Rh conflict and pregnancy: what to do

For many “different Rhesus” parents, the risk of Rh conflict becomes a serious cause for concern. Others claim that they already have Rh-positive children, and each of them was born healthy. So why does Rh conflict not occur in all cases? And how can you know for sure its risk?

What is Rh incompatibility?

The Rh factor of the blood is a special protein on the surface of red blood cells (erythrocytes).

When such a protein enters a Rh-negative (Rh-) organism, the latter’s immune forces develop protection - antibodies that attack the “enemy” when they encounter him again.

In the case of pregnancy, we are talking about maternal antibodies “attacking” the red blood cells of the fetus. As a result, pregnancy can end in hemolytic disease of the newborn (HDN), miscarriage or intrauterine death of the child.

Why doesn’t everyone have “conflict”?

In order for the mother to develop Rh antibodies, the fetal blood must enter her bloodstream in sufficient volume.

This situation practically does not occur during a healthy pregnancy, and according to statistics it accounts for only about 10% of cases.

The threat of conflict increases significantly if the pregnancy was preceded by abortions, miscarriages, threats of termination with placental abruption, or complications in previous births.

In this case, class M antibodies first appear in the mother’s blood, which, due to their size, do not pose a danger to the fetus. IgM is simply not able to penetrate the placental barrier, which cannot be said about the class G antibodies that replace them.

IgG is much smaller than its predecessors, easily penetrates the fetus and remains in the mother’s blood for many years.

Thus, a high risk of Rh conflict even during the current pregnancy occurs only in women with a burdened obstetric and gynecological history. Whereas in other cases this risk is minimal.

How to check

When registering, all Rh-negative women are given a blood test for Rh factor and blood group.

The same analysis is recommended for the child's father.

If the Rh factor of both parents is negative, there is simply nothing to worry about. But, if the father turns out to be “positive”, the pregnant woman will have to donate blood monthly for anti-Rhesus antibodies until 28 weeks.

If antibodies do not appear in the blood by the specified date, the woman will be referred for prophylactic administration of anti-Rhesus immunoglobulin, and at this point the search for antibodies will stop.

The administration of immunoglobulin is also permissible in the first 72 hours after birth, at the birth of a Rh-positive baby, if immunization has not been previously carried out.

If antibodies nevertheless appear before 28 weeks and increase, the pregnant woman will be sent for a more in-depth examination to determine the degree of Rh conflict, treatment and, if necessary, emergency delivery.

How to find out your risk

Today, the only conflict prediction measure recommended and funded by the Ministry of Health is a blood test for anti-Rhesus antibodies.

However, there is another option for solving the “problem”.

Already from 10 (for a singleton) and 12 weeks (for a multiple) pregnancy, it is possible to determine the Rh of the fetus from the mother’s blood.

The study does not require special preparation and there are practically no contraindications. And its reliability is 99%.

The analysis is actively used in the USA, Japan and most Western European countries. And during its existence it has proven itself to be absolutely safe and highly effective.

Alloimmune anti-erythrocyte antibodies (including anti-Rhesus antibodies), titer

This is the detection of antibodies to a specific protein located on the surface of red blood cells - the Rh factor. These antibodies are one of the main causes of hemolytic disease of newborns.

Synonyms Russian

Anti-Rhesus antibody titer.

English synonyms

Anti Rh, Rh Typing.

Research method

Agglutination reaction.

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

Do not smoke for 30 minutes before donating blood.

General information about the study

The Rh factor (Rh) is inherited and is a protein on the surface of red blood cells. Those people who have it (and this is the majority, about 85%) are called Rh positive. However, some people who are Rh negative lack this protein. Negative Rh does not affect the health of the person himself. However, problems can arise between the mother and the baby she is carrying if they have different Rh factors or if the mother develops antibodies that react with factors in the baby's blood cells. The most common example: a woman with a negative Rh factor (Rh-) is pregnant with a child with a positive Rh factor (Rh). This woman's immune system may develop antibodies against her baby's Rh-positive blood. Despite this, the firstborn is quite rarely sick, because the mother’s immunity does not come into contact with the child’s blood until birth. However, antibodies produced during the first pregnancy can freely cross the placenta in subsequent pregnancies and thus create problems for the Rh-positive baby.

To reduce the chance that an Rh- mother will develop antibodies to the baby's Rh blood, she is sometimes given injections of anti-D-gamma globulin 28-34 weeks before giving birth, and also immediately after the birth of an Rh-positive baby. Additional injections may be required during pregnancy if there is a suspicion that the mother's blood has come into contact with the blood of the Rh fetus (for example, during puncture of the amniotic sac or abdominal trauma). The injection of the antibody clears the baby's blood of any antigens present and thus prevents the mother's immune system from reacting to them.

What is the research used for?

The anti-Rh antibody test is used primarily to detect antibodies to the Rh factor. An Rh negative mother and an Rh positive father can conceive an Rh child, and there is a chance that some of the baby's red blood cells will enter the mother's bloodstream during pregnancy and childbirth. In response to foreign Rh red blood cells, the mother's body produces anti-Rh antibodies. They pose a threat to this mother's future children. Every woman before or during pregnancy must be tested for the Rh factor. It will help determine whether her blood is Rh negative and also determine whether the Rh negative woman has acquired antibodies against Rh red blood cells. A pregnant woman whose body has not yet formed anti-Rhesus antibodies can use immunoglobulin injections to prevent their appearance. An Rh-negative woman during pregnancy should undergo additional treatment with immunoglobulins immediately after any situation where fetal blood could enter her bloodstream. Analysis for anti-Rh antibodies helps to identify these processes and promptly prescribe and adjust treatment to prevent Rh conflict.

When is the study scheduled?

If necessary, prescribe treatment with immunoglobulin injections to a pregnant woman with a negative Rh factor.
In the case when the red blood cells of the fetus could enter the bloodstream of a pregnant woman with an Rh-negative factor, if she had miscarriages, ectopic pregnancy, artificial birth or abortion, puncture of the amniotic sac, abdominal trauma, artificial change in the position of the fetus.

The test may be prescribed to a woman who is Rh negative, who has given birth to a Rh positive child and has been treated with immunoglobulin injections, to determine whether the child has antibodies against Rh red blood cells.

What do the results mean?

Reference values: negative.

Positive result

Antibodies have been detected, there is a possibility of Rh conflict.

Negative result

Antibodies were not detected, the likelihood of Rh conflict is low.

Proper treatment with anti-D-gamma globulins prevents the formation of anti-Rhesus antibodies in almost all pregnant women with a negative Rh factor.
However, such prevention does not work if the woman has already formed anti-Rhesus antibodies. Important Notes

Anti-Rhesus antibodies are sometimes present in very low, undetectable quantities.
The blood of young children can react with the antibody, even if the test is negative.
If the mother has had an anti-D-gamma globulin injection within the last six months, the antibody test may give positive results.
A woman who is Rh negative does not need to be treated with anti-D-gamma globulin injections if the child's father is also Rh negative, since the child will also be Rh negative, so there is no risk of hemolytic disease.

Detailed description of the study

In the human body, there are different proteins on the surface of blood cells - red blood cells. Among them is the Rh factor, a protein so named because it was first identified in rhesus monkeys. Its other name is antigen D.

The Rh factor is detected in almost 2/3 of people, while 1/3 does not have it on the surface of red blood cells. Its presence or absence does not affect human health in any way. The presence of the Rh factor on red blood cells is determined by heredity. If at least one of the parents has this protein, then there is a possibility of its presence in the child’s blood.

The Rh factor appears in the child’s body during the development of the circulatory system and the production of red blood cells, that is, already during intrauterine development. The problem arises when this protein is present on the fetal red blood cells but not in the mother. In such a situation, there is a possibility of Rh sensitization followed by Rh conflict.

For Rh conflict to occur, fetal blood must enter the mother's bloodstream. Placental blood circulation is designed in such a way that this does not happen directly; there is a so-called placental barrier. However, during childbirth it is disrupted, and if red blood cells with a foreign protein (Rh-antigen, or D-antigen) enter the mother’s body, the production of antibodies (AT) to it begins. This process is called Rh sensitization; it occurs unnoticed in a woman’s body and does not affect her health in any way.

It is believed that medical procedures during pregnancy (chorionic villus sampling, amniocentesis), abortion, as well as bleeding and abdominal trauma during pregnancy increase the likelihood of Rh sensitization and conflict.

If antibodies to Rh have been formed in a woman’s body, then during pregnancy (present or next) a Rh conflict may develop. These antibodies are able to penetrate the placental barrier into the fetal bloodstream, where their target is the D-antigen on the surface of red blood cells. Antibodies bind to this protein, which leads to accelerated destruction of blood cells (hemolysis).

As a result of hemolysis, many adverse consequences occur for the developing child in utero. Firstly, there is a deficiency of red blood cells, the function of which, namely the transport of oxygen to tissues, is vital. Secondly, bilirubin released into the blood damages the nervous system, including the brain. Collectively, this condition is called hemolytic disease of the fetus (HDF). With severe HDP, fetal death is possible; in other cases, the child may be born prematurely. Hemolytic disease of the newborn varies in severity, usually manifesting as jaundice and multiple disturbances in the functioning of the nervous system.

Timely determination of the antibody titer to the Rh factor can prevent the development of HDP. This indicator should be assessed regularly during pregnancy. Together, diagnostic and preventive measures against Rh-conflict in women without the Rh factor help prevent HDP.

Conflicting rhesus and conception

What should women with negative Rh blood factor keep in mind when planning pregnancy? Readers' questions are answered by a gynecologist at the Research Institute of Obstetrics and Gynecology named after. BEFORE. Otta RAMS in St. Petersburg Marina Vladislavovna BONDARENKO.

We recommend that you read the article on our website: “Conceiving with a negative Rh factor”

“I have negative Rh blood, and my husband is positive. Is Rh conflict a threat to our unborn child? “Lidiya K, Pyatigorsk

— A conflict can arise if the mother has a negative Rh factor, the father has a positive Rh factor, and the baby has inherited a positive Rh factor from his father. And if during pregnancy the fetal red blood cells enter the mother’s blood, then her immune system destroys them as “foreign”. Such exposure may occur during childbirth, abortion, or miscarriage. So women with negative Rhesus need to do an appropriate blood test before conception. And based on its results, engage in family planning.

If this is your first pregnancy, you should regularly check your blood for Rh antibodies. Standard deadlines have been developed for this. In the first half of pregnancy, antibody testing should be carried out once a month. In the second half - 2 times a month. After 36 weeks of pregnancy, antibodies in the blood are determined once a week, and immediately before childbirth - once every 3 days. This allows you to understand in time whether your unborn child is at risk of Rh conflict and take action.

“Is it possible to carry out some kind of prophylaxis during pregnancy to prevent Rh conflict from developing, and for what period? What affects the formation of antigen?”Natalia, Cherepovets

— Various complications during pregnancy can trigger the production of Rh antibodies. For example, placental abruption and any other violation of its integrity, gestosis, infections or abdominal injuries. In all these cases, fetal red blood cells can also enter the mother's blood and trigger a response from her immune system. Antibodies can appear if a woman has been transfused with Rh-incompatible blood in the past.

Increases the risk of a conflict situation and caesarean section. Even if antibodies are not detected in your blood, it is still worthwhile to prevent Rh conflict. This way you will protect yourself and your baby in case you want to become a mother again. It is carried out three times: at 10-12, 24-25 and 32-33 weeks of pregnancy. There are several drug regimens used for this purpose. The most effective combinations of ascorbic acid with glucose, sigetin, methionine, calcium gluconate, and rutin. Another regimen includes vitamin E, vitamin Bis and rutin. And at night it is recommended to take diphenhydramine.

“I heard that Rh conflict can lead to hemolytic disease in a child. What is this? “Anna Gromova, Arkhangelsk

— In hemolytic disease, bilirubin, a tissue poison, reaches the child through the blood. It disrupts the delivery of oxygen, damages the fetal brain, leads to hearing and speech impairment and turns the baby’s skin yellow. Such violations arise from which the child may die.

Currently, hemolytic disease can be diagnosed in utero. In particular, based on ultrasound examination. It shows an enlarged fetal liver, thickening of the placenta, and polyhydramnios. The diagnosis can be made by taking blood from the umbilical cord. It determines the level of bilirubin and hemoglobin in the fetus, which show how far the process has progressed. Bilirubin is also tested in amniotic fluid. The higher this indicator, the more severe the disease. The main method of treatment is intrauterine blood transfusion to the child. In this case, the “infected” blood is replaced with healthy one. Vitamins are an essential component of successful treatment.

“During the first pregnancy, no antibodies were found in the blood. I would like to become a mother two more times. How realistic is this? How many children can a woman with Rh incompatibility give birth to without risking their health? How often is it better to give birth? “G. Volkova, St. Petersburg

— There is no clear answer to the first two questions, because it is impossible to predict which parent’s Rh factor will be inherited by their next child. Only general patterns are known. During the first pregnancy, the level of Rh antibodies, if they appear, is usually not too high. This is due to the fact that the woman’s immune system encounters “foreign” cells for the first time.

In subsequent pregnancies, thanks to 'cellular memory', the woman's immune system produces antibodies much faster and in much larger quantities. This is why Rh-negative women are advised to avoid terminating their first pregnancy.

Keep in mind: once Rh antibodies have formed, it will not be possible to get rid of them once and for all. Therefore, the frequency of birth does not play a big role. If antibodies are already present, their number will not change between births. The only rule is that the birth of each new child must be approached responsibly and try to eliminate possible complications of pregnancy.

“I heard that a Rh-negative woman should be vaccinated with anti-Rh gamma globulin after every birth or abortion. Only then are her subsequent children protected from the consequences of Rh conflict. I'm going to have more than one child. What if antibodies are still detected in the blood during the next pregnancy?” Maria Menshova, Perm

— Anti-Rhesus gamma globulin must be administered to a woman after any manipulation of the uterus. Injection of this drug reliably protects against Rh conflict in subsequent pregnancies. It can be administered at 28 weeks of pregnancy or after childbirth. But this must be done within 72 hours. It doesn't make sense later.

In advance, ask the maternity hospital where you will give birth if it is available. If not, then buy gamma globulin at one of the city blood transfusion stations.

“Six years ago I had a daughter, after that there were three more pregnancies that ended in early miscarriage. Could this be due to the fact that I am Rh negative? Will I be able to have another child? “Gulnara V., 30 years old

— A test for Rh antibodies will help answer this question. It is done in any clinic. If they are discovered, it is possible that they were the cause of the miscarriage. Depending on the amount of antibodies in the blood, the doctor may suggest lowering their levels using plasmapheresis. During this procedure, the plasma is purified, and thus the risk of developing Rh conflict in subsequent pregnancies is reduced. This procedure is carried out before conception.

However, it is not only Rhesus conflict that can lead to miscarriage. Therefore, at the stage of pregnancy planning, it is necessary to undergo a full examination.

Elena DOPGANOVA Source: “Women's Health” Take the first step - make an appointment!

or call 8 800 550-05-33

free phone in Russia

The authors presented literature data concerning the role of autoantibodies in the development of pathology in pregnant women. Based on our own data, it has been established that analysis of the content of many natural antibodies in a woman preparing for pregnancy allows us to give a reasonable prognosis for the development and result of the planned pregnancy, and to prescribe adequate preventive therapy.

Autoantibodies and immunopathology of pregnancy

The authors presented data in the literature concerning the role of autoantibodies in the development of pathology in pregnancy. based on own data revealed that analysis of the content of many natural antibodies in women preparing for pregnancy, can give a reasonable prognosis and outcome of planned pregnancies, prescribed adequate preventive therapy.

Up to 40% of all pregnancies end in the death of the fertilized egg or early embryo in the first 1-3 weeks [1]. Moreover, in another 10-15% of cases, pregnancy is terminated at a later stage or ends in the birth of a child with certain disorders [3]. Moreover, if gene and/or chromosomal aberrations make a significant contribution to stopping the development of pregnancy at the initial stages [2], then at later stages of the development of the gestational process the relative role of genetic disorders is significantly reduced. As a result, considering the entire period of pregnancy, it is usually believed that genetic abnormalities underlie approximately 5-13% of adverse pregnancy outcomes [4], and in approximately 90% of cases the pathology is caused by non-genomic disorders, primarily immune [1, 5, 6].

At the level of phenomena, it has been established that intrauterine development directly depends on the functional state of the mother’s immune system and is regulated, in particular, by many interleukins, interferons and embryotropic antibodies of the IgG class [5, 6]. This is due to the fact that many cytokines are pluripotent growth factors [7], and a number of antibodies can stimulate the growth and differentiation of target cells and perform many other regulatory functions [8]. Taking into account such data, the concept of the participation of the immune system in the regulation of cell differentiation during the individual development of the organism was formulated [9, 10].

Embryotropic antibodies

The serum concentration of embryotropic antibodies in healthy women (as well as any other regulatory molecules) is maintained within a narrow range, while in women suffering from miscarriage, who have a history of fetal death or the birth of children with developmental defects, the concentration of many embryotropic antibodies goes beyond the physiological limits norms in more than 90% of cases [5]. Even small deviations (about 10-15% from the norm) in the content of embryotropic antibodies in approximately every eighth case lead to a halt in the development of pregnancy or the birth of a child with disorders, and a persistent twofold excess (or decrease) of their level leads to unfavorable outcomes in more than 60 % of cases [11, 12]. The dependence of the course of the gestational process on the serum content of certain maternal IgG antibodies today is beyond doubt. However, which antibodies should be determined for diagnostic and prognostic purposes remains open.

Every year, many publications appear describing the negative obstetric consequences of increased production of antibodies to DNA, but it is clear that an excess of antibodies to DNA is nothing more than a private manifestation of immunoregulation disorders that negatively affect reproductive functions. With the description of antiphospholipid syndrome, the attention of obstetricians was drawn to antibodies to cardiolipin, phosphatidylserine, phosphoinositol and the main phospholipid-binding protein of blood serum - β2-glycoprotein I [6, 13]. Let us note that the most reliable, early and sensitive reflection of clinically significant changes in the body of patients with APS, including those causally associated with miscarriages and fetal growth arrest, is not so much changes in antibodies to cardiolipin, but rather shifts in the content of antibodies to β2-glycoprotein I [ 5, 6, 13]. Thanks to the work of G. Talwar [14], we know about the dependence of reproductive functions on the level of antibodies to LH, FSH and prolactin. In the same series are works devoted to anti-hCG syndrome [6]. Excess antibodies to specific ovarian antigens are accompanied by premature ovarian aging syndrome [15]. Data are emerging on new antibodies, the excess of which negatively affects the development of pregnancy. Here we can note the glycoproteins of the PSG group (pregnancy-specific glycoproteins), the Mater protein (Maternal Antigen that Embryos Require) and many others [16, 17].

It seems that the causative factors of infertility, miscarriage, the development of fetoplacental insufficiency and various fetal malformations may be pathological changes in the production of many maternal antibodies, and any natural antibodies of the IgG class (that is, penetrating the placental barrier [18]) synthesized in the body a pregnant woman, in fact, can be considered as "embryotropic". Based on the fact that natural antibodies, which are biologically active molecules, are needed by the body in strictly defined quantities, it is clear that not only an increase, but also a pathological decrease in the content of many (any?) autoantibodies can lead to pregnancy pathology, including recurrent miscarriage, developmental arrest pregnancy, gestosis and fetal malformations [12, 19] - a deficiency of any regulatory molecules (as well as an excess) can be accompanied by clinically significant changes. To illustrate, it is enough to recall the excess or insufficient production of thyroid hormones.

Conditionally pathogenic flora and changes in the content of embryotropic antibodies

The cause of changes in the content of embryotropic antibodies is most often chronic infections that can induce both an increase and a pathological decrease in the production of these molecules. The ability to activate different clones of immunocompetent cells and cause a persistent increase in the production of different types of antibodies is inherent, for example, in herpes simplex viruses, Epstein-Barr viruses, cytomegaloviruses, etc. Some bacteria can also directly trigger polyclonal activation of B lymphocytes using so-called superantigens [5 ]. Representatives of opportunistically pathogenic flora can also be the cause of pathological immunosuppression, since suppression of the general activity of the immune system is one of the most important elements of the microflora’s survival strategy in the body’s conditions [20].

Less commonly, changes in antibody levels can also be caused by various types of chronic intoxication (including those associated with unjustified use of medications), endocrine pathology, and systemic immune disorders in the form of autoimmune diseases or immunodeficiencies [5]. If anomalies in the content of embryotropic antibodies, caused by any reason, turn out to be transient (lasting no more than 1-3 weeks), as a rule, they do not have time to cause noticeable harm to the embryo. However, the presence of a persistent infection in the body (viral, urogenital) often causes long-term, persistent changes in the mother’s immune system, and the development of pregnancy against the background of persistent disturbances in the production of embryotropic antibodies is accompanied by a significant increase in the risk of developmental pathology.

Excessive production of many maternal antibodies creates the prerequisites for the formation of pathological changes in the fetus both due to direct antibody-mediated aggression and due to prenatal programming of the child’s immune system for increased production of the same antibodies as its mother (the phenomenon of epigenetic immune imprinting [5, 21] ]). Along with this, the lack of production of many antibodies involved in the clearance of the body (including antibodies to DNA, phospholipids, etc.) can also lead to pregnancy pathology due to the accumulation of excess reactive catabolites and the formation of chronic progressive intoxication of the woman’s body, which is especially negative affects the condition of the fetus.

Altered levels of embryotropic antibodies are a characteristic feature of many women suffering from infertility, including those who have repeatedly and unsuccessfully undergone in vitro fertilization (IVF). Anomalies in the content of embryotropic antibodies are detected in approximately 80-90% of such cases and are a likely causative factor causing the failure of nidation or the death of the attached embryo in the early stages of its development [5]. Successful drug treatment of women with altered levels of embryotropic antibodies, infectious etiology, or endocrine problems is, in more than 90% of cases, accompanied by a significant improvement in immunochemical parameters. Moreover, already in the first 6 months after correction of the content of embryotropic antibodies, in approximately 30% of infertile women pregnancy occurs and develops successfully [12, 22]. O.F. Serova [22] noted that etiotropic therapy of women suffering from miscarriage gives the most significant results if the treatment is carried out under the control of the content of embryotropic antibodies, and a significant improvement in “antibody” indicators is an indication of the effectiveness and sufficiency of the therapy. On the contrary, the absence of positive dynamics objectively indicates the ineffectiveness of the treatment regimen used [22].

Why do opportunistic infections lead to miscarriage and other developmental disorders of pregnancy or infertility in some women, while in others the presence of the same factors may not have a noticeable effect on the development of pregnancy? The answer is that in some women these factors cause persistent systemic immune compensation (affecting the mechanisms of immunoregulation of pregnancy), while in others they are not accompanied by noticeable systemic disorders (they cause only local changes). These findings are consistent with the experimental data from Cronise a. Kelly [23], who showed that asymptomatic urogenital infection may or may not be a factor in the development of the embryo and fetus, depending on whether its presence is accompanied by systemic immune changes in the woman’s body.

In this regard, we note that the father of microbiology, Louis Pasteur, referring to the relationship between micro- and macroorganisms, emphasized that “the microbe is nothing, the substrate (that is, the host organism) is everything” (cited from [20]).

Thus, the identification of opportunistic pathogens (many viruses, mycoplasmas, gardnerella, etc.), usually present in an asymptomatic form, is not always an indication for intensive drug therapy. At the same time, analysis of the content of embryotropic antibodies in the blood serum of a woman preparing for pregnancy or already pregnant allows us to assess the degree of individual pathogenicity of the present microflora and decide on the advisability of etiotropic therapy in each specific case. Awareness of this allows a rational approach to the prescription of preventive and therapeutic measures used before and during pregnancy to reduce the risk of negative consequences. If there is an obvious need for therapy, the prescribed measures should be aimed at achieving not one (elimination of the infection), but at least two important goals. On the one hand, they should suppress the reproduction and/or eliminate pathogenic microorganisms, and on the other hand, they should help normalize the functional activity of the immune system, manifested in inadequate synthesis and secretion of natural antibodies.

Papilloma viruses and reproductive disorders

It is known that human papillomaviruses (HPV) are among the most common sexually transmitted infectious agents. The results of HPV exposure are not limited to cosmetic problems and an increased risk of cancer. HPV disrupts the implantation of a fertilized egg [25]. The presence of HPV infection at least halves the chances of success of the IVF procedure [25]. Pregnancy in women infected with HPV is often accompanied by disturbances in the development of the fetal neural tube, which leads to a 10-12-fold increase in the incidence of neurological disorders in children born to infected mothers [26].

It is assumed that the influence of HPV on the gestational process is due to the fact that more than half of HPV carriers experience a selective increase in the production of antibodies to S100 group proteins, associated with the phenomenon of molecular mimicry, that is, the presence of common epitope fragments in S100 proteins and HPV antigens [5, 35, 25]. These observations allow us to recommend that for women with signs of human papillomavirus infection, mass screening tests for the level of antibodies to S100 proteins and, if necessary, correction/treatment in the preconception period. Given the population prevalence of HPV, these measures can significantly increase the effectiveness of preventing adverse pregnancy outcomes.

Maternal immune imprinting

Epigenetic maternal immune imprinting involves the child’s “inheritance” of the individual characteristics of the mother’s (but not the father’s) immune status that occurred during pregnancy [5, 21]. Thanks to it, a newborn child, even before meeting ubiquitous infectious agents, acquires a certain resistance to them. Moreover, the more intense the mother’s specific immunity, the higher is her child’s immunoresistance to the same infections. However, through immune imprinting, a mother can negatively influence the health of her child if she has persistent immune disorders. For example, maternal SLE can induce the development of “neonatal lupus” in a child aged 4-8 months. A mother who has elevated levels of antibodies to insulin and/or insulin receptors often passes these characteristics on to her child, which can persist until 4-6 years of age and beyond, being a risk factor for the development of diabetes. It can be assumed that the repeatedly noted tendency of children to develop the same forms of pathology (endocrine, renal, cardiac, joint, etc.) that their mothers had [27], at least in some cases, is based on the phenomenon of epigenetic immune imprinting [ 28].

Maternal immune imprinting, which may not be directly related to developmental disorders of pregnancy, is one of the most important factors determining the health of the unborn child [21]. Therefore, taking into account abnormalities in the immune status of a pregnant woman, which can be persistently fixed by the immune system of her child, is important for assessing the risks of developing somatic, endocrine and neurological changes in the child in the first months and years of life.

Conclusion. Clinical illustrations

In conclusion, we present the results of some clinical observations and conclusions of our colleagues, which clearly illustrate the practical importance of assessing the content of embryotropic antibodies for obstetric and pediatric practice. The corresponding observations were made mainly using the immunoenzyme method ELI-P-Complex [5], which makes it possible to determine the content of antibodies to human chorionic gonadotropin, double-stranded DNA, b2-glycoprotein, Fc fragment of immunoglobulins (rheumatoid factor), collagen in one blood serum sample , sperm antigen SPR-06, protein S100, platelet antigen TrM-03, vascular endothelial antigen ANCA, insulin, thyroglobulin and kidney antigen KiM-05.

According to O.G. Litvak [24] and L.V. Grigorova [28], abnormalities in the serum content of embryotropic antibodies are detected in approximately 70% of women suffering from tubo-peritoneal infertility. It is characteristic that as a result of surgical (laparoscopic) treatment alone, restoration of fertility can be achieved in 20-30% of cases, while when combined treatment is prescribed, carried out under the control of serum levels of embryotropic antibodies, the effectiveness exceeds 70%.

According to S.G. Zhegulina [29], 94% of women with thyroid pathology had abnormalities in the content of embryotropic antibodies. Timely diagnosis and adequate therapy, carried out under the control of embryotropic antibodies, mainly during the period of preconceptional preparation, made it possible to reduce the number of adverse outcomes of subsequent pregnancy in women with thyroid dysfunction by 2.5 times.

According to M.A. Nyukhnin [30], only in 7.4% of pregnant women with a burdened obstetric history, the content of embryotropic antibodies corresponds to normative values (in 93.6% it is outside the normal range). Moreover, the development of pregnancy in women with a reduced level of antibodies is characterized by the threat of miscarriage, gestosis, and placental insufficiency. Increased antibody levels are associated with spontaneous abortion and chronic placental insufficiency. An imbalance of autoantibodies is accompanied by recurrent miscarriage, undeveloped pregnancy and preeclampsia. With a low level of antibodies, DIC syndrome developed in 63% of pregnant women, with an increased level - in 59%, and with an imbalance of antibody levels - in 91%. The most severe changes in the hemostatic system were observed in women with imbalance and pathologically elevated levels of antibodies.

According to N.A. Cherepanova [19], disturbances in the content of embryotropic autoantibodies in the initial stages of pregnancy make it possible to assess the risks of developing premature placental abruption, preeclampsia, uterine bleeding, and the dynamics of changes in antibody levels can serve as a criterion for the adequacy of treatment and prognosis of pregnancy outcome. Both excess and lack of production of embryotropic antibodies can be accompanied by disturbances in the regulation of hemostasis.

According to O.V. Makarova and N.A. Osipova [31], determination of the serum content of a number of natural antibodies makes it possible to preclinically identify pregnant women at risk of developing preeclampsia, which allows timely initiation of therapy aimed at improving hemodynamics and stabilizing the condition of the fetus. It is characteristic that the development of the clinical picture of gestosis is preceded by pronounced immunosuppressive changes, manifested in a pathological decrease in the serum content of embryotropic antibodies.

According to O.F. Serova [22], both excess production of embryotropic antibodies and their deficiency have a detrimental effect on the development of the embryo and fetus, and with increased frequency leads to intrauterine fetal death or developmental defects. Effective elimination of the main etiological factors (whether infectious and inflammatory processes, endocrine disorders, etc.) is accompanied by normalization of the synthesis of embryotropic antibodies and reduces the incidence of adverse pregnancy outcomes by 5-8 times.

According to R.S. Zamaleeva and S.O. Klyuchnikova [32], an integral assessment of the health status of children from the neonatal period to 4-6 years of age, indicates: if children were born to women with a normal content of embryotropic antibodies during pregnancy, more than 70% of such children by 4-6 years are practically healthy . On the contrary, the more pronounced the immune disorders in the body of pregnant women, the lower percentage of cases they give birth to healthy children. Only 1 child out of 7 from a woman with moderate disorders of embryotropic antibodies could be considered practically healthy, and among children born from women with severe disorders, there were no healthy children.

Despite the fact that many aspects of the immunoregulation of pregnancy remain practically unstudied, we believe that analysis of the content of many natural antibodies in a woman preparing for pregnancy allows us to give a reasonable prognosis for the development and outcome of the planned pregnancy, and, if necessary, to prescribe in advance preventive measures that are adequate to the situation. therapy that takes into account the individual characteristics of the patient.

A.B. Poletaev, F. Alieva

Research Institute of Normal Physiology named after. P.K.Anokhin RAMS, Moscow.

Research Institute of Obstetrics and Gynecology, Baku, Azerbaijan

Poletaev Alexander Borisovich - Doctor of Medical Sciences, Professor, Scientific Director of the Immunculus Medical Research Center, Leading Researcher at the Research Institute of Normal Physiology named after. PC. Anokhin RAMS, Moscow.

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Antibodies to Rhesus system erythrocyte antigens (specificity, titer)

What are antibodies to Rh system antigens (anti-erythrocyte antibodies, alloimmune antibodies)?

These are antibodies to the most important erythrocyte antigens. Rh antibodies are alloimmune antibodies that appear in the body in the case of:

transfusion of immunologically incompatible donor blood;
pregnancy, when fetal red blood cells carrying paternal antigens that are immunologically foreign to the mother penetrate the placenta into the woman’s blood.

There are several types of main antigens in the Rh system, the main one of which is D, for which incompatibility most often occurs. Less commonly, incompatibility with other antigens of the Rh system occurs (C, E, c, d, e). Any of these antigens, when introduced into the blood of an antigen-negative patient, causes the formation of specific antibodies in his body.

The determination of anti-erythrocyte alloantibodies is of great clinical importance for preventing the development of hemolysis of donor erythrocytes, identifying allosensitized individuals, and preventing hemolytic disease of newborns using Rhesus system antigens and other antigens.

Hemolytic disease of the fetus (newborn) develops only when a woman with Rh-negative blood is pregnant with a fetus with Rh-positive blood and the woman has already been sensitized to the Rh factor. Of all the antibodies to Rh system antigens, the most severe hemolytic disease of the fetus (newborn) is caused by antibodies to the D antigen.

Hemolytic disease of the fetus is a disease of repeated pregnancies, since the process of immunization of the mother with fetal red blood cells and the immune response - the production of appropriate antibodies - usually does not fit within one gestational age. This is possible if the first-time mother had abortions, blood transfusions without taking into account the Rh factor, a minor cesarean section, artificial termination of pregnancy in the second trimester by amniocentesis, when it is possible for fetal blood to enter the mother’s bloodstream - sensitization of the maternal body.

It is imperative to investigate the presence of anti-erythrocyte alloantibodies before each blood transfusion, and always before discharge from the hospital (15-30 days after red blood cell transfusion) to determine sensitization by red blood cell antigens and give appropriate recommendations. If the recipient has undergone even one transfusion of erythrocyte-containing components, then he subsequently falls into the “risk” group, because in most cases, unfortunately, the transfusion takes place without typing of erythrocyte antigens, and the body can be sensitized by the erythrocyte antigen that is absent in the person. With repeated transfusion of donor red blood cells (ingress of the same foreign antigen), a rapid immune response is possible with the production of anti-erythrocyte alloantibodies and the development of extravascular hemolysis. Indications for the purpose of analysis:

prevention of Rh conflict in pregnant women;
dynamic monitoring of the level of Rh antibodies in pregnant women;
miscarriage;
hemolytic disease of newborns;
preparation for blood transfusion.