Prof. Marzena Dębska explains what the serological conflict is, who is the most vulnerable and how it is detected.
Joanna Myrcha: Professor, what is a serological conflict? What is it at risk and who is at risk?
Prof. dr hab. n. med. Marzena Dębska: Most often, when we say serological conflict, we mean a situation where a pregnant woman produces antibodies against antigens present on the red blood cells of her developing baby.
Antigens are structures on the surface of cells that serve us, among other things, to recognize our own cells. In pregnancy, there is a natural antigenic incompatibility between mother and child, due to the fact that the child inherits half the antigens from the mother and half from the father. Most often, because of these differences, nothing happens because, thanks to the placental barrier, the mother’s blood does not mix with the fetal blood. For a conflict to occur, a woman’s immune system must be in contact with the baby’s blood cells sufficient for it to recognize the foreign blood cells and make antibodies against them. These antibodies will later be able to cross the placenta from mother to baby and attack the baby’s blood cells.
The serological conflict may have various causes, as well as the anemia itself, but the most common and classic example of both is the conflict in the D antigen from the Rh system. This antigen is found on the surface of red blood cells. The anti-D antibodies made by the mother pass across the placenta into the baby’s bloodstream, where they bind with it, destroying the blood cells. The child develops anemia gradually, and if the child is left untreated, further complications may develop – enlargement of the heart, ascites, hypoxia and tissue swelling. In the most severe cases, anemia can lead to the death of an intrauterine child or the death of a newborn, but this is extremely rare nowadays because we deal with this disease very effectively.
Why is it said that the first pregnancy is usually safe?
Antibodies rarely develop during pregnancy, and when they do, it usually happens in the third trimester. This is usually so late that the levels are not high enough to endanger the baby. Usually, an allergy to the child’s antigens occurs during the termination of pregnancy (childbirth or miscarriage), and then there is greater contact of the mother with the child’s blood.
The problem usually arises in the next pregnancy as the antibodies have a long time to “mature” and gain strength. If the woman is in her first pregnancy and has not had any other possibility of “allergy” to certain antigens (by contact with foreign blood, for example during transfusion of incompatible blood, using contaminated syringes, using tattoo equipment, etc.), the first pregnancy does not involve usually with the risk of serious complications.
What tests allow for the diagnosis of conflict risk? When should they be made?
The diagnosis of serological conflict is quite simple. It basically consists of two steps – the first is to assess the antibodies circulating in the mother’s blood, and the second is to test the fetus for anemia.
The first step is, of course, to test the blood type of the pregnant woman and her partner. In the case of antigen incompatibility (in anti-D conflict it is the situation when the mother is Rh negative, the father is Rh positive, the mother has no antibodies), tests for the presence of antibodies against the D antigen from the Rh system are performed once a trimester. If there are no antibodies, it means no conflict and the diagnosis is over.
If antibodies are detected, their titer is checked monthly. If their level is dangerously high (exceeds the so-called critical titer, usually 1: 8), a pregnant woman is referred to a specialized center dealing with the diagnosis and therapy of serological conflict. In women with high levels of anti-D antibodies, the ultrasound examination, which directly assesses the condition of the fetus, is of fundamental importance. Ultrasound examinations are performed every 1-2 weeks, depending on the situation.
The first symptom of fetal anemia on ultrasound is acceleration of blood flow in the fetal circulation. The blood flow velocity in the fetal middle cerebral artery (MCA PSV) is tested, if it is accelerated then there is a very high probability of significant anemia. This is usually the same as starting treatment, which consists of intra-infusion blood transfusions, which are carried out at 2 – 3 week intervals until delivery. A concentrate of Rh negative red blood cells, insensitive to circulating antibodies, is administered to the child into the umbilical vein. This procedure has been performed since the 80s, but because it is technically difficult and requires some experience, it is still performed only in specialized centers.
A novelty in diagnostics is that, starting from the 11th week of pregnancy, it is also possible to perform a non-invasive test for the presence in the mother’s blood of the gene encoding the child’s D antigen. This test is completely safe and involves taking a blood sample from the woman. On its basis of pregnancy, it can be detected whether the baby has the D gene or not, and therefore whether the baby is Rh positive or Rh negative. Any Rh negative woman at risk of conflict can do this test. If the baby is found to be Rh negative, there is no need for further monitoring for serological conflict. This test is of particular importance in women who have antibodies from previous pregnancies and it is not known whether the baby is at risk in the current pregnancy or not.
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What is intra-pregnancy prophylaxis in terms of fetal hemolytic disease?
Prevention of serological conflict consists in administering immunoglobulin to the woman, i.e. a preparation containing natural anti-D antibodies. Its role is to bind and neutralize the fetal red blood cells that have entered the woman’s circulation, which blocks the development of the immune response. There are two types of serological conflict prevention. The first, classic, is the administration of anti-D immunoglobulin after childbirth or miscarriage. The idea of intra-pregnancy prophylaxis is analogous – by administering anti-D immunoglobulin to Rh negative women in the third trimester (between the 3th and 28th week of pregnancy), we try to protect them against the possibility of immunization from the moment of immunmoglobulin administration until delivery.
This is a way to further reduce the risk of serological conflict. Following intra-pregnancy prophylaxis, the newborn’s blood group is checked after delivery, and immunoglobulin is re-administered if it is Rh positive.
Patients in Poland should feel safe, immunoglobulin is reimbursed. Unfortunately, the reality is different and access to the guaranteed service leaves much to be desired, and patients do not receive proper prophylaxis. Who is affected and why?
The attending physician should propose such prophylaxis to a woman after a negative test result for anti-D antibodies, which is performed between the 21st and 26th week of pregnancy. The resignation from prophylaxis can only take place when it is known that the child is Rh negative or the patient for some reason does not consent to the administration of immunoglobulin.
All women should have universal access to immunoprophylaxis, because, like other benefits for pregnant women, it is reimbursed by the National Health Fund. In practice, however, it happens that women who carry out pregnancies outside the NHF reimbursement system have trouble obtaining this benefit for free. In order to obtain them, it is usually enough to register with a clinic that has a contract with the National Health Fund. If you have any problems, it’s best to talk to your doctor about it.
Is administration of immunoglobulin safe for pregnant women in view of the ongoing epidemic? Does my immunity drop after giving it?
There are no data to suggest that anti-D immunoglobulin administration has any effect on resistance to SARS-Cov – 2 virus infection. Standard practice is recommended.
Due to the COVID-19 epidemic, some patients, fearing infection, give up intra-pregnancy prophylaxis or come too late, believing that the risk of falling ill is more dangerous than the serological conflict itself. Are you right, Professor?
I understand the concerns of pregnant women about getting sick, but there is no reason to avoid serological conflict prevention due to the COVID-19 pandemic. Before going to the doctor, you need to be properly protected, just like before any other medical visit or any other way out of the house.
The epidemic will pass and the serological conflict will remain, because immunization of a woman’s body, once it occurs, will be remembered in each subsequent pregnancy in which the baby has the appropriate antigen. A winter-immunized woman who decides to have further pregnancies is then faced with frequent diagnostics of the child’s condition, possibly even intrauterine treatment, certainly with great stress and, however, a certain risk of pregnancy loss.
In the event of a conflict, as in other situations – the slogan is still valid – it is much better to prevent than to cure. Prophylaxis is very effective, safe and much simpler than treatment.
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