Hemolytic Disease of the Fetus and Newborn

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About Hemolytic Disease of the Fetus and Newborn

Hemolytic disease of the fetus and newborn (HDFN) is a rare and potentially life-threatening condition that affects approximately 4,000 – 8,000 United States (US) pregnancies per year. The disease is caused by antibodies from the mother which target proteins (also called antigens) on the fetal red blood cells (a process known as red cell alloimmunization). The most common antigen is RhD, although other antigens, such as Rhc, RhE, and Kell, may also be involved in the process.

During pregnancy, antibodies can cross the placenta and bind to the antigens on the surface of the fetus’ red blood cells, leading to fetal red blood cell destruction (hemolysis) and anemia (low red blood cell count). Anemia causes less oxygen to be delivered to all the fetal tissues and can lead to organ damage and ultimately lead to fetal heart failure and even fetal death. In addition, sometimes fetuses that have suffered anemia during pregnancy may have significant consequences like cerebral palsy.

In the case of RhD antigen incompatibility, this antibody formation is typically preventable. However, it is not always 100% effective. Moreover, HDFN can occur with other antigen incompatibilities where there is no preventative treatment.

Although current screening and management of HDFN have significantly improved perinatal outcomes, some of these treatments, such as transfusing blood to the fetus during pregnancy, may be associated with significant complications. Thus, non-invasive, safe, and effective treatment alternatives are needed.


Most Western countries have implemented screening programs for detection of RBC alloimmunization in pregnancy; however, the frequency and timing of those screening programs vary.

To properly diagnose HDFN, the physician will conduct a detailed review of the mother’s past medical history including any past blood transfusions and past pregnancies. In addition, the physician may conduct a number of tests and assessments, such as:

Free Fetal DNA

To check the antigen status of the fetus by looking for fetal DNA in the mother’s bloodstream.


To determine the antigen status of the fetus. In this test, a needle is put into the mother's amniotic sac and a sample of amniotic fluid is collected for analysis.

Antibody Titer

To look for the amount and type of red blood cell antibodies in the mother’s blood.

Doppler Ultrasound

To detect fetal anemia by measuring the speed of blood moving through the fetal brain. The type of ultrasound is called Doppler. Doppler measures the speed of blood in a specific vessel in the brain called the middle cerebral artery (MCA).


To determine the degree of fetal anemia. In this test, a fetal blood sample is taken from the umbilical cord under ultrasound guidance. If the fetus is found to be anemic, an intrauterine blood transfusion may be performed at the same setting.

Disease Management Strategies

Depending on the stage of pregnancy and severity of the condition, as well as in consultation with a physician, HDFN may be managed in a number of ways.

During pregnancy


The physician will check the baby’s blood flow in the brain (MCA Doppler) to check for signs of anemia.

Intrauterine blood transfusion (IUT)

In this procedure, a needle is placed through the mother’s uterus, either directly into the umbilical cord or the part of the umbilical cord that enters the fetal liver. An ultrasound is used to guide the needle. Once reaching the vein, healthy red blood cells are delivered into the fetal circulation, replacing those lost or damaged by HDFN. In almost all cases, multiple transfusions are required several weeks apart for the remainder of the pregnancy.

Intravenous immunoglobulin (IVIG)

IVIG is a product made up of a large mixture of normal antibodies given to the mother as an infusion through a vein. Exactly how IVIG works is not known, but may be related to various mechanisms that helps to reduce the levels of harmful antibodies or it may help to block the passage of harmful antibodies through the placenta.

Therapeutic plasma exchange

Also called plasmapheresis, it involves removing the mother’s plasma, which contains the harmful antibodies, and replacing it with albumin-rich fluid by passing the mother’s blood through a cell separator. The mother’s red and white blood cells are returned to the mother during the procedure.

Early delivery

Depending on how far along the pregnancy is, and if certain complications arise and the symptoms of HDFN are getting worse, the physician may recommend early delivery.

After Birth

Depending on the health status of the newborn, the newborn may require supportive management and close monitoring in the neonatal intensive care unit.


If the baby has high levels of bilirubin, phototherapy may be used. In this procedure, the baby is put under a special blue light which helps get rid of extra bilirubin.

Blood transfusions

If the baby has severe anemia, red blood cell transfusions may be required to manage the anemia.

Exchange transfusion

Exchange transfusion is a potentially lifesaving, complex procedure that is performed in a neonatal intensive care unit. It involves removing portions of the neonate’s blood and replacing it with compatible donor blood. This is done in order to remove bilirubin and the harmful antibodies that are destroying the baby’s red blood cells.

Intravenous immunoglobulin (IVIG)

IVIG may be given to the baby after he or she is born to help reduce the level of harmful antibodies. Exactly how IVIG works is not known.


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Gajjar K, Spencer C. Diagnosis and management of non-anti-D red cell antibodies in pregnancy. The Obstetrician & Gynaecologist. 2009;11(2):89-95.

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Calhourn DA. Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. Kim SM, ed. UpToDate. Waltham, MA; UpToDate Inc. http://www.uptodate.com (Accessed on August 24, 2018).