The antenatal screening programme of blood group antibodies in Finland

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 fetus or the newborn. The aim is to identify the risk pregnancies already early in the pregnancy. Therefore a blood sample is taken from all mothers visiting the maternity clinic between 8 and 12 weeks of pregnancy. In addition, additional samples are taken from RhD negative mothers between 24 and 26 weeks of pregnancy and during the 36th week of pregnancy, 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 is taken from RhD negative mothers between 24 and 26 weeks of pregnancy for determining the RhD blood group factor of the fetus. The test allows routine antenatal anti-D prophylaxis to be given only to those mothers with an RhD positive fetus.

Centralised testing at the Blood Service

The Blood Service’s Antenatal Blood Group Laboratory performs all antenatal blood group typings 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 antenatal care. These screenings have been performed at the Blood Service since 1990. The screening results are stored in a national database, 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 if the newborn or the mother need blood transfusions. The nationwide database of antibodies allows us to follow the number of immunisations on an annual basis.

Testing the mother’s blood sample

The blood samples sent by maternity clinics is ABO and RhD typed and screened for blood group antibodies. If antibodies are found, further tests are carried out: the antibodies are identified and their concentration in the mother’s blood is measured by titration. Blood group antibodies are screened in each pregnancy, because the more pregnancies the mother has had, the more likely she is to form antibodies.

If the mother is RhD negative, the fetus’ RhD blood group can be determined from the fetal DNA separated from the mother’s blood. If the fetus is RhD positive, the mother is given a routine anti-D prophylaxis to prevent antenatal immunisation. Also postnatal anti-D profylaxis can be administered based on the fetal RhD blood group. Newborn RhD blood group has to be determined only in those cases where the fetal result in not available.

Monitoring of the antibody concentration

The Blood Service screens the samples of approximately 60,000 expecting mothers a year. In the screening, approximately 1 % of the mothers are found to have an antibody that may pose a risk of haemolytic disease of the fetus and newborn. Changes in the antibody concentration in these mothers are monitored. Maternity clinics are given instructions on how often the testing should be repeated during the pregnancy, and it is evaluated whether the antibody in question could cause haemolytic disease of the fetus and newborn. If the antibody poses a risk to the child, information of the result is also sent to the university hospital covering the area of the mother’s maternity clinic. On the basis of the result, the university hospitals estimate whether further examinations are needed for monitoring the pregnancy and plan for the management of the pregnancy.

Haemolytic disease of the fetus and newborn

The haemolytic disease of the fetus and newborn is caused by antibodies that have formed in the mother’s body against the child’s red cells. The antibodies adhere to the fetus’ red cells, causing them to be prematurely destroyed. Accelerated destruction of red cells may cause anaemia, increase the level of bilirubin in the blood, or the newborn may become jaundiced. Sometimes antibodies may also form if the mother has been given blood transfusions.

Different blood group antibodies affect the fetus in different ways

Antibodies do not always cause problems. For example the following factors determine how dangerous the antibody is:

• Which antibody is it?
• What is the antibody concentration in the mother’s blood (titre)?
• Has the child inherited the corresbonding blood group factor 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 fetus.

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 a blood sample of the child’s father. The sample is typed for ABO and Rh, and 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 there is no danger of the fetus or newborn developing haemolytic disease. In this case, the frequency of the mother’s antibody tests can be reduced to a few checks to make sure that no new antibodies have formed.

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 fetus and 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 an RhD negative mother developes antibodies against the child’s RhD positive red cells. RhD negative mothers lack the RhD blood group factor, in which case their bodies identify the RhD blood group factor the child has inherited from his/her father as alien. In Finland, the anti-D antibody is found in approximately 60 mothers a year. About half of them have a high antibody concentration.

Other significant antibodies that may cause haemolytic diseases in the fetus or newborn include 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 that antenatal care is usually not needed. Severe anti-K and anti-c immunisations may require treatment already during pregnancy, but it happens less frequently than in the case of anti-D immunisation. Many other antibodies may also be significant in pregnancy and their concentrations are monitored during pregnancy.

In case of severe immunisation, the blood group of the fetus is determined

In case of severe immunisation, where the antibody concentrations are high, the blood group of the fetus may be determined. The fetus’ RhD blood group factor may be determined from the mother’s blood sample after the 16th week of pregnancy. Fetal DNA is separated from the mother’s blood, and presence of the RhD gene is detected. The D, c, C, E, e (Rh) and K (Kell) blood group factors of the fetus can be identified from an amniotic fluid sample taken after the 16th week of pregnancy. If the blood group gene is found, the monitoring and antenatal treatment can be planned in good time. If the gene is not found, there is no risk of haemolytic disease. In this case, the frequency of the mother’s antibody tests can be reduced, to a few checks to make sure that no new antibodies have formed.

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 an RhD positive child, the mother is given an anti-D immunoglobulin injection. The anti-D immunoglobulin prevents the formation of antibodies against the RhD factor.

All RhD negative mothers who are expecting an RhD positive child are given antenatal prophylaxis during 28-30 weeks of pregnancy. The fetal RhD factor is analysed from the mother’s blood sample using the PCR method. The sample for the determination of the fetal RhD is taken at the same time as the second antibody screening sample is taken from an RhD negative mother, during 24-26 weeks of pregnancy.

The prophylaxis is also given to RhD negative mothers during pregnancy in situations with elevated risk of bleeding from the fetus into the mother, when the fetus is RhD positive or his/her RhD blood group is not known. These situations include for example, amniocentesis or external cephalic version.

Anti-D prophylaxes for different indications are given independently of each other: even if the mother has been given prophylaxis in early pregnancy, she will also be given anti-D prophylaxis during 28–30 weeks of pregnancy and at the delivery, if the child is RhD positive.

The child can be treated

When the antibodies are found in time, it is possible to treat the child. In serious immunisation cases, the fetus can be transfused with red cells during the pregnancy, to restore the oxygen supply. 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. The the blood group antibodies cause the baby’s red cells to be destroyed and release bilirubin, causing jaundice. In such cases, the newborn can be treated with phototherapy to break up the bilirubin. In more severe immunisation cases, the newborn is treated with immunoglobulin or  exchange transfusion, during which both antibodies and toxic bilirubin are removed. About 10 children a year need exchange transfusion.

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