Rh Sensitization During Pregnancy

Topic Overview

What is Rh sensitization during pregnancy?

If you are Rh-negative, your red blood cells do not have a marker called Rh factor on them. Rh-positive blood does have this marker. If your blood mixes with Rh-positive blood, your immune system will react to the Rh factor by making antibodies to destroy it. This immune system response is called Rh sensitization.

What causes Rh sensitization during pregnancy?

Rh sensitization can occur during pregnancy if you are Rh-negative and pregnant with an unborn baby (fetus) who has Rh-positive blood. In most cases, your blood will not mix with your baby's blood until delivery. It takes a while to make antibodies that can affect the baby, so during your first pregnancy, the baby probably would not be affected.

But if you get pregnant again with an Rh-positive baby, the antibodies already in your blood could attack the baby's red blood cells. This can cause the baby to have anemia, jaundice, or more serious problems. This is called Rh disease. The problems will tend to get worse with each Rh-positive pregnancy you have.

During your first pregnancy, your baby could be at risk for Rh disease if you were sensitized before or during pregnancy. This can happen if:

• You had a previous miscarriage, abortion, or ectopic pregnancy and you did not receive Rh immune globulin to prevent sensitization.
• You had a serious injury to your belly during pregnancy.
• You had a medical test such as an amniocentesis or chorionic villus sampling while you were pregnant, and you did not receive Rh immune globulin. These tests could let your blood and your baby's blood mix.

Rh sensitization is one reason it's important to see your doctor in the first trimester of pregnancy. It doesn't cause any warning symptoms, and a blood test is the only way to know you have it or are at risk for it.

• If you are at risk, Rh sensitization can almost always be prevented.
• If you are already sensitized, treatment can help protect your baby.

Who gets Rh sensitization during pregnancy?

Rh sensitization during pregnancy can only happen if a woman has Rh-negative blood and only if her unborn baby has Rh-positive blood.

• If the mother is Rh-negative and the father is Rh-positive, there is a good chance the baby will have Rh-positive blood. Rh sensitization can occur.
• If both parents have Rh-negative blood, the baby will have Rh-negative blood. Since the mother's blood and the baby's blood match, sensitization will not occur.

If you have Rh-negative blood, your doctor will probably treat you as though the baby's blood is Rh-positive no matter what the father's blood type is, just to be on the safe side.

How is Rh sensitization diagnosed?

All pregnant women get a blood test at their first prenatal visit during early pregnancy. This test will show if you have Rh-negative blood and if you are Rh-sensitized.

If you have Rh-negative blood but are not sensitized:

• The blood test may be repeated between 24 and 28 weeks of pregnancy. If the test still shows that you are not sensitized, you probably will not need another antibody test until delivery. (You might need to have the test again if you have an amniocentesis, if your pregnancy goes beyond 40 weeks, or if you have a problem such as placenta abruptio, which could cause bleeding in the uterus.)
• Your baby will have a blood test at birth. If the newborn has Rh-positive blood, you will have an antibody test to see if you were sensitized during late pregnancy or childbirth.

If you are Rh-sensitized, your doctor will watch your pregnancy carefully. You may have:

• Regular blood tests, to check the level of antibodies in your blood.
• Doppler ultrasound, to check blood flow to the baby's brain. This can show anemia and how severe it is.
• Amniocentesis after 15 weeks, to check the baby's blood type and Rh factor and to look for problems.

How is Rh sensitization prevented?

If you have Rh-negative blood but are not Rh-sensitized, your doctor will give you one or more shots of Rh immune globulin (such as RhoGAM). This prevents Rh sensitization in about 99 women out of 100 who use it.¹

You may get a shot of Rh immune globulin:

• If you have a test such as an amniocentesis.
• Around week 28 of your pregnancy.
• After delivery if your newborn is Rh-positive.

The shots only work for a short time, so you will need to repeat this treatment each time you get pregnant. (To prevent sensitization in future pregnancies, Rh immune globulin is also given when an Rh-negative woman has a miscarriage, abortion, or ectopic pregnancy.)

The shots won't work if you are already Rh-sensitized.

How is it treated?

If you are Rh-sensitized, you will have regular testing to see how your unborn baby is doing. You may also need to see a doctor who specializes in high-risk pregnancies (a perinatologist).

Treatment of the baby is based on how severe the loss of red blood cells (anemia) is.

• If the baby's anemia is mild, you will just have more testing than usual while you are pregnant. The baby may not need any special treatment after birth.
• If anemia is getting worse, it may be safest to deliver the baby early. After delivery, some babies need a blood transfusion or treatment for jaundice.
• For severe anemia, a baby can have a blood transfusion while still in the uterus. This can help keep the baby healthy until he or she is mature enough to be delivered. You will most likely have an early C-section, and the baby may need to have another blood transfusion right after birth.

In the past, Rh sensitization was often deadly for the baby. But improved testing and treatment mean that now most babies with Rh disease survive and do well after birth.

Frequently Asked Questions

Cause

Rh sensitization can occur when a person with Rh-negative blood is exposed to Rh-positive blood. About 90% of women who become sensitized do so during childbirth, when their blood mixes with the Rh-positive blood of their fetus.¹ Once exposed, a mother's immune system produces antibodies against Rh-positive red blood cells. For more information about events and procedures that can put you at high risk for Rh sensitization, see the What Increases Your Risk section of this topic.

The minimum amount of blood mixing necessary to cause sensitization is not known. However, many women become sensitized during pregnancy or childbirth after being exposed to as little as 0.1 mL of Rh-positive fetal blood.^{1, 2} Fortunately, Rh sensitization can almost always be prevented with the Rh immune globulin injection.

When an Rh-negative person's immune system is first exposed to Rh-positive blood, it takes several weeks to develop immunoglobulin M, or IgM, antibodies. IgM antibodies are too large to cross the placenta. Therefore, the Rh-positive fetus that first triggers maternal sensitization is usually not harmed.

A previously Rh-sensitized immune system rapidly reacts to Rh-positive blood, as during a second pregnancy with an Rh-positive fetus. Usually within hours of Rh-positive blood exposure, smaller immunoglobulin G, or IgG, antibodies are formed. IgG antibodies can cross the placenta and destroy fetal red blood cells. This causes Rh disease, which is dangerous for the fetus.

Some Rh-negative people never become sensitized, even after exposure to large amounts of Rh-positive blood. The reason for this is not known.

Symptoms

If you are already Rh-sensitized or become Rh-sensitized while pregnant, you will not have any unusual symptoms.

Fetal problems from Rh sensitization are detected with Doppler ultrasound testing and sometimes with amniocentesis. It is possible, however, that a fetus with severe Rh disease will move less frequently than it did earlier in the pregnancy.

Other conditions with symptoms similar to Rh sensitization include other blood type incompatibility problems and fetal infections.

What Happens

If you are Rh-negative

Unless you are given Rh immune globulin just before or after a high-risk event, such as miscarriage, amniocentesis, abortion, ectopic pregnancy, or childbirth, you have a chance of becoming sensitized to an Rh-positive fetus's blood.

If you have been Rh-sensitized in the past

If you have been Rh-sensitized in the past, you must be closely monitored during any pregnancy with an Rh-positive partner because your fetus is more likely to have Rh-positive blood. In response to an Rh-positive fetus, your immune system may quickly develop IgG antibodies, which can cross the placenta and destroy fetal red blood cells. Each subsequent pregnancy with an Rh-positive fetus may produce more serious problems for the fetus. The resulting fetal disease (called Rh disease, hemolytic disease of the newborn, or erythroblastosis fetalis) can be mild to severe.

• Mild Rh disease involves limited destruction of fetal red blood cells, possibly resulting in mild fetal anemia. The fetus can usually be carried to term and requires no special treatment but may have problems with jaundice after birth. Mild Rh disease is more likely to develop in the first pregnancy after sensitization has occurred.
• Moderate Rh disease involves the destruction of larger numbers of fetal red blood cells. The fetus may develop an enlarged liver and may become moderately anemic. The fetus may need to be delivered before term and may require a blood transfusion before (while in the uterus) or after birth. A newborn with moderate Rh disease is watched closely for jaundice.
• Severe Rh disease (fetal hydrops) involves widespread destruction of fetal red blood cells. The fetus develops severe anemia, liver and spleen enlargement, increased bilirubin levels, and fluid retention (edema). The fetus may need one or more blood transfusions before birth. A fetus with severe Rh disease who survives the pregnancy may need a blood exchange. This procedure replaces most of the infant's blood with donor blood (usually type O, Rh-negative).
• A history of pregnancy with Rh disease is a sign that you will need special treatment when you are pregnant with an Rh-positive fetus.

If you have been Rh-sensitized in the past, an Rh-negative fetus cannot trigger an immune reaction.

What Increases Your Risk

Rh sensitization can occur when a person with Rh-negative blood is exposed to Rh-positive blood. During pregnancy, an Rh-negative woman can become sensitized if she is carrying an Rh-positive fetus.

Factors that increase the risk of blood mixing and sensitization during pregnancy include:³

• Delivery.
• Abdominal trauma, such as from a car accident.
• Abdominal surgery, such as a cesarean section.
• Placenta abruptio or placenta previa, both of which can cause placental bleeding.
• External cephalic version for a breech fetus.
• Obstetric procedures such as amniocentesis, fetal blood sampling, or chorionic villus sampling (CVS).
• Miscarriage (spontaneous abortion), ectopic pregnancy, or elective abortion (medical or surgical abortion) after 8 weeks of fetal age (when fetal blood cell production begins).
• Partial molar pregnancy involving fetal growth beyond 8 weeks.

Although rare, Rh sensitization has been known to occur after needle sharing between intravenous drug users. Transfusing Rh-positive blood in an Rh-negative person can also trigger sensitization; however, this is extremely rare because blood is always tested prior to transfusion.

When To Call a Doctor

If you are already Rh-sensitized and are pregnant

Your pregnancy will be closely monitored. Discuss possible symptoms early in pregnancy with your health professional. Repeated diagnostic testing will be necessary to monitor the fetus.

Call your health professional immediately if you note a decrease in your fetus's movement after 24 to 26 weeks of pregnancy.

If you are Rh-negative

Call your health professional immediately if you:

• Think you may have been pregnant and miscarried.
• Are pregnant and have had an accident that may have injured your abdomen.

Regular prenatal visits are essential. You will need an Rh immune globulin shot at 24 to 28 weeks and again after delivery if your baby has Rh-positive blood. This is the only way you can prevent Rh sensitization.

Watchful Waiting

Watchful waiting is not appropriate for Rh sensitization. It is important to keep all prenatal appointments so that your developing fetus can be closely monitored throughout your pregnancy.

Who To See

A woman who may have problems with Rh incompatibility or sensitization can be treated by:

• A family medicine doctor, for mild fetal Rh disease.
• An obstetrician, for mild to moderate Rh disease.
• A perinatologist, for moderate to severe fetal Rh disease (hydrops).

If you test positive for Rh sensitization, your health care system or health professional may want you to be followed and treated by a perinatologist or an obstetrician who can easily call in a perinatologist.

To prepare for your appointment, see the topic Making the Most of Your Appointment.

Exams and Tests

If you are pregnant, you will have your first prenatal tests during your first trimester. At your first prenatal visit, every woman has her blood tested to see what her blood type is. If your blood is Rh-negative, it will also be tested for antibodies to Rh-positive blood. If you have antibodies, that means that you have been sensitized to Rh-positive blood. The antibodies can now kill Rh-positive red blood cells.

If you are Rh-negative and your partner is Rh-positive, your fetus is likely to be Rh-positive.

If you are pregnant or have miscarried, or if you have had an elective abortion, a partial molar pregnancy, or an ectopic pregnancy, you will need testing to see if you have been sensitized to Rh-positive blood.

If you are Rh-negative

All pregnant women have an indirect Coombs' test during early pregnancy.

• At the first prenatal visit, your blood is tested to see if you have been previously sensitized to Rh-positive blood. If you are Rh-negative and test results show that you are not sensitized, a repeat test may be done between 24 and 28 weeks.
• If test results at 28 weeks show that you have not been sensitized, no additional tests for Rh-related problems are done until delivery (barring complications such as placenta abruptio). You will also have a shot of Rh immune globulin. This lowers your chances of being sensitized during the last weeks of your pregnancy.
• If your newborn is found to be Rh-positive, your blood will be screened again at delivery with an indirect Coombs' test to see if you have been sensitized during late pregnancy or childbirth. If you have not been sensitized, you will have another shot of Rh immune globulin.

If you are sensitized to the Rh factor

If you are already Rh-sensitized or become sensitized while pregnant, close monitoring is important to determine whether your fetus is being harmed.

• An indirect Coombs' test is done periodically during your pregnancy to see if your Rh-positive antibody levels are increasing. This is the typical course of treatment for most sensitized women during pregnancy.
• Fetal Doppler ultrasound of blood flow in the brain shows fetal anemia and how bad it is. At a medical center with Doppler experts, this test can give you the same anemia information as amniocentesis, without the risks.⁴
• Amniocentesis may be done:
  • At or after 15 weeks to check amniotic fluid for signs of fetal problems.
  • To learn the fetal blood type and Rh factor.
  • On a repeated basis to check fetal anemia. This tells how much a fetus is being affected by sensitization.
• Fetal blood sampling (cordocentesis) may be done to directly assess your fetus's health. This procedure is used on a limited basis, usually for monitoring known sensitization problems (as when a mother has had previous fetal deaths, or when other testing has shown signs of fetal distress).
• Electronic fetal heart monitoring (nonstress test) may be done in the third trimester to check your fetus's condition. Unusual fetal heart rhythms detected during a nonstress test may be a sign that the fetus has anemia related to the sensitization.
• Fetal ultrasound testing can be used as a pregnancy progresses to detect sensitization problems, such as fetal fluid retention (a sign of severe Rh disease).

Early Detection

Early prenatal Rh blood typing and testing for Rh sensitization is necessary to ensure that every vulnerable fetus can be properly monitored and treated.

Treatment Overview

If you are sensitized to the Rh factor

If your blood is Rh-negative and you have been sensitized to Rh-positive blood, you now have antibodies to Rh-positive blood. The antibodies kill Rh-positive red blood cells. If you become pregnant with an Rh-positive baby (fetus), the antibodies can destroy your fetus's red blood cells. This can cause anemia.

If you are already Rh-sensitized and are pregnant, your treatment will focus on preventing or minimizing fetal harm and on avoiding early (preterm) delivery.

Treatment options depend on how well or poorly the fetus is doing.

• If possible, the father will be tested to see if the fetus could be Rh-positive. If the father is Rh-negative, the fetus is Rh-negative and is not in danger. If the father is Rh-positive, amniocentesis will probably be used to learn the fetus's blood type. In some medical centers, the mother's blood can be tested to learn her fetus's blood type. This is a new test that is not widely available.
• If testing shows that your fetus Rh-positive but is only mildly affected by your Rh factor antibodies, you will be closely monitored until your pregnancy reaches term. Your fetus will be delivered early only if his or her condition worsens.
• If testing shows that your fetus is moderately affected by your Rh antibodies, your fetus's condition will be closely monitored until his or her lungs are mature enough for a preterm delivery. A cesarean section may be used to deliver the baby quickly or to avoid the difficulty of inducing labor before term. A moderately affected newborn sometimes requires a blood transfusion immediately after birth.
• If testing shows that your fetus is severely affected by your Rh factor antibodies, a blood transfusion may be given before birth (intrauterine fetal blood transfusion). This can be done through the fetus's abdomen or directly into the fetus's umbilical cord. A preterm delivery is likely to be needed. Multiple blood transfusions are sometimes necessary to keep a fetus healthy until the fetal lungs mature enough to function after birth. Often a cesarean section is done to deliver the baby quickly. A blood transfusion is sometimes necessary immediately after birth.

Prevention

If you are Rh-negative and pregnant

If you are an Rh-negative woman and you have conceived with an Rh-negative partner, you are not at risk of Rh sensitization during pregnancy. (Most health professionals treat all Rh-negative pregnant women as though the father might be Rh-positive.)

If you are already sensitized to the Rh factor, your pregnancy will need to be closely monitored to prevent fetal harm. For more information on fetal and newborn treatment, see the Treatment Overview section of this topic.

If you are unsensitized Rh-negative, treatment focuses on preventing Rh sensitization during pregnancy and childbirth. Rh immune globulin (such as RhoGAM) is a highly effective treatment for preventing sensitization.

• To prevent sensitization from occurring late in the pregnancy or during delivery, you must have a shot of Rh immune globulin around week 28 of your pregnancy. This treatment prevents your immune system from making antibodies against your fetus's Rh-positive red blood cells.
• Rh immune globulin injection is also necessary if you have had any vaginal bleeding or an obstetric procedure such as amniocentesis or external cephalic version.
• If your newborn is Rh-positive, you are given Rh immune globulin again within 72 hours of delivery. By preventing Rh sensitization from delivery, you are protecting your next Rh-positive fetus.
• If your newborn is Rh-negative, sensitization cannot happen, and no treatment is necessary.

Rh immune globulin is also necessary after a miscarriage, partial molar pregnancy, ectopic pregnancy, or abortion.

Home Treatment

There is no home treatment for Rh sensitization.

Medications

Use of Rh immune globulin is 99.8% effective in preventing Rh sensitization.¹ Rh immune globulin contains Rh antibodies that have been purified from human donors. This treatment prevents an unsensitized Rh-negative mother from making antibodies against her fetus's Rh-positive blood.

If an affected fetus younger than 34 weeks needs to be delivered, corticosteroid medication (betamethasone or dexamethasone) may be given to the mother to speed fetal lung development before a premature birth.

Surgery

There is no surgical treatment for Rh sensitization during pregnancy.

Other Treatment

An intrauterine fetal blood transfusion is sometimes used to supply healthy blood to a fetus with severe hemolytic disease of the newborn (also called Rh disease or erythroblastosis fetalis).

A newborn blood transfusion or exchange transfusion is sometimes given to treat severe anemia or jaundice related to Rh disease.

Other Places To Get Help

Organization

Related Information

• Ectopic Pregnancy
• Iron Deficiency Anemia
• Jaundice in Newborns (Hyperbilirubinemia)
• Miscarriage
• Molar Pregnancy
• Premature Infant

References

Citations

1. American College of Obstetricians and Gynecologists (1999). Prevention of Rh D alloimmunization. ACOG Practice Bulletin No. 4. Obstetrics and Gynecology, 93(5): 1-7.

2. Hartwell EA (1998). Use of Rh immune globulin: ASCP practice parameter. American Journal of Clinical Pathology, 110(3): 281-292.

3. Porter TF, et al. (2003). Immunologic disorders in pregnancy. In JR Scott et al., eds., Danforth's Obstetrics and Gynecology, 9th ed., pp. 313-338. Philadelphia: Lippincott Williams and Wilkins.

4. American College of Obstetricians and Gynecologists (2006). Management of alloimunization during pregnancy. ACOG Practice Bulletin No. 75. Obstetrics and Gynecology, 108(20): 457-464.

Other Works Consulted

• Moise KJ Jr (2003). Management of rhesus alloimmunization in pregnancy. Obstetrics and Gynecology, 100(3): 600-611.

• Roman AS, Pernoll ML (2007). Rh isoimmunization and other blood group incompatibilities section of Late pregnancy complications. In AH DeCherney et al., eds., Current Diagnosis and Treatment Obstetrics and Gynecology, pp. 282-287. New York: McGraw-Hill.

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