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Hemolytic Disease of the Newborn

(Erythroblastosis Fetalis; Erythroblastosis Neonatorum)

By Andrew W. Walter, MS MD, Associate Professor of Pediatrics;Attending Physician, Sidney Kimmey Medical College at Thomas Jefferson University;A. I. duPont Hospital for Children

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Hemolytic disease of the newborn is a condition in which red blood cells are broken down or destroyed more rapidly than normal by the mother's antibodies. Hemolysis is the breakdown of red blood cells.

  • This disorder may occur if a mother's blood is incompatible (not a match) with her fetus's blood.

  • The diagnosis is based on blood tests of the mother and sometimes the father.

  • Sometimes, the mother is given immune globulin during pregnancy to help prevent this disorder in the newborn.

  • Treatment may include blood transfusions for the fetus before delivery and for the newborn after delivery.

Hemolytic disease of the newborn may result in high levels of bilirubin in the blood (hyperbilirubinemia), a low red blood cell count (anemia), and, very rarely, in the most severe forms, death. Bilirubin is a yellow pigment produced during the normal breakdown of red blood cells.

Rh incompatibility

The Rh factor is a molecule on the surface of red blood cells in some people. Blood is Rh-positive if a person's red blood cells have the Rh factor. Blood is Rh-negative if a person's red blood cells do not have the Rh factor. Most people are Rh-positive.

When a baby has Rh-positive blood and the mother has Rh-negative blood, the two have Rh incompatibility. As a result, the immune system of an Rh-negative mother may recognize the Rh-positive fetus’s red blood cells as "foreign" and produce antibodies against the Rh factor on the fetus's red blood cells (this process is called Rh sensitization). The mother's antibodies can pass from her blood through the placenta into the fetus's blood before delivery. The mother’s antibodies attach to and destroy (hemolyze) the fetus's red blood cells. The rapid breakdown of red blood cells begins while the fetus is still in the womb and continues after delivery.

A mother who is Rh-negative can produce the Rh antibodies if she is exposed to Rh-positive red blood cells. The most common way women are exposed to Rh-positive blood is when they have a fetus who is Rh-positive. Mothers are exposed to the most blood from the fetus during delivery, so that is when most Rh sensitization occurs. However, mothers also can be exposed earlier in pregnancy, for example, during a miscarriage or elective abortion, during a diagnostic test on the fetus (such as amniocentesis or chorionic villus sampling), if they have an injury to their abdomen, or if the placenta separates too early (placental abruption). Thus, most hemolytic disease happens to a fetus whose mother was sensitized during an earlier pregnancy. However, rarely, a mother may produce antibodies early in a pregnancy and then these antibodies affect the same fetus later during that pregnancy. Exposure may also occur outside of pregnancy, for example if the mother was transfused with Rh-positive blood at any time earlier in her life. Once the mother has been exposed and developed antibodies, problems are more likely with each subsequent pregnancy in which the fetus is Rh-positive.

ABO incompatibility

Sometimes other blood group incompatibilities may lead to a similar (but milder) hemolytic disease. For example, if the mother has blood type O and the fetus has blood type A or B, then the mother’s body produces anti-A or anti-B antibodies that can cross the placenta, attach to fetal red blood cells, and cause their breakdown (hemolysis), leading to mild anemia and hyperbilirubinemia. This type of incompatibility is called ABO incompatibility. ABO incompatibility usually leads to less severe anemia than Rh incompatibility and, unlike Rh incompatibility, it usually gets less severe with each subsequent pregnancy.

Symptoms

After delivery, newborns who have hemolytic disease may be swollen, pale, or yellow (a condition called jaundice) or may have a large liver or spleen, anemia, or accumulations of fluid in their body.

Diagnosis

  • Blood tests of the mother during pregnancy and sometimes the father

At the first prenatal visit during a pregnancy, the mother gets a blood test to determine whether she has Rh-negative or Rh-positive blood. If the mother has Rh-negative blood and tests positive for anti-Rh antibodies or if she tests positive for another antibody that can cause hemolytic disease of the newborn, the father's blood is checked. Rh sensitization is a risk if the father has Rh-positive blood. In these situations, the mother is given periodic blood tests during the pregnancy to check for Rh antibodies. The pregnancy can proceed as usual as long as no antibodies are detected. If antibodies are detected, special tests on the mother and fetus are done during the pregnancy.

Prevention

  • Injection of immune globulin during pregnancy and after delivery

To prevent Rh-negative women from developing antibodies against their fetus's red blood cells, they are given an injection of an Rh0(D) immune globulin preparation at about 28 weeks of pregnancy and again within 72 hours after delivery. The immune globulin rapidly coats any Rh-positive fetal red blood cells that have entered the mother’s circulation so they are not recognized as "foreign" by the mother’s immune system and thus do not trigger formation of anti-Rh antibodies. This treatment usually prevents hemolytic disease of the newborn from developing.

Treatment

  • Before delivery, sometimes blood transfusion for the fetus

  • After delivery, sometimes more transfusions

  • Treatment of jaundice if present

If anemia is diagnosed in the fetus, the fetus may be given a blood transfusion before birth. Transfusions may be done until the fetus has matured and can be delivered safely. Before delivery, the mother may be given corticosteroids to help the fetus's lungs mature to prepare for the possible delivery of the fetus earlier than usual if necessary. After delivery, the newborn may need more transfusions.

Severe anemia caused by hemolytic disease of the newborn is treated in the same way as any other anemia (see treatment of anemia). Doctors also observe the newborn for jaundice. Jaundice is likely to occur because the rapid breakdown of red blood cells produces a lot of bilirubin. Bilirubin is a yellow pigment, and it gives the newborn’s skin and whites of the eyes a yellow appearance. If the bilirubin level gets too high, it can injure the baby. High bilirubin levels can be treated by exposing the newborn to special bright lights (phototherapy or bili lights) or, occasionally, by having the newborn undergo an exchange transfusion. Very high levels of bilirubin in the blood can lead to brain damage (kernicterus), unless it is prevented by these measures.