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What is Rh factor?

The Rhesus (Rh) factor is a protein on the surface of red blood cells

If you are pregnant or considering becoming pregnant, you may have heard of the Rh factor. You probably want to know if it’s something you need to be concerned about, and you may be confused about what it actually is. This is common—it’s a bit of a confusing concept!

Here, we’ll go through the ins and outs of Rh factor, including what it is, what causes it, who is at risk for complications, and what treatment options are available. 

What is Rh factor?

Simply put, the Rhesus factor, or Rh factor, refers to a protein that’s located on the surface of red blood cells. Some people are positive for this protein, while others are negative. During pregnancy, if a pregnant person is Rh negative, but their fetus is Rh positive, complications can occur. Thankfully, though, this kind of blood type incompatibility is rare, it’s usually caught early, and treatment is effective.

When you think of blood types, you usually think of the different letter types that identify the absence or presence of A or B antigens (Type O, Type A, and Type B, etc.). The Rh factor is another component that determines if your blood type is positive or negative. When you have this protein, you are considered positive. If you don’t have this protein, you are negative. For example, if you are Type A positive, that means that you have A antigen blood and that your blood cells are positive for the Rh factor. If you are Type A negative, that means that your blood doesn’t contain the Rh factor. The antigen type and Rh factor both determine if your blood is compatible with another person’s blood—either as a blood transfusion recipient or during pregnancy.

Rh factor isn’t something to worry about in pregnancy unless a pregnant woman is Rh negative and her fetus is Rh positive. When this happens, Rh incompatibility between the fetus and the pregnant person can develop (also known as Rh alloimmunization), which can cause hemolytic disease of the neonate (HDN), a serious, but treatable complication.

What causes Rh incompatibility? 

If you have a negative blood type and you are exposed to Rh positive blood, via pregnancy or blood transfusion, you begin to produce antibodies against the Rh positive blood. Although blood doesn’t typically mix between the expectant mother and the fetus during pregnancy, Rh antibodies can cross the placenta. Additionally, blood mixing may occur during medical procedures like amniocentesis, chorionic villus sampling, or during labor and delivery. If your Rh-negative blood is exposed to your fetus’s Rh-positive blood, a phenomenon called alloimmunization occurs, where you begin to produce anti-Rh antibodies.

 When this happens, your antibodies may become harmful to your fetus. “The antibodies from the immune response of the patient can pass to the fetus and destroy the red blood cells [of the fetus], leading to fetal anemia,” explains Fouad Atallah, MD, a board-certified physician in obstetrics and maternal-fetal medicine subspecialist at Staten Island University Hospital in New York.

This response may be weak at the beginning of pregnancy or during a first pregnancy. “Fetal anemia may not occur until later in pregnancy or in the subsequent pregnancy,” Dr. Atallah explains.

According to the American College of Obstetricians and Gynecologists (ACOG), it is not usually until a second pregnancy (or a pregnancy that has occurred after a miscarriage) that Rh incompatibility becomes a concerning issue. This is because maternal antibody numbers are much higher during second, third, and subsequent pregnancies, increasing the risk to the fetus. The incompatibility may cause early pregnancy complications like miscarriage or ectopic pregnancy.

Who is at risk for Rh incompatibility?

“In an Rh alloimmunized pregnant individual [a pregnant person who is already Rh sensitized], it is the fetus and/or newborn and not the pregnant person who is at risk for hemolytic disease,” says Alex Juusela, MD, MPH, a board-certified OB-GYN at Wayne State University. Even then, the severity of the disease is variable. “It can range from mild breakdown of red blood cells (hemolysis) to severe fetal/neonatal anemia requiring blood transfusion(s) and even medically indicated preterm delivery,” says Dr. Juusela.

Again, it’s important to keep in mind that Rh factor only becomes an issue if the pregnant individual is Rh negative and their gestating fetus is Rh positive. Rh factor is an inherited trait and can only be passed on if one of the parents is Rh positive. So, if both parents are Rh negative, there is no chance that they will have a Rh positive baby. The main concern is if you are a pregnant person who is Rh negative, your partner is Rh positive, and you have an Rh-positive fetus.

Here is a chart to clarify Rh factor inheritance and in what circumstances it may become an issue.

Risk for Rh incompatibility
Pregnant parent Second parent Fetus’s Rh factor Risk level
Rh positive Rh positive Rh positive Low
Rh negative Rh negative Rh negative Low
Rh positive Rh negative Could be either Rh positive or Rh negative Low, because pregnant parent is also positive
Rh negative Rh positive Could be either Rh positive or Rh negative High risk if fetus is Rh negative

What is the Rh factor test? 

Here’s the good news: Rh factor is something that your healthcare provider will monitor for during pregnancy with routine prenatal tests. Any issues with Rh factor are usually caught early, which increases the likelihood of successful treatment.

Typically, there are two screening tests that are performed to determine your risk of Rh incompatibility. The first is a simple blood test to determine if the mother’s blood is Rh negative. If they are a Rh negative mother, then another test will be performed to find out if they have already formed antibodies against Rh factor.

“Rh incompatibility during pregnancy is typically diagnosed through a blood test (antibody screen),” says Matthew J. Blitz, MD, director of clinical research, maternal-fetal medicine at Northwell Health. “The test checks for the presence of Rh antibodies in the pregnant person’s blood, which indicates that they have been sensitized to the Rh factor and are at risk for Rh incompatibility.” This test is usually performed during your first prenatal visit in the first trimester and then again around 28 weeks.

And what happens if antibodies are found? “If Rh antibodies are detected, additional testing may be done to determine the severity of the Rh incompatibility and the potential risk to the fetus,” Dr. Blitz explains. This may include measuring the levels of antibodies in the pregnant person’s blood and performing tests like ultrasounds to monitor the fetus for signs of anemia.

Rh incompatibility treatment

Rh incompatibility treatment varies depending on where you are in your pregnancy and what your antibody levels are. “If Rh incompatibility is detected early in pregnancy and the pregnant parent has not yet produced significant levels of Rh antibodies, treatment may involve administering a medication called Rh immune globulin (RhoGAM or RhIg),” says Dr. Blitz. “RhoGAM is a blood product that can prevent the expectant parents’ immune system from producing antibodies against the Rh factor in the fetus’s blood.” Rh immunoglobulin shots are typically administered at 28 weeks of pregnancy to an Rh-negative parent, and then again within 72 hours after delivery to an Rh-positive infant.  

Treatment is different if Rh incompatibility is detected later in pregnancy or if the pregnant person has already produced high levels of Rh antibodies. In this case, treatment will involve closely monitoring the fetus for signs of anemia and other complications, such as jaundice or anemia. “Treatment may include phototherapy (light therapy) or blood transfusions,” Dr. Blitz says. 

Complications associated with Rh incompatibility

Thankfully, the risks of complications from Rh incompatibility are greatly reduced with preventive RhoGAM treatment. But if Rh incapability isn’t treated or if treatment isn’t successful, serious complications and health problems can result in newborns. “Rh alloimmunization is the leading cause of hemolytic disease of the fetus/newborn,” explains Dr. Juusela. “This is a condition characterized by fetal anemia of varying degrees and can range from mild anemia to severe anemia with elevated bilirubin levels, hydrops, heart failure, growth restriction, and fetal death.” 

Again, preventing complications in the first place is the goal and is widely successful, reminds Dr. Atallah. But if the treatment fails, there are ways that the fetus can be treated to prevent the most serious complications. “The treatment, in that case, would be to transfuse the fetus in cases of severe anemia,” he says. “Often, multiple transfusions are required.” Most of these fetuses will survive, unless they develop hydrops (fluid build-up in their body) or anemia in early pregnancy, which reduces survival rate, according to Dr. Atallah.

If your pregnancy is impacted by Rh factor, you can be assured that you’ll be carefully monitored. “Given the potential for fetal anemia, the pregnancy should be considered high-risk and be monitored closely,” Dr. Atallah says. Newborns of untreated or treatment resistant Rh-incompatible pregnancies are very closely monitored for signs of jaundice or anemia.

Luckily, it’s rare for infants to develop complications from Rh incompatibility because of the effectiveness of preventive treatments. In countries where treatment is given widely, the incidences of Rh incompatibility complications have been reduced to 2.5 per every 100,000 births. 

If you have any further questions about Rh factor, or if you are concerned that it might impact a current or future pregnancy, reach out to an OB-GYN or other medical professional.