Hemolytic Disease of the Fetus and Newborn

What is Hemolytic Disease of the fetus and newborn?

Hemolytic disease of the fetus and newborn is understood to mean hemolytic anemia due to the antigenic difference between mother and child erythrocytes, antibody production by the mother’s immunocompetent system against this antigen, penetration of antibodies through the placenta and destruction of the erythrocytes of the fetus or child under the influence of these antibodies. Most often, antibodies are directed against rhesus antigens. They are produced by the immune system of the Rh-negative woman. Less commonly, antibodies are directed against group antigens A or B of a child and are produced in the body of the mother of group 0.

Causes of Hemolytic Disease of the fetus and newborn

Hemolytic disease associated with Rh incompatibility, develops as a result of the penetration of antibodies to the mother through the placenta. These antibodies are fixed on the surface of the erythrocytes of the fetus, as a result of which they are destroyed by macrophages. Hemolytic anemia develops with foci of extramedullary (extracostal cerebral) blood formation, an increase in the amount of indirect bilirubin, which is highly toxic to the fetus.

Pathogenesis during Hemolytic Disease of the fetus and newborn

Immunization of the mother with Rh-positive erythrocytes of the fetus occurs during childbirth, much less often a woman is immunized before pregnancy, usually during transfusion of erythrocytes with the antigen absent in women. It was shown that the probability of immunization of a woman is significantly higher when the husband and wife have the same blood group in the AB0 system.

The term “hemolytic disease of the newborn” is often used to refer to anemia associated with Rh incompatibility. However, this term implies other forms of hemolytic anemia, in particular hemolytic anemia, associated with AB0 system incompatibility, which exists in approximately 20% of all pregnancies. Only in 10% of pregnancies incompatible with the AB0 system, the mother’s antibodies affect the fetus. Hemolytic disease AB0 occurs in 0 children whose mothers have blood group 0. Normal isoagglutinins AB belong to the IgM class. They do not pass through the placenta. However, 10% of healthy people in group 0 have antibodies against antigens A and B belonging to the IgG class. Such antibodies are found in both women and men and are not dependent on prior immunization. These antibodies pass through the placenta and can cause hemolytic anemia in the fetus or newborn. Among the first-born children, AB0 hemolytic anemia occurs as often as among children born from the second and third genera.

The frequency of hemolytic disease of the newborn, associated with Rh incompatibility, increases with each subsequent birth.

Symptoms of Hemolytic Disease of the fetus and newborn

The clinical picture of hemolytic disease varies depending on the amount of antibodies that cross the placenta. In the most severe cases, the fetus develops extensive swelling, ascites, a transudate appears in the pleural cavity. A child may be born dead or in a critical condition. Severe edema is associated with circulatory failure due to severe anemia. With less severe forms in children at birth, the liver and spleen are enlarged, the skin is pale. Jaundice develops in the first day. Due to anemia, cardiomegaly (an increase in the size and mass of the heart) and circulatory failure occur.

One of the most dangerous symptoms of hemolytic disease of newborns is nuclear jaundice with symptoms of damage to the nervous system: rhythmic contractions of the eyeballs, convulsive jerking, increased vascular tone, cry of high tonality, in the most severe cases – generalized convulsions. In the future, children who survived severe jaundice develop irreversible changes in the nervous system: deafness, asymmetric spasticity. Sometimes, intellect and cognitive functions are further affected. The critical level of indirect bilirubin at which nuclear jaundice develops is 310–344 μmol / l.

There is also a mild form of the disease, in which the pallor of the skin is noted almost without jaundice, the level of hemoglobin and erythrocytes decreases, the liver and spleen slightly increase.

With incompatibility in the AB0 system, the clinical picture of the disease is much easier than with Rh incompatibility. Quite rarely there is a significant increase in the size of the liver and spleen, less pronounced anemia, hyperbilirubinemia.

Nuclear jaundice is highly uncharacteristic of AB0 hemolytic disease.

The blood picture depends on the severity of the disease. The content of hemoglobin in severe forms of the disease decreases at birth to 60-80 g / l. The content of reticulocytes is significantly increased (up to 10-15%), in the peripheral blood a large number of erythrocaryocytes. The content of leukocytes is increased, neutrophilic shift to the left is characteristic.

L. S. Persianinov divided the hemolytic disease of the newborn into 3 degrees according to severity. As a criterion, 2 laboratory parameters (hemoglobin and bilirubin) and one clinical (edema) are used.

When I severity of hemoglobin exceeds 150 g / l, the concentration of bilirubin is not higher than 86 µmol / l and there is only swelling of the subcutaneous tissue; in grade II, hemoglobin levels range from 100 to 150 g / l, bilirubin ranges from 80 to 137 μmol / l, and puffiness and ascites are detected; at III – hemoglobin content is below 100 g / l, bilirubin is above 139 μmol / l, universal edema is detected. Gradually, the hemoglobin content decreases, sometimes to 30-40 g / l, there is a pronounced erythrocytosis, sometimes megaloblasts. In rare cases, cells that resemble blasts are found. There are pronounced anisocytosis, polychromasia. The presence of spherocytes is not characteristic of Rh incompatibility. In the most severe cases, platelet count decreases.

With incompatibility in the AB0 system, anemia is much easier than with Rh incompatibility. However, the level of reticulocytes is also elevated. Erythrocaryocytes are found in peripheral blood, although there are few of them (5-10 per 100 leukocytes). In this form, spherocytes appear, which are indistinguishable from spherocytes in hereditary microspherocytosis.

Diagnosis of Hemolytic Disease of the fetus and newborn

Studies should be carried out when the hemoglobin level decreases in the newborn, and the amount of indirect bilirubin increases. Child erythrocytes contain antibodies detected in a direct Coombs test. Mother’s serum contains incomplete antibodies detected by an indirect Coombs test with a pool of donor Rh-positive erythrocytes of the same group or group 0. If the baby’s Rhesus accessories and the mother match or the child is Rh-negative, the mother has blood group 0 B or AB and there are signs of hemolytic anemia, then there is an assumption that the AB0 system is incompatible. This is supported by the detection in the mother of antibodies against antigens A or B in serum (depending on the blood type of the child) belonging to the IgG class. The test for “immune” isoagglutinins, which give hemolysis at 37 ° C in the presence of complement, is not specific enough, since it can sometimes be given by IgM class antibodies that are not related to the hemolytic disease of the newborn. The negative result of the test is important, as well as the determination of antibodies against this antigen in the serum of a child of group A, and antibodies against antigen B in a child of group B. therefore, in a number of patients, the direct Coombs test is negative.

Antenatal diagnosis of hemolytic disease of the newborn, associated with Rh incompatibility, primarily involves the dynamic study of antibodies in the serum of the mother against the Rh antigen (D). The increase in antibody titer during pregnancy indicates the possibility of Rh incompatibility in the fetus. For antenatal diagnosis, transabdominal amniocentesis is used. This procedure should be carried out only after ultrasound examination of the placenta and fetus.

An increase in the level of bilirubin and, therefore, a dynamic study of this indicator are important.

Differential diagnosis of hemolytic disease of the newborn is carried out with other types of anemia in the newborn, especially with neonatal anemia as a result of blood loss from various causes, including blood penetration from fetus to mother or inter-twin transfusion, when one twin can have anemia and another erythrocytosis. In acute hemorrhage, normochromic anemia and shock are observed, in chronic it is severe hypochromic anemia with increased levels of reticulocytes and the appearance of erythrokaryocytes. Not characterized by an increase in the spleen, increased levels of bilirubin. Fetomaterinskoe bleeding is confirmed by the discovery in the mother’s blood of a large amount of fetal hemoglobin, detected both chemically and histochemically by the method of Kleyhauer. Hemolytic disease has to be differentiated from other types of hemolytic anemia in boys with deficiency of the activity of the enzyme G-6-PD. The use of drugs that can cause hemolysis, lubrication of the umbilical cord with such drugs can lead to a hemolytic crisis in a child with a sharp drop in hemoglobin, increased levels of reticulocytes and erythrocaryocytes, and an enlarged spleen. In this case, the direct Coombs test is negative, the mother does not find antibodies against the erythrocyte antigens of the child.

Treatment of Hemolytic Disease of the fetus and newborn

Treatment of hemolytic disease of the newborn is quite a long and difficult task. In severe cases, the fight against asphyxia and the correction of acidosis are in the first place. One method of treating severe forms of hemolytic disease of the newborn is still exchange transfusion.

For the first time, red blood cell transfusion in hemolytic disease of the newborn was used in 1927. At that time, blood was transfused, compatible only with the AB0 system, and often used the blood of the father. Mortality in this manipulation was 40%. After the discovery of the Rh factor and finding out the causes of hemolytic disease of the newborn, Rh-negative blood was infused into children, which reduced mortality by up to 30%. Subsequently, women began to be delivered 2-3 weeks before the prescribed period and transfused with Rh-negative blood; mortality decreased to 20%, and after the introduction into the practice of exchange blood transfusions, the mortality rate is about 10%.

It should be noted that the replacement transfusions often give serious complications, primarily in case of a violation of the transfusion techniques. It is necessary to use only fresh blood stored in no case more than 4 days (preferably not more than 2 days). Blood should not be injected very quickly, not faster than 10 ml / min. Sometimes the cause of death is air embolism. The introduction of cold blood can lead to cardiac arrest, asthma attack. One of the complications of replacement transfusions may be disseminated intravascular coagulation syndrome, as with massive blood transfusions. At the first stage of this syndrome, thrombotic complications, including portal vein thrombosis, are possible, and severe bleeding can occur with a drop in platelet levels. Insufficient aseptic can cause septic complications. Like all transfusions, replacement transfusions are fraught with the danger of serum hepatitis. Replacement transfusions that save many newborns can only be used for serious indications. For their determination, monitor the level of indirect bilirubin, investigate its growth. In full-term infants, an increase in excess of 5.2 µmol / l, and in premature infants – 1.7 µmol / l, requires a replacement blood transfusion. It should be borne in mind that the maximum level of bilirubin in this form is observed on the 3-4th day of illness. Replacement transfusions are recommended only when the level of bilirubin is increased to 250-300 µmol / l. Used blood group 0, which coincides with the Rh-belonging of the child.

In full-term newborns, hemolytic anemia associated with Rh incompatibility is often more severe than in children born 2–3 weeks before the due date. This is due to the smaller amount of Rh antigen on the surface of red blood cells in a premature baby. Unlike rhesus conflict, AB0 disease never resorts to early delivery.

In non-severe forms of hemolytic disease of the newborn, associated with both Rh incompatibility and AB0 incompatibility, it is possible to use phenobarbital, which activates the enzyme glucocuronyltransferase, which is necessary for glukuronirovaniya bilirubin. Sometimes phenobarbital is prescribed to a woman for 2 weeks before giving birth, but more often phenobarbital is administered to a newborn with mild hyperbilirubinemia at a dose of 4 mg / (kg / day). In mild cases of hemolytic disease of the newborn, light therapy is used. Electromagnetic waves in the visible part of the spectrum (420-460 mmk) translate indirect bilirubin into harmless water-soluble compounds (dipyrols), which are easily excreted from the body. The effectiveness of this therapy is low.

Prevention of Hemolytic Disease of the fetus and newborn

Prevention of Rhesus immunization is primarily a caution for blood transfusions in girls, girls, young women, when Rh-positive blood can be mistakenly administered. This is possible when false-positive results are obtained, and immunization often occurs with some antigens missing from the girl. Further, this leads to hemolytic disease of the newborn. Therefore, transfusion of blood-substituting solutions should be used strictly for health reasons. However, most often the immunization of women comes in childbirth, and therefore the prevention of Rh-incompatibility in childbirth has been developed.

This method of preventing Rhesus-Conflict Anemia is currently widely used.

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