Rh Incompatibility


The information provided below is for readers based in the United States of America. Readers outside of the United States of America should seek the information from local sources.

What is Rh-negative blood type?

Blood types result from different molecules that can be present on the outside surfaces of red blood cells (RBCs). One set of such RBC surface molecules is called rhesus factors, because they were first discovered in rhesus monkeys. Health issues of Rh-negative blood types involve a particular Rh factor called factor D (RhD), because this is an Rh factor that is noticed by, and stimulates, the human immune system. If you have Rh-negative blood, it means that your RBCs do not express the D factor on their surfaces. Consequently, if any RBCs with D factor meaning Rh-positive blood come into your system, your immune system will perceive those RBCs as being foreign to the body. You can receive Rh-positive RBCs if you are given a transfusion of the wrong blood type (for instance, you received O-positive blood, instead of O-negative blood), but the most common way for an Rh-negative woman to acquire Rh-positive RBCs is during pregnancy or delivery, if you are carrying an Rh-positive baby.

Normally, the placenta keeps mother’s and baby’s blood separate, preventing mixing of blood, but moderate trauma, a spontaneous abortion (miscarriage), and sometimes the breaking of blood vessels during delivery can lead to Rh-positive baby’s RBCs entering your blood stream. This teaches your immune system to manufacture antibodies that attach to D factor on Rh-positive RBCs, causing the RBCs to clump together (hemagglutinate) and ultimately to break up. If your immune system is making these antibodies for the first time, it doesnt hurt the developing baby, for a couple of reasons. First, if the blood mixing occurs during labor and delivery, the baby will soon be out of your body anyway, safe from your immune system. Second, the type of antibody thats made initially against factor D is called IgM, which is unable to pass through the placenta to get into the baby’s blood.

The problem develops when its your second pregnancy with an Rh-positive baby (or when its your first pregnancy with an Rh-positive baby and you have been exposed to Rh-positive blood through an unlikely transfusion error). In this case, your immune system makes anti-D IgM, but it also makes anti-D of a different type of antibody, called IgG, which does enter the baby’s blood, because it is able to move smoothly between the mother’s and baby’s blood vessels of the placenta.

How common is Rh-negative blood during pregnancy?

About 14 percent of pregnancies occur in mothers who are Rh-negative. Some of these women carry babies who are Rh-negative themselves, but in the United States doctors like to treat all cases of maternal Rh-negative blood as if the babies were Rh-positive. In Europe, there is a growing preference to test the baby’s Rh status.

How is Rh-negative blood diagnosed?

The mothers Rh-status is diagnosed by drawing blood and testing for the presence of RhD antigen on her RBCs. If the RhD antigen is absent, then she is Rh-negative. In the US, finding that the mother is Rh-negative generally means that the pregnancy will be treated as a case of maternal negative Rh with a positive Rh baby. In Europe, however there is a growing preference to test the baby’s Rh status, because if the baby is also Rh-negative, then the treatment, called RhoGAM, can be avoided, and there is concern about an emerging RhoGAM shortage. Along with testing the baby directly, its also possible to know whether the baby is Rh-positive or negative by knowing about the father; knowing for sure that the father and mother are both Rh-negative assures that the baby will be Rh-negative, but knowing only that a father is Rh-positive leaves uncertainty, because there are two genetic types for Rh-positivity. Knowing which type he is requires either genetic tests, or knowledge of the blood types of his other children.

Does Rh-negative blood cause problems during pregnancy?

There is no problem for the mother herself if she is Rh-negative. Furthermore, if she is Rh-negative and the fetus is Rh-positive, if its the first pregnancy and she has never been exposed to Rh-positive blood, the mother will experience no problems and everything will appear normal right up through delivery. Maternal Rh-negative blood is an issue for an Rh-positive fetus who is not the first Rh-positive fetus that the mother has carried, and it is an issue for future fetuses.

Does Rh-negative maternal blood during pregnancy cause problems for the baby?

Yes, if the baby is Rh-positive, and if the mother has had even tiny amounts of Rh-positive RBCs mixed into her blood in the past, typically during a previous pregnancy, the mother will be making IgG antibodies that enter through the placenta into the baby’s blood attach to RBCs. This can lead to what is called “hemolytic disease of the fetus and newborn” (HDFN). In the developing baby, HDFN shows up as anemia (low number of RBCs) and hydrops fetalis (fluid inside the baby). In the newborn, the condition shows up also with anemia, as well as hyperbilirubinemia, which means that bilirubin, a product of the breakdown of RBCs, accumulates in the blood. Bilirubin also accumulates in the brain, where it causes a kind of brain damage called kernicterus.

What to consider about taking medications when you are pregnant or breastfeeding:

  • The risks to yourself, your baby, and future babies, if you do not treat the Rh negative status
  • The risks and benefits of each medication you use when you are pregnant
  • The risks and benefits of each medication you use when you are breastfeeding

What should I know about using medication to treat Rh-negative status during pregnancy?

The treatment for an Rh-negative mother is Rho(D) immune globulin (RhoGAM), an antibody that works by attaching to D factor molecules on fetal Rh-positive RBCs, eliminating the cells, or at least covering D factor, before it can trigger your immune system. Rho(D) immune globulin is given as an injection into muscle. When administered to the mother after delivery, and also at 28 weeks gestation, the treatment reduces the rate of immune response to Rh-positive RBCs by 99.9 percent.

Who should NOT stop taking medication for Rh-negative blood during pregnancy?

Every Rh-negative pregnant woman should receive Rho(D) immune globulin, unless it can be demonstrated 100 percent that the baby is also Rh-negative.

What should I know about choosing a medication for my Rh-negative blood during pregnancy?

You may find Pregistrys expert reports about the individual medications used to treat Rh-negative women here. Additional information can also be found in the sources listed at the bottom of this report.

What should I know about taking a medication for my Rh-negative blood when I am breastfeeding?

Rho(D) immune globulin is not harmful to a nursing infant.

What alternative therapies besides medications can I use to treat my Rh-negative blood during pregnancy?

There is no logical alternative to Rho(D) immune globulin, as it is exquisitely effective and safe, whereas the consequences of not using it are dire.

What can I do for myself and my baby when I have Rh-negative blood during pregnancy?

Have your recommended injections of Rho(D) immune globulin, unless you are able to know for sure that the baby, or the father, also is Rh-negative.

Resources for Rh in pregnancy:heck

For more information about Rh-negative blood during and after pregnancy, contact http://www.womenshealth.gov/ (800-994-9662 [TDD: 888-220-5446]) or contact the following links:


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General information

It is very common for women to worry about having a miscarriage or giving birth to a child with a birth defect while they are pregnant. Many decisions that women make about their health during pregnancy are made with these concerns in mind.

For many women these concerns are very real. As many as 1 in 5 pregnancies end in a miscarriage, and 1 in 33 babies are born with a birth defect. These rates are considered the background population risk, which means they do not take into consideration anything about the health of the mom, the medications she is taking, or the family history of the mom or the baby’s dad. A number of different things can increase these risks, including taking certain medications during pregnancy.

It is known that most medications, including over-the-counter medications, taken during pregnancy do get passed on to the baby. Fortunately, most medicines are not harmful to the baby and can be safely taken during pregnancy. But there are some that are known to be harmful to a baby’s normal development and growth, especially when they are taken during certain times of the pregnancy. Because of this, it is important to talk with your doctor or midwife about any medications you are taking, ideally before you even try to get pregnant.

If a doctor other than the one caring for your pregnancy recommends that you start a new medicine while you are pregnant, it is important that you let them know you are pregnant.

If you do need to take a new medication while pregnant, it is important to discuss the possible risks the medicine may pose on your pregnancy with your doctor or midwife. They can help you understand the benefits and the risks of taking the medicine.

Ultimately, the decision to start, stop, or change medications during pregnancy is up to you to make, along with input from your doctor or midwife. If you do take medications during pregnancy, be sure to keep track of all the medications you are taking.

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