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Hemolytic Disease of the Newborn

(Erythroblastosis Fetalis; Erythroblastosis Neonatorum; Rh Incompatibility)


Andrew W. Walter

, MS, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Reviewed/Revised Nov 2022

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 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.

Red blood cells contain hemoglobin, a protein that gives blood its red color and enables it to carry oxygen from the lungs and deliver it to all body tissues. Oxygen is used by cells to help produce from food the energy that the body needs, leaving carbon dioxide as a waste product. Red blood cells carry carbon dioxide away from the tissues and back to the lungs. When the number of red blood cells is too low, blood carries less oxygen, and fatigue and weakness develop.

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 red blood cells and the mother has Rh-negative red blood cells, the two have Rh incompatibility Hemolytic Disease of the Fetus and Newborn 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... read more . 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.

When a mother has Rh antibodies, they can pass from her blood through the placenta into the fetus's blood before delivery. If the fetus is Rh-positive, the mother’s Rh antibodies can 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. This breakdown can cause anemia.

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. Thus, most hemolytic disease happens to a fetus whose mother was sensitized during an earlier pregnancy.

Mothers also can be exposed to Rh-positive blood earlier in pregnancy, for example, during a miscarriage Miscarriage A miscarriage is a pregnancy loss before 20 weeks of pregnancy. Miscarriages are very common, especially early in pregnancy. Most of the time, the cause of a miscarriage is unknown, but it may... read more or elective abortion Abortion Induced abortion is the intentional ending of a pregnancy by surgery or medications. A pregnancy may be ended by surgically removing the contents of the uterus or by taking certain medications... read more , during a diagnostic test on the fetus (such as amniocentesis Amniocentesis Prenatal testing for genetic disorders and birth defects involves testing a pregnant woman or fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including... read more or chorionic villus sampling Chorionic Villus Sampling Prenatal testing for genetic disorders and birth defects involves testing a pregnant woman or fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including... read more ), if they have an injury to their abdomen, or if the placenta separates too early (placental abruption Placental Abruption Placental abruption is the premature detachment of the placenta from the wall of the uterus, usually after 20 weeks of pregnancy. Women may have abdominal pain and tenderness and vaginal bleeding... read more ). In that case, 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 in large amounts, 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 of Hemolytic Disease of the Newborn

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

Diagnosis of Hemolytic Disease of the Newborn

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

  • Sometimes blood tests of the father and of the newborn

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, and thus the baby may also be Rh-positive. In these situations, the mother is given periodic blood tests during the pregnancy to check for Rh antibodies.

Nothing further needs to be done as long as no antibodies are detected. If antibodies are detected, special blood tests on the mother and fetus are done during the pregnancy, and the newborn is tested after birth.

Prevention of Hemolytic Disease of the Newborn

  • 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. They are also given an injection after any episode of vaginal bleeding during pregnancy and after amniocentesis or chorionic villus sampling. The Rh0(D) 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 of Hemolytic Disease of the Newborn

  • Before delivery, sometimes blood transfusions 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 blood transfusions Overview of Blood Transfusion A blood transfusion is the transfer of blood or a blood component from one healthy person (a donor) to a sick person (a recipient). Transfusions are given to increase the blood's ability to... read more Overview of 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.

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 too much of it (hyperbilirubinemia 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 ) gives the newborn’s skin and whites of the eyes a yellow appearance.

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