Rh Incompatibility in Newborns

Rh incompatibility is one of the blood type incompatibilities that can cause severe hemolysis in a fetus and newborn baby, resulting in severe anemia and jaundice. Fortunately, it is less common nowadays because we have a preventive treatment that we offer to women, whenever they are at risk of getting sensitized with Rh factor.

Rh blood incompatibility describes a situation in which the mother is Rh-negative (does not have Rh factor), and the baby is Rh-positive (has Rh factor = D-antigen on its red cells). Additionally, it may exist when the mother develops antibodies against other antigens of the Rh blood type system that she does not possess. 

In this article, I will focus on Rh incompatibility, its definition, physiology, clinical significance for babies, and available treatments. ABO incompatibility can cause hemolysis, anemia, and jaundice in a similar fashion. Therefore, I dedicated another post on the topic of ABO incompatibility. 

Rh blood type explained

All cells in our body, including red blood cells, have protein markers on their walls called antigens. An antigen is like a name. It serves the purpose of differentiating between our cells and foreign cells or foreign objects such as microbes. Once our body recognizes cells as foreign to us, it will try to fight them off using antibodies. The antibodies are also proteins; they will attach to antigens on foreign cells or microbes and cause their destruction. In the case of red cells, such destruction or breakage of cells is called hemolysis. 

Rh system relies on numerous antigens, but the most important are D, C, E, c, and e. The presence of antigen D determines if an individual is Rh-positive or Rh-negative. Antigen-D is the strongest of them all, and even as a small amount of blood as 0.1 ml can sensitize the mother against it. 

Definitions and statistics regarding Rh incompatibility

Rh incompatibility

Rh incompatibility will occur when the mother is Rh-negative, and the baby is Rh-positive. It will also exist when the baby has Rh blood group antigens that the mother does not. In the latter situation, the mother may also develop antibodies against the baby’s red blood cells. 

Hemolysis due to Rh incompatibility:

For the hemolytic disease due to Rh incompatibility to occur, the mother has to be exposed to the unknown to her antigen within the Rh system (usually D-antigen). It may happen after poorly matched blood transfusion, abortion, miscarriage, previous pregnancy, and obstetric procedures such as amniocentesis or biopsies. 

If exposure and sensitization of the mother took place during non-obstetric events, her baby might get affected during the first pregnancy. Otherwise, Rh incompatibility usually affects the second or subsequent pregnancies. 

How common is Rh incompatibility?

Rh-positive blood type is a predominant variant among all populations. Rh-negative blood type occurs in 15% of Caucasian white people, 4%-8% of African -Americans, and only 0.3% of Asians. The estimated worldwide incidence of Rh disease is 276 cases per 100 000 births. The prevalence of this disease in countries with advanced health care (USA included) is only 2.5 cases per 100 000 live births (Source).

What happens in Rh incompatibility? 

• If a mother who does not have specific antigens within the Rh system gets exposed to them, she will get sensitized – meaning she will develop antibodies against those antigens
• Maternal antibodies will cross the placenta and reach the baby’s circulation
• Maternal antibodies will identify red cells in the baby’s circulation carrying specific antigens and will attach to those cells
• After attachment, maternal antibodies will cause destruction or lysis, also called “hemolysis.”
• Rapid hemolysis will lead to anemia and increased bilirubin load.
•  Increased bilirubin load will cause visible jaundice and may result in severe hyperbilirubinemia endangering the baby’s brain. 
• If anemia is severe, it may lead to cardiac failure, generalized edema, and even death. Also, the baby may develop severe anemia even before birth.

Can Rh incompatibility be prevented?

The occurrence of Rh-induced hemolysis can be significantly diminished by the administration of RhD immunoglobulin to all Rh-negative women in situations where there was a chance of exposure and sensitization to Rh-positive red cells.

The Rh immunoglobulin for Rh-negative women should be considered after: 

• Mismatched blood transfusion with Rh-positive blood
• Pregnancy with an Rh-positive fetus or baby
• Miscarriage
• Amniocentesis
• Chorionic villus biopsy
• AbortioEctopic pregnancy
• Abdominal trauma during pregnancy
• Manual removal of the placenta

The goal for the Rh immunoglobulin is to destroy all foreign red cells in circulation before the mother’s immune system gets sensitized and starts producing its antibodies. The actual medication is called anti-D immunoglobulin G or RhoGAM.

Management of Rh incompatibility during the pregnancy

All pregnant women should have blood typing done early during pregnancy. Furthermore, if a woman is Rh-negative, the screening for antibodies needs to be done. For all positive screens with anti-D antibodies, titers should be requested. Surveillance of those titers during pregnancy allows us to have an idea if it is getting worse over time. 

In addition to maternal tests, the obstetrician will be conducting periodic ultrasound exams of the fetus. Evaluation of cerebral artery flows, cardiac function, and the presence or lack of edema will help us to assess if the fetus is affected by severe anemia or not. In cases where there is a doubt, sampling of the fetal blood from the umbilical vessels can be done and, if needed in utero transfusion can be performed. 

At birth, a baby may already have severe anemia, but rarely significant bilirubinemia above 5 mg/dl is present. During pregnancy, the maternal placenta is actively filtering out bilirubin from the baby’s body. However, in severe Rh-induced hemolysis, bilirubin will be rising very rapidly soon after birth. 

How do we evaluate babies with Rh incompatibility?

We will use numerous tests while evaluating Rh incompatibility:

• Mother’s blood type
• During pregnancy: maternal antibodies, ultrasounds, umbilical cord blood sampling
• Baby’s blood type
• DAT test – also known as Coombs test
• CBC – complete blood count
• Reticulocyte count
• Bilirubin levels

If the mother is Rh-negative, most hospitals will test the baby’s blood for blood type, DAT, and initial bilirubin levels.

DAT test (Coombs test), if positive, proves that maternal antibodies against the baby’s erythrocytes (red cells) got into the baby’s circulation, and they react with them, causing hemolysis. 

CBC – complete blood count gives us information on the number of different blood cells. We also get the Hemoglobin level. An abnormally low number of red cells or Hemoglobin are indicators of anemia in a baby. Even if a baby with Rh-induced hemolytic disease is not significantly anemic after birth, it can become severely anemic within few days, therefore frequently repeated CBCs are essential.

The reticulocyte count is an indicator of bone marrow activity. Reticulocytes are the new red blood cells that did not lose their nucleus yet, as it is common for mature red blood cells to do. The reticulocyte count is reported as a percentage of the total number of red blood cells. 

The higher the reticulocyte count, the baby has more rapid hemolysis. Normal reticulocyte count for newborns is below 5%, counts above 10% are considered very abnormal.

Doctors should order Bilirubin levels soon after the birth of the baby to Rh-negative mother. Bilirubin is an indicator of the severity of jaundice. High bilirubin levels or rapidly increasing bilirubin concentration may be dangerous for the baby’s brain and cause irreversible neurological damage. 

Treatment of newborns with Rh incompatibility

We have several treatments that we can use in a step-up fashion:

Treatment options for Rh incompatibility:

• Hydration and proper nutrition
• Phototherapy
• IV IgG infusion
• Fluid therapy and pressors
• Thoracentesis, Paracentesis, cardiocentesis
• Double volume exchange blood transfusion
• Supplementary blood transfusion

Hydration and nutrition are always crucial in the treatment of jaundice. Proper nutrition will make sure that the baby is regularly passing bowel movements, and that bilirubin is not being reabsorbed from the gut. 

In newborns, circulating bilirubin undergoes chemical changes in the liver and then is excreted into the intestines with bile. Some of the excreted bilirubin may get reabsorbed. Larger amounts of the bilirubin get reabsorbed if the food is not moving fast in a downward (caudal) direction. 

Phototherapy is always the first line of therapy for jaundice (hyperbilirubinemia). It uses a specific light wave spectrum to influence the transformation of bilirubin in the skin into a water-soluble compound that can be excreted from the body more easily. Read my whole article on phototherapy here and pay attention to the bilirubin levels at which it is indicated. Most babies tolerate phototherapy very well, and it is rare for them to have any adverse effects. You can also find the newest guidelines (from 09/2022) for starting phototherapy published in the American Academy of Pediatrics publication. 

IV IgG infusion – Intravenous IgG (Immunoglobulin G) can be given to a baby to interrupt the immune process that causes hemolysis. We think that immunoglobulin can block antigen sites on the baby’s red cells, thus decreasing the rate of hemolysis. As a result, anemia and hyperbilirubinemia will be progressing more slowly. 

Fluid therapy and pressors (medications to maintain blood pressure)

Babies who are born with severe anemia and low blood pressure will need therapy with intravenous fluids and medicines able to increase blood pressure. Usually, the best treatment will be supplementary blood transfusion, but until it can be arranged, fluid boluses and pressor medications will be essential. 

Thoracentesis, Paracentesis, Pericardiocentesis

Some babies who developed severe anemia before delivery are born with profound edema, including water being present around their lungs, heart, and inside their abdomen. Whenever a massive amount of water interferes with the vital functions of those organs, doctors have to place a needle to aspirate it out. 

• Thoracentesis – a needle is inserted into the pleural space between the chest wall and the lungs
• Paracentesis – a needle is inserted into a peritoneal cavity between the abdominal wall and organs residing in the abdomen
• Pericardiocentesis – a needle is inserted into the sack surrounding the heart. If there is blood or fluid in this sack, it can be aspirated and removed.

Double volume exchange blood transfusion – Whenever bilirubin reaches very high levels becoming dangerous to the baby’s brain, exchange transfusion may be indicated. The goal of double-volume exchange transfusion is to remove both bilirubin and maternal antibodies from the baby’s circulation. If the baby is anemic, we can also transfuse some extra blood at the same time to rectify that. 

We conduct exchange transfusion to prevent severe acute encephalopathy, chronic neurological abnormalities, and even death. You can read more about those complications of severe hyperbilirubinemia in my article on Jaundice. 

Supplementary blood transfusion – Some babies with Rh-incompatibility-induced hemolytic disorder are born with severe anemia, and some develop it within a few days. If anemia is severe and clinically significant, causing hemodynamic abnormalities (increase in the heart rate and low blood pressure), we may have to give a blood transfusion, usually PRBCs (Packed Red Blood Cells). Blood will have to be perfectly matched, so it does not have any antibodies against the baby’s erythrocytes.

The prognosis for babies with Rh incompatibility

The vast majority of babies with Rh-induced hemolysis treated in the USA and other developed countries do well. In rare cases, especially if the condition was not detected early enough or the treatment was delayed, some babies may develop neurological sequelae due to high bilirubin levels such as acute encephalopathy or chronic neurological damage (More on these complications in my article on jaundice).

Unfortunately, in developing countries where Rh-sensitization preventive measures (RhoGAM) and good perinatal care is not available, up to 50% of babies with severe Rh-incompatibility and hemolysis may end up having severe neurological complications. 

Other conditions causing anemia and jaundice due to hemolysis

Many other conditions may lead to increased hemolysis in newborn babies:

• ABO incompatibility (Read my article)
• Minor blood groups incompatibilities (Duffy, MNS, P, and other)
• Many enzymatic defects (for example G6PD)
• Wall defects of red cells causing a change in their shape (spherocytosis, elliptocytosis)
• Infection

Similarities and differences between Rh-incompatibility and ABO-incompatibility

If you are interested to know more about jaundice, I want to encourage you to read my extensive article on this topic here.

Disclaimer:

This article is only for general information purposes. It should not be viewed as any medical advice. There is a chance that the information here may be inaccurate. It would be best if you always discussed all health-related matters with your doctor before making any decisions that may affect your health or the health of your family members.