White people in North America and Europe: About 15%

  • African American people: About 8%

  • People of Chinese descent: About 0.3%

  • People of Indian descent: About 5%

Did You Know...

  • Rh incompatibility 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 Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more 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. If red blood cells are destroyed faster than the fetus can produce new ones, the fetus can develop anemia. Such destruction is called hemolytic disease of the fetus Hemolytic Disease of the Newborn Hemolytic disease of the newborn is a condition in which red blood cells are broken down or destroyed by the mother's antibodies. Hemolysis is the breakdown of red blood cells. This disorder... read more (erythroblastosis fetalis) or of the newborn (erythroblastosis neonatorum).

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 Jaundice in the Newborn Jaundice is a yellow color to the skin and/or eyes caused by an increase in bilirubin in the bloodstream. Bilirubin is a yellow substance formed when hemoglobin (the part of red blood cells... read more Jaundice in the Newborn ). In severe cases, the brain may be damaged (called kernicterus Complications of jaundice Complications of jaundice ), and severe anemia can result in the fetus's death. Miscarriage can occur.

Usually, Rh incompatibility 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 Rh incompatibility.

Diagnosis of Rh Incompatibility

  • 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 known and is available for testing, his blood type is determined.

  • If the father is unavailable for testing or if he was tested and he 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 test small fragments of the fetus's DNA, which 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 Doppler ultrasonography Ultrasonography is a type of medical imaging that uses high-frequency sound (ultrasound) waves to produce images of internal organs and other tissues. During an ultrasound, a device called a... read more Doppler ultrasonography may be done periodically to evaluate blood flow in the fetus’s brain. If it is abnormal, the fetus may have anemia.

Prevention of Rh Incompatibility

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

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 reduces the risk that the fetus's red blood cells will be destroyed in subsequent pregnancies from about 12 to 13% (without treatment) to about 0.1%.

Treatment of Rh Incompatibility

  • 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 or 24 weeks or longer. Corticosteroids help the fetus's lungs mature and help prevent the common complications that can affect a preterm newborn Preterm (Premature) Newborns A preterm newborn is a baby delivered before 37 weeks of gestation. Depending on when they are born, preterm newborns may have underdeveloped organs that are not be ready to function outside... read more .

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

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