What is Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )?
Hemolytic disease of the fetus and newborn (HDFN), also known as alloimmune HDFN or erythroblastosis fetalis, is a condition that occurs when a mother’s immune system attacks her baby’s red blood cells. This happens because of certain antibodies, a type of protein that the immune system uses to fight off foreign substances, that the mother produces.
This process begins when the mother’s system doesn’t recognize some of the baby’s red blood cells as its own, but thinks of them as foreign bodies. These unrecognized cells, which contain specific molecules called antigens that are absent in the mother, are passed onto the mother’s body through the placenta (which is an organ connecting the mother and baby during pregnancy).
In response, the mother’s body creates antibodies to defend itself. However, these antibodies can cross back over the placenta into the baby’s bloodstream and start to destroy the baby’s red blood cells, causing anemia (a condition where the body lacks enough healthy red blood cells) and releasing a compound called bilirubin.
The danger to the baby depends on many factors, like how many and how effective the mother’s antibodies are, the age of the fetus, and how well the fetus can produce new red blood cells and remove the excessive bilirubin.
What Causes Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )?
Several different types of blood groups can play a role in Hemolytic Disease of the Newborn (HDFN). These include groups like ABO, Rhesus (Rh), Kell, Duffy, Kidd, MNS, Diego, P, Lutheran, and Xg. However, the two most common types involved are ABO and Rhesus.
HDFN usually happens due to ABO incompatibility, often when the mother has O type blood and the baby has either A or B type. Despite being common, ABO incompatibility causes a milder form of HDFN compared to Rhesus (Rh-D) incompatibility.
Babies affected by this condition typically don’t show any symptoms at birth except for mild anemia, or lack of healthy red blood cells. They usually develop yellowing of the skin and eyes, known as neonatal jaundice, which is usually effectively treated with light therapy (phototherapy).
Because complications from Rhesus factor incompatibility are more serious, the rest of this discussion will focus on that.
Risk Factors and Frequency for Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
After the introduction of post-birth measures in 1970, the chances of a mother experiencing RhD carried over from a different source, also known as maternal RhD alloimmunization, decreased from 14% to just 1-2%. More reductions were observed when these measures were also applied before birth, minimizing the occurrence to 0.1%. Currently, in the western portion of the world, ABO mismatching has taken over as the major cause of blood-related problems in newborns.
How common Rh factor mismatching is can be different based on race and human groups. For instance, about 15% of white people are Rh-negative. Meanwhile, just 5-8% of African Americans have this trait, and the percentage drops to 1-2% for Asians and Native Americans. An interesting data among whites shows that an Rh-negative woman has about an 85% likelihood of being with an Rh-positive man. Among these men, 60% have the gene present with another gene, while 40% possess it alone.
- Postnatal immunoprophylaxis introduced in 1970 significantly decreased maternal RhD alloimmunization from 14% to 1-2%.
- The addition of immunoprophylaxis before birth further dropped the occurrences to 0.1%.
- Today, ABO incompatibility is the leading cause of blood-related health problems in newborns in the western world.
- Rh incompatibility varies among different races and ethnicities.
- About 15% of whites, 5-8% of African Americans, and 1-2% of Asians and Native Americans are Rh-negative.
- An Rh-negative woman has an 85% chance of pairing with an Rh-positive man, 60% of whom carry the gene in both copies and 40% in one.
Signs and Symptoms of Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
Babies with a mild to moderate form of this disease usually show symptoms of hemolytic disease, which includes signs like excessive bilirubin in the body, within the first day of their life. These symptoms are self-limiting and typically resolve on their own.
On the other hand, babies with a more severe condition known as hydrops fetalis present with symptoms like skin swelling, fluid buildup around the lungs or heart, or fluid in the abdominal cavity. Certain blood group incompatibilities, such as RhD and Kell, especially in babies without proper care before birth, can increase the risk of developing hydrops fetalis.
Testing for Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
If you are pregnant and your blood type is Rh-negative, it’s important to prevent a condition known as sensitization. Sensitization can occur when you are exposed to your unborn baby’s blood. This might happen through miscarriage, amniocentesis (a medical procedure to examine the baby’s chromosome characteristics), vaginal bleeding, placental abruption (a serious complication where the placenta separates from the womb’s inner wall), and abdominal trauma. If you experience any of these situations, you should get a dose of RhoGAM, which is a type of medication that can help prevent sensitization.
If you test positive for Rh antibodies during your first prenatal visit, your doctor will monitor the concentration of these antibodies, known as a ‘titer’. High titers, usually greater than 1:16, might put the baby at risk of a condition known as fetal hydrops, which causes an abnormal accumulation of fluid in the fetus. If the baby’s father is definitely known, the father’s blood type can be checked to understand the risk to the fetus. That said, since in some cases there might be uncertainty or misinformation about the biological father, to be on the safe side, doctors often treat all pregnancies as if the baby might be at risk.
Your doctor will keep an eye on the antibody titer during your pregnancy, usually every 4 weeks. If the titer stays below 1:16, the pregnancy can be managed normally. But if it goes above 1:16, the doctor may start a series of amniocentesis as early as 16 to 20 weeks. Through amniocentesis, the doctor could collect some cells from the fetus to check if the Rh antigen is present, essentially, to see whether the baby is Rh-positive. If the baby is Rh-negative, you can proceed as normal. But if the baby is Rh-positive, the doctor will need to check for possible fetal anemia, which refers to low levels of red blood cells in the baby.
Doctors use a test called fetal middle cerebral artery (MCA) Doppler measurements to check for fetal anemia. This test measures the peak systolic velocity (PSV), which gives an impression of how fast blood flows to the fetus’s brain. Faster blood flow indicates anemia, and the baby might need more tests and treatment. Before the MCA Doppler test was introduced, to evaluate an Rh-positive fetus in an Rh-negative mother with high titers, doctors would perform a series of amniocentesis to study the amniotic fluid using a device called a spectrophotometer.
Treatment Options for Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
Rho(D) immune globulin is a type of medicine made from human antibodies that works against a specific protein, known as the Rho(D) antigen, found on red blood cells. This medicine is used to prevent Rh hemolytic disease, a serious condition that can occur in newborn babies. This condition happens when the blood type of a mother and her baby are incompatible.
Administering Rho(D) immune globulin to mothers who don’t have the Rh(D) antigen (known as being Rho(D) negative) at the time they might be exposed to it (like giving birth to a Rh(D) positive baby) can prevent the mother’s immune system from attacking the baby’s cells. This medicine does this by preventing the mother’s immune system from recognizing the baby’s cells as a threat. This means that in future pregnancies, the mother’s body will not produce harmful antibodies against an Rh-positive baby, preventing hemolytic disease from developing in the newborn.
Rho(D) immune globulin, also known by the brand name RhoGAM, is generally given at around 28 weeks of pregnancy. It lasts in the body for about 12 weeks, providing protection until the end of pregnancy, also known as term, or 40 weeks. It is also given after birth if the baby is Rh-positive.
In some instances, such as when there is bleeding during pregnancy, trauma to the abdomen, amniocentesis (a type of test during pregnancy), or if the placenta gets detached prematurely, more baby’s cells can move into the mother’s circulation than usual, and the standard dose of RhoGAM might not be sufficient. In these cases, a special blood test can be performed to determine how many baby’s red blood cells are in the mother’s blood, and if necessary, additional doses of RhoGAM might need to be given.
To establish the severity of anemia (condition of having low red blood cells or hemoglobin) in the baby before birth when certain measurements are high, a procedure called cordocentesis and measurement of the baby’s hemoglobin (a protein in red blood cells that carries oxygen) can be used. The results of these tests can help determine if a fetal blood transfusion is needed to treat severe anemia in the baby.
What else can Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn ) be?
Elevated levels of unconjugated bilirubin in the body can be caused by several factors. The most common is a condition known as physiologic jaundice, which often appears around the second or third day after birth. This represents a high presence of serum bilirubin of less than 12 mg/dL. It’s primarily found in newborn babies where 60% are full-term, and 80% are premature, due to their immature liver function. It usually disappears by the end of the infant’s first week of life.
There are quite a few risk factors, including the mother having diabetes, having a lot of red blood cells (polycythemia), the baby having a blood-filled swelling on the head due to labor (cephalohematoma), being born prematurely, being male, being of Asian descent, having Down syndrome, having a delayed bowel movement or having an Upper Gastrointestinal obstruction, having an underactive thyroid and having a sibling who has previously had physiologic jaundice.
If an infant has jaundice within the first 24 hours after birth, that’s not considered physiologic jaundice and should be examined further. In fact, during the first week of life, breastfeeding often intensifies physiologic jaundice because the lack of enough calories leads to a decrease in bilirubin reabsorption from the gut. To decrease the risk of high bilirubin levels, successful breastfeeding every 2 to 3 hours, monitoring the baby’s stool, and urine output ensures that the baby is feeding adequately.
Breast milk jaundice is another cause. It happens after the first week of life due to breast milk’s ability to block an enzyme called 2,3 UDP glucuronyltransferase, which has the job of processing bilirubin.
There are also genetic causes of high unconjugated bilirubin. Gilbert syndrome, for instance, develops later in life and is characterised by jaundice, usually after a mild illness, fasting, or physical stress. This is due to a defect in the UDP glucuronosyltransferase gene. Crigler-Najjar syndrome, on the other hand, is caused by an absence or decrease in a portion or all of this enzyme.
Lastly, a spike in bilirubin production, similar to Rh/ABO incompatibility, can also cause high unconjugated bilirubin levels. Other reasons can include an enzyme defect, a structural cell defect, birth trauma, and having too many red blood cells in the bloodstream (polycythemia).
The medical examination for high unconjugated bilirubin levels would include various tests such as a complete blood count, reticulocyte count, blood smear, serum haptoglobin, direct and indirect coombs test, testing the variation in the structure of haemoglobin, and a spherocytosis test.
What to expect with Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
The outlook for people suffering from this disease has greatly improved over the past few years. This is because of the development of advanced tools and non-invasive treatments. These tools can help with early detection and treatment, especially when used before birth.
Research that put together data from several studies showed encouraging survival rates for unborn babies undergoing blood transfusion treatment. It found out that the survival rate was 94% for babies without excess fluid in their body tissues and cavities and 74% for those with an abnormal accumulation of this fluid (a condition known as hydrops).
In another big study involving over 300,000 pregnancies, newborns at risk of Hemolytic Disease of the Fetus and Newborn (HDFN) due to certain immune antibodies were prone to suffer from jaundice (yellowish or greenish pigmentation of the skin and whites of the eyes due to high bilirubin levels) more often than those not at risk (25% versus 10%). These at-risk newborns were also more likely to require phototherapy (a common treatment for jaundice using light) (17% versus 5%).
Possible Complications When Diagnosed with Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
Anemia can result in severe heart conditions due to the heart’s struggle to meet the body’s oxygen needs. When the heart muscle can’t function properly, an increase in liquid pressure causes fluid build-up in the body. This can happen in different parts of the body, including the body cavity (ascites), lungs (pleural effusion) or under the skin (subcutaneous edema). This condition is known as hydrops fetalis.
A substance called unconjugated bilirubin, found in the blood, can pass into the brain and cause a condition known as kernicterus. It becomes a risk when its levels get high—above 20 or keep increasing even after phototherapy. It can manifest with symptoms like lethargy, poor feeding, and even respiratory distress, and decreased deep-tendon reflexes. It can be mistaken for several other conditions such as infection, oxygen deprivation, low blood sugar, or bleeding in the brain. Certain factors can increase this risk, such as a blood condition called acidosis, infection, low albumin levels that impact the transport of the bilirubin to the liver, and some drugs like ceftriaxone that affects bilirubin transport. Using light therapy or phototherapy on infants with high bilirubin levels is a common preventive measure against kernicterus.
Common Issues:
- Heart conditions due to anemia
- Fluid build-up in body due to increased liquid pressure
- Condition known as kernicterus due to high levels of unconjugated bilirubin
- Manifestation of kernicterus symptoms
- Increased risk of kernicterus due to certain conditions and drugs
- Preventive measure like phototherapy for infants with elevated bilirubin levels
Preventing Erythroblastosis Fetalis (Hemolytic Disease of the Fetus and Newborn )
The outlook for this disease has gotten much better thanks to a team-based effort in diagnosing and treating it. This team, made up of nurses and doctors, now have the resources and noninvasive tests at their disposal. These tests, done before birth, help with early detection and treatment, which greatly improve patient care.
