Why don't blood group antibodies cross the placenta and kill the baby
Hi - Antibodies against ABO antigens are almost always IgM antibodies. The IgM antibody consists of 5 antibody units connected together, in a star-like pattern. The protein is simply too large to cross the placenta. However, if a break in the placental-fetal barrier happens, the mother may generate a smaller immunoglobulin, IgG, against the ABO antigens on the fetal red cells. This Ig-type can cross the placenta. If early enough in the pregnancy, she may develop sufficient IgG antibody to affect the current pregnancy. The presence of the antibody can certainly affect future ones.
IgG antibodies against the Rh(D) antigen were once tbe most common cause of hemolytic disease of the newborn. In such cases the mother lacks the Rh(D) antigen on her red cells but the baby inherits the antigen from the father, and so has it on his or her red cells. The mother may generate antibody when exposed to the antigen from a prior pregnancy, or (far less commonly) from transfusion. Anti-Rh antibodies of the IgG subclass readily cross the placenta and can destroy the fetal red cells.
The introduction of RhoGam greatly decreased the number of HDN cases caused by Rh(D) incompatibility between the mother and the fetus. RhoGam consists of antibody against the Rh antigen. It is believed to act by rapidly binding to, and removing Rh-positive fetal red cells in the mother's circulation before she can generate antibody against the antigen.
ABO incompatibility disease afflicts newborns whose mothers are blood type O, and who have a baby with type A, B, or AB.
Ordinarily, the antibodies against the foreign blood types A and B that circulate in mother's bloodstream remain there, because they are of a type that is too large to pass easily across the placenta into the fetal circulation. Some fetal red cells always leak into mother's circulation across the placental barrier (mother and fetal blood theoretically do not mix, but in actuality, they do to a small degree).
These fetal red cells stimulate the formation of a smaller type of anti-A or anti-B antibody which can pass into the baby's circulation and there cause the destruction of fetal red cells. The increased rate of destruction of red cells causes a subsequent increase in waste product production. This excess waste product, bilirubin, can overwhelm the normal waste elimination processes and lead to jaundice, the presence of excess bilirubin.
This condition is one of the hemolytic anemias. Jaundice is the most common problem encountered, which may require phototherapy or even exchange transfusion.
Anemia sometimes becomes an issue some weeks after the initial jaundice problems are resolved. This is caused by ongoing faster than normal breakdown of the baby's fetal cells by the maternal antibodies, which linger in the baby's bloodstream for weeks after birth. For this reason, babies with ABO incompatibility disease may need to be tracked with periodic blood counts. If the anemia were to become severe, a blood transfusion might be required to restore a normal level of red blood cells in the baby's circulation. Such a transfusion would add blood to the baby's circulation to prevent possible complications of the anemia (in distinction to the exchange transfusion, which replaces the baby's red cells with adult cells). This complication is rare; I personally have yet to see a case severe enough to justify transfusion.
For reasons that are unclear, B-O incompatibility (mother type O, baby type B) seems to be in general more severe than A-O incompatiblity.
Rh Blood Types
Rh blood types were discovered in 1940 by Karl Landsteiner and Alexander Wiener. This was 40 years after Landsteiner had discovered the ABO blood groups. Over the last half century, we have learned far more about the processes responsible for Rh types. This blood group may be the most complex genetically of all blood type systems since it involves 45 different antigens on the surface of red cells that are controlled by 2 closely linked genes on chromosome 1.
The Rh system was named after rhesus monkeys, since they were initially used in the research to make the antiserum for typing blood samples. If the antiserum agglutinates your red cells, you are Rh+ . If it doesn't, you are Rh- . Despite its actual genetic complexity, the inheritance of this trait usually can be predicted by a simple conceptual model in which there are two alleles, D and d. Individuals who are homozygous dominant (DD) or heterozygous (Dd) are Rh+. Those who are homozygous recessive (dd) are Rh- (i.e., they do not have the key Rh antigens).
Clinically, the Rh factor, like ABO factors, can lead to serious medical complications. The greatest problem with the Rh group is not so much incompatibilities following transfusions (though they can occur) as those between a mother and her developing fetus. Mother-fetus incompatibility occurs when the mother is Rh- (dd) and the father is Rh+ (DD or Dd). Maternal antibodies can cross the placenta and destroy fetal red blood cells. The risk increases with each pregnancy. Europeans are the most likely to have this problem--13% of their newborn babies are at risk. Actually only about ½ of these babies (6% of all European births) have complications. With preventive treatment, this number can be cut down even further. Less than 1% of those treated have trouble. However, Rh blood type incompatibility is still the leading cause of potentially fatal blood related problems of the newborn. In the United States, 1 out of 1000 babies are born with this condition.
Rh type mother-fetus incompatibility occurs only when an Rh+ man fathers a child with an Rh- mother. Since an Rh+ father can have either a DD or Dd genotype, there are 2 mating combinations possible:
Only the Rh+ children (Dd) are likely to have medical complications. When both the mother and her fetus are Rh- (dd), the birth will be normal.
Human fetus in a mother's uterus
(the umbilical cord and placenta
connect the fetus to its mother)
The first time an Rh- woman becomes pregnant, there usually are not incompatibility difficulties for her Rh+ fetus. However, the second and subsequent births are likely to have life-threatening problems. The risk increases with each birth. In order to understand why first born are normally safe and later children are not, it is necessary to understand some of the placenta's functions. Nutrients and the mother's antibodies regularly transfer across the placental boundary into the fetus, but her red blood cells usually do not (except in the case of an accidental rupture). Normally, anti-Rh+ antibodies do not exist in the first-time mother unless she has previously come in contact with Rh+ blood. Therefore, her antibodies are not likely to agglutinate the red blood cells of her Rh+ fetus.
Placental ruptures do occur normally at birth so that some fetal blood gets into the mother's system, stimulating the development of antibodies to Rh+ blood antigens. As little as one drop of fetal blood stimulates the production of large amounts of antibodies. When the next pregnancy occurs, a transfer of antibodies from the mother's system once again takes place across the placental boundary into the fetus. The anti-Rh+ antibodies that she now produces react with the fetal blood, causing many of its red cells to burst or agglutinate. As a result, the newborn baby may have a severe life-threatening anemia because of a lack of oxygen in the blood. The baby also usually is jaundiced, fevered, quite swollen, and has an enlarged liver and spleen. This condition is called erythroblastosis fetalis . The standard treatment is immediate massive transfusions of Rh+ blood into the baby with the simultaneous draining of the existing blood to flush out Rh+ antibodies. This is usually done immediately following birth, but it can be done to a fetus prior to birth.
Erythroblastosis fetalis can be prevented for women at high risk (i.e., Rh- women with Rh+ mates or mates whose blood type is unknown) by administering a serum (Rho-GAM ) containing anti-Rh+ antibodies into the mother around the 28th week of pregnancy and again within 72 hours after the delivery of an Rh+ baby. This must be done for the first and all subsequent pregnancies. The injected antibodies quickly agglutinate any fetal red cells as they enter the mother's blood, thereby preventing her from forming her own antibodies. The serum provides only a passive form of immunization and will shortly leave her blood stream. Therefore, she does not produce any long-lasting antibodies. This treatment can be 99% effective in preventing erythroblastosis fetalis. Rho-GAM is also routinely given to Rh- women after a miscarriage, an ectopic pregnancy, or an induced abortion. Without the use of Rho-GAM, an Rh- woman is likely to produce larger amounts of Rh+ antibodies every time she becomes pregnant with an Rh+ baby because she is liable to come in contact with more Rh+ blood. Therefore, the risk of life-threatening erythroblastosis fetalis increases with each subsequent pregnancy.
Anti-Rh+ antibodies may be produced in an individual with Rh- blood as a result of receiving a mismatched blood transfusion. When this occurs, there is likely to be production of the antibodies throughout life. Once again, Rho-GAM can prevent this from happening.
Mother-fetus incompatibility problems can result with the ABO system also. However, they are very rare--less than .1% of births are affected and usually the symptoms are not as severe. It most commonly occurs when the mother is type O and her fetus is A, B, or AB. The symptoms in newborn babies are usually jaundice, mild anemia, and elevated bilirubin levels. These problems in a baby are usually treated successfully without blood transfusions.
Practice Quiz for Rh Blood Types
No. of Questions= 9
1. Which of the following statements is true of the Rh blood system?
a) It was the first blood type system to be discovered.
b) It is more complex genetically than the ABO system.
c) There are 45 Rh blood types.
d) b and c
2. The greatest medical problem with the Rh blood group is:
a) transfusion incompatibility
b) chronic anemia for Rh negative individuals
c) chronic anemia for Rh positive individuals
d) none of the above
3. Mother-fetus Rh blood type incompatibility problems can occur if the mother is _____ and her fetus is _____ .
a) Rh positive; Rh positive
b) Rh positive; Rh negative
c) Rh negative; Rh positive
d) Rh negative; Rh negative
e) b and c
4. Which of the following is true of Rh positive people?
a) They are either homozygous dominant (DD) or heterozygous (Dd) for this trait.
b) They are all homozygous dominant (DD).
c) They are all homozygous recessive (dd).
d) They are either homozygous recessive (dd) or heterozygous (Dd) for this trait.
5. Who is at greatest risk for Rh mother-fetus incompatibility problems?
c) Native Americans
d) all are equally at risk
6. If the father of a fetus is Rh positive and the mother is Rh negative, what are the chances that there will be a mother-fetus incompatibility problem? Assume that the couple has already had a child and that there has been no medical treatment to prevent this problem.
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b) at least 50%
c) less than 50%
d) 0 %
7. Mother-fetus incompatibility problems result from:
a) the mother's antibodies agglutinating the fetus' Rh positive red blood cells
b) the fetus' antibodies agglutinating its own red blood cells
c) the fetus' antibodies agglutinating its mother's red blood cells
8. When a fetus' blood is agglutinated by its mother's Rh antibodies, the severe anemia that results is called:
b) ectopic pregnancy
c) erythroblastosis fetalis
9. Which of the following are true of mother-fetus Rh incompatibility problems?
a) They can be prevented by injecting Rho-GAM into the mother's blood system.
b) They are much less likely to occur during the first pregnancy compared to later pregnancies.
c) Medical treatment can be nearly 100% effective in preventing such problems.
d) all of the above