What are the other Names for this Condition? (Also known as/Synonyms)

• Alloimmune Hemolytic Disease of Newborn
• Hemolytic Disease of Fetus and Newborn due to Isoimmunization
• Hemolytic Disease of Newborn (HDN)

What is Erythroblastosis Fetalis? (Definition/Background Information)

• Erythroblastosis Fetalis, also known as Hemolytic Disease of the Newborn (HDN), is a condition in which there is an incompatibility between the blood types of a pregnant woman and her developing fetus
• The most common form of this condition arises when a Rh-negative mother is carrying a Rh-positive baby. If the mother's immune system is sensitized to Rh-positive blood, usually due to a previous pregnancy or blood transfusion, she may produce antibodies that can cross the placenta and attack the red blood cells of the Rh-positive fetus
• This immune response can destroy fetal red blood cells, causing anemia, jaundice, and potentially serious complications in the newborn. In severe cases, Erythroblastosis Fetalis can result in hydrops fetalis, a condition characterized by excessive fluid accumulation in the fetus even leading to heart failure
• Preventive measures include the administration of Rh immunoglobulin (RhIg) to Rh-negative pregnant women, which can prevent the sensitization of the immune system and reduce the risk of Erythroblastosis Fetalis. Treatment for severe cases may involve intrauterine blood transfusions or postnatal interventions to manage the effects of hemolysis (the premature destruction of red blood cells), and suitable treatment for jaundice
• The prognosis of Erythroblastosis Fetalis depends on the extent of the destruction of the red blood cells. The prognosis may be ascertained on a case-by-case basis; however, Erythroblastosis Fetalis needs prompt diagnosis and urgent care

Who gets Erythroblastosis Fetalis? (Age and Sex Distribution)

• Erythroblastosis Fetalis is a condition that develops during the fetal stage and is manifested in newborns (at birth)
• The condition is observed worldwide among all races and ethnic groups
• It is researched that about 85-99% of the mothers are known to be Rh-positive

What are the Risk Factors for Erythroblastosis Fetalis?

• Mothers with the following blood types are at risk for the fetus developing Erythroblastosis Fetalis (in decreasing order of incidence):
  • ABO
  • Anti-RhD
  • Anti-RhE
  • Anti-Rhc
  • Anti-Rhe
  • Anti-RhC
• Mothers with multiantigen combinations
• Incompatibility between the mother and the fetus of any of other blood groups such as Kell, Duffy, Lutheran or Diego may also give similar features

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Erythroblastosis Fetalis? (Etiology)

Erythroblastosis Fetalis is primarily caused by an incompatibility between the blood types of a pregnant woman and her developing fetus.

• The primary factor contributing to this condition is the Rh factor, a protein present on the surface of red blood cells. The Rh factor can be either Rh-positive or Rh-negative
• The specific cause of Erythroblastosis Fetalis is Rh incompatibility between the Rh status of the mother and the fetus. The key scenarios leading to this condition include:
  • Rh-negative mother and Rh-positive fetus: When a Rh-negative mother is carrying a Rh-positive fetus, there is a risk of the mother's immune system producing antibodies against the Rh-positive blood cells of the fetus
  • Sensitization: Sensitization typically occurs during a previous pregnancy or, less commonly, after a blood transfusion with Rh-positive blood. If the mother becomes sensitized to Rh-positive blood, her immune system may produce antibodies that can cross the placenta and attack the red blood cells of a Rh-positive fetus in subsequent pregnancies
• The immune response triggered by sensitization can lead to the destruction of fetal red blood cells, resulting in hemolytic anemia in the fetus

Destruction of the red blood cells results in severe anemia. When red blood cells are destroyed, hemoglobin (a protein in the red blood cells carrying oxygen) is released into circulation. Hemoglobin is metabolized into bilirubin; excess bilirubin in the blood causes jaundice (yellowish discoloration of the eyes and skin). This excess bilirubin can get deposited in the brain, causing mental retardation or cerebral palsy in infants.

Mother can develop antibodies to Rh antigen in the fetus. Usually, the first fetus may not develop any consequences of the incompatibility, meaning it can be a normal childbirth. During the second pregnancy, if the fetus is Rh positive again, antibodies already present in the mother can react with Rh blood group antigen in the fetus, destroying the red blood cells and causing other serious consequences. Newborn babies may develop severe anemia and jaundice due to destruction of the red blood cells.

What are the Signs and Symptoms of Erythroblastosis Fetalis?

The signs and symptoms of Erythroblastosis Fetalis include: 

• Anemia (low hemoglobin) occurs because of destruction of the red blood cells
• Jaundice (yellowish discoloration) of eyes and skin due to an increase in bilirubin levels in the blood
• There may be enlargement of the liver and spleen
• Hydrops fetalis:
  • Fluid may accumulate in the lungs and may cause breathing trouble in the infant
  • Heart may be affected due to low hemoglobin and accumulation of fluid
  • High levels of insulin and low blood sugar may lead to fluid accumulation in the fetus, resulting in generalized swelling

How is Erythroblastosis Fetalis Diagnosed?

A diagnosis of Erythroblastosis Fetalis may involve the following tests and procedures:

• Blood typing and Rh factor testing:
  • Blood typing of the mother and father to identify their ABO and Rh blood groups
  • Determination of the Rh status (positive or negative) of the mother and the Rh factor of the fetus
• The mother’s blood group is routinely tested during pregnancy. If it is Rh negative, then the father’s blood is tested. If the father’s blood group is Rh positive, the indirect Coomb’s test is performed
  • Indirect Coomb’s test: The test demonstrates antibodies in the mother’s blood developed against Rh antigen on the fetal blood cells. This test is repeated at 28 weeks of pregnancy if it is negative the first time the test is performed
  • Direct Coomb’s test: This test demonstrates maternal antibodies that are attached to the Rh antigen on the fetus's red blood cells
• Amniocentesis: Amniocentesis, a prenatal diagnostic procedure, may be done to analyze a sample of amniotic fluid surrounding the fetus. This can provide information about the fetal Rh status and assess the severity of hemolysis
• Ultrasound imaging: Ultrasound examinations can be used to monitor the development of the fetus and assess for signs of anemia, including enlargement of the fetal spleen and liver
• Doppler ultrasound: Doppler ultrasound can help measure blood flow in the fetal middle cerebral artery, providing insights into the severity of fetal anemia
• Fetal blood sampling (cordocentesis): In some cases, a fetal blood sample may be obtained through cordocentesis (sampling blood from the umbilical cord) to assess the degree of anemia directly

Also, after the baby is born, signs and symptoms such as anemia or jaundice may raise suspicion for Erythroblastosis Fetalis, leading to further testing and confirmation.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Erythroblastosis Fetalis?

The complications of Erythroblastosis Fetalis may include:

• Severe anemia (low hemoglobin)
• Accumulation of bilirubin in the brain may result in brain damage. This condition is also called ‘kernicterus’
• Increased insulin levels may cause hypoglycemia
• Lung growth may be affected, and frequent breathing problems may occur
• Anemia and fluid accumulation may result in heart failure
• Spleen and liver may be severely enlarged

How is Erythroblastosis Fetalis Treated?

The treatment measures for Erythroblastosis Fetalis may include giving Rh immune globulins to the mother during pregnancy to prevent the development of antibodies in the mother.

Serial ultrasound scans and amniotic fluid analysis (fluid present inside the mother’s womb surrounding the baby) are performed to monitor fetus growth and potential complications of Erythroblastosis Fetalis.

• An accumulation of bilirubin in the amniotic fluid is a dangerous sign. It is indicative of impending fetus death. This condition is treated by giving blood transfusions to the fetus inside the womb
• Frequent transfusions may be needed depending on the severity of the condition. Transfusions may be done directly into the baby’s abdominal cavity or via the umbilical cord, which is located by sonogram
• After the baby is born, several blood transfusions may be necessary, depending on the judgment of the healthcare provider
• Phototherapy is provided if the fetus develops jaundice. Phototherapy involves placing the baby under a special light that converts bilirubin into a water-soluble form that can be easily excreted in urine
• Supportive treatment may be provided to the baby that includes oxygen therapy, intravenous fluids, and electrolyte administration

How can Erythroblastosis Fetalis be Prevented?

In the case of Erythroblastosis Fetalis, prevention is often the best cure. With regular checkups and routine follow-up visits during pregnancy, this condition can be safely prevented.

Routine testing should be done to check the mother's blood group during pregnancy. Rh positive or negative is to be determined first.

Administration of RhoGAM:

• Rh immune globulin (RhIG, also called RhoGAM) is administered to all Rh-negative mothers at 28 weeks of pregnancy. Once the baby is born, his/her blood group is checked. If the baby is Rh-positive, another dose of RhoGAM is given within 72 hours of delivery. If the baby is Rh-negative, another dose may not be required
• During pregnancy, the baby’s blood group cannot be discovered unless an invasive procedure such as an amniocentesis (removal of amniotic fluid that is surrounding the fetus in the mother’s womb) is performed. RhoGAM is administered safely, considering the baby’s blood group is Rh-positive. After birth, if the baby’s blood group is Rh negative, another dose of RhoGAM is generally not required
• RhoGAM immune globulin binds the Rh antigen on the fetal red blood cells before the mother’s immune system realizes them and mounts an immune response. 
• RhoGAM immunoglobulin should be administered during the first pregnancy, considering the mother’s Rh-positive blood group. If the mother has a miscarriage or abortion, RhoGAM prophylaxis is generally administered

What is the Prognosis of Erythroblastosis Fetalis? (Outcomes/Resolutions)

The prognosis of Erythroblastosis Fetalis depends on the severity of the condition and the extent of the reaction between the mother’s antibodies and the fetus’ red blood cells.

• Minor symptoms of Erythroblastosis Fetalis can be treated successfully without any significant complications
• Severe complications may occur in some cases, such as deposition of bilirubin in the brain (kernicterus), leading to mental retardation, cerebral palsy, deafness, or speech defects. 
• Heart failure and hydrops fetalis (accumulation of fluid in the fetus) are other serious consequences that may not present a favorable outcome

Additional and Relevant Useful Information for Erythroblastosis Fetalis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/health-topics/focused-health-topics/coombs-test-unraveling-its-role-blood-typing-and-autoimmune-hemolytic-anemia