The blood type of the mother and the blood type of her baby can have a significant effect on the health of the fetus or newborn baby. Usually in discussions on this topic we are concerned when a mother has Rh- blood and her husband has Rh+ blood. This combination can lead to a baby with Rh+ blood. If the mother is already sensitized to Rh+ blood cells, the Rh+ baby she is carrying will be affected to some degree by Rh hemolytic disease. If the mother becomes sensitized after delivery, every future Rh+ baby is at risk.
To thoroughly understand this topic it is best to start with an understanding of how the ABO blood system works.
The ABO Blood System
The understanding of blood types began during one of the major wars of the last century. Battlefield surgeons discovered that the plight of a badly injured soldier was sometimes dramatically improved by putting someone else’s blood into his veins. At other times, however, the procedure hastened him to his death. Medical researchers began studying different people’s blood. They would collect samples from several people and study what happened when different bloods were mixed. Sometimes nothing unusual happened and at other times the blood cells began to clump together when mixed.
After much study, four distinct blood types were identified, A, B, AB and O. Type O red blood cells (RBC’s) could be added to any of the other types without causing clumping or agglutination. Type O blood was considered to be a universal donor. Type A blood cells could be mixed with type A or AB blood without. If they were mixed with type B or O, clumping occurred. Similarly, type B red blood cells could be safely mixed with type B or AB blood, but not with type O or A. Type AB cells would cause clumping when mixed with any type of blood except AB.
Today much more is known about how and why blood groups act the way they do. We now know that if a woman has type A blood, she carries a type A antigen on her red blood cells. You can think of an antigen as a wart that is on each of her blood cells. There are type A "warts" and type B "warts" which identify those cells as belonging to her. This woman with type A blood was born with antibodies against type B blood cells called anti-B antibodies. These anti-B antibodies will destroy any type B blood cells that are put into her body. If she had a blood transfusion with type B blood, her antibodies would cause the blood she was receiving to coagulate as her anti-B antibodies went to work destroying the type B blood cells. If the transfusion was not immediately stopped it could kill her.
If a woman has type B blood, she has type B antigens (B warts) on her red blood cells and is born with antibodies against the type A antigen (anti-A antibodies). If a woman has type O blood, she has neither type A nor type B antigens on her red blood cells and is born with both anti-A and anti-B antibodies. There is no such thing as anti-O antibodies, because if a person has type O blood it simply means that they do NOT have type A or type B antigens on their red blood cells. If a woman has type AB blood she has both type A and B antigens on her red blood cells and has neither anti-A nor anti-B antibodies.
A woman with type O blood can only receive a transfusion from a person with type O blood. She cannot receive a transfusion from a person with type A, type B, or type AB blood, because her anti-A and anti-B antibodies would cause coagulation of the incoming blood as they destroyed the blood cells containing the A or B antigens. However, a person with type AB blood, can receive a transfusion from type A, type B or type O blood as well as type AB blood. A person with type AB blood has neither anti-A nor anti-B antibodies to hinder such transfusions. It is always best, however, to match the blood type exactly.To make things much more confusing, there are many more antigens than just A and B. There are C, c, D, E, e, K, k, M, N, and many others. The only one that usually impacts pregnant women is the D antigen in the Rh system. If a woman has this antigen, she is called Rh+ or D+ (Rh positive or D positive).1 If her ABO blood type is B and she has the D antigen, she has a B+ blood type. If she does not have the D antigen, she has a B- blood type.
|The terms Rh+ and D+ are usually used interchangeably, but it is actually more correct to use the term D+. There are several antigens in the Rh system: D, C, c, E, and e. The D antigen results in the most problems, so lay people rarely even hear of the other ones. Even medical personnel will call a woman who has the D antigen, Rh+. In this article both terms will be used.|
Other Blood Types
There is a difference between these blood antigens and the A and B antigens. We are not born with antibodies against these blood antigens. For example, an Rh- person is not born with anti-D (anti-Rh) antibodies. However, if we are exposed to blood with one of these unfamiliar antigens, we can develop antibodies against blood with those antigens. We can get exposed to these blood antigens by getting a transfusion with a foreign type of blood or carrying a child with a different blood type from our own. When a woman is pregnant, a few of the baby’s blood cells will often leak through the placenta and show up in her blood system.
We do not develop the antibodies immediately. We use the blood cells that are circulating in our system, as if they were our own. When these cells get old they are processed through our spleen to reuse all the spare parts. At this point, antibody production may be started. Pregnant women do not always develop antibodies against new foreign blood cells during pregnancy. A pregnant woman’s immune system is somewhat suppressed when it finds new antigens. If it was not, her body would be more likely to reject the pregnancy. This immune suppression does not always afford protection from Rh sensitization, however.
Once Sensitized Always Sensitized
After Doctors learned how to successfully perform blood transfusions without killing a high percentage of patients in the process, they branched out to using blood transfusions at other times. One of the most obvious times to give a blood transfusion was to a woman who had hemorrhaged during labor. After doctors started giving more transfusions they began to see an increase in stillborn babies and liveborn babies who developed severe jaundice shortly after birth and died. It took quite a while for doctors to realize that both conditions were caused from the same disease, and it took even longer to identify the cause of the disease and even longer to find a way to prevent it. Today there is still no cure for the severe cases.
Even though reports of this type of stillborn go back to the time of Hippocrates, doctors began seeing them more often. The increase was due to the fact that Rh- mothers were being transfused with Rh+ blood. No deaths occurred immediately as with an ABO transfusion reaction, but often when the woman gave birth to her next baby it was stillborn. Once she had one stillborn baby, every Rh+ baby after that was likely to be stillborn. If the baby was Rh-, it would be healthy. It was simply heart wrenching to see baby after baby born grossly macerated. It was torment to give birth to baby after baby who was doomed to die soon after.
The most severely affected babies have a condition known as erythroblastosis fetalis or hydrops fetalis. These babies have anemia because the mother’s antibodies keep killing off their blood cells. Since their little bodies have had to work very hard to replace all the destroyed blood cells, their blood forming centers are abnormally large. Specifically, they have more bone marrow than normal, and their spleen and liver are also enlarged. The enlargement of the liver may in turn cause it to be damaged. The babies’ bodies and placentas are very edematous (swollen). The babies have a large number of immature red blood cells called erythroblasts in their bloodstreams, hence the name eryrthroblastosis fetalis. If untreated, these babies will die in utero 30% of the time.2
Prenatal treatment may consist of amniocentesis to determine the severity of the disease, intrauterine blood transfusion, and/or premature delivery by cesarean section.
Babies who are not quite so affected, may be born and look normal, but very rapidly begin to develop severe jaundice. While in the womb, the mother’s bloodstream was clearing the excess bilirubin from the baby’s bloodstream. Bilirubin is a byproduct of the breakdown of RBC’s and is what causes a person to look jaundiced. Once the baby is born, he has to clear his own bilirubin and usually cannot keep up. If nothing is done and the baby has a severe problem, he will die or have brain damage. Usual treatment is exchange transfusion and/or phototherapy (putting the baby under the bili-lights).
Prevention is the Best Policy
Medical protocols today have greatly decreased the problem of women becoming sensitized. All D- women are encouraged to receive postnatal, and often prenatal, RhoGAM. This greatly reduces the risk of the woman being sensitized. Once the mother is sensitized, all D+ babies born after that point will be in danger of severe brain damage or will be born dead. Exchange transfusions may prevent some damage.
Unfortunately many traditional midwives are uninformed as to the danger of allowing a woman to become sensitized. To add to the problem many of our clients want to have as many children as God will give them. A D- woman having only two babies does not have a great chance of becoming sensitized. If she decides to have ten children, her probability of eventually becoming sensitized is much greater.
How Does the D Antigen Cause All These Problems?
Fortunately, most blood antigens do not cause any problems. The D antigen can be very dangerous, however. If a pregnant woman is D- and has developed antibodies against D+ blood cells (called anti-D antibodies), these antibodies will cross the placenta and start destroying any D+ blood cells that they find. This is only dangerous if the baby has D+ blood. Since the D- trait is recessive, the baby will not have D+ blood if both parents are D-. If the father is D+ the baby may or may not be D+.
If a woman who is D- is married to a man who is D+, she usually will have no problem during her first pregnancy, even if the baby is D+. After she gives birth to her first D+ baby, she may develop anti-D antibodies unless she is given an injection of a blood product called RhoGAM. RhoGAM is a generous dose of someone else’s anti-D antibodies. These antibodies destroy the few D+ blood cells that may be in her circulation from placental leakage or as a result of delivery. These fetal cells are destroyed before her immune system has a chance to break them down and learn how to make anti-D antibodies. Once her immune system knows the pattern for making anti-D antibodies, RhoGAM will be of no help to her. During the next pregnancy that she carries a D+ baby, the smaller anti-D antibodies will cross the placenta and go to work destroying the baby’s blood cells.
The Indirect Coombs Test
If a woman does develop her own antibodies against D+ blood cells, she is said to be sensitized. The danger to a D+ baby depends on how much the woman is sensitized. Degree of sensitization is measured by titres. Usually an indirect Coombs test is done on the mother’s serum. Some of the serum is mixed with a 2 or 3 percent suspension of D+ cells. If the red blood cells do not clump it means that the mother is not sensitized. If the cells clump or agglutinate it means that she has antibodies against D+ red blood cells in her serum and she is sensitized. Her serum is then diluted to half strength and the same test is done again. If there is clumping, her serum is diluted to 1/4th strength and tested again. Her serum is diluted in this fashion over and over to find the greatest dilution that will still cause clumping when mixed with a 2 or 3 percent mixture of D+ red blood cells.
If her serum willagglutinate the D+ cells when mixed full strength, but not when diluted half strength, she has a titre of 1:1. If the mixture clumps at half strength, but not at 1/4th strength, the titre is 1:2. If they clump at 1/4th strength but not at 1/8th strength, the titre is 1:4. If they clump at 1/16th strength, but not at 1/32nd strength, the titre is 1:16. A titre of 1:16 is higher than a titre of 1:8. The higher the titre the more danger there is to the child.3
According to the 19th edition of Williams Obstetrics, a titre no higher than 1:16 almost always means the baby will not die in utero from hemolytic disease (hydrops fetalis). Some practitioners anticipate good outcomes with titres of 1:32 and under.4 The 14th edition claimed that many doctors considered chances of survival excellent with a titre of 1:64 or less. With ratios higher than that the chances of survival were 60%.5 Any amount of sensitization should be closely monitored throughout pregnancy as the titre can increase.
How ABO type can Relate to Risk of Isoimmunization
Not all D- women who are married to D+ men have the same risk of being sensitized. It is not unusual for midwives to run across some D- clients who do not want to take RhoGAM. These clients may know other women who did not received RhoGAM and had no problem, even after several pregnancies. It is important for these clients to realize how dangerous it is for their future children if the mother becomes sensitized. It is also important to be able to explain to these parents the relative risks of Rh hemolytic disease. Not all women have the same risk of developing a problem.
If a baby’s ABO blood type is not compatible with the mother’s ABO blood type, the mother’s risk of being sensitized is much less than if the baby’s ABO type is compatible with hers. Another way of saying this, is that if a mother would have an ABO blood transfusion reaction if she received blood from the baby, her chance of developing anti-D antibodies after the birth of that baby is less. The reason for this is that if there is such an incompatibility, the mother’s anti-A or anti-B antibodies will destroy the baby’s blood cells in her system, before she produces anti-D antibodies. That means her anti-A or anti-B antibodies work much the same way that RhoGAM does.
The following chart details the percentage chance that mothers have of being sensitized.
|D- Mother and a D+ Baby|
|ABO Type of Mother||ABO Type of Baby||Percentage of Mothers
Sensitized Without RhoGAM
|AB-||A+,B+,O+ or AB+||16%|
From the above table you can see that if you have a mother with type AB- blood, married to an Rh+ husband, she will have a 16% chance of being sensitized after each pregnancy that RhoGAM is not given. Once she is sensitized, every D+ baby conceived thereafter will be at risk of dying from Rh disease.
Some midwives may not want to wait until they know the baby’s blood type to have this discussion with parents who do not want RhoGAM. One cannot always predict what a baby’s blood type will be just knowing the parent’s blood types. In some cases, however, you will know that the combination will always result in a 16% sensitization risk.
|Mother's Blood Type||Father's Blood Type||Risk of Developing Rh Disease
|A+, B+, O+, or AB+||A+, B+, O+, AB+,
A-, B-, O-, or AB-
|A-, B-, O-, or AB-||A-, B-, O-, or AB-||no risk|
|B+||from 2% to 16% risk depending
on ABO type of baby
|AB+||from 2% to 16% risk depending
on ABO type of baby
|B-||A+||from 2% to 16% risk depending
on ABO type of baby
|AB+||from 2% to 16% risk depending
on ABO type of baby
|O-||A+||from 2% to 16% risk depending
on ABO type of baby
|B+||from 2% to 16% risk depending
on ABO type of baby
|AB-||A+,B+,O+ or AB+||16%|
A woman can become sensitized from other events that may result in a mixing of fetal blood with maternal blood. A woman has a 2% chance of being sensitized after a miscarriage, and a 5% chance of sensitization following an induced abortion. To avoid autoimmunization, an Rh- woman should be given RhoGAM after miscarriage, abortion, ectopic pregnancy, hydatidiform mole, amniocentesis, or uterine bleeding.
Among Rh- women who are given RhoGAM within 72 hours of delivery and after each of the above mentioned events, 1.8% still become sensitized. Researchers believe that some women are being sensitized by fetal blood leaking into the maternal circulation during pregnancy. To eliminate this risk, two prenatal doses of RhoGAM are recommended. One given at 28 weeks, and one at 34 weeks. Rh- women taking this added precaution as well as those previously mentioned have a 0.07% chance of isoimmunization. If the 28 week dose is taken, but not the 34 week dose the chance is almost as low: 0.11%.6
Procedure for Giving RhoGAM
There are certain regulations which must be adhered to when administering RhoGAM. An Indirect Coombs test must be run on the mother’s blood before administration. From this test, if it is decided that the mother is sensitized, RhoGAM is not given. Determining sensitization can be a little tricky if the mother received prenatal RhoGAM. If she received a prenatal dose, the titre taken after delivery can be as high as 1:8 as a result of the unused RhoGAM still in her system.7 A titre higher than 1:8 in a mother who received prenatal RhoGAM indicates that the mother has been sensitized and RhoGAM is not given.
Massive Fetal-Maternal Bleeds at Delivery
Delivery is the time when there is the greatest risk of the mother getting fetal red blood cells into her system. This is why RhoGAM has typically been given shortly after delivery. One 300 microgram dose of RhoGAM is calculated to be able to destroy 15 ml of Rh+ red blood cells. This corresponds to 30 ml of whole fetal blood. About 1% of the time, a mother will accumulate more than 30 ml of fetal blood in her bloodstream after delivery. In these cases one dose of RhoGAM will not be enough to destroy all the Rh+ cells from the baby that are in the mother’s bloodstream. These mothers are still at risk of sensitization unless they receive more RhoGAM.
There seem to be no identifiable risk factors that would indicate which women have large fetal-maternal bleeds. How does one determine if such is the case? When you give the mother the postpartum shot of RhoGAM, you can draw blood for a Kleinhauer/Betke test. The results of this test and others similar to it will indicate the quantity of fetal red blood cells or whole blood that has been transferred to the mother’s system. From this information you can determine the number of vials of RhoGAM to administer.
It seems that the more we understand blood types, the more questions we have. In this section I will try to answer some common questions that come up.
If a woman does not want to receive prenatal RhoGAM how can I know that she is not being sensitized during the current pregnancy?
With all Rh- women an indirect Coombs test should be done at the first prenatal visit. If this comes back negative it assures you that she is not starting out already sensitized. Another indirect Coombs can be done at 28 weeks, and another at 34 weeks. If one of these tests comes back positive, titres need to be run on the woman weekly to determine the severity of the sensitization. Physician consultation is highly recommended under these circumstances.
If the woman chooses to receive prenatal RhoGAM, no other testing is needed until after delivery unless the mother has an amniocentesis or significant uterine bleeding.
If an Rh- mother can be sensitized by blood from an Rh+ baby, why are not Rh- babies sensitized by Rh+ mothers?
They are very rarely. It happens so infrequently that routine testing of Rh- babies is not considered necessary.
What does it mean for a person to be Du positive?
If a person is Du positive they are D+, but the type of D gene that they carry is very weakly antigenic. That means that there are very few antigenic sites (warts) on their RBCs. These people will often be told that they are Rh-. Very rarely, (once in 150,000 cases)8, a Du positive woman will develop anti-D antibodies. In none of these cases has the baby been severely affected.
Can a woman get AIDS from RhoGAM since it is a blood product?
According to the Centers for Disease Control in 1987, 500,000 doses of RhoGAM were given yearly to 350,000 women with no verified cases of AIDS transmission.
If a woman is slightly sensitized at the beginning of pregnancy, can RhoGAM prevent the titre from increasing?
Giving RhoGAM to a sensitized mother during pregnancy is useless. She already has anti-D antibodies in her system that will kill off invading D+ RBC’s. Giving her RhoGAM is the same as giving her more anti-D antibodies. It will not prevent her from producing more antibodies on her own. It would not physically hurt her either, but RhoGAM is expensive.
1. The terms Rh+ and D+ are usually used interchangeably, but it is actually more correct to use the term D+. There are several antigens in the Rh system: D, C, c, E, and e. The D antigen results in the most problems, so lay people rarely even hear of the other ones. Even medical personnel will call a woman who has the D antigen, Rh+. In this article both terms will be used.
2. Cunningham, F. Gary, et al. Williams Obstetrics 19th ed. (Norwalk, Conn.: Appelton & Lange, 1993), p. 1010.
3. In actual practice, the indirect Coombs is done to test for all known IgG blood type antibodies. The IgG type of antibodies are the size that can cross the placenta. If the test comes back positive (meaning that there are abnormal antibodies present), a hospital lab may send the serum sample to another lab where the specific antibody is identified and a titre is done. The specific antibody is almost always the anti-D antibody.
4. Cunningham, et al., pp.1003 - 1013
5. Louis M. Hellman, Jack A. Pritchard, and Ralph M. Wynn, Williams Obstetrics, 14th ed. (New York: Appleton-Century-Crofts, 1971), pg.1038.
6. Cunningham et al., p. 1008.
7. Helen Varney, Nurse Midwifery, 2nd ed. (Sudbury, Mass.: Jones and Bartlett Publishers, 1987) p. 182.
8. Cunningham, et al., p. 1009.