stillborn. In the newborn, Rh disease can result in jaundice (yellowing of the skin and eyes), anemia, brain damage, heart failure and death. It does not affect the mother's health.
Rh disease once affected at least 16,000 babies in the United States each year (1). Since 1968, however, there has been a treatment that usually can prevent Rh disease. The number of babies born with the disease has declined dramatically since then. But not all women who need the treatment get it, and a small number of women cannot benefit from it. As a result, there are still some 4,000 infants born each year with Rh disease (2).
What causes Rh disease?
Most people have Rh-positive blood. This means that their blood has the Rh factor, an inherited protein found on the surface of red blood cells. A minority of individuals lack the Rh factor and are considered Rh-negative. About 15 percent of the white population, 5 to 8 percent of the African-American and Hispanic populations, and 1 to 2 percent of the Asian and Native American populations are Rh-negative (3). The health of an Rh-negative person is not affected in any way. However, an Rh-negative woman is at risk of having a baby with Rh disease.
An Rh-negative mother and an Rh-positive father may conceive an Rh-positive baby. There is then a danger that, during pregnancy and especially during labor and delivery, some of the fetus's Rh-positive red blood cells may get into the mother's bloodstream. Since red blood cells containing the Rh factor are foreign to the mother's system, her body tries to fight them off by producing antibodies against them. This is called sensitization.
Once a woman becomes sensitized, her Rh antibodies can cross the placenta and destroy some of an Rh-positive fetus's red blood cells. This results in Rh disease in the baby. In a first pregnancy with an Rh-positive baby, there usually are no serious problems because the baby often is born before the mother is sensitized, or at least before the mother produces substantial Rh antibodies. Each later Rh-positive baby of a sensitized mother becomes at greater risk for more severe Rh disease because the woman will continue to produce antibodies as part of her blood throughout her life.
How can a woman find out if she is Rh-negative?
A simple blood test can tell if a woman is Rh-negative. Every woman should be tested at her first prenatal visit, or before pregnancy, to find out if she is Rh-negative. A blood test also can show if an Rh-negative woman has become sensitized.
How can Rh disease be prevented?
An unsensitized Rh-negative woman can be treated with injections (shots) of a purified blood product called Rh immune globulin (RhIg) to prevent sensitization. Her health care provider will most likely recommend that she receive an RhIg injection at 28 weeks of pregnancy, and another within 72 hours of delivery, if a blood test shows that her baby is Rh-positive. She will not need an injection after delivery if her baby is Rh-negative. Some health care providers also recommend an additional RhIg injection if a woman's pregnancy goes past her due date.
An Rh-negative woman also should be treated with RhIg after any situation in which the fetal red blood cells can mix with her blood. This includes after a miscarriage, an ectopic pregnancy, an induced abortion, or a blood transfusion with Rh-positive blood (4). Treatment also is recommended after certain prenatal tests, including amniocentesis and chorionic villus sampling (CVS).
Do all unsensitized Rh-negative women need treatment with RhIg?
An Rh-negative woman does not need treatment with RhIg if blood tests show that the baby's father is Rh-negative (4). If the father is Rh-negative, the baby also will be Rh-negative. An Rh-negative baby is not at risk of Rh disease.
How does RhIg work?
RhIg contains antibodies to the Rh factor. The antibodies attach to and may help mask any Rh-positive fetal cells in the mother's bloodstream. As a result, the mother's body does not recognize these Rh-positive fetal blood cells as foreign and does not produce antibodies against them.
Protection by RhIg lasts only about 12 weeks (4). An Rh-negative woman must be treated during each pregnancy.
Does RhIg treatment always work?
Proper treatment with RhIg can prevent sensitization in just about all unsensitized Rh-negative women (5). However, RhIg will not work for an Rh-negative woman who already is sensitized. The main reason Rh-negative women become sensitized is that they do not receive the treatment when they need it, such as after an unrecognized miscarriage.
Is there any way to get rid of a sensitized mother's antibodies?
No. Although a woman will have no symptoms and stay as healthy as ever, she can continue to produce antibodies as part of her blood. If she has any more Rh-positive babies, they could develop Rh disease.
What special treatment does a sensitized Rh-negative woman need during pregnancy?
The health care provider will probably recommend that the baby's father have a blood test to see whether he is Rh-positive or Rh-negative. If the father is Rh-negative, the baby is not at risk of Rh disease and the pregnant woman does not need any special tests or treatment.
If the father is Rh-positive (or if his Rh status is not known), the health care provider usually offers a sensitized pregnant woman a test called amniocentesis to determine whether the baby is Rh-positive or Rh-negative. Even if the father is Rh-positive, he may carry an Rh-negative gene, which the baby has a 50 percent chance of inheriting (so each fetus would have a 50/50 chance of being Rh-negative).
During amniocentesis, the doctor inserts a needle into a woman's abdomen to withdraw a small amount of amniotic fluid for testing. Amniocentesis poses a very small risk of miscarriage.
An experimental maternal blood test appears to be highly accurate in determining whether the fetus is Rh-positive or negative (3, 6). This blood test is not yet widely available in the United States, but it may soon reduce the need for amniocentesis.
If the fetus is Rh-positive (or fetal Rh status is unknown because the woman didn't have amniocentesis), the health care provider will measure the levels of antibodies in the mother's blood as pregnancy progresses. If she develops high levels of antibodies, the health care provider will recommended tests that can help determine if the baby is developing Rh disease.
Which tests are used to monitor the baby's health?
Some doctors use amniocentesis to determine if a fetus is developing anemia and how severe it may be. This test, which poses a small risk of miscarriage, must be repeated every 10 days to two weeks (7).
Some major medical centers have begun offering an examination with a special form of ultrasound, called Doppler ultrasound, to determine if the fetus is developing anemia. This test measures the speed of blood flowing through an artery in the fetus's head. A 2006 study reported that a Doppler ultrasound examination, which poses no risk to the fetus, is more accurate than amniocentesis in detecting anemia (8).
This test is starting to reduce the need for amniocentesis to monitor fetuses at risk of Rh disease. However, this test is not yet available everywhere and should be done only at medical centers where the health professionals have had adequate training and experience with the technique (3).
If amniocentesis or Doppler ultrasound shows that the fetus may be developing severe anemia, the doctor may recommend another test called cordocentesis. In this test, the doctor inserts a thin needle through the mother's abdomen, guided by ultrasound, into a tiny blood vessel in the umbilical cord to take a blood sample from the fetus. This test also poses a small risk of miscarriage.
How are fetuses and newborns with Rh disease treated?
If the fetus is near term and tests show that the baby is developing anemia, the health care provider may recommend inducing labor early, before the mother's antibodies destroy too many fetal blood cells. After delivery, if the baby has jaundice, he may be placed under special blue lights (phototherapy). In some cases, the baby may need a blood transfusion. Some cases of Rh disease are so mild that the baby does not need any treatment.
About 10 percent of fetuses with Rh disease develop severe anemia, which in the past was usually fatal (2). Today these fetuses can be treated in the uterus as early as 18 weeks gestation with blood transfusions, which are given using cordocentesis. About 90 percent of treated babies now survive (8).
Can the RhIg treatment transmit the AIDS or hepatitis viruses?
Although RhIg is a blood product, there is minimal to no risk of contracting the AIDS or hepatitis viruses from it (4). The donated blood is screened for the AIDS and hepatitis viruses and treated with a substance that kills viruses and bacteria.
Animations
Animated figures showing the development of erythroblastosis fetalis, how Rh disease develops, and how RhoGAM prevents Rh disease.
Figure 1: The Development of Erythroblastosis Fetalis
Figure 2: How Rh Disease Develops. How RhoGAM Prevents Rh Disease.
References
- Center for Disease Control. Rh Hemolytic Disease Surveillance. August 1976.
- Mari, G., et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. New England Journal of Medicine, volume 342, number 1, January 6, 2000, pages 9-14.
- American College of Obstetricians and Gynecologists (ACOG). Management of Alloimmunization During Pregnancy. ACOG Practice Bulletin, number 75, August 2006.
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American College of Obstetricians and Gynecologists (ACOG). Prevention of Rh D Alloimmunization. ACOG Practice Bulletin, number 4, May 1999.
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Queenan, J.T. Noninvasive Fetal Rh Genotyping: The Time Has Come. Obstetrics and Gynecology, volume 106, number 4, October 2005, pages 682-683.
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Bianchi, D.W. Noninvasive Prenatal Diagnosis of Fetal Rhesus D. Obstetrics and Gynecology, volume 106, number 4, October 2005, pages 841-844.
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Moise, K.J. Rh Disease: It's Still a Threat. Contemporary Ob/Gyn. May 2004, pages 34-48.
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Oepkes, D. Doppler Ultrasonography versus Amniocentesis to Predict Fetal Anemia. New England Journal of Medicine, volume 355, number 2, July 13, 2006, pages 156-164. October 2006
October 2006
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