Rh Sensitization During Pregnancy

What is Rh sensitization during pregnancy?

If your blood is Rh-negative and your unborn baby’s blood is Rh-positive, your body’s natural defense system can make your unborn baby (fetus) sick. This happens because your body makes a substance that can destroy the baby’s red blood cells. This reaction is called Rh sensitization.

Rh sensitization can only happen to women with Rh-negative blood. You cannot become Rh-sensitized if your blood is Rh-positive.

This condition does not happen often and can almost always be prevented. It is one reason why you need to see your doctor regularly when you are pregnant.

What causes Rh sensitization during pregnancy?

Rh sensitization happens when the mother’s Rh-negative blood mixes with the baby’s Rh-positive blood. For most women, this happens during childbirth. It may also happen during a miscarriage or abortion, or in women who share needles to take illegal drugs.

If you are pregnant and have Rh-negative blood, and the father of the baby has Rh-positive blood, your fetus could have Rh-positive blood.

If both you and the baby’s father have Rh-negative blood, your baby will be Rh-negative. In this case, there is no chance of Rh sensitization.

Does Rh sensitization in the mother harm the fetus?

Rh sensitization usually does not hurt your unborn baby (fetus) the first time you are pregnant. But in your next pregnancy, it can make your fetus sick. The fetus can develop anemia, also known as hemolytic disease of the fetus and newborn. If untreated, sensitization can cause severe swelling of the fetus's body (hydrops fetalis). In rare cases, the fetus may die.

What are the symptoms of Rh sensitization?

You will not have any unusual symptoms when you are Rh sensitive, so your doctor will closely watch your pregnancy. Regular blood tests can help your doctor watch the health and growth of your fetus.

As the pregnancy progresses, a fetus with severe Rh disease may move less often than before.

How is Rh sensitization diagnosed?

A simple blood test can check for Rh incompatibility. This is usually done at the first visit early in your pregnancy, before the 12th week.

If this test shows that your blood is Rh-negative, your doctor will know to watch your pregnancy carefully. You will also have a blood test to see if you are already Rh-sensitized.

If the test shows that you are not Rh-sensitized, you may have another test between your 24th and 28th weeks of pregnancy. If that test also shows that you are not sensitized, you will not have more Rh tests until delivery unless you get another problem, such as placenta abruptio.

If your newborn is Rh-positive, you will have more blood tests to find out if you were sensitized in late pregnancy or childbirth.

If your first blood test shows that you are Rh-sensitized (or if you become sensitized during this pregnancy), your doctor will watch closely to see if your fetus is being harmed. This will include regular blood tests and other tests.

How is Rh sensitization treated?

A shot of medicine called immune globulin can greatly lower your chances of Rh sensitization. You must get the shot around week 28 of your pregnancy to prevent sensitization late in your pregnancy or during delivery. If your baby is Rh-positive at birth, you will have another shot of Rh immune globulin after delivery.

For pregnant women who are already Rh-sensitized from a past pregnancy, Rh immune globulin cannot help. Instead, the goal of treatment is to prevent or reduce harm to the fetus and prevent early (preterm) delivery. Treatment choices depend on how badly your fetus may be harmed by the Rh sensitization.

Frequently Asked Questions

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.

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

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 diagnostic testing. It is possible, however, that a fetus with severe Rh disease will move less frequently than before.

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

If you are Rh-negative

Unless you are given Rh immune globulin prior to or just after a high-risk event, such as miscarriage, amniocentesis, 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 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). One or more blood transfusions may be necessary 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 severe 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.

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

• 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) or elective abortion (medical 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.

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. Repeated diagnostic testing will be necessary to monitor for Rh antibodies in your blood.

Watchful Waiting

Watchful waiting is not appropriate when Rh sensitization has occurred. 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 certified nurse-midwife under physician supervision, for mild fetal Rh disease.
• 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.

Initial tests for determining Rh incompatibility are done by testing your blood, usually at the first prenatal visit in the first trimester. If you are Rh-negative and your partner is Rh-positive, your fetus is likely to be Rh-positive.

The following tests are also used when a woman has miscarried or has had a medical abortion, a partial molar pregnancy, or an ectopic pregnancy.

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 determine whether 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 sensitization has not occurred, no additional tests for Rh-related problems are done until delivery (barring complications such as placenta abruptio).
• If your newborn is found to be Rh-positive, your blood will be screened again at delivery with an indirect Coombs' test to determine whether you have been sensitized during late pregnancy or childbirth.

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 determine whether your Rh-positive antibody levels are increasing. This is the typical course of treatment for the majority of sensitized women during pregnancy.
• Fetal Doppler ultrasound of blood flow in the brain shows fetal anemia and how bad it is. This test can give you the same information as amniocentesis, without the risks.⁴
• Amniocentesis may be done:
  • At or after 15 weeks to examine amniotic fluid for substances that indicate 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 other testing has indicated 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.

If you are Rh-negative

If you are unsensitized Rh-negative and your partner is Rh-positive, 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 be injected with Rh immune globulin around week 28 of your pregnancy. This treatment prevents your immune system from producing 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.

If you are sensitized to the Rh factor

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

Treatment options depend on the severity of fetal harm.

• If testing shows that your fetus 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. Multiple blood transfusions are sometimes necessary to keep a fetus healthy until the fetal lungs mature enough to function after birth. Frequently, a cesarean section is done to deliver the baby quickly. A blood transfusion is sometimes necessary immediately after birth.

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.

If you are Rh-negative and your partner is Rh-positive, Rh sensitization is almost entirely preventable with Rh immune globulin injection. This will protect future pregnancies from Rh problems.

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.

There is no home treatment for Rh sensitization. However, you can take measures that ensure the healthiest pregnancy possible.

• Keep a regular prenatal exam schedule.
• Follow guidelines for a healthy pregnancy.

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.

There is no surgical treatment for Rh sensitization during pregnancy.

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.

Organization

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

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

• Jackson M, Branch DW (2002). Alloimmunization in pregnancy. In SG Gabbe et al., eds., Obstetrics: Normal and Problem Pregnancies, 4th ed., pp. 893–929. New York: Churchill Livingstone.

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

Author:	Kathe Gallagher, MSW	Last Updated November 10, 2005
Medical Review:	Patrice Burgess, MD - Family Medicine Gregory A L Davies, MD, FRCSC, FACOG - Maternal-Fetal Medicine Kirtly Jones, MD - Obstetrics and Gynecology
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