Hemolytic disease of the fetus causes. Hemolytic disease of the newborn (HDN). Obstruction of the portal and umbilical veins

The reason for this is the immune conflict (incompatibility) of the blood of the child and mother. This process is based on the antigen-antibody reaction.

An antigen is a specific substance that is located on the surface of cells (also on the cells of infectious agents - bacteria, viruses, fungi). It carries information about the cell.

An antibody is an immune cell that protects the body from foreign agents. Namely, they receive information about the cell from the antigen. An antibody binds to an antigen and defines it as "self" or "foreign". When the cell has passed the control, the antibodies release it. Otherwise, the alien agent is destroyed.

So why do antibodies attack fetal red blood cells (they are not foreign)? The fact is that blood incompatibility can be for two reasons: due to incompatibility for the blood type or for the Rh factor.

In the first case, the immunological conflict arises in connection with the individual set of antigens on the erythrocytes of each blood group. In simple terms, then:

• I blood type has no antigens, which means that antibodies have nothing to attack. Such people are also called universal donors, that is, this blood with this group can be transfused to all patients.
• The II blood group has its own antigen A.
• Group III - own antigen B.
• Group IV - antigens A and B. That is, such people can be transfused with any blood.

As discussed above, antigens are foreign to the body and the immune system must destroy these agents. Therefore, incompatibility by blood group, in most cases, occurs when the mother has group I, and the child - II. This means that antigen A enters the mother's body, and for her immune system this substance is foreign. It is the same with the III group - antigen B is also a stranger. Since these antigens are located on the surface of the erythrocyte, the antibodies attack them.

This would not have happened if the mother had type II blood. Because when antigen A (blood group II) of the fetus enters the mother's bloodstream, her immune system would take this antigen as her own.

In the case of Rhesus conflict, the principle is about the same. Rhesus is an antigen (called D-antigen) located on the inner surface of the red blood cell. People who have it are considered Rh-positive, while those who do not are Rh-negative. Therefore, an immunological conflict over the Rh factor occurs when the mother's Rh-negative blood and the fetus's Rh-positive blood. That is, when the child's erythrocytes with the D-antigen enter the mother's body, the latter begins to synthesize antibodies against a foreign substance.

When does fetal hemolytic disease occur?

Blood type incompatibility occurs when:

• The mother has group I, and the fetus has II, III or IV.
• The mother has group II, and the child has group III.
• The mother has the ІІІ group, and the child has the ІІ.

What blood type the child will have depends on the blood type of the parents. Since each group has its own set of genes that are inherited. For example, if the mother has group II, and the father has group III, then the child may have group II, III and IV. And the conflict will arise only when the fetus has group III (and a small probability with IV) because antigen B will be foreign to the body of the pregnant woman.

In case of incompatibility for the Rh factor, the conflict will be only if the mother is Rh-negative and the fetus is Rh-positive. If the situation is the opposite, then hemolytic disease will not occur. Because if the fetus is Rh-negative (there is antigen D), then there is simply nothing to attack the mother's immune system.

Why does fetal hemolytic disease occur?

The main condition for the development of this disease is the penetration of fetal erythrocytes into the mother's body. This condition may occur:

• At the birth of a child. During childbirth, there is always contact with blood. Usually, about 3-4 ml of blood enters the mother's bloodstream, but this is enough for the synthesis of antibodies.
• When performing diagnostic manipulations (damage to the placenta when receiving amniotic fluid through a puncture, cordocentesis - obtaining cord blood by puncture).
• With premature detachment of a normally located placenta.
• In case of placenta previa.
• When there is a violation of the integrity of the tissues of the placenta with late gestosis (preeclampsia), diabetes mellitus, high blood pressure, surgical interventions during childbirth (cesarean section, manual separation of placental remains) and the threat of termination of pregnancy.
• During abortion or miscarriage.

The appearance of one or another degree or form of the disease depends on how aggressively the mother's immune system responds to the penetration of foreign antigens. Also, the degree of immune response is affected by the activity of substances that muffle immune activity.

In the case of an Rhesus conflict, there is one point. With Rh incompatibility and the penetration of fetal erythrocytes, the woman's immunity begins to produce antibodies. But only produce. The destruction of red blood cells and the appearance of the disease does not occur. This condition is called Rh sensitization or isoimmunization. It occurs during the first pregnancy. And hemolytic disease will appear already in the next pregnancies, when the mother's bloodstream is full of antibodies ready to attack.

But with incompatibility for the blood group in 15-20% of cases, antibodies can already attack red blood cells during the first pregnancy. However, hemolytic disease will occur in 8-10% of children. The reason for this is not fully understood.

Sensitization can also occur when transfusing Rh-positive blood to an Rh-negative mother. As a result, antibodies begin to be produced and Rh conflict may occur already during the first pregnancy.

What happens in the body with hemolytic disease

Starting from the 17-18th week of pregnancy, fetal erythrocytes already regularly circulate in the mother's bloodstream. In response, the immune system begins to synthesize the very first class M antibodies. They do not cross the placenta, as they are too large for this. Later, the formation of class G antibodies occurs, which can already penetrate. The placenta in most cases holds back antibodies. But during childbirth, the barrier properties are sharply violated and antibodies penetrate into the fetus.

Since there are few fetal erythrocytes in the body of a pregnant woman, the immune response is still weak. After the birth of a child, the number of fetal red blood cells in the mother's blood increases markedly. This contributes to the active synthesis of antibodies (isoimmunization). And during the second pregnancy, the immune system will already constantly attack the red blood cells of the fetus. And if the integrity of the placenta is violated, a severe course of the disease often occurs.

In the antigen-antibody reaction, red blood cells are damaged. They can no longer perform their functions normally. Therefore, special cells (macrophages) capture them and transport them to the liver, bone marrow and spleen. There, defective erythrocytes are utilized, that is, their death (hemolysis). Since red blood cells deliver oxygen to the cells, the tissues begin to starve.

Hemolysis produces a substance called bilirubin. It is a toxic product that must be removed from the body. With intensive destruction of red blood cells, anemia (anemia) develops and bilirubin accumulates excessively (hyperbilirubinemia). The organs can't get it out. In addition, these organs in the fetus are not quite mature and cannot cope with the load. And the amount of bilirubin actively increases in the blood. which damages the internal organs.

The liver is especially affected. Due to the increased load, fibrosis occurs (the formation of connective tissue) and its function is impaired. This is manifested by a decrease in the formation of protein, which contributes to the occurrence of edema, the accumulation of fluid in all cavities of the body and the deterioration of blood circulation in internal organs.

In severe forms of the disease, bilirubin enters the brain and damages its structures. This is called bilirubin encephalopathy. Especially often this form of hemolytic disease occurs in premature babies.

What are the forms of hemolytic disease of the fetus and newborn

In medical practice, the following classification of this disease is distinguished:

For the type of immunological conflict:

Behind the clinical picture:

For the severity (the definition of one form or another depends on the amount of hemoglobin and bilirubin in the blood of the fetus):

Clinical picture of hemolytic disease of the fetus

With the appearance of hemolytic disease due to incompatibility for the blood type, the course is mild and easily treatable. The opposite situation is with Rhesus conflict.

This disease has a wide range of manifestations - from minor hemolysis to the development of severe anemia and damage to internal organs. Symptoms depend on several factors:

• The amount of antibodies that have penetrated into the body of the fetus.
• The number of red blood cells in the mother's bloodstream.
• The amount of bilirubin and hemoglobin in the blood.
• How well the liver and other organs cope with the disposal of toxins.

Severe forms of hemolytic disease (edematous form or intrauterine death) develop when antibodies penetrate the fetus for a long time and actively throughout pregnancy. With a small amount of maternal antibodies, hemolysis will not be so intense, and the liver will cope with the excretion of bilirubin. In this case, the child often develops moderate anemia with slight jaundice.

icteric form

This type of disease is observed most often. The course can be from mild (symptoms are similar to physiological jaundice) to severe - with damage to vital organs. The characteristic symptoms are:

• Yellow color of the whites of the eyes, skin and visible mucous membranes.
• Yellowish color of amniotic fluid.

The baby is first born with a normal skin color and looks healthy on the outside. The appearance of jaundice occurs 2-3 hours or within a day after birth. If jaundice appears earlier and progresses rapidly, then this indicates a severe course of hemolytic disease of the newborn. That is, the later it appeared, the easier the course of the disease will be. On the 3rd-4th day of life, the most pronounced yellow skin color is observed. This color is due to the high content of bilirubin in the blood, and the higher it is, the more yellow the child.

Also characterized by an increase in the liver, spleen and moderate anemia. As the disease progresses, the child's condition worsens. The newborn is lethargic, refuses to breastfeed, sucks poorly, normal reflexes are weak, sometimes vomiting and periods of respiratory arrest can be observed.

anemic form

Usually this variant of hemolytic disease has a benign outcome. If hemolysis is insignificant, then the liver will eventually cope with the utilization of bilirubin. Signs of anemia usually appear immediately after birth. It is characterized by a pale skin color, which is noticeable for a long time. The child sucks sluggishly at the breast and slowly gains body weight. Symptoms gradually decrease over 2-3 months. Reflexes are normal, the liver and spleen are slightly enlarged. The general condition of the child is not disturbed.

Sometimes signs of anemia appear at 2 and 3 weeks of age. This may be due to the development of an infection, the appointment of certain medications, or during breastfeeding (antibodies can enter the fetus through breast milk). This can lead to a sharp increase in hemolysis.

edematous form

This form of hemolytic disease is one of the most severe. Usually the baby is born prematurely or other pregnancy complications are present.

After birth, the newborn reveals swelling of the whole body, especially on the face, legs and genitals. A barrel-shaped abdomen is observed due to the accumulation of fluid in it. Water may also be present in other body cavities (cardiac and lung).

The skin is pale due to severe anemia. There may be hemorrhages on it, the liver and spleen are significantly enlarged in size. The entire cardiovascular system suffers, which is manifested by insufficient blood circulation of the internal organs. The placenta is also enlarged. The edematous form often ends lethally.

Bilirubin encephalopathy

This form occurs when the level of bilirubin is sufficient to penetrate the fetal brain. This central organ of the nervous system is surrounded by a special barrier through which most substances (including most drugs) do not penetrate. However, there are a number of factors that contribute to an increase in the penetration of bilirubin at a relatively low concentration, namely:

• Hypoxia (oxygen starvation).
• Blood acidity.
• Infection penetration.
• Birth before 37 weeks.
• Severe form of anemia.
• Low body temperature.
• Decrease in the concentration of protein in the blood (in case of impaired liver function).
• Reducing the amount of sugar in the blood.

The brain is sensitive to the effects of bilirubin. Therefore, when it penetrates, it damages the structures of this organ. This is manifested by such symptoms:

• Lethargy, depression of consciousness or increased excitability.
• Muscular hypotonia (lack of tone in the muscles).
• Weak reflexes.

Bilirubin encephalopathy occurs in 3 phases. At first, at birth, a monotonous cry is observed, the child sucks sluggishly at the breast, there may be vomiting, he has a "wandering" look. Then there are convulsions, the body temperature rises. At the end, muscle tone drops or completely disappears.

Often, newborns die, and if they survive, they remain disabled due to damage to brain structures. At first, in the 2nd week, the symptoms decrease, which gives the impression of a recovery of the child. But somewhere from 3 months there are such complications as:

• Infantile cerebral palsy (ICP).
• Spontaneous muscle twitches.
• Paralysis of the limbs.
• Deafness.
• Delayed mental and mental development.

How is hemolytic disease diagnosed?

Diagnosis includes the collection of the necessary information from the parents of the child (anamnesis), the identification of threatening pregnancy factors (toxicosis, diseases of the internal organs, pathology of the placenta and genital organs), examination and assessment of clinical symptoms, as well as laboratory and instrumental examinations.

The diagnostic plan looks like this:

• Determination of the blood group and Rh factor of the mother and child.
• Coombs test - detection of anti-erythrocyte antibodies in the blood of the mother and at birth - in a child.
• General and biochemical analysis of the child's blood.
• Dynamic study of bilirubin.

The first thing doctors start with in diagnosing is determining the blood type and Rh factor of the pregnant woman, the father and the unborn child. All women with Rh-negative blood are examined at least 3 times for the presence of anti-Rh antibodies, that is, sensitization. The first time is done when registering with a antenatal clinic. Then it is desirable to do at 18-20 weeks of pregnancy. In the third trimester, examine every month.

If the level of antibodies is high, then amniocentesis is prescribed at 26-28 weeks of pregnancy. This is a procedure in which amniotic fluid is collected by means of a puncture in the uterine area for examination. The test is necessary to determine the concentration of bilirubin. This will be required to assess the severity of the destruction of red blood cells, which is determined by special tables.

It is also important to determine the maturity of the lungs 2-3 weeks before the expected birth. This is due to the fact that in the case of a severe form of the disease or its progression, the child may be born prematurely. In case of their immaturity, hormonal preparations are prescribed.

An important point is the diagnosis of the edematous form still in utero. For this, an ultrasound examination is used, in which edema can be visualized. Also, at the same time, the level of hemoglobin in a child is determined using cordocentesis. This procedure is based on taking blood from the umbilical cord. In case of low hemoglobin level (70-100), blood transfusion is indicated.

When a child is born, the following must be done:

• A general blood test, which determines the number of red blood cells and hemoglobin (to diagnose anemia), platelets (assessment of coagulability), leukocytes and ESR (to detect an inflammatory process).
• A biochemical blood test, which determines the concentration of bilirubin (assessment of the intensity of hemolysis) and proteins (diagnosis of edematous form and liver dysfunction).
• Coombs test - determination of the presence of antibodies against red blood cells in the blood of the mother and child.
• Dynamic study of bilirubin concentration. This is necessary to find out if the hemolytic disease is progressing.

After that, an analysis of the level of sugar is regularly done (about 4 times in the first 3-4 days), bilirubin (about 2-3 times a day until the start of the decline), hemoglobin (for indications), liver enzymes (to assess the condition of the liver) and other studies depending on the clinical picture.

Subsequently, a diagnosis of the disease is made if most of the signs of fetal hemolytic disease are found (anemia, high bilirubin in the amniotic fluid and blood, antibodies against red blood cells, negative Rh in the mother and positive in the child).

Diagnosis - hemolytic disease of the newborn is made when the same symptoms are detected, only at birth. After the severity of the disease is determined:

• A mild course is accompanied by moderately severe symptoms (anemia or jaundice) and changes in laboratory tests (more than 140 hemoglobin and less than 60 bilirubin in cord blood).
• In the middle course, there will definitely be signs of jaundice and the risks of bilirubin encephalopathy (prematurity, oxygen deficiency, simultaneous development of infection, low body temperature and sugar levels in the child). The level of hemoglobin is in the redistribution of 100-140, and bilirubin is up to 85.
• Symptoms of bilirubin intoxication of internal organs (lethargy, weakness of reflexes, monotonous cry at birth, edema of the whole body, impaired breathing and cardiovascular system) testify to a severe course. The hemoglobin level is less than 100, and the bilirubin level is more than 85.

After that, treatment of hemolytic disease is prescribed, taking into account the clinical picture and severity.

How is fetal hemolytic disease treated?

Children with hemolytic disease should receive adequate nutrition. The baby needs to be fed every 2 hours, day and night. Since the main route of excretion of bilirubin is through the intestines, this will enhance its excretion.

The main goal of treating the disease is to prevent brain damage by bilirubin, that is, the development of bilirubin encephalopathy.

The choice of treatment tactics depends on the development of hemolytic disease. If the diagnosis was made in utero (edema was detected on ultrasound, a high level of bilirubin, anemia), then intrauterine transfusion of Rh-negative blood into the umbilical cord vein is done. This procedure allows you to get rid of a high concentration of toxic bilirubin, remove anti-erythrocyte antibodies and damaged red blood cells. This will make it possible to protect the fetus from the toxic effects of bilirubin, eliminate anemia and normalize the functioning of internal organs.

In the case of diagnosing the disease after birth, the choice of treatment tactics depends on the situation.

Therapy for icteric and anemic forms

In this case, the feeding of the child begins 2-6 hours after birth and only with donor milk (antibodies can penetrate milk to the child). So they feed until the disappearance of antibodies against red blood cells in the mother's body. They disappear in about 2-3 weeks. After that, it is necessary to lower the level of bilirubin in the blood. This is done using conservative and operative methods.

• Phototherapy. It is a safe and effective treatment method. It begins on the first or second day of life. The child is irradiated with special lamps. With their help, photooxidation of bilirubin occurs and its transformation into a water-soluble form. This contributes to its easier removal from the body. Irradiation is carried out continuously until the level of bilirubin in the blood is normalized. Usually 3-4 days. It all depends on the rate of decline of a given substance.
• infusion therapy. Simultaneously with irradiation, physiological or glucose solutions are infused into the body to accelerate the excretion of bilirubin. On the 2nd day, microelements such as potassium and calcium are added. In case of low protein levels, albumin is prescribed (a protein in the blood that maintains water balance in the vessels).
• Pharmacological preparations. Appointed on the first day of jaundice. Such medicines are used that contribute to the rapid emptying of the intestines, reduce the formation of bilirubin, improve the outflow of bile and the absorption of this substance into the blood through the intestines. All this is connected with the main route of excretion of bilirubin - through the intestines.
• A cleansing enema and glycerin suppositories are used to stimulate bowel movements and accelerate the elimination of excess bilirubin.

The surgical treatment of hyperbilirubinemia includes exchange transfusion. In most cases, this procedure is prescribed for severe cases.

The indications are:

• Signs of bilirubin encephalopathy.
• The level of bilirubin in the blood is above 200.
• Failure of phototherapy.
• Decrease in hemoglobin to 100 and below on the first day after birth.
• If there is at the same time incompatibility of blood for both Rh and group.

The procedure is carried out under sterile conditions using a catheter that is inserted into the umbilical cord. The correctness of its position is checked by x-ray. Blood is injected in equal volumes depending on the body weight of the child. To prevent infection, 2-3 day antibiotic therapy is carried out. There are 3 types of exchange transfusion:

• Conventional transfusion - administered in an amount equal to 2 volumes of the child's blood.
• Isovolumic - 2 volumes are injected into the artery and at the same time the same amount is removed through the vein (they purify the blood of bilirubin and antibodies). This procedure is used in premature babies and with an edematous form of the disease.
• Partial - about 90 ml of blood per kg of the child's weight is injected.

If the catheter is no longer required, then a sterile dressing is applied after removal. Simultaneously with transfusion and after it, phototherapy is used. Bilirubin, hemoglobin and blood sugar levels are measured every 4-6 hours.

Therapy of the edematous form

Children with an edematous form of hemolytic disease require intensive treatment, as vital organs are affected here. After birth, the umbilical cord is immediately clamped to stop blood flow, reduce the load on the heart and the supply of antibodies. Next, the child is wrapped up to maintain body temperature.

Within an hour, an urgent replacement blood transfusion is needed according to a specially developed scheme. The volume is calculated per kg of body weight and takes into account the state of the cardiovascular system by measuring blood pressure and heart rate. Taking into account that such children often have respiratory disorders, an additional supply of oxygen is indicated.

Be sure to introduce an albumin solution to eliminate edema, and in case of heart failure, drugs are prescribed that enhance the work of the heart. If edema persists, diuretics are administered for 2-3 days.

Prevention of hemolytic disease

All pregnant women must donate blood to determine the group and Rh factor.

Given the importance of sensitization (only the synthesis of antibodies) in the development of this disease, it is necessary to consider every girl with Rh-negative blood as a future mother. And in this regard, transfuse Rh-positive blood only as a last resort.

Also, for the prevention of sensitization, and as we know, it develops during the first pregnancy, after determining the Rh factor of the child, anti-Rhesus immunoglobulin is administered. It is used on the first day after childbirth or at 28-30 weeks of pregnancy. This procedure is necessary for the destruction of Rh-positive red blood cells. Six months later, you need to donate blood for the presence of antibodies.

If a woman has a high level of antibodies against fetal erythrocytes, then plasmapheresis is performed. This is a procedure whose purpose is to cleanse the blood of antibodies. It is performed 2-3 times, starting from the 14th week, with an interval of 4-6-8 weeks. If the fetus has reached maturity (beginning of 37 weeks), then it is recommended to do a caesarean section.

Also in this case, pregnant women are hospitalized in the antenatal department at 8, 16, 24, 28 and 32 weeks, where they are given an intravenous infusion of glucose with vitamin C, E, B6, oxygen and antianemic therapy. With the threat of miscarriage, progesterone is prescribed.

Prevention of the edematous form is the use of intrauterine replacement blood transfusion.

What are the prognosis of fetal hemolytic disease

Mortality in hemolytic disease varies widely. It depends on the severity of the course, the clinical picture, how timely the diagnosis was, and how medical care was provided.

By comparison, the mortality rate in the 40s was 45%, and now it has decreased to 2.5%. In a statistical study of children under 3 years of age who had an icteric form, a slowdown in physical and mental development was found only in 5% of children. Also, these children had an increased incidence of infectious diseases. Another 50% were found to have skin diseases (neurodermatitis, eczema, diathesis).

In the case of the edematous form of the disease, mortality remains at a high level (approximately 50%).

Jaundice is a visual manifestation of hyperbilirubinemia. Bilirubin, one of the end products of catabolism of the heme protoporphyrin ring, accumulates in the body in large quantities, causes a yellow coloration of the skin and mucous membranes. With the breakdown of 1 g of hemoglobin, 34 mg of bilirubin is formed. In adults, it appears at a bilirubin level of more than 25 μmol / l, in full-term newborns - 85 μmol / l, and in premature infants - more than 120 μmol / l.

A transient increase in the concentration of bilirubin in the blood in the first 3-4 days after birth is observed in almost all newborns. Approximately half of full-term and most preterm infants are accompanied by the development of icteric syndrome. An important task of a medical worker during the period of monitoring the state of health of a newborn child is to distinguish between physiological features and pathological disorders of bilirubin metabolism.

Physiological jaundice

Clinical Criteria:

appears 24-36 hours after birth;

increases during the first 3-4 days of life;

begins to fade from the end of the first week of life;

disappears in the second or third week of life;

the general condition of the child is satisfactory;

the sizes of a liver and a spleen are not increased;

normal color of feces and urine.

Laboratory criteria:

the concentration of bilirubin in the umbilical cord blood (the moment of birth) -< 51 мкмоль;

the concentration of hemoglobin in the blood is normal;

the maximum concentration of total bilirubin on days 3-4 in peripheral or venous blood: ≤240 µmol/l in full-term and ≤ 150 µmol/l in premature babies;

total blood bilirubin increases due to the indirect fraction;

the relative proportion of the direct fraction is less than 10%.

Pathological hyperbilirubinemia

Are present at birth or appear on the first day or on the second

week of life

Combined with signs of hemolysis (anemia, high reticulocytosis, in a blood smear - nuclear erythroid forms, excess spherocytes), pallor, hepatosplenomegaly;

Last more than 1 week. in full-term and 2 weeks. - in premature babies;

They proceed in waves (the yellowness of the skin and mucous membranes increases in intensity after a period of its decrease or disappearance);

The rate of growth (increase) of unconjugated bilirubin (NB, indirect bilirubin) is >9 µmol/l/h or 137 µmol/l/day.

The level of NB in ​​cord blood serum -> 60 µmol/l or 85 µmol/l - in the first 12 hours of life, 171 µmol/l - on the 2nd day of life, the maximum values ​​of NB on any day of life exceed 221 µmol/l

The maximum level of bilirubin diglucuronide (RDG, direct biliru-

bin) - >25 µmol/l

Deterioration of the general condition of the child against the background of a progressive increase in jaundice,

Dark urine or discolored stools

Physiological jaundice is a diagnosis of exclusion of pathological jaundices.

There are four main mechanisms for the development of pathological hyperbilirubinemia:

1. Hyperproduction of bilirubin due to hemolysis;

2. Violation of bilirubin conjugation in hepatocytes;

3. Violation of the excretion of bilirubin in the intestine;

4. Combined violation of conjugation and excretion.

In this regard, from a practical point of view, it is advisable to single out four types of jaundice:

1) hemolytic;

2) conjugation;

3) mechanical;

4) hepatic.

Hemolytic disease of the newborn (HDN) is an isoimmune hemolytic anemia that occurs in cases of incompatibility of the blood of the mother and fetus for erythrocyte antigens, while the antigens are localized to the mother and fetus, and antibodies to them are produced in the mother's body. HDN in Russia is diagnosed in approximately 0.6% of all newborns.

Classification HDN provides for the establishment of:

Type of conflict (Rh-, AB0-, other antigenic systems);

Clinical form (intrauterine fetal death with maceration, edematous, icteric, anemic);

Degrees of severity in icteric and anemic forms (mild, moderate and severe);

Complications (bilirubin encephalopathy - nuclear jaundice, other neurological disorders; hemorrhagic or edematous syndrome, damage to the liver, heart, kidneys, adrenal glands, "bile thickening" syndrome, metabolic disorders - hypoglycemia, etc.);

Concomitant diseases and background conditions (prematurity, intrauterine infections, asphyxia, etc.)

Etiology. A conflict may occur if the mother is antigen-negative and the fetus is antigen-positive. There are 14 main erythrocyte group systems that combine more than 100 antigens, as well as numerous private and common erythrocyte antigens with other tissues. HDN usually causes incompatibility between the fetus and mother for Rh or ABO antigens. It has been established that the Rhesus antigenic system consists of 6 main antigens (the synthesis of which is determined by 2 pairs of genes located on the first chromosome), designated either C, c; D, d; Ε, e (Fischer's terminology), or Rh", hr", Rho, hr0, Rh", hr" (Winner's terminology). Rh-positive erythrocytes contain the D-factor (Rho-factor, in Winner's terminology), and the so-called Rh-negative erythrocytes do not have it. ABO antigen incompatibility leading to TTH usually occurs in maternal blood type 0(1) and child blood type A (II). If HDN develops with a double incompatibility of the child and mother, i.e. mother O (I) Rh (-), and the child A (II) Rh (+) or B (III) Rh (+), then, as a rule, it is caused by A- or B-antigens. Sensitization of a Rh-negative mother to the Rh-O antigen usually leads to Rh-THN, which usually precedes pregnancy. Sensitizing factors are primarily previous pregnancies (including ectopic and ended in abortion), and therefore Rh-HDN, as a rule, develops in children born not from the first pregnancy. With ABO-conflict, this pattern was not noted, and ABO-THN may occur already during the first pregnancy, but in violation of the barrier functions of the placenta due to the presence of somatic pathology in the mother, preeclampsia, which led to intrauterine fetal hypoxia.

Pathogenesis.

Previous abortions, miscarriages, ectopic pregnancy, childbirth, etc. predispose to the entry of antigen-positive fetal erythrocytes into the bloodstream of an antigen-negative mother. In this case, the mother's organism produces anti-Rhesus or group antibodies. Incomplete anti-erythrocytic antibodies related to class G immunoglobulins damage the erythrocyte membrane, leading to an increase in its permeability and metabolic disorders in the erythrocyte. These erythrocytes, changed under the action of antibodies, are actively captured by macrophages of the liver, spleen, bone marrow and die prematurely; in severe forms of the disease, hemolysis can also be intravascular. The resulting large amount of NB entering the blood cannot be excreted by the liver, and hyperbilirubinemia develops. If hemolysis is not too intense with a small amount of incoming maternal antibodies, the liver actively removes NB, then the child's clinical picture of HDN is dominated by anemia in the absence or minimal severity of jaundice. It is believed that if anti-erythrocyte alloimmune antibodies penetrated to the fetus for a long time and actively during pregnancy before the onset of labor, then intrauterine maceration of the fetus or edematous form of HDN develop. In most cases, the placenta prevents the penetration of alloimmune antibodies to the fetus. At the time of delivery, the barrier properties of the placenta are sharply violated, and maternal isoantibodies enter the fetus, which, as a rule, causes the absence of jaundice at birth and its appearance in the first hours and days of life. Anti-erythrocyte antibodies can be supplied to the baby with mother's milk, which increases the severity of HDN.

Features of pathogenesis in edematous form of HDN. Hemolysis begins at 18-22 weeks. pregnancy, has an intense character and leads to severe anemia of the fetus. As a result, severe fetal hypoxia develops, which causes deep metabolic disorders and damage to the vascular wall, albumin synthesis decreases, albumin and water move from the fetal blood to the tissue interstitium, which forms a general edematous syndrome.

Features of pathogenesis in icteric form of HDN. Hemolysis begins shortly before delivery, the level of bilirubin rises rapidly and significantly, which leads to its accumulation in the lipid substances of tissues, in particular in the nuclei of the brain, an increase in the load on liver glucuronyl transferase and an increase in the excretion of conjugated (direct) bilirubin, which leads to a violation of bile excretion .

Features of the pathogenesis of the anemic form of HDN. The anemic form of HDN develops when small amounts of maternal antibodies enter the fetal circulation shortly before delivery. At the same time, hemolysis is not intense, and the newborn's liver actively removes bilirubin.

Although hyperbilirubinemia with NB leads to damage to various organs and systems (brain, liver, kidneys, lungs, heart, etc.), damage to the nuclei of the base of the brain has a leading clinical significance. Staining of the basal ganglia, the globus pallidus, the caudal nuclei, the shell of the lenticular nucleus is maximally expressed, less often the hippocampal gyrus, the cerebellar tonsils, some nuclei of the thalamus, olives, the dentate nucleus, etc .; this condition, at the suggestion of G. Schmorl (1904), was called "nuclear jaundice".

clinical picture.

edematous form - the most severe manifestation of Rh-THN. A burdened history of the mother is typical - the birth of previous children in a family with HDN, miscarriages, stillbirths, prematurity, transfusions of Rh-incompatible blood, repeated abortions. An ultrasound examination of the fetus is characterized by a Buddha pose - the head is at the top, the lower limbs are bent at the knee joints due to a barrel-shaped increase in the abdomen, unusually far from the body; "halo" around the cranial vault. Due to edema, the mass of the placenta is significantly increased. Normally, the mass of the placenta is 1/6-1/7 of the body weight of the fetus, but with an edematous form, this ratio reaches 1:3 and even 1:1. The villi of the placenta are enlarged, but their capillaries are morphologically immature, abnormal. Characterized by polyhydroamnios. As a rule, mothers suffer from severe gestosis in the form of preeclampsia, eclampsia. Already at birth, the child has: a sharp pallor (rarely with an icteric tinge) and a general edema, especially pronounced on the external genitalia, legs, head, face; sharply enlarged barrel-shaped abdomen; significant hepato- and splenomegaly (a consequence of erythroid metaplasia in the organs and severe fibrosis in the liver); expansion of the boundaries of relative cardiac dullness, muffled heart sounds. Ascites is usually significant even in the absence of general fetal edema. The absence of jaundice at birth is associated with the release of NB from the fetus through the placenta. Very often, immediately after birth, respiratory disorders develop due to hypoplastic lungs or hyaline membrane disease. The cause of lung hypoplasia is seen in an elevated diaphragm with hepatosplenomegaly, ascites. Often in children with edematous form of HDN hemorrhagic syndrome (bleeding into the brain, lungs, gastrointestinal tract). A minority of these children have decompensated DIC, but all have very low plasma levels of procoagulants, which are synthesized in the liver. Characteristic: hypoproteinemia (the level of blood serum protein falls below 40-45 g/l), an increase in the level of BDH in the cord blood (and not just NB), severe anemia (hemoglobin concentration less than 100 g/l), normoblastosis and erythroblastosis of varying severity, thrombocytopenia. Anemia in such children is so severe that, in combination with hypoproteinemia, damage to the vascular wall can lead to heart failure. Survivors after active treatment of children with congenital edematous form of HDN (about half of these children die in the first days of life) often develop severe neonatal infections, liver cirrhosis, and encephalopathy.

icteric form is the most common form of HDN. At birth, amniotic fluid, umbilical cord membranes, and primary lubrication may be icteric. The early development of jaundice is characteristic, which is noticed either at birth or within 24-36 hours of a newborn's life. The earlier jaundice appeared, the more severe the course of HDN is usually. Jaundice is predominantly warm yellow in color. The intensity and hue of the icteric color gradually change: first orange, then bronze, then lemon, and finally the color of unripe lemon. Also characteristic are an increase in the liver and spleen, icteric staining of the sclera, mucous membranes, and pastosity of the abdomen is often observed. As the level of NB in ​​the blood increases, children become lethargic, adynamic, suck poorly, their physiological reflexes for newborns decrease, other signs of bilirubin intoxication appear. Blood tests reveal anemia of varying severity, pseudoleukocytosis due to an increase in the number of normoblasts and erythroblasts, often thrombocytopenia, rarely leukemoid reaction. Significantly increased and the number of reticulocytes (more than 5%).

With untimely started or inadequate treatment, the icteric form of HDN can be worsened by bilirubin encephalopathy and bile thickening syndrome. Bile thickening syndrome is diagnosed when jaundice acquires a greenish tint, the liver increases in size compared to previous examinations, and the intensity of urine color increases.

Bilirubin encephalopathy(BE) is clinically rarely detected in the first 36 hours of life, and usually its first manifestations are diagnosed on the 3-6th day of life. The first signs of BE are manifestations of bilirubin intoxication - lethargy, decreased muscle tone and appetite up to food refusal, monotonous, unemotional cry, rapid depletion of physiological reflexes, regurgitation, vomiting. Then the classic signs of nuclear jaundice appear - spasticity, stiff neck, forced position of the body with opisthotonus, stiff limbs and hands clenched into a fist; periodic excitation and a sharp "brain" high-frequency cry, bulging of a large fontanelle, twitching of the muscles of the face or complete amimia, large-scale tremor of the hands, convulsions; symptom of "setting sun"; the disappearance of the Moro reflex and the visible reaction to a strong sound, the sucking reflex; nystagmus, Graefe's symptom; respiratory arrest, bradycardia, lethargy. The outcome of BE will be athetosis, choreoathetosis, paralysis, paresis; deafness; cerebral palsy; impaired mental function; dysarthria, etc.

Risk factors for bilirubin encephalopathy are hypoxia, severe asphyxia (especially complicated by severe hypercapnia), prematurity, hypo- or hyperglycemia, acidosis, hemorrhages in the brain and its membranes, convulsions, neuroinfections, hypothermia, starvation, hypoalbuminemia, certain drugs (sulfonamides, alcohol, furosemide , difenin, diazepam, indomethacin and salicylates, methicillin, oxacillin, cephalothin, cefoperazone).

anemic form diagnosed in 10-20% of patients. Babies are pale, somewhat lethargic, suckle poorly, and put on weight. They find an increase in the size of the liver and spleen, in the peripheral blood - anemia of varying severity in combination with normoblastosis, reticulocytosis, spherocytosis (with ABO conflict). Sometimes hypogenerative anemia is observed, i.e. there is no reticulocytosis and normoblastosis, which is explained by inhibition of bone marrow function and a delay in the release of immature and mature forms of erythrocytes from it. NB levels are usually normal or moderately elevated. Signs of anemia appear at the end of the first or even the second week of life.

Diagnostics.

The studies required for the diagnosis of HDN are presented in Table 3.

Table 3

Examinations of the pregnant woman and the fetus with suspected

hemolytic disease of the fetus.

In all women with Rh-negative blood, the titer of anti-Rh antibodies is examined at least three times. The first study is carried out when registering with a antenatal clinic. It is optimal to further conduct a second study at 18-20 weeks, and in the third trimester of pregnancy, it should be done every 4 weeks. Maternal RH antibodies do not accurately predict the future severity of HDN in a child, and determination of amniotic fluid bilirubin levels is of great value. If the titer of Rh antibodies is 1:16-1:32 or more, then at 6-28 weeks. conduct amniocentesis and determine the concentration of bilirubin-like substances in the amniotic fluid. If the optical density with a 450 mm filter is more than 0.18, an intrauterine exchange transfusion is usually necessary. It is not carried out on fetuses older than 32 weeks. gestation. Another method for diagnosing congenital edematous form of HDN is an ultrasound examination that reveals fetal edema. It develops with a deficiency of hemoglobin levels of 70-100 g / l.

Since the prognosis for HDN depends on the content of hemoglobin and the concentration of bilirubin in the blood serum, first of all, it is necessary to determine these indicators to develop further medical tactics, and then conduct an examination to identify the causes of anemia and hyperbilirubinemia.

Examination plan for suspected HDN:

1. Determination of the blood group and Rh affiliation of the mother and child.

2. Analysis of the peripheral blood of the child with an assessment of the blood smear.

3. Blood test with counting the number of reticulocytes.

4. Dynamic determination of the concentration of bilirubin in blood serum

you baby.

5. Immunological studies.

Immunological research. In all children of Rh-negative mothers, the blood group and Rh-affiliation, serum bilirubin level are determined in the cord blood. In case of Rh incompatibility, the titer of Rh antibodies in the mother's blood and milk is determined, as well as a direct Coombs reaction (preferably an aggregate-agglutination test according to L.I. Idelson) with the child's erythrocytes and an indirect Coombs reaction with the mother's blood serum, analyze the dynamics of Rh antibodies in the mother's blood during pregnancy and the outcome of previous pregnancies. With ABO incompatibility, the titer of allohemagglutinins (to the erythrocyte antigen present in the child and absent in the mother) is determined in the mother's blood and milk, in protein (colloidal) and salt media, in order to distinguish natural agglutinins (they have a large molecular weight and belong to immunoglobulins class M, do not cross the placenta) from immune (have a small molecular weight, belong to class G immunoglobulins, which easily cross the placenta, and after birth - with milk, i.e. responsible for the development of HDN). In the presence of immune antibodies, the titer of allohemagglutinins in the protein medium is two steps or more (i.e., 4 times or more) higher than in the salt medium. Direct Coombs' test in case of ABO-conflict in a child, as a rule, is weakly positive, i.e. a slight agglutination appears after 4-8 minutes, while with a Rhesus conflict, pronounced agglutination is noticeable after 1 minute. In case of a conflict between the child and the mother over other rare erythrocyte antigenic factors (according to various authors, the frequency of such a conflict is from 2 to 20% of all cases of HDN), the direct Coombs test in the child and the indirect test in the mother are usually positive, and incompatibility of the child's erythrocytes and mother's serum in the test for individual compatibility.

Changes in the peripheral blood of the child: anemia, hyperreticulocytosis, when viewing a blood smear - an excessive number of spherocytes (+++, +++++), pseudoleukocytosis due to an increased amount of nuclear forms of the erythroid series in the blood.

The plan for further laboratory examination of the child includes regular determination of the level of glycemia (at least 4 times a day in the first 3-4 days of life), NB (at least 2-3 times a day until the level of NB in ​​the blood begins to decrease), plasma hemoglobin (in the first day and further according to indications), platelet count, transaminase activity (at least once) and other studies, depending on the characteristics of the clinical picture.

Table 4

Investigations for suspected HDN.

Diagnostic criteria for HDN:

Clinical Criteria:

* Dynamics of jaundice

Appears in the first 24 hours after birth (usually the first 12 hours);

Increases during the first 3-5 days of life;

Begins to fade from the end of the first to the beginning of the second week of life;

Disappears by the end of the third week of life.

*Features of the clinical picture

The skin in AB0-conflict is usually bright yellow, with Rh-conflict it can have a lemon tint (jaundice on a pale background),

The general condition of the child depends on the severity of hemolysis and the degree of hyperbilirubinemia (from satisfactory to severe)

In the first hours and days of life, as a rule, there is an increase in the size of the liver and spleen;

usually - the normal color of feces and urine, against the background of phototherapy, there may be a green color of the stool and a short-term darkening of the urine.

Laboratory Criteria:

Concentration of bilirubin in umbilical cord blood (moment of birth) - in mild forms of immunological conflict in Rh and in all cases of AB0 incompatibility -<=51 мкмоль/л; при тяжелых формах иммунологического конфликта по Rh и редким факторам – существенно выше 51 мкмоль/л;

The concentration of hemoglobin in cord blood in mild cases is at the lower limit of normal, in severe cases it is significantly reduced;

The hourly increase in bilirubin in the first day of life is more than 5.1 µmol/l/hour, in severe cases - more than 8.5 µmol/l/hour;

The maximum concentration of total bilirubin on days 3-4 in peripheral or venous blood: >> 256 µmol/l in full-term babies, >> 171 µmol/l in premature babies;

Total blood bilirubin rises mainly due to the indirect fraction,

The relative proportion of the direct fraction is less than 20%;

decrease in hemoglobin level, erythrocyte count and increase in the number of reticulocytes in clinical blood tests during the 1st week of life.

Based on clinical and laboratory data, three degrees of severity are distinguished:

a) A mild form of hemolytic disease (1st degree of severity) is characterized by some pallor of the skin, a slight decrease in the concentration of hemoglobin in the cord blood (up to 150 g/l), a moderate increase in bilirubin in the cord blood (up to 85.5 µmol/l), hourly an increase in bilirubin up to 4-5 μmol / l, a moderate increase in the liver and spleen less than 2.5 and 1 cm, respectively, a slight pastiness of the subcutaneous fat.

b) The moderate form (2nd degree of severity) is characterized by pallor of the skin, a decrease in cord blood hemoglobin in the range of 150-110 g / l, an increase in bilirubin in the range of 85.6-136.8 μmol / l, an hourly increase in bilirubin up to 6- 10 µmol / l, pastosity of subcutaneous fat, an increase in the liver by 2.5 - 3.0 cm and the spleen by 1.0 - 1.5 cm.

c) Severe form (3rd degree of severity) is characterized by a sharp pallor of the skin, a significant decrease in hemoglobin (less than 110 g / l), a significant increase in bilirubin in the cord blood (136.9 μmol / l or more), generalized edema, the presence of symptoms bilirubin brain damage of any severity and at all times of the disease, respiratory and cardiac disorders in the absence of data indicating concomitant pneumo- or cardiopathy.

Differential diagnosis of HDN carried out with hereditary hemolytic anemia (spherocytosis, elliptocytosis, stomatocytosis, deficiencies of certain erythrocyte enzymes, anomalies in hemoglobin synthesis), which are characterized by a delayed (after 24 hours of life) appearance of the above clinical and laboratory signs, as well as a change in the shape and size of erythrocytes during a morphological examination of a smear blood, violation of their osmotic stability in dynamics, changes in the activity of erythrocyte enzymes and the type of hemoglobin.

Diagnosis examples.

Hemolytic disease on the basis of Rh-conflict, edematous-icteric form, severe, complicated by bile thickening syndrome.

Hemolytic disease on the basis of the conflict according to the ABO system, icteric form, moderate severity, uncomplicated.

Modern principles of prevention and treatment.

Treatment of hemolytic disease of the fetus is carried out with Rh isoimmunization during the period of intrauterine development of the fetus in order to correct anemia in the fetus, prevent massive hemolysis, and maintain pregnancy until the fetus reaches viability. Plasmapheresis and cordocentesis with intrauterine transfusion of erythrocyte mass are used (they use "washed" erythrocytes of the 0 (II) blood group, Rh-negative).

Management tactics for HDN.

An important condition for the prevention and treatment of hyperbilirubinemia in newborns is the creation of optimal conditions for early neonatal adaptation of the child. In all cases of illness in a newborn, it is necessary to take care of maintaining an optimal body temperature, providing his body with a sufficient amount of fluid and nutrients, and preventing metabolic disorders such as hypoglycemia, hypoalbuminemia, hypoxemia and acidosis.

In cases of clinical signs of a severe form of hemolytic disease at the time of the birth of a child in a woman with Rh-negative blood (severe pallor of the skin, icteric staining of the skin of the abdomen and umbilical cord, swelling of the soft tissues, an increase in the size of the liver and spleen), an emergency operation of the PPC is indicated without waiting for laboratory tests. data. (In this case, the technique of partial PBV is used, in which 45-90 ml / kg of the child’s blood is replaced with the same volume of donor red blood cells of the 0 (1) group, Rh-negative)

In other cases, the tactics of managing such children depends on the results of the primary laboratory examination and dynamic observation.

In order to prevent PKD in newborns with isoimmune TTH for any of the blood factors (Coombs' test is positive), who have an hourly increase in bilirubin of more than 6.8 µmol/l/h, despite phototherapy, it is advisable to prescribe standard immunoglobulins for intravenous administration. Human immunoglobulin preparations for newborns with HDN are administered intravenously slowly (within 2 hours) at a dose of 0.5-1.0 g/kg (800 mg/kg on average) in the first hours after birth. If necessary, re-introduction is carried out after 12 hours from the previous one.

The tactics of managing children with HDN at the age of more than 24 hours of life depends on the absolute values ​​of bilirubin or the dynamics of these indicators. It is necessary to assess the intensity of jaundice with a description of the number of skin areas stained with bilirubin.

At the same time, it should be remembered that there is a relative correspondence between the visual assessment of jaundice and the concentration of bilirubin: the larger the skin surface has a yellow color, the higher the level of total bilirubin in the blood: Staining of the 3rd zone in premature and 4th zone in full-term newborns require an urgent determination concentration of total blood bilirubin for further management of children.

Scale of indications for exchange transfusion (N.P. Shabalov, I.A. Leshkevich).

The y-axis shows the concentration of bilirubin in the blood serum (in µmol/l); along the abscissa axis - the age of the child in hours; dotted line - concentrations of bilirubin, which require PKC in children with no risk factors for bilirubin encephalopathy; solid lines - bilirubin concentrations at which ZPK is necessary in children with risk factors for bilirubin encephalopathy (with ABO and Rhesus conflict, respectively)

One of the most common pathologies that occur in pregnant women is fetal hemolytic disease. It develops on the basis of the immune conflict between the organisms of the mother and the unborn child. Immunological incompatibility is associated with a conflict in the Rh factor. Its manifestation is observed in 97% of cases. It is much rarer to find incompatible blood types. Under the influence of pathological mechanisms, the functions of the liver and spleen are impaired.

What is hemolytic disease

Hemolytic disease of the fetus is considered a pathological abnormality that occurs during intrauterine development. Its essence lies in the immunological conflict between the mother's body and the fetus. This situation arises due to the incompatibility of the composition of the blood of the mother and child, which contains a different amount of antigens.

As a result of such a conflict, erythrocytes die in the fetal body. Maternal antibodies overcome the protective barrier of the placenta and help remove hemoglobin from red blood cells. In the process of their decay, the formation of toxic elements occurs, which increase the amount of bilirubin and immature red blood cells. This happens when the fetus has paternal antigens, but they are not in the mother's body. Such a violation causes anemia, jaundice and edema, and sometimes the death of the unborn child.

The cause of hemolytic disease is the development of a conflict between different Rh factors. Sometimes there is incompatibility for blood groups and some types of antigens. Timely detection of pathology in conjunction with the correct treatment increases the chances of a favorable prognosis.

Causes of hemolytic disease

The main cause of the pathology lies in the immunological conflict associated with blood incompatibility. In this case, the maternal Rh factor is negative, and the fetus is positive. Thus, a Rh conflict occurs, especially when this is not the first pregnancy for a woman.

A serious reason is the incompatibility of blood types. The mother has the 1st group, and the child has any other. When antigens A and B enter the maternal blood through the placenta, protective antibodies are produced. Then there is a conflict between antigens and antibodies. Such incompatibility often develops already during the first pregnancy, but proceeds in a milder form.

In rare cases, conflicts can also occur between different types of antigens. Basically, these are M, N, S and P antigens, Duffy, Kell systems and other factors that can cause incompatibility.

Symptoms and signs

The early stage of the disease proceeds without any specific features and is practically not determined. Pregnancy proceeds normally, without deviations. With further intrauterine development of the fetus, symptoms are observed that manifest themselves individually.

The main manifestations of hemolytic disease:

• The most severe manifestation is associated with intrauterine fetal death occurring in the period from the 20th to the 30th week of development. In the absence of timely ultrasound or blood tests, the deceased child may be in the womb for 10-14 days. There is no bleeding, and the woman feels well and does not suspect anything. Failure to take urgent measures can lead to blood poisoning and other unpleasant consequences.
• The occurrence of edema in the fetus, manifested in the growth of its mass. Fiber gradually accumulates in the body, internal organs increase, including the heart, liver, kidneys and spleen. There is an increase in the size of the placenta. Severe anemia often leads to fetal death. This can happen while still in the womb or during childbirth.
• With an icteric variety of fetal disease, pregnancy proceeds in the usual manner and ends in natural childbirth. Further activities are carried out in relation to an already born child a couple of hours after his birth. Bilirubin appears in the baby's blood, causing irreversible processes.
• The mildest manifestations are observed in anemic hemolytic disease. The newly born fetus looks pale, lethargic, cyanotic, with a vascular network located on the body.

Diagnostics

Diagnostic measures are carried out with a decrease in the level of hemoglobin in the fetus and an increase in the amount of bilirubin contained in the body. Erythrocytes containing antibodies are detected using a direct Coombs test. For the study of maternal serum with incomplete antibodies, an indirect Coombs test is used. Identified Rh-conflicts give reason to assume the presence of incompatibility.

Further research on the subject of Rh incompatibility is carried out by antenatal diagnosis. For this purpose, the behavior of antibodies in the maternal serum in relation to the Rh antigen D is studied. Preliminary ultrasound examination of the fetus and placenta is carried out, after which direct antenatal diagnosis is carried out by transabdominal amniocentesis.

At the same time, dynamic studies of the amount of bilirubin are performed, especially if its level increases.

Treatment of fetal hemolytic disease

In order for the treatment to be effective, the Rh conflict must be established even during the intrauterine development of the fetus. The severity of the pathology is preliminarily assessed, a prognosis is made, which allows prescribing treatment as early as possible. All therapeutic measures are carried out in two main areas.

Non-invasive treatments include plasmapheresis, an immunoglobulin given intravenously to a pregnant woman. Contraindications to plasmapheresis are a weak immune system, the presence of severe cardiovascular diseases, anemia, allergic reactions to the administration of anticoagulants, protein and colloid preparations.

In another direction, hemolytic disease of the fetus is treated with invasive methods. This includes conducting cordocentesis and intrauterine transfusion of the entire mass of red blood cells. These activities are carried out with low hemoglobin and hematocrit in a certain period of pregnancy.

Description:

Hemolytic disease of the fetus and newborn is an immune conflict between the mother and fetus. The mother's body synthesizes antibodies in response to fetal erythrocyte antigens that are foreign to it. The most common type of immunological incompatibility between mother and fetus is Rh factor incompatibility - 97%, blood group incompatibility is much less common. The Rh factor in the fetus is detected at the 8-9th week of intrauterine development, the number of Rh antigens gradually increases. Through the placenta, they enter the mother's blood and anti-Rhesus antibodies are formed to them if the mother is Rh-negative. Penetrating through the placenta into the body of the fetus, the mother's antibodies cause the breakdown of red blood cells. The second name of this pathology is connected with this - erythroblastosis. Develops, with hemolysis, an increased amount of bilirubin is formed; as compensatory mechanisms in the fight against anemia in the liver and spleen of the fetus, foci of hematopoiesis are formed, which leads to an increase in these organs and a violation of their function.

Causes of hemolytic disease of the fetus:

An immunological conflict leading to hemolytic disease of the fetus most often develops with isoserological incompatibility of blood according to the Rhesus (Rh) system, when the mother has Rh-negative blood, and the fetus is Rh-positive. In this case, it is called. Isoimmunization in this case can occur in two ways: iatrogenic (when a woman was sensitized by transfusions of Rh (+) blood in the past) or with the fetal-maternal transplacental transfer of fetal erythrocytes into the maternal circulation during pregnancy and childbirth. In the case of Rh incompatibility, hemolytic disease of the fetus is rarely associated with the first pregnancy; more often develops from the 2nd or 3rd pregnancy with increasing risks with each subsequent gestation.
Another possible cause of hemolytic disease is the incompatibility of the blood of the fetus and mother according to the AB0 system, that is, with the mother's blood group 0 (I), and the fetus has any other. At the same time, antigens A and B from the fetus cross the placenta into the maternal circulation and cause the production of immune α- and β-antibodies, followed by an antigen-antibody conflict. Hemolytic disease of the fetus with ABO incompatibility has a milder course than with Rh incompatibility. With AB0 incompatibility, hemolytic disease of the fetus may develop already during the 1st pregnancy.
In relatively rare cases, fetal hemolytic disease may be associated with immunological conflicts in the Duffy, Kell, MNSs, Kidd, Lutheran, etc. systems or P, S, N, M antigens.

Symptoms of hemolytic disease of the fetus and newborn:

Hemolytic anemia is the mildest form. The newborn has a low hemoglobin level, as well as the number of erythrocytes. The skin is pale, the liver and spleen are slightly enlarged. The content of hemoglobin and bilirubin is at the lower limit of the norm. The anemic form of HMB appears due to the effect of a small amount of Rh antibodies on a full-term or near-term fetus. Isoimmunization of the fetus occurs more often in childbirth. The main symptom of mild injury is anemia.
in combination with jaundice - occurs more often, is characterized as a more severe form of the disease. It is characterized by hyper- or normochromic anemia, jaundice and hepatosplenomegaly. Amniotic fluid has an icteric coloration, as well as primordial lubricant, umbilical cord, fruit membranes and umbilical cord. The content of indirect bilirubin is more than the upper limit of the norm by 10-20 µmol/l.  The condition of the newborn is severe and worsening. If the hourly increase in bilirubin is 5-10 times, then "nuclear jaundice" develops, which indicates damage to the central nervous system. In such cases, blindness, deafness, mental disability may occur. The hemoglobin content is below normal. The icteric form occurs if antibodies act on a mature fetus for a short time. Infectious complications often join - omphalitis. After 7 days of life, the pathogenic effect of antibodies that have entered the blood of the fetus stops.

Hemolytic anemia in combination with jaundice and dropsy is the most severe form of the disease. Newborns are either stillborn or die in the early neonatal period. Symptoms of the disease are: anemia, jaundice and general edema (ascites, anasarca), severe. It may develop. The penetration of maternal antibodies through the placenta does not always occur, the severity of the fetal lesion does not always correspond to the titer (concentration) of Rh antibodies in the blood of a pregnant woman.

Diagnostics:

All women who have had children with hemolytic disease, and all women who have been diagnosed with Rh sensitization, are subject to observation by an obstetrician and immunologist. In the blood of women, the titer of Rh antibodies is determined once a month until the 32nd week of pregnancy; 2 times a month from 32 to 35 weeks and weekly from 36 weeks.

In the antenatal diagnosis of hemolytic disease, ultrasound is important, in which signs such as an increase in the size of the liver and spleen, thickening of the placenta, dropsy of the fetus can be detected. According to the indications and prescription of the doctor, the amniotic fluid is examined, which is obtained by puncture of the fetal bladder (amniocentesis). The puncture is carried out through the abdominal wall. Preliminary ultrasound determines the location of the placenta and fetus, in order to avoid injury during puncture. In the amniotic waters, the content of antibodies, the bilirubin index, the blood type of the fetus are determined - which are essential for assessing its condition and prescribing appropriate therapy. According to indications, cordocentesis is also performed - taking blood from the umbilical cord of the fetus.

Treatment of hemolytic disease:

The following methods are most effective:

In the presence of immunological incompatibility of the blood of the mother and the unborn child, the occurrence of hemolytic disease of the fetus (newborn)- a disease in which there is an increased breakdown of red blood cells. Due to the development of this process, various organs and the hematopoietic system of the baby are affected.

information The incompatibility of the blood of a pregnant woman and the fetus can be both according to the Rh factor (at) and according to blood groups. The hemolytic disease is the most severe, the cause of which is.

Clinical forms

There are three main clinical forms of hemolytic disease of the newborn:

• Light- without jaundice and dropsy. It is characterized by a slight increase in the spleen and liver, pallor of the skin, absence.
• Medium- with jaundice: the most common form. It is manifested by an increase in the size of the liver, damage to the central nervous system, the occurrence and disturbances in the movement of the eyeballs.
• heavy- with jaundice and dropsy. It is distinguished by the appearance of generalized edema, enlargement of the liver and spleen, heart failure and anemia.

The reasons

Hemolytic disease can occur in the fetus under the influence of the following factors:

• Rh-negative maternal blood with Rh-positive fetus. The opposite variant of incompatibility for this indicator is also possible, but in more rare cases.
• Difference in blood types of mother and child(for example, in the first group in the mother and the presence of antibodies to antigens A and B).

important In the presence of a Rh conflict, the severity of the hemolytic disease increases with each subsequent birth. In case of blood type incompatibility, the amount of antibodies increases during pregnancy.

Manifestations

Hemolytic disease of the fetus (newborn) is characterized by the appearance of the following symptoms:

• jaundice on the second or third day after birth;
• enlargement of the spleen and liver in size;
• swelling of tissues during intrauterine development of the fetus or after the birth of a child;
• convulsive twitching of muscles and eyes, generalized convulsions;
• pallor of the skin.

With hemolytic disease, a child can be diagnosed with deafness, paralysis, paresis (weakening of voluntary movements), mental disorders.

Diagnostics

Hemolytic disease is established using the following methods:

• determination of the Rh factor and the titer of Rh antibodies in ;
• (ultrasound) of the fetus in order to possibly detect an increase in the size of the liver, thickening of the walls, polyhydramnios or dropsy;
• amniocentesis- a study by conducting a puncture of the fetal bladder in order to determine the amount of antibodies, the level of bilirubin and the blood type of the unborn baby;
• cordocentesis- taking blood from the umbilical cord of the fetus for analysis.

Treatment

In case of confirmation of the diagnosis, the following methods of treatment of the disease are used:

• blood transfusion- blood transfusion into the abdominal cavity of the fetus or into the umbilical vein under ultrasound control (the procedure is carried out starting from the 18th week of pregnancy);
• prescription of phenobarbital a newborn or pregnant woman two weeks before the expected date of birth;
• carrying out phototherapy to destroy toxic bilirubin;
• serum administration, plasmapheresis, skin flap transplantation during pregnancy to prevent the growth of antibodies;
• replacement blood transfusion for a child during the first two days after birth;
• prescribing B vitamins to a newborn.

Breastfeeding is allowed no earlier than 20 days of age, after the disappearance of Rh antibodies from mother's milk.

Prevention

Prevention of hemolytic disease of the fetus is desirable to carry out even before the onset of pregnancy.

important To reduce the likelihood of developing this disease, women with Rh-negative blood factors are strongly advised to avoid abortion, especially during the first pregnancy.

Conclusion

Hemolytic disease is a fairly serious disease that can lead to serious consequences in the development of the baby. Even if the expectant mother has a negative Rh factor, one should not despair. Regular conduct of all prescribed examinations and strict adherence to all treatment points will minimize possible damage to the fetus and increase the likelihood of having a healthy baby.