Hemolytic Disease of the Newborn Overview

Hemolytic disease of the newborn (HDN) is a condition of red blood cell mismatch between a mother and her baby. This occurs when the mother's blood type is Rh-negative and the baby is Rh-positive. During the pregnancy the mother produces antibodies that attack and destroy red blood cells, resulting in anemia in the fetus. A similar condition occurs with platelets called neonatal alloimmune thrombocytopenia.

Newborn undergoing phototherapy
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Our red blood cells are coated with antigens, substances that induce an immune response. Some of these antigens give us our blood type (A, B, O, AB) and others our Rh group (positive, negative). The Rh group is also called the D antigen. Women who are Rh-negative do not have the D antigen on their red blood cells. If their unborn baby is Rh-positive (inherited from the father), they have a D antigen present. When maternal immune cells are exposed to the blood cells of the fetus (which can occur during delivery, bleeding during the pregnancy, or due to previous miscarriage), the maternal immune system recognizes the D antigen as "foreign" and develop antibodies against them.

The first pregnancy with an Rh-positive baby is not affected as the antibodies formed initially cannot cross the placenta. However, in future pregnancies, if the maternal immune cells come into contact with the D antigen on the fetal blood cells, the immune system rapidly produces anti-D antibodies that can cross the placenta. These antibodies attach to the fetal blood cells, marking them for destruction, causing anemia. A similar condition can occur when there is a mismatch in blood type called ABO incompatibility.

How the Infant Is Affected

As discussed above, in he first pregnancy with an Rh-positive baby, there are no problems. If this mismatch is unknown in the first pregnancy (occurs sometimes if first pregnancy results in a miscarriage) or if proper preventative measures (which will be discussed later) are not taken, future pregnancies can be affected. After the first affected pregnancy, the severity of hemolytic disease of the newborn worsens with each pregnancy.

Symptoms are determined by the severity of the red blood cell breakdown (called hemolysis). If the infant is only mildly affected, there may be minimal problems such as mild anemia and/or jaundice that do not require treatment. If the amount of hemolysis is severe, he/she will have significant jaundice (elevated bilirubin) shortly after birth.

Unfortunately, the hemolysis doesn't stop when the baby is born as the maternal antibodies linger for several weeks. These excessive levels of bilirubin can cause damage to the brain. In some cases, the anemia is so severe in utero (prior to birth) that the liver and spleen enlarge to increase red blood cell production leading to liver failure. The hemolytic disease may also lead to hydrops fetalis with generalized edema (swelling), fluid around organs, and even death.


Today all women receiving prenatal care have blood work drawn to determine their blood type and group. If she is Rh-negative, blood work is sent to determine if she already has anti-D antibodies. If she doesn't already have antibodies, she will receive a medication called RhoGAM. RhoGAM or anti-D Ig is an injection given at 28 weeks, episodes of bleeding (including miscarriages after 13 weeks gestation), and at delivery. The RhoGAM is similar to the antibody the mother would make to the D-antigen. The goal is for the RhoGAM to destroy any fetal red blood cells in the mom's circulation before she can develop antibodies.

If anti-D antibodies are found, RhoGAM will not be helpful but additional screening of the fetus will be performed as outlined below.


If the mother is determined to have anti-D antibodies and the father is Rh-positive, there is the possibility of hemolytic disease of the newborn. In this situation, testing is performed on the amniotic fluid or blood from the umbilical cord to determine the blood type and group of the baby. If the baby is found to be Rh-negative, no further treatment is required.

However, if the baby is Rh-positive, the pregnancy will be monitored closely. Ultrasounds will be used to assess for fetal anemia and to determine the need for intrauterine transfusions (transfusion given to the fetus while still in the uterus). The mother's blood will be tested serially during pregnancy to determine how much antibody she is producing. If the baby is found to be anemic, blood transfusions can be given during the pregnancy to prevent complications (intrauterine transfusions). If the baby is found to be anemic and is near full term, early delivery might be recommended.

After the baby is born, blood work is sent to monitor for anemia and bilirubin levels. The breakdown of red blood cells doesn't stop as soon as the baby is born so the bilirubin can rise to dangerous levels in the first couple of days. The elevated bilirubin levels (jaundice) are treated with phototherapy where the baby is placed under blue lights. The lights break down the bilirubin allowing the body to get rid of it. Transfusions are also used to treat anemia. If the anemia and jaundice are severe, the baby is treated with an exchange transfusion. In this type of transfusion, small amounts of blood are removed from the baby and are replaced by transfused blood.

Once discharged from the hospital, it is important to have close follow-up with the pediatrician or hematologist to monitor for anemia. The maternal red blood cell antibodies can cause destruction for 4-6 weeks after delivery and additional transfusions may be needed.

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  • Nandyal RR. Hemolytic Disease of the Newborn. Journal of Hematology and Thromboembolic Disease. 2015.  

By Amber Yates, MD
Amber Yates, MD, is a board-certified pediatric hematologist and a practicing physician at Baylor College of Medicine.