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The screening programme of prenatal blood group antibodies in Finland

Screening at the beginning of each pregnancy
Testing centralised at the Blood Service
Testing made from the mother's blood sample
Monitoring of the development of antibody concentration
How do the antibodies form
Different blood group antibodies affect the foetus in different way
Father's sample is requested if necessary
Severe blood group immunisations
In case of severe immunisation, the blood group of the foetus is determined
RhD immunisation can be prevented
It is possible to treat the child


Screening at the beginning of each pregnancy
The purpose of the blood group antibody screening is to find those mothers, whose babies are at a risk of developing a haemolytic disease of the foetus or the newborn. The aim is to find the risk pregnancies at the very beginning of the pregnancy. Therefore a blood sample is taken from all mothers visiting the maternity clinic between pregnancy weeks 8 to 12. In addition, additional samples are taken from RhD negative mothers between pregnancy weeks 24 to 26 and in week 36, because they have an elevated risk of forming blood group antibodies. If an RhD positive mother has been given blood transfusions or she has given birth to a child that has been treated for jaundice, an additional sample is taken during the pregnancy week 36.

In addition to the antibody screening sample, an additional sample may be taken from RhD negative mothers for determining the RhD blood group factor of the foetus between the pregnancy weeks 24 and 26. With the help of the test, prenatal routine anti-D prophylaxis can be given to those mothers with an RhD positive foetus only.


Testing centralised to the Blood Service
The Blood Service's maternity clinic sample laboratory performs all prenatal blood type and blood group antibody screenings in Finland. These operations have been centralised into one laboratory in accordance with the recommendations of the National Institute for Health and Welfare's (THL) working group on prenatal care. These screenings have been performed at the Blood Service for more than 20 years. The screening results are stored in a national archive, where they are available during the mother's next pregnancies regardless of her place of residence. The results are used for the monitoring of the pregnancy, or in case the newborn or the mother need blood transfusions. The number of immunisation cases can be monitored on an annual basis on the basis of antibody data covering the whole country.


Testing made from the mother's blood sample
The blood samples sent by maternity clinics is ABO and RhD typed and screened for blood group antibodies. If any antibodies are found, further tests are made: the antibodies are identified and their concentration in the mother's blood is measured by titration. The blood group antibodies are tested in connection with every pregnancy, because the more pregnancies the mother has had, the more likely she is to form antibodies.

If the mother is RhD negative, the foetus' RhD blood group can be determined from the foetal DNA separated from the mother's blood. If the foetus is RhD positive, the mother is given a routine anti-D prophylaxis to prevent her prenatal immunisation.


Monitoring of the development of antibody concentration
The Blood Service screens the samples of approximately 65,000 expecting mothers a year. In the screenings, some 500 mothers are found to have an antibody that may pose a risk of a haemolytic disease to the foetus or the newborn. The development of the antibody concentration of these mothers is monitored. Maternity clinics are given instructions on how often the testing should be repeated during the pregnancy and assessments are made whether the antibody in question could cause a haemolytic disease of the foetus or the newborn. If the antibody poses a risk to the child, information of the result is also sent to the university hospital within the area of which the mother's maternity clinic belongs. On the basis of the result, university hospitals estimate whether other examinations are needed for monitoring the pregnancy and make plans for treatment during pregnancy.

How do the antibodies form
The haemolytic disease of the foetus or the newborn is caused by the antibodies that have formed in the mother's body against the child's red cells. The antibodies adhere to the foetus' red cells, causing them to decompose prematurely. Accelerated decomposition of red cells may cause anaemia, increase the level of bilirubin in the blood, or the newborn may have jaundice. Sometimes antibodies may also form if the mother has been given blood transfusions.

Different blood group antibodies affect the foetus in different way
Antibodies do not always cause problems. For example the following factors determine how dangerous the antibody is:

• Which antibody it is?
• What is the antibody concentration in the mother's blood (titre)?
• Has the child inherited the blood group factor which the mother's antibody attacks from his/her father?

The significance of the antibody is assessed by determining the antibody concentration at regular intervals during the pregnancy. Most mothers have such low antibody concentration that it poses no danger to the foetus.

Father's sample is requested if necessary
When an antibody that may pose a danger to the child is discovered in the mother, the Blood Service requests the maternity clinic to send the father's blood sample. The sample is ABO and Rh typed and screened for the blood group factor against which the mother has formed antibodies.

If the father does not have the blood group factor in question, the child does not have it either, and then there is no danger of the newborn developing a haemolytic disease. In this case, the amount of mother's antibody testing can be reduced, making only occasional checks that no new antibodies have begun to form.

If the father has the blood group factor in question, he may be heterozygous or homozygous for the blood group factor. If he is heterozygous, half of his children inherit the said blood group factor. If, on the other hand, he is homozygous, all his children inherit the said blood group factor. Both cases pose a risk of a haemolytic disease to the foetus or the newborn. Therefore the mother's antibody concentration is monitored on a regular basis throughout the pregnancy.

Severe blood group immunisations
Anti-D is the antibody that poses the highest risk to the child. The antibody forms when the RhD negative mother form antibodies against the child's RhD positive red cells. RhD negative mothers lack the RhD blood group factor, in which case her body identifies the RhD blood group factor the child has inherited from his/her father as alien. In Finland, the anti-D antibody is found in some 130 mothers a year. About half of them have a high antibody concentration.

Other significant antibodies that may cause haemolytic diseases in the foetus or the newborn include the anti-c, anti-K and sometimes anti-E as well. In Finland, these antibodies are found in approximately 250 mothers a year. In most cases the concentration of these antibodies in the mother's body is low, so the child does not usually need prenatal care. Severe anti-K and anti-c immunisations may require treatment already during pregnancy, but it happens less frequently than in case of anti-D immunisation. Many other antibodies may also be significant with a view to pregnancy and their concentrations are monitored during pregnancy.

In case of severe immunisation, the blood group of the foetus is determined
In case of severe immunisation, where the antibody concentrations are high, the blood group of the foetus may be determined. The foetus' RhD blood group factor may be determined from the mother's blood sample after the pregnancy week 16. Foetal DNA is separated from the mother's blood, and its RhD gene is duplicated. Foetus' D, c, C, E, e (Rh) and K (Kell) blood group factors can be identified from an amniotic fluid sample taken after the pregnancy week 16. If the blood group gene is found, the monitoring and prenatal treatment can be planned in good time. If the gene is not found, there is no risk of the foetus or the newborn developing a haemolytic disease. In this case, the amount of mother's antibody testing can be reduced, making only occasional checks that no new antibodies have begun to form.

RhD immunisation can be prevented
RhD immunisation is the only form of blood group immunisation that can be prevented. When an RhD negative mother gives birth to a RhD positive child, the mother is given an anti-D immunoglobulin injection. The anti-D immunoglobulin protects the mother from formation of antibodies caused by the RhD factor. The prophylaxis is also given to RhD negative mothers during pregnancy in situations with elevated risk of bleeding from the foetus into the mother. For this reason, the mother is protected in the event of, for example, amniocentesis or external cephalic version.

All RhD negative mothers are given prenatal prophylaxis during pregnancy weeks 28 to 30.
Only mothers expecting an RhD positive child need the prophylaxis. The foetal RhD factor can be analysed from the mother's blood sample using the PCR method. The sample for the determination of the foetal RhD is taken at the same time as the second antibody screening sample is taken from an RhD negative mother, during pregnancy weeks 24–26.

All precautionary measures are taken regardless of each other: when the child is RhD-positive, if the mother has been given prophylaxis in the early pregnancy, she will also be protected during pregnancy week 28–30 and in connection with the delivery.

It is possible to treat the child
When the antibodies are found in time, it is possible to treat the child. In serious immunisation cases, the foetus can be given red cells during the pregnancy, repairing the foetus’ oxygen supply with the help of fresh red cells. Intrauterine blood transfusions are needed in the treatment of approx. 10 pregnancies a year.

In less serious immunisation cases, labour may be induced a few weeks prior to the due date. Due to the blood group antibodies, the baby’s red cells decompose and release bilirubin, causing jaundice. In such cases, the new-born can be treated with phototherapy which breaks up the bilirubin. In more severe immunisation cases, the newborn is treated with immunoglobulin or through an exchange transfusion, during which both antibodies and toxic bilirubin are removed. About 15 children a year need exchange transfusion.

In Finland, some 150 children a year need treatment due to a haemolytic disease of the foetus or the newborn. With modern treatment methods, the prognosis of the disease is usually good.

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