The fundamental diagnostic method for GBN is. Hemolytic disease of the newborn: causes, diagnosis, treatment

HEMOLYTIC DISEASE OF THE NEWBORN

Hemolytic disease of the newborn(morbus haemoliticus neonatorum) - hemolytic anemia newborns, due to the incompatibility of the blood of the mother and fetus according to Rh factor y, blood type and other blood factors. The disease is observed in children from the moment of birth or is detected in the first hours and days of life.

Hemolytic disease of the newborn, or fetal erythroblastosis, is one of the most serious diseases of children in the neonatal period. Occurring in the antenatal period, this disease can be one of the causes of spontaneous abortions and stillbirths. According to WHO (1970), hemolytic disease of the newborn is diagnosed in 0.5% of newborns, mortality from it is 0.3 per 1000 children born alive.

Etiology, causes of hemolytic disease of the newborn.

The cause of hemolytic disease of newborns became known only at the end of the 40s of the XX century. in connection with the development of the doctrine of the Rh factor. This factor was discovered by Landsteiner and Wiener in 1940 in Macacus rhesus monkeys. Later, these same researchers found that the Rh factor is present in the erythrocytes of 85% of people.

Further studies have shown that hemolytic disease of the newborn may be due to the incompatibility of the blood of the mother and fetus, both in terms of the Rh factor and the blood type. In rare cases, the disease occurs as a result of incompatibility of the blood of the mother and fetus for other blood factors (M, N, M5, N3, Rell, Kidd, Luis, etc.).

The Rh factor is located in the stroma of red blood cells. It has no connection with gender, age and belonging to the ABO and MN systems. There are six main antigens of the Rhesus system, inherited by three pairs of genes and designated either C, c, D, d, E, e (according to Fisher), or rh", hr", Rh 0, hr 0, rh ", hr" (according to Winner). In the occurrence of hemolytic disease of the newborn, the most importance has a D-antigen that is absent in the mother and present in the fetus as a result of its inheritance from the father.

Hemolytic disease of the newborn, due to incompatibility according to the ABO system, is more common in children with blood types A (II) or B (III). The mothers of these children have 0(I) blood group, which contains agglutinins α and β. The latter can block fetal red blood cells.

It has been established that mothers whose children were born with manifestations of hemolytic disease, in most cases, even before the onset of this pregnancy, were sensitized to the erythrocyte antigens of this fetus due to previous blood transfusions, as well as pregnancies with a Rh-positive fetus.

Currently, there are three types of Rh antibodies that are formed in the sensitized body of people with Rh-negative blood: 1) complete antibodies, or agglutinins, 2) incomplete, or blocking, 3) hidden.

Complete antibodies are antibodies capable of causing agglutination of erythrocytes specific to a given serum by ordinary contact; this reaction does not depend on the salt or colloid state of the medium. Incomplete antibodies can cause erythrocyte agglutination only in a medium containing high-molecular substances (serum, albumin, gelatin). Latent Rh antibodies are found in the serum of a person with Rh-negative blood in very high concentrations.

In the occurrence of hemolytic disease of the newborn, the most important role belongs to incomplete Rh antibodies, which can easily cross the placenta into the fetus due to the small size of the molecule.

Pathogenesis. Development of hemolytic disease of the newborn

The normal course of pregnancy involves the synthesis by a woman of antibodies to the genetically alien antigens of the fetus of paternal origin that come to her. It has been established that in the placenta and amniotic fluid, maternal antibodies are bound by fetal antigens. With previous sensitization, with a pathological course of pregnancy barrier functions placenta are reduced, and maternal antibodies can reach the fetus. This happens most intensely during childbirth. Therefore, hemolytic disease of the newborn usually begins after birth.

In the pathogenesis of hemolytic disease, the occurrence of hemolysis of erythrocytes in a fetus or a newborn child due to damage to the membrane of red cells by maternal antibodies is of primary importance. This leads to premature extravascular hemolysis. With the breakdown of hemoglobin, bilirubin is formed (35 mg of bilirubin is formed from each gram of hemoglobin).

Intensive hemolysis of erythrocytes and enzymatic immaturity of the liver of the fetus and newborn child lead to the accumulation of free (indirect) bilirubin in the blood, which has toxic properties. It is insoluble in water, not excreted in the urine, but it easily penetrates lipid-rich tissues: the brain, adrenal glands, liver, disrupting the processes of cellular respiration, oxidative phosphorylation and the transport of certain electrolytes.

A severe complication of hemolytic disease is nuclear jaundice (kernicterus), caused by the toxic effect of indirect bilirubin on the nuclei of the base of the brain (subthalamic, hypocampus, striatal body, cerebellum, cranial nerves). Prematurity, acidosis, hypoalbuminemia, infectious diseases, as well as a high level of indirect bilirubin in the blood (more than 342 µmol/l) contribute to the occurrence of this complication. It is known that when the level of bilirubin in the blood serum is 342-428 µmol/l, kernicterus occurs in 30% of children.

In the pathogenesis of hemolytic disease of the newborn, dysfunction of the liver, lungs, and cardiovascular system plays a certain role.

Symptoms. Flow. Clinical picture of hemolytic disease of the newborn.

Clinically, there are three forms of hemolytic disease of the newborn: edematous, icteric and anemic.

The edematous form is the most severe. It is characterized by pronounced edema with accumulation of fluid in the cavities (pleural, abdominal), pallor skin and mucous membranes, a significant increase in the size of the liver and spleen. Some newborns have small bruises and petechiae.

Large changes are observed in the composition of peripheral blood. In such patients, the amount of hemoglobin is reduced to 30-60 g / l, the number of erythrocytes often does not exceed 1x10 12 / l, anisocytosis, poikilocytosis, polychromasia, normo- and erythroblastosis are expressed; the total number of leukocytes is increased, neutrophilia is noted with a sharp shift to the left. Anemia in such children is so pronounced that, in combination with hypoproteinemia and damage to the capillary wall, it leads to the development of heart failure, which is considered the main cause of death before the birth of a child or shortly after it.

The icteric form is the most common clinical form of hemolytic disease of the newborn. The first symptom of the disease is jaundice, which occurs on the 1st-2nd day of life. The intensity and shade of jaundice gradually change: first orange, then bronze, then lemon, and finally the color of an unripe lemon. There is icteric staining of the mucous membranes, sclera. The size of the liver and spleen increase. At the bottom of the abdomen, pastosity of the tissues is observed. Children become lethargic, adynamic, suck badly, they have reduced reflexes of newborns.

In the study of peripheral blood, anemia of varying severity, pseudoleukocytosis, which occurs due to an increase in young nucleated red cells, which are perceived in the Goryaev's chamber as leukocytes, are revealed. The number of reticulocytes significantly increases.

For the icteric form of hemolytic disease of the newborn, an increase in the level of indirect bilirubin in the blood is characteristic. Already in the cord blood, its level can be above 60 µmol/l, and later it reaches 265-342 µmol/l or more. There is usually no clear relationship between the degree of skin icterus, the severity of anemia, and the severity of hyperbilirubinemia, but it is believed that icterus of the palms indicates a bilirubin level of 257 µmol/l and above.

Severe complications of the icteric form of hemolytic disease of the newborn are damage to the nervous system and the development of kernicterus. When these complications occur, the child first appears increasing lethargy, decreased muscle tone, absence or inhibition of the Moro reflex, regurgitation, vomiting, pathological yawning. Then the classic signs of nuclear jaundice appear: muscular hypertension, stiff neck, forced body position with opisthotonus, stiff limbs, hands clenched into a fist, a sharp “brain” cry, hyperesthesia, bulging fontanel, twitching of facial muscles, convulsions, symptom "setting sun", nystagmus, Graefe's symptom; apnea occurs intermittently.

Others relatively frequent complication is a syndrome of thickening of bile. Its signs are discolored stools, saturated color urine, liver enlargement. When examining blood, an increase in the level of direct bilirubin is detected.

The anemic form is observed in 10-15% of patients with hemolytic disease of the newborn. Its early and permanent symptoms should be considered a general pronounced lethargy and pallor of the skin and mucous membranes. Paleness is clearly revealed by the 5-8th day after birth, since at first it is masked by a slight jaundice. There is an increase in the size of the liver and spleen.

In peripheral blood with this form, the hemoglobin content is reduced to 60-100 g/l, the number of erythrocytes is in the range of 2.5x10 12 /l-3.5x10 12 /l, normoblastosis, reticulocytosis is observed. The bilirubin level is normal or moderately elevated.

The diagnosis of hemolytic disease of the newborn is based on anamnesis data (sensitization of the mother due to previous blood transfusions; the birth of children in this family with jaundice, their death in the neonatal period; indications of the mother to her earlier late miscarriages, stillbirths), on the assessment clinical symptoms and on data laboratory research. The latter are of paramount importance in the diagnosis of diseases.

First of all, the blood group and Rh affiliation of the mother and child are determined, the content of reticulocytes in the peripheral blood and the level of bilirubin in the venous blood of the child are examined.

In case of Rh incompatibility, the titer of Rh antibodies in the blood and milk of the mother is determined, a direct Coombs test is performed with the child's erythrocytes and an indirect test with the mother's blood serum. In case of incompatibility according to the ABO system in the blood and milk of the mother, the titer of a- or p-agglutinins in salt and protein media is determined. Immune antibodies in a protein medium have a titer four times higher than in saline. These antibodies belong to class G immunoglobulins and cross the placenta, causing the development of hemolytic disease of the newborn. Direct Coombs reaction with ABO incompatibility is usually negative.

If the clinical and laboratory data clearly indicate hemolysis, and the blood of the mother and child are compatible according to the Rh factor and the ABO system, then it is advisable to put the Coombs reaction, conduct a test for individual compatibility of the mother's blood and the child's erythrocytes, look for antibodies to antigens, rarely causing hemolytic disease of the newborn: c, d, e, Kell, Diffy, Kidd.

For antenatal diagnosis, the prognostic value is the determination of bilirubin in amniotic fluid at 32-38 weeks of gestation: with an optical spectrophotometric density of amniotic fluid (with a filter of 450 nm) 0.15-0.22 units. develops mild form hemolytic disease of the newborn, above 0.35 units. - heavy form. The edematous form of hemolytic disease of the newborn in the antenatal period can be diagnosed using ultrasound.

The detection of women sensitized to Rh antigens is facilitated by the determination of the titer of Rh antibodies in the blood of pregnant women. However, the degree of increase in the titer of Rh antibodies in the blood of a pregnant woman does not always correspond to the severity of the hemolytic disease. A jumping titer of Rh antibodies in a pregnant woman is considered unfavorable prognostically.

Diagnostics. Differential diagnosis of hemolytic disease of the newborn.

Hemolytic disease of the newborn has to be differentiated from a number of diseases and physiological conditions. First of all, it is necessary to establish the hemolytic nature of the disease and exclude hyperbilirubinemia of hepatic and mechanical origin.

Among the reasons causing the appearance jaundice of the second group in newborns, congenital diseases of an infectious nature are of the greatest importance: viral hepatitis, syphilis, tuberculosis, listeriosis, toxoplasmosis, cytomegalovirus infection, as well as sepsis acquired not only in utero, but also after birth.

The common signs of this group of jaundices are the following: the absence of signs of hemolysis (anemia, signs of irritation of the red series of hematopoiesis, an increase in the level of indirect bilirubin, an increase in the spleen) and an increase in the level of direct bilirubin.

It should also be remembered that newborns may experience obstructive jaundice, which appears, as a rule, in connection with an anomaly in the development of the biliary tract - agenesis, atresia, stenosis and intrahepatic cysts. bile ducts. In these cases, jaundice usually appears by the end of the 1st week, although it may appear in the first days of life. It progressively intensifies, and the skin acquires a dark green, and in some cases a brownish tint. Feces may be slightly colored. With anomalies in the development of the biliary tract, the amount of bilirubin in the blood serum is very high, it can reach 510-680 µmol / l due to an increase in direct bilirubin. In severe and advanced cases, indirect bilirubin may also increase due to the impossibility of its conjugation due to the overflow of liver cells with bile bilirubin. The urine is dark and stains the diaper in yellow. The amount of cholesterol and alkaline phosphatase is usually increased. The liver and spleen are enlarged and thicken with increased jaundice. Gradually, dystrophy develops in children, signs of hypovitaminosis K, D and A appear. Biliary cirrhosis of the liver develops, from which children die before reaching the age of 1 year.

With a high level of indirect bilirubin in the blood and in the absence of other signs of increased hemolysis of erythrocytes, a suspicion arises of the conjugative nature of jaundice. In such cases, it is advisable to investigate the activity of lactate dehydrogenase and its first fraction, hydroxybutyrate dehydrogenase, in the child's blood serum. With hemolytic disease of the newborn, the level of these enzymes is sharply increased, and with conjugative jaundice, it corresponds to the age norm.

We must not forget about the existence of a fairly rare disease known as the Krigler-Najar syndrome (Krigler and Najar). This is non-hemolytic hyperbilirubinemia, accompanied by the development of kernicterus. The disease is inherited in an autosomal recessive manner. Boys get sick more often than girls.

The Crigler-Najjar syndrome is based on a sharp disruption in the formation of bilirubin diglucoronide (direct bilirubin) due to the complete absence of UDP-glucuronyl transferase, which conjugates bilirubin. The main symptom of the disease is jaundice, which appears on the first day after birth and grows rapidly, remaining throughout the life of the child. Jaundice is associated with a sharp increase in indirect bilirubin in the blood, the amount of which very quickly reaches 340-850 µmol / l. Against the background of a sharp increase in indirect bilirubin in the blood, symptoms of nuclear jaundice develop. Anemia is not observed. The number of young forms of erythrocytes is not increased. The amount of urobi-lin in the urine is within the normal range. Bile is devoid of direct, conjugated bilirubin. The defeat of the central nervous system leads to the death of the child in the first months of life. Children rarely live beyond the age of 3.

Hereditary hemolytic anemias are diagnosed on the basis of (specific morphological features of erythrocytes, measurement of their diameter, osmotic stability, studies of the activity of erythrocyte enzymes (primarily glucose-6-phosphate dehydrogenase, etc.), types of hemoglobin.

Treatment of hemolytic disease of the newborn.

Treatment of hemolytic disease of newborns with a high level of indirect bilirubin can be conservative or operative (exchange transfusion surgery).

Adequate nutrition is very important for newborns with hemolytic disease.

Conservative treatment of hemolytic disease of the newborn includes the following activities:

1. measures aimed at reducing hemolysis by stabilizing the erythrocyte membrane (intravenous injections of 5% glucose solution, administration of ATP, erevita);
2. therapy that accelerates the metabolism and excretion of bilirubin from the body (taking phenobarbital at the rate of up to 10 mg / kg per day, divided into three doses, orally);
3. the appointment of substances that adsorb bilirubin in the intestine and accelerate its excretion with faeces ( agar agar 0.1 g three times a day inside; 12.5% ​​solution of xylitol or magnesium sulfate orally 1 teaspoon three times a day or allochol for "/2 crushed dragees also three times a day inside);
4. the use of means and measures to reduce the toxicity of indirect bilirubin (phototherapy); Recently, there have been reports of the effectiveness of low doses of ultraviolet radiation in combating the toxic effects of indirect bilirubin.

It is useful to carry out infusion therapy. The volume of infusion therapy is as follows: on the first day - 50 ml/kg, and then add 20 ml/kg per day, bringing it up to 150 ml/kg by the 7th day.

The composition of the infusion solution: 5% glucose solution with the addition of 10% calcium solution for every 100 ml, from the second day of life - 1 mmol of sodium and chlorine, from the third day - 1 mmol of potassium. Infusion rate - 3-5 drops per 1 minute. The addition of a 5% albumin solution is indicated only for children with infectious diseases, premature, when hypoproteinemia is detected (below 50 g / l). Infusions of gemodez and rheopolyglucin are not indicated for hemolytic disease of the newborn.

Replacement blood transfusion is carried out according to certain indications. An absolute indication for exchange transfusion is hyperbilirubinemia above 342 µmol/l, as well as the rate of increase of bilirubin above 6 µmol/l per hour, its level in cord blood above 60 µmol/l.

Indications for exchange transfusion on the first day of life are anemia (hemoglobin less than 150 g/l), normoblastosis, and proven incompatibility of the blood of mother and child by group or Rh factor.

In case of Rh-conflict, blood of the same group as that of the child is used for replacement blood transfusion, Rh-negative for no more than 2-3 days of preservation, in the amount of 150-180 ml / kg (with an indirect bilirubin level of more than 400 μmol / l - in the amount of 250-300 ml / kg). In case of ABO conflict, blood of group 0 (I) is transfused with a low titer of a- and ß-agglutinins, but in an amount of 250-400 ml; in this case, as a rule, the next day it is necessary to do a second replacement transfusion in the same volume. If the child has both incompatibility for Rhesus and ABO antigens, then the child needs to be transfused with blood of the 0 (I) group.

When performing an exchange transfusion, the catheter is inserted into the umbilical vein to a length of no more than 7 cm. The blood must be heated to a temperature of at least 28 ° C. The contents of the stomach are aspirated before the operation. The procedure begins with the removal of 40-50 ml of the child's blood, the amount of blood injected should be 50 ml more than the output. The operation is carried out slowly (3-4 ml per 1 min), the excretion and administration of 20 ml of blood alternate. The duration of the entire operation is at least 2 hours. It should be remembered that for every 100 ml of injected blood, 1 ml of a 10% calcium gluconate solution must be injected. This is done to prevent citrate shock. 1-3 hours after the replacement blood transfusion, the level of glucose in the blood should be determined.

Complications of exchange transfusion include: acute heart failure with the rapid administration of large amounts of blood, cardiac arrhythmias, transfusion complications with improper selection of a donor, electrolyte and metabolic disorders (hyperkalemia, hypocalcemia, acidosis, hypoglycemia), hemorrhoids -gic syndrome, thrombosis and embolism, infectious complications (hepatitis, etc.), necrotizing enterocolitis.

After exchange transfusion, conservative therapy is prescribed. The indication for repeated replacement blood transfusion is the growth rate of indirect bilirubin (replacement blood transfusion is indicated when the growth rate of bilirubin is more than 6 µmol/l per hour).

To perform an exchange transfusion, you must have the following set of tools: sterile polyethylene catheters No. 8, 10, a bellied probe, scissors, two surgical tweezers, a needle holder, silk, four to six syringes with a capacity of 20 ml and two or three syringes with a capacity of 5 ml, two glasses of 100-200 ml.

The umbilical vein catheterization technique is as follows: after processing the surgical field, the end of the umbilical cord residue is cut across at a distance of 3 cm from the umbilical ring; the catheter is inserted with careful rotational movements, directing it after passing the umbilical ring up along abdominal wall, towards the liver. If the catheter is inserted correctly, then blood is released through it.

Prevention of hemolytic disease of the newborn.

The basic principles for the prevention of hemolytic disease of the newborn are as follows. First, considering great importance previous sensitization in the pathogenesis of hemolytic disease of the newborn, each girl should be treated as a future mother, and therefore girls need to carry out blood transfusions only for health reasons. Secondly, an important place in the prevention of hemolytic disease of newborns is given to work to explain to women the harm of abortion. To prevent the birth of a child with hemolytic disease of the newborn, all women with an Rh-negative blood factor, on the first day after an abortion (or after childbirth), are recommended to administer anti-O-globulin in an amount of 250-300 mcg, which contributes to the rapid elimination of the child's red blood cells from the mother's blood, preventing the synthesis of Rh antibodies by the mother. Thirdly, pregnant women with a high titer of anti-Rhesus antibodies are hospitalized for 12-14 days in the antenatal department at 8, 16, 24, 32 weeks, where they are non-specific treatment: intravenous infusions of glucose with ascorbic acid, cocarboxylase, prescribe rutin, vitamin E, calcium gluconate, oxygen therapy; with the development of a threat of termination of pregnancy, progesterone is prescribed, endonasal electrophoresis of vitamins B 1, C. 7-10 days before delivery, the appointment of phenobarbital 100 mg three times a day is indicated. Fourthly, with an increase in anti-Rhesus antibody titers in a pregnant woman, delivery is carried out ahead of schedule at the 37-39th week by caesarean section.

Consequences and prognosis in hemolytic disease of the newborn.

Hemolytic disease of the newborn: the consequences can be dangerous, up to the death of the child, the functions of the liver and kidneys of the child may be impaired. You need to start treatment right away.

The prognosis of hemolytic disease of the newborn depends on the form of the disease and the adequacy of the preventive and therapeutic measures taken. Patients with edematous form are not viable. The prognosis for the icteric form is favorable, provided that adequate treatment is carried out; the development of bilirubin encephalopathy and kernicterus is unfavorable prognostically, since the percentage of disability is very high in the group of such patients. The anemic form of hemolytic disease of the newborn is prognostically favorable; in patients with this form, self-healing is observed.

The modern level of development of medicine, the correct diagnostic and therapeutic tactics make it possible to avoid the pronounced consequences of hemolytic disease of the newborn.

doctor of medical sciences, Nikolai Alekseevich Tyurin et al., Moscow (edited by MP site)

After the birth of a child, his body adapts to completely different conditions. environment and undergoes many changes. One of the adaptive mechanisms is the physiological jaundice of newborns. In the intrauterine life of a child, his blood contains much more red blood cells than in an adult. This is due to the fact that he receives oxygen by transporting it from maternal blood through the umbilical cord, and for sufficient saturation, a large amount of hemoglobin, which is part of red blood cells, is required, because it is hemoglobin that carries oxygen to organs and tissues. After the birth of a child, his body no longer needs such in large numbers red blood cells, they are destroyed, releasing fetal hemoglobin, which in turn is destroyed and releases bilirubin, and a large amount of free bilirubin stains the mucous membranes and skin in a yellow color. Physiological jaundice usually appears on 3-4 days of life and disappears on its own after 2-3 weeks.

Bilirubin is a toxic substance. The body tries to remove it by binding to albumin protein. But if there is much more bilirubin than albumin, it affects nervous system causing nuclear jaundice. In addition to physiological jaundice, there are pathological forms: conjugative hereditary jaundice, hemolytic disease of the newborn, infectious-toxic hepatic jaundice.

One of the most effective methods reducing the toxicity of bilirubin is phototherapy, or phototherapy.

Phototherapy is one of the physiotherapy procedures based on the therapeutic effect of the ultraviolet spectrum. sunlight with a wavelength of 400–550 nm. Under the influence of a light wave of the required range, bilirubin is converted into an isomer, which the body of a newborn is able to excrete with physiological functions, which reduces the level of bilirubin in the blood and protects the body from its toxic effects.

Procedure technique

A completely undressed child is placed in the incubator, for protection from ultraviolet radiation, the eyes are closed with special glasses, and the genitals of the boys are covered with an opaque cloth. A dense, light-tight gauze dressing is often used.

Ultraviolet lamps are installed at a distance of about 50 cm from the child. Moreover, the combination of four ultraviolet lamps with two fluorescent lamps turned out to be more effective, but healing effect comes from an ultraviolet source.

During the procedure, the maximum break can last from two to four hours in a row. In cases of a pronounced increase in bilirubin, phototherapy is carried out in a continuous course.

The course lasts an average of 96 hours.

Every hour the child is in the incubator, it is necessary to change the position of his body - on the back, on the stomach, on the side, and every 2 hours to measure his body temperature to avoid overheating.

Not to mention the need to continue breastfeeding, because breast milk helps to accelerate the removal of bilirubin from the baby's blood. Moreover, it should be applied to the breast of the child as often as possible. If breastfeeding is not possible for certain reasons, it is necessary to try to feed the newborn with mother's milk using a spoon or bottle.

It is worth knowing that during phototherapy, the daily volume of necessary fluid for a child should exceed the physiological need by 10-20%.

It is necessary daily (and if there is a threat of developing encephalopathy - every 6 hours) to take the baby's blood for biochemical analysis, this is the only method that serves as a criterion for the effectiveness of the treatment.

Indications for phototherapy

Indications for phototherapy of newborns are:

• the risk of developing hyperbilirubinemia in a child, identified during pregnancy;
• morphofunctional immaturity of the child;
• Availability extensive hemorrhages and hematomas;
• newborns in need of resuscitation;
• identified high risk of developing a hereditary form of hemolytic anemia;
• physiological jaundice of newborns;
• hemolytic disease of the newborn with incompatibility by blood type - as the main method of treatment;
• hemolytic disease of the newborn with Rh-conflict - as additional method treatment after a blood transfusion to prevent a recurrence of bilirubin levels;
• preparation for replacement blood transfusion and rehabilitation after surgery;
• an increase in bilirubin of more than 5 µmol / l per hour for full-term babies and more than 4 µmol / l per hour for premature babies.

Indications for newborns in the first week of life depending on weight and bilirubin level (*):

• body weight less than 1.5 kg, bilirubin level from 85 to 140 µmol/l;
• body weight up to 2 kg, bilirubin level from 140 to 200 µmol/l;
• body weight up to 2.5 kg, bilirubin level from 190 to 240 µmol/l;
• body weight over 2.5 kg, bilirubin level - 255–295 µmol/l.

In addition to the listed indications, it is worth assessing the risks of developing bilirubin encephalopathy:

• Apgar score at the 5th minute - 4 points;
• development of anemia;
• deterioration in the general condition of the child against the background of hyperbilirubinemia;
• plasma albumin concentration not more than 25 g/l;
• partial pressure of oxygen less than 40 mm Hg. Art., acidity arterial blood less than 7.15 more than 1 hour;
• rectal temperature is not higher than 35 C.

Criteria for stopping phototherapy

If the level of total bilirubin in the blood decreases, and free bilirubin does not increase, the therapy is considered completed.

Side effects

During the phototherapy procedure, the following may occur: adverse reactions, not affecting general condition child:

• dryness and peeling of the skin;
• drowsiness;
• increased stool;
• the appearance of an allergic rash;
• bronze skin coloration.

These changes do not require drug treatment and disappear without a trace a few days after the cessation of phototherapy.

Contraindications for light therapy

Phototherapy is contraindicated if the newborn has the following disorders:

• high levels of conjugated bilirubin;
• liver dysfunction;
• obstructive jaundice.

In seven out of ten children born, doctors of maternity hospitals reveal yellowness of the skin. Some babies are already born with jaundice, while others turn yellow hours or even days after birth.

In 90% of cases, everything ends well: the diagnosis of physiological jaundice in newborns is confirmed. But in 10% of cases, doctors are forced to ascertain the fact that an infant has a congenital or acquired, often serious illness which caused the skin and mucous membranes to turn yellow. One such disease is hemolytic disease of the newborn.

THE CONCEPT OF HEMOLYTIC DISEASE OF THE NEWBORN (HDN)

Hemolytic disease of the fetus and newborn is congenital disease, which can declare itself both when the baby is still in the womb, and when he has already been born.

At its core, this is an immunological confrontation between two related organisms - the body of the mother and the body of the child. The reason for this conflict, paradoxically, is the incompatibility of the mother's blood with the blood of the fetus, as a result of which the child's red blood cells are destroyed.

The mechanism of development of HDN

The shell of a human erythrocyte is "populated" with various antigens (AG), there are more than 100 types of them. Scientists have grouped all AGs into erythrocyte systems, of which more than 14 are already known (AB0, Rh, Kid, Kell, Duffy, etc.).

The Rhesus (Rh) system includes antigens responsible for the Rh status of the blood: Rh (+) or Rh (-). In the AB0 - AG system, which determine the group affiliation of human blood: B and A. The antigens of both of these systems are capable and ready, upon meeting with the corresponding antibodies (AT), to instantly launch an immune response. In the normal blood, antibodies to AG of their own erythrocytes are absent.

What happens with hemolytic disease of the fetus and newborn? Antigens of the erythrocytes of the fetus penetrate into the child's blood through the placenta from the mother's blood. Their meeting gives rise to an immune reaction, the result of which is hemolysis (destruction) of the child's red blood cells. But where did the antibodies to the child's erythrocyte antigens come from in the mother's blood?

REASONS FOR THE DEVELOPMENT OF HEMOLYTIC DISEASE

Hemolytic disease: causes of conflict in the Rhesus system

This form of HDN develops when a Rh (-) sensitized woman is pregnant with an Rh (+) fetus.

What does the term "sensitized" mean? This means that Rh (+) erythrocytes have already entered the woman's blood at least once, for example, during previous pregnancies with Rh (+) fetuses that ended in childbirth, abortion or miscarriage. Fetal erythrocytes penetrate the placenta into the mother's bloodstream both during pregnancy (especially active at 37–40 weeks) and during childbirth. Sensitization could occur during blood transfusion, organ transplantation.

The table shows the probability of developing an Rh-conflict between mother and fetus.

The mother's body reacts to the first "acquaintance" with foreign erythrocytes by producing appropriate antibodies. From that moment on, antibodies circulate in the mother's blood and "wait for a new meeting" with foreign Rh (+) erythrocytes. And if the first meeting of antibodies with antigens could end quite well, then the second and all subsequent ones will be an aggressive, escalating confrontation that affects the child every time.

Hemolytic disease: causes of conflict in the AB0 system

The conflict in the AB0 system is much more common than the Rhesus conflict, but it usually proceeds easier than the latter.

In the table: agglutinogens are group antigens (in erythrocytes), agglutinins are group antibodies (in blood plasma). The blood of each group is a certain set of AG and AT. Note that if A antigens are present in the blood, then there are always no α antibodies, and if there are B, then there is no β. Why? Because their meeting triggers an immune reaction of agglutination (gluing) of red blood cells with their subsequent destruction. This is the conflict according to the AB0 system, in which hemolytic blood disease of newborns develops.

Sensitization of a woman by the AB0 system can occur both during pregnancy and before it, for example, when the diet is saturated with animal proteins, during vaccination, and during an infectious disease.

The table shows the probability of developing a conflict between the mother and the fetus by blood type.

FORMS OF HDN AND THEIR CLINICAL FEATURES

According to the severity of the course, in 50% of cases, hemolytic blood disease of the newborn is mild, in 25–30% of cases its course is regarded as moderate, in 20–30% - as severe.

According to the type of conflict, there are HDN according to the Rh system, according to the AB0 system and according to antigens related to other erythrocyte systems. Clinical forms of hemolytic disease of the newborn are largely determined by the type of conflict that has arisen.

Dropsy fetus

If there is an Rh-conflict, and at 20–29 weeks of gestation, antibodies massively attack the immature fetus, dropsy of the fetus develops.

With this form of hemolytic disease of the newborn, the baby is born without jaundice, but with severe edema of the body and all internal organs. The child has signs of immaturity, reduced muscle tone, weak reflexes, he moves little. The skin is pale, it may have hemorrhages. Respiratory disorders and signs of acute heart failure are recorded.

In the blood test - severe anemia and a very low content of total protein.

If antibodies begin to attack the baby after the 29th week, then clinical form HDN and whether it will be congenital or acquired depend on how much and when (in utero and (or) during childbirth) maternal antibodies penetrated to the baby.

This form is the result of a massive hit of mother's Rh antibodies to the child from the 37th week before birth (congenital) and during birth (acquired). Distinctive feature the most common (90% of all cases) icteric form is the early (in the first hours or days) appearance of jaundice. It reaches its maximum by 2-4 days, accompanied by mild anemia, some tissue swelling, enlarged liver and spleen. The earlier jaundice appears, the more severe the course of the disease.

anemic form

This form is diagnosed in 10% of all children with hemolytic disease, its cause is a long-term effect on the fetus, starting from the 29th week, of small “portions” of Rh antibodies. The child is born very pale, jaundice or not, or it is very mild. There are gradually increasing signs of bilirubin intoxication (adynamia, lethargy, "bad" reflexes).

edematous form

If, after the 29th week of pregnancy, Rh antibodies begin a massive attack on the fetus, an edematous form of HDN develops. Its clinical manifestations are similar to those of fetal dropsy.

HDN according to the AB0 system: clinical features:

• late (2-3 days) jaundice appears;
• rarely increase the liver and spleen;
• extremely rarely develop congenital icteric and edematous forms;
• often there are acquired icteric-anemic forms;
• the frequency of development of terrible complications approaches zero.

Why is the AB0 conflict less common thanRh-conflict, results in a manifest severe form of HDN?

1. For AB0 sensitization of a woman, much more fetal blood must enter her blood than with Rh sensitization.
2. Unlike Rh antigens, group antigens, in addition to erythrocytes, are found in all other tissues of the fetus, in the placenta and in amniotic fluid. When meeting with maternal antibodies, the immune “hit” falls not only on erythrocytes, but is distributed to all these tissues.
3. The mother's body has its own group antibodies that can cope with the erythrocytes of the fetus that have entered the bloodstream.

HEMOLYTIC DISEASE: CONSEQUENCES AND COMPLICATIONS

1. Disseminated intravascular coagulation syndrome or DIC develops as a result of a sharp increase in blood clotting. In small and large vessels, blood clots are formed, heart attacks and necrosis of organs, hemorrhages in organs occur. The reason is the massive intake of tissue thromboplastin from hemolyzed erythrocytes into the blood.
2. Hypoglycemia is a decrease in blood glucose levels.
3. Bilirubin encephalopathy is the result of kernicterus, in which extremely toxic indirect bilirubin "impregnates" the structures of the brain, thereby destroying neurons. It manifests itself neurological symptoms and the subsequent formation of bilirubin encephalopathy (paralysis, deafness, etc.).
4. Bile thickening syndrome, in which the bile ducts are clogged with mucous and bile plugs.
5. Secondary lesions of the heart muscle, liver, kidneys.
6. Secondary immunodeficiency - develops due to damage to the components of the immune system by indirect bilirubin and immune complexes.

Prenatal diagnosis is aimed at identifying women with a high risk of developing a hemolytic disease in the fetus, the consequences of which are no less dangerous than itself.

Therefore, the obstetrician-gynecologist carefully and accurately in terms of HDN asks the patient, finds out the necessary details of the anamnesis (abortions, number of pregnancies, etc.). Throughout pregnancy, in women at risk for HDN, doctors monitor the antibody titer in the blood and amniotic fluid, perform ultrasound of the fetus and placenta, fetal CTG, doplerometry.

Postnatal diagnosis involves identifying among newborns those who are at high risk of developing TTH and those who already have TTH. To do this, the neonatologist regularly examines all newborns for jaundice, edema, and other signs of illness.

Laboratory studies are monitoring the level of bilirubin and glucose in the child's blood in dynamics, determining the blood group and Rh factor, immunological studies for the presence of antibodies in the child's blood, in the mother's blood and milk.

HEMOLYTIC DISEASE OF THE NEWBORN: TREATMENT AND PREVENTION

With hemolytic disease of the newborn, treatment can be operative and conservative. When choosing treatment tactics, doctors are guided by the severity of the baby's condition and the level of hyperbilirubinemia.

Surgical treatment is a replacement blood transfusion operation. It is prescribed if the newborn has signs of severe HDN, aggravated anamnesis, when symptoms of bilirubin intoxication appear. Hemosorption and plasmapheresis are used.

Conservative treatment is primarily phototherapy, irradiation with a special lamp, the rays of which make toxic bilirubin non-toxic.

Assigned infusion therapy (albumin, saline, glucose solution) is aimed at removing bilirubin intoxication and the speedy removal of bilirubin from the body.

Apply medications(ziksorin, etc.), activating the enzyme system of the liver. Adsorbents (carbolene, agar-agar, etc.), choleretic (by electrophoresis), vitamins (E, ATP, A), stabilizing cell membranes, hepatoprotectors (Essentiale, etc.), antihemorrhagic agents (adroxon, etc.) are used.

Zaluzhanskaya Elena, pediatrician

According to the etiological factor (type of serological conflict):

a) according to the Rh system; b) according to the ABO system; c) by antigens of other systems.

According to the timing of the onset of the clinical syndrome:

a) in utero; b) postnatally.

According to clinical and morphological forms of the disease:

a) intrauterine death of the fetus with maceration; b) edematous; c) icteric and d) anemic forms.

By severity:

a) easy; b) moderate; c) severe course.

Complications:

a) DIC; b) hypoglycemia; c) bilirubin encephalopathy; d) bile thickening syndrome; e) damage to the liver, myocardium, kidneys.

Classification of GBN by microbial x revision.

I Fetal dropsy due to isoimmunization.

II Hemolytic disease of the fetus and newborn due to isoimmunization (meaning icteric and anemic forms).

III Nuclear jaundice due to isoimmunization.

Features of the course of individual forms of HDN according to the Rh factor.

Dropsy fetus (edematous form of HDN).

This form of the disease develops as a result of prolonged exposure to a large amount of antibodies on an immature fetus in the period of 20-29 weeks of gestation.

The action of Rh antibodies on immature fetal erythrocytes leads to their intravascular hemolysis with the development hyperbilirubinemia and hemolytic anemia. The resulting indirect bilirubin binds to albumin and is removed through the placenta, which causes absence of jaundice and development hypoproteinemia.

Due to hypoproteinemia, oncotic pressure in the vascular bed decreases, extravasation of the liquid part of the blood occurs with the development hypovolemia and edema.

Hemolytic anemia leads to fetal hemic hypoxia with characteristic metabolic disorders that cause increased vascular permeability, development hemorrhage, hemorrhagic syndrome.

Hemic hypoxia also activates extramedullary hematopoiesis in the liver and spleen, which manifests itself hepatosplenomegaly.

Activation of hematopoiesis is also manifested by the appearance in the vascular bed of immature forms of erythrocytes (reticulocytes, normo- and erythroblasts).

Hypovolemia, edema, anemia and hemic hypoxia lead first to centralization of blood circulation, then - to the depletion of the compensatory possibilities of hemodynamics and the development heart failure.

Clinic of dropsy of the fetus. A child is born with severe general edema and an enlarged abdomen (due to ascites, hepatosplenomegaly). With a large body weight, there are signs of morpho-functional immaturity. Symptoms of CNS depression (adynamia, atony, areflexia) are revealed. Sharp pallor, hemorrhagic manifestations are characteristic. The boundaries of relative cardiac dullness are extended, signs of acute heart failure are often observed. Respiratory disorders in these patients are due to hypoplasia of the lung, which was preloaded in utero by an enlarged liver and often developing due to the immaturity of the lungs, BGM.

Data from laboratory studies.

1. In general analysis blood - anemia (hemoglobin level is usually 50-70 g / l; erythrocyte content - 1-2 x 1-12 / l; reticulocytosis up to 150% 0; normoblastosis).

2. In the biochemical analysis of blood - hypoproteinemia (o. protein below 40 - 45 g / l).

3. In the coagulogram - a low level of procoagulants.

Hemolytic disease of the fetus and newborn (icteric and edematous forms).

It develops due to the ingress of antibodies to the fetus after 29 weeks of intrauterine development and / or during childbirth. The form of the disease will also depend on when and in what quantity the antibodies penetrated to the fetus or child: congenital or postnatal, icteric or anemic.

icteric form the most common form of HDN (in 90% of cases). The main clinical sign is the early onset of jaundice.

At congenital form of jaundice is detected already at birth, with extrauterine appears in the first hours or days of life. The earlier jaundice occurs, the more severe HDN is. The maximum severity of jaundice reaches 2-4 days of life.

Patients also have a moderate enlargement of the liver and spleen, moderate anemia, pastosity of tissues.

anemic form occurs in less than 5% of patients with HDN. With a Rh conflict, it is a consequence of a long-term supply of small amounts of antibodies to the fetus against the background of the individual characteristics of the fetal hematopoietic system (decrease in regenerative capabilities). Manifested by pallor of the skin and mucous membranes (anemia from birth), mild hepatosplenomegaly, systolic murmur may be heard. Jaundice is absent or insignificant.

Nuclear jaundice - damage to the nuclei of the base of the brain by indirect bilirubin. It is a formidable complication of HDN. The first manifestations of brain damage by bilirubin are usually noted on the 3rd - 4th day of life, when the content of indirect bilirubin in the blood serum reaches its maximum figures (in full-term newborns - more than 400 μmol / l). The sensitivity of brain cells to the toxic effect of bilirubin in premature, immature newborns, children who have undergone asphyxia, birth trauma, RDS and other severe conditions is much higher and signs of bilirubin intoxication may appear in them with a lower level of bilirubin.

There are 4 phases of the course of kernicterus:

1) the appearance of signs of bilirubin intoxication- lethargy, hypotension, hyporeflexia, pathological yawning, regurgitation, vomiting, reduced sucking activity, monotonous cry.

2) The appearance of classic signs of nuclear jaundice(after 3-4 days) Prolonged apnea, bradycardia, adynamia, areflexia are characteristic, rapidly changing into a spastic stage (opisthotonus appears, stiff neck, spastic "stiff" limbs, hands clenched into fists). Excitation, "brain" cry, a symptom of the "setting sun", convulsions are periodically noted.

3) The period of imaginary well-being(at 3 - 4 weeks of life). There is a reverse development of neurological symptoms: spasticity decreases, motor activity and the severity of unconditioned reflexes improve. It appears that the child is recovering.

4) The period of formation of neurological complications(on 3 - 5 months of life). There are extrapyramidal disorders, motor and hearing disorders. Formed:

· choreoathetosis;

· paresis, paralysis;

· hearing loss up to deafness;

· delayed psychomotor development;

· cerebral palsy (mainly hyperkinetic form).

Features of clinical manifestations of HDN according to the ABO system.

1. It most often develops in the mother's blood group O (I) and the child's A (II).

2. The disease develops more often during the first pregnancy.

3. HDN in ABO is easier than with Rhesus conflict.

4. There are practically no edematous and congenital icteric forms of the disease, because antibodies to the fetus penetrate only in childbirth.

5. Jaundice appears later (at 2-3 days of life), which is due to the immaturity of the erythrocyte receptors of newborns to group anti-erythrocyte antibodies.

6. Rarely there is an increase in the liver and spleen.

7. More often than with HDN by the Rh factor, postnatal anemic forms of the disease are observed with slight jaundice and the development of anemia at 2–3 weeks of life

8. There are practically no formidable complications in the form of nuclear jaundice, DIC.

Clinical characteristics of the degrees of severity of HDN.

easy current is set at the level of hemoglobin at birth more than 140 g / l, cord blood bilirubin less than 60 μmol / l. In the dynamics of the disease, moderately expressed clinical and laboratory data are noted, requiring only conservative treatment. Complications are absent.

At moderate course jaundice appears in the first 5 hours of life with Rhesus conflict and in the first 11 hours of life with ABO conflict. The level of hemoglobin at birth is less than 140 g/l. Dynamics of clinical and laboratory data requires replacement blood transfusion.

At severe course already at birth, there are: severe jaundice (cord blood bilirubin more than 85 µmol/l), severe anemia (hemoglobin less than 100 g/l). The course of the disease is characterized by the presence of signs of bilirubin intoxication. Requires 2 or more exchange transfusions.

Diagnosis of HDN.

Prenatal diagnosis:

1) careful collection of obstetric anamnesis, identification of women at risk for TTH (estimate the number of pregnancies and the interval between them, whether there have been blood transfusions, organ transplants, the presence of TTH in previous children, complications of this pregnancy);

2) determination of antibody titer. During pregnancy, it is carried out at least 3 times: when registering a pregnant woman, at 18-20 weeks of gestation and further according to the indication, depending on the presence and titer of antibodies (with an increase in titer - weekly control);

3) amniocentesis (examination of amniotic fluid). If the antibody titer is 1:16 - 1: 32, then at 26 - 28 weeks of gestation, the optical density of amniotic fluid (increases), the content of glucose, protein (increased) and estrogens (reduced) are examined.

4) Ultrasound of the fetus and placenta at 20-22, 24-26, 30-32, 34-36 weeks. It is possible to identify the edematous form of HDN (ascites, Buddha posture), thickening of the placenta, hepatosplenomegaly.

Postnatal diagnosis:

1) identification of newborns at risk of developing HDN;

2) assessment of possible clinical manifestations: (jaundice and / or pallor of the skin, edema, hepatosplenomegaly, neurological symptoms);

3) laboratory diagnostics:

Determination of the blood group and Rh factor in newborns born to mothers with O (I) group and Rh - negative blood affiliation;

Biochemical blood test: determination of the level of bilirubin in cord blood (more than 51-61 μmol / l), dynamics of the level of bilirubin by its fractions, determination of the hourly increase in bilirubin (more than 6 - 8 μmol / l), determination of the level of glycemia;

Complete blood count: there is a decrease in hemoglobin, erythrocytes, platelets, the content of reticulocytes is more than 7 ‰, normoblasts is more than 50%, moderate leukocytosis;

Immunological studies: direct Coombs reaction, detects the presence of antigen-antibody complexes. The test material is newborn erythrocytes, to which antiglobulin serum is added, which promotes the agglutination of existing complexes. With group incompatibility, this reaction is positive in the first 2-3 days, Rh-conflict - positive from birth; indirect Coombs reaction, indicates the presence of free blocking antibodies - IgG, for this, the serum of a mother or a sick child is used, where erythrocytes of a known antigenic structure (group and Rh affiliation) are added, then after a certain period of time the erythrocytes are washed, followed by the addition of antiglobulin serum. The reaction is positive for 1-2 days.

Catad_tema Neonatal pathology - articles

Hemolytic disease of the fetus and newborn (HDN). Clinical guidelines.

Hemolytic disease of the fetus and newborn (HDN)

ICD 10: P55

Year of approval (revision frequency): 2016 (review every 3 years)

ID: KR323

Professional associations:

• Russian Association of Perinatal Medicine Specialists

Approved

Russian Association of Specialists in Perinatal Medicine 2016

Agreed

Scientific Council of the Ministry of Health Russian Federation __ __________201_

newborn

phototherapy

blood transfusion surgery

kernicterus

fetal dropsy

rhesus - isoimmunization of the fetus and newborn

ABO - isoimmunization of the fetus and newborn

List of abbreviations

AG? antigen

HELL? arterial pressure

ALT? alanine aminotransferase

AST? aspartate aminotransferase

AT? antibody

BE? bilirubin encephalopathy

HDN? hemolytic disease of the newborn

GGT? gamma-glutamyl transpeptidase

ICE? disseminated intravascular coagulation

KOS? acid-base state

ICD? international classification of diseases -10

ABOUT? total bilirubin

OZPK? exchange transfusion surgery

NICU? intensive care unit and intensive care newborns

bcc? circulating blood volume

PITN - resuscitation and intensive care unit for newborns

FFP - fresh frozen plasma

FT? phototherapy

BH? breathing rate

heart rate? heart rate

AP? alkaline phosphatase

hb? hemoglobin

IgG? immunoglobulin G

IgM? immunoglobulin M

Terms and Definitions

- isoimmune hemolytic anemia, which occurs in cases of incompatibility of the blood of the mother and fetus for erythrocyte antigens, while the antigens are localized on the erythrocytes of the fetus, and antibodies to them are produced in the mother's body.

1. Brief information

1.1 Definition

Hemolytic disease of the fetus and newborn (HDN)- isoimmune hemolytic anemia, which occurs in cases of incompatibility of the blood of the mother and fetus for erythrocyte antigens (AH), while the AHs are localized on the erythrocytes of the fetus, and antibodies (AT) to them are produced in the mother's body.

1.2 Etiology and pathogenesis

The emergence of an immunological conflict is possible if antigens are present on the erythrocytes of the fetus that are absent on the cell membranes of the mother. Thus, the immunological prerequisite for the development of HDN is the presence of an Rh-positive fetus in an Rh-negative pregnant woman. With an immunological conflict due to group incompatibility in the mother, in most cases, the O (I) blood type is determined, and in the fetus A (II) or (less often) B (III). More rarely, HDN develops due to a mismatch between the fetus and the pregnant woman in other group (Duff, Kell, Kidd, Lewis, MNSs, etc.) blood systems.

Prior isosensitization due to abortions, miscarriages, ectopic the immune system mother produces antibodies to erythrocyte antigens. If antibodies belong to class G immunoglobulins (subclasses IgG1, IgG3, IgG4)? they freely cross the placenta. With an increase in their concentration in the blood, the likelihood of developing hemolytic disease of the fetus and newborn increases. Antibodies of the IgG2 subclass have a limited ability of transplacental transport, antibodies class IgM, which include α- and β-agglutinins, do not cross the placenta.

The implementation of HDN by the Rh factor, as a rule, usually occurs during repeated pregnancies, and the development of HDN as a result of a conflict over blood group factors is possible already during the first pregnancy. In the presence of immunological prerequisites for the implementation of both variants, HDN often develops according to the ABO system. At the same time, the occurrence of hemolysis due to the ingestion of group II maternal anti-A antibodies into the blood of a child is more common than when it enters the blood of a child. Group III anti-B antibodies. However, in the latter case, penetration of anti-B antibodies leads to more severe hemolysis, often requiring exchange transfusion. The severity of the child's condition and the risk of developing kernicterus in HDN according to the ABO system are less pronounced compared to HDN according to the Rh factor. This is due to the fact that group antigens A and B are expressed by many cells of the body, and not only by erythrocytes, which leads to the binding of a significant amount of antibodies in non-hematopoietic tissues and prevents their hemolytic effects.

1.3 Epidemiology

HDN in Russia is diagnosed in approximately 0.6% of all newborns.

1.4 ICD 10 codes

Hemolytic disease of the fetus and newborn(P55):

P55.0 - Rhesus isoimmunization of fetus and newborn

P55.1 ABO fetal and newborn isoimmunization

P55.8 Other hemolytic disease of fetus and newborn

P55.9 Hemolytic disease of fetus and newborn, unspecified

1.5 Classification

1.5.1 According to the conflict between the mother and fetus according to the ABO system and other erythrocyte blood factors:

• incompatibility according to the ABO system;
• incompatibility of erythrocytes of the mother and fetus according to the Rh factor;
• incompatibility for rare blood factors.

1.5.2 By clinical manifestations distinguish forms of the disease:

edematous (hemolytic anemia with dropsy);

icteric (hemolytic anemia with jaundice);

anemic (hemolytic anemia without jaundice and dropsy).

1.5.3 According to the severity of jaundice in the icteric form:

medium severity;

severe degree.

1.5.4 According to the presence of complications:

bilirubin encephalopathy: acute damage to the central nervous system;

kernicterus: irreversible chronic damage to the central nervous system;

bile thickening syndrome;

hemorrhagic syndrome.

2. Diagnostics

2.1 Complaints and medical history

• When taking anamnesis, it is recommended to pay attention to:

Rh - affiliation and blood type of the mother;

infections during pregnancy and childbirth;

hereditary diseases (deficiency of G6PD, hypothyroidism, other rare diseases);

the presence of jaundice in parents;

the presence of jaundice in a previous child;

weight and gestational age of the baby at birth;

feeding the baby (underfeeding and/or vomiting).

2.2 Physical examination

Edematous form of HDN

General edematous syndrome (anasarca, ascites, hydropericardium), severe pallor of the skin and mucous membranes, hepatomegaly and splenomegaly, jaundice is absent or mild. Possible hemorrhagic syndrome, the development of DIC syndrome.

Icteric form of HDN

At birth, amniotic fluid, umbilical cord membranes, and primordial lubrication may be ictericly stained. Characteristically early development jaundice, pallor of the skin and visible mucous membranes, enlarged liver and spleen.

Anemic HDN

Against the background of pallor of the skin, lethargy, poor sucking, tachycardia, an increase in the size of the liver and spleen are noted, muffled heart sounds, systolic murmur are possible.

Complications of HDN

Nuclear jaundice - bilirubin intoxication - lethargy, loss of appetite, regurgitation, pathological yawning, muscle hypotension, disappearance of the 2nd phase of the Moro reflex, then there is a clinic of encephalopathy - opisthotonus, "brain" cry, bulging of the large fontanel, convulsions, pathological oculomotor symptoms - a symptom of "setting sun, nystagmus. Bile thickening syndrome - jaundice acquires a greenish tint, the liver is enlarged, urine is saturated.

2.3 Laboratory diagnostics

• It is recommended to determine the Rh-factor already in the first hours of a child's life based on the anamnesis (an increase in the titer of anti-D antibodies in Rh (-)

All women with a negative Rh factor during pregnancy are recommended to determine the level of immune antibodies in the blood in dynamics.

Comments:HDN according to the AB0 system, as a rule, does not have specific signs in the first hours after birth.

If the mother's blood is characterized by a negative Rh factor or belonging to the O (I) group, it is recommended that the newborn be sure to conduct a study of the concentration of total bilirubin in the umbilical cord blood and determine the group and Rh factor of the blood

1. Group and Rh affiliation of the blood of the mother and child.
2. General blood analysis.
3. Biochemical blood test (total bilirubin and fractions, albumin, glucose level; other parameters (bilirubin fractions, acid-base state (KOS), electrolytes, etc.) - according to indications);
4. Serological tests: Coombs reaction.

Comments:Direct Coombs test becomes positive in the presence of fixed antibodies on the surface of erythrocytes, which, as a rule, is observed with Rh type HDN. Due to the small amount of antibodies fixed on erythrocytes, with TTH by ABO, a weakly positive direct Coombs test is more often observed on the first day of life, which can already become negative 2-3 days after birth.

The indirect Coombs test is designed to detect incomplete antibodies present in the test serum. This is a more sensitive test for detecting maternal isoantibodies than the direct Coombs test. The indirect Coombs test can be used in individual cases where the cause of hemolysis is unclear.

It should be remembered that the severity of the Coombs reaction does not correlate with the severity of jaundice! (Evidence level D)

2.4 Instrumental diagnostics

• An abdominal ultrasound is recommended;

• Neurosonography is recommended.

2.5 Other diagnostics

• It is recommended to conduct a laboratory and blood test:

blood for ELISA (for the presence of infection);

blood for PCR (for the presence of infection);

coagulogram;

bacteriological examination of blood.

3. Treatment

3.1 Conservative treatment

Comments:Features of PT in HDN:

It is possible to use both standard lamps and fiber-optic and LED FT, it is advisable to combine several FT methods;

The light source is located at a distance of 50 cm above the child. To enhance the effect of phototherapy, the lamp can be brought closer to a distance of 10-20 cm from the child with constant supervision of medical personnel and control of body temperature;

Phototherapy for TTH (especially in children at risk of PAD) should be continuous;

The surface of the child's body against the background of PT should be as open as possible. The diaper can be left in place;

Eyes and genitals should be protected with opaque material;

The daily volume of fluid that the child receives enterally or parenterally must be increased by 10-20% compared to the physiological need of the child;

12 hours after the end of phototherapy, it is necessary to perform a control study of bilirubin;

Phototherapy is carried out before, during (with the help of a fiber optic system) and after an exchange transfusion operation.

Recommended intravenous administration normal human immunoglobulin. High doses of standard immunoglobulins block the Fc receptors of the cells of the reticuloendothelial system and thereby reduce hemolysis and, consequently, the level of bilirubin, which in turn reduces the number of PRPs.

Comments:Human immunoglobulin preparations for newborns with HDN are administered according to the following scheme:

in the first hours of a newborn's life, intravenously slowly (if possible, within 2 hours), but with the obligatory observance of the requirements of the instructions for the drug;

dose? 0.5-1.0 g/kg (average 0.8 g/kg)*

* In the case of prescribing an immunoglobulin dose exceeding that specified in the instructions for the drug, it is necessary to justify this action in the medical history as much as possible and issue a collegial permission for the off-label therapy for the child. The use of “off-label” therapy also requires the mandatory issuance of a voluntary informed consent of the patient’s legal representative, which explains in detail the features of the use of such therapy, possible risks and side effects and clarifies the right to refuse off-label therapy;

repeated administration of immunoglobulin, if necessary, is carried out 12 hours after the previous one;

the introduction of immunoglobulin in HDN is possible during the first 3 days of life.

Comments:The exception is when breast milk not enough to increase daily volume by 10-20%. If the child's condition does not allow to increase the volume of fluid enterally, only then is infusion therapy carried out.

Administration of human albumin. There is no evidence that human albumin infusion improves long-term outcomes in children with severe hyperbilirubinemia, so its routine use is not recommended.

Phenobarbital ** - the effect in HDN has not been proven, the use is not allowed.

Other medications (drugs of the hepatoprotector group) - use in HDN has not been proven and is not permissible.

3.2 Surgical treatment

Comments:Indications for OZPK:

in the event of the appearance of clinical symptoms of acute bilirubin encephalopathy (muscle hypertonicity, opisthotonus, fever, "brain" cry), a replacement blood transfusion is performed regardless of the level of bilirubin;

in HDN caused by an isolated Rh conflict, Rh-negative single-group EM and FFP are used with the child's blood, if possible, AB (IV) blood groups in the ratio of EM to FFP - 2:1;

in case of tension-type headache caused by an isolated group conflict, the EM of the first (I) group is used, coinciding with the Rh-belonging of the child's erythrocytes and one-group or AB (IV) of the FFP group in a ratio of 2:1;

in case of incompatibility of the mother's blood and the blood of the child due to rare factors, it is necessary to use blood from individually selected donors.

In HDN, only freshly prepared EO is used (shelf life is not more than 72 hours);

OZKP is performed under aseptic conditions in the intensive care unit or operating room;

During the operation, monitoring of the heart rate, respiration rate, blood pressure, saturation of hemoglobin with oxygen, body temperature. Before the start of the operation, a nasogastric tube is inserted into the patient;

Transfusion is performed through the umbilical vein using a polyvinyl catheter (No. 6, 8, 10). The depth of the catheter insertion depends on the patient's body weight (no more than 7 cm).

Volume calculation for OZPK

V total \u003d m? BCC? 2, where V is the volume, m is body weight in kg,

BCC - for premature babies - 100-110 ml / kg, for full-term ones - 80-90 ml / kg.

Example: a child weighing 3 kg.

Total volume (V total) = 3?85?2 = 510 ml

The absolute volume of erythrocytes (V abs.) required to obtain Ht 50% V total: 2 = 510: 2 = 255 ml

Actual volume of EM

(V er.mass) \u003d Vabs: 0.7 (approximate Ht of erythrocytes) \u003d 255: 0.7 \u003d 364 ml

The actual volume of FFP = V total. - V er. Masses = 510 - 364 = 146 ml

First, 10 ml of blood is released through the catheter, which is used to determine the concentration of bilirubin. Then the same volume of donor blood is injected at a rate of 3-4 ml/min.

The introduction and excretion of blood alternate with a volume of 20 ml in full-term and 10 ml in premature babies.

The volume of one exfusion-infusion should not exceed 5-10% of the BCC. The total duration of the operation is about 2 hours.

After the operation, OAM should be performed and two hours after the end of the transfusion, it is recommended to determine the concentration of glucose in the blood.

More than a twofold decrease in the concentration of bilirubin at the end of the operation testifies to the effectiveness of the OZKK.

4. Rehabilitation

• It is recommended to carry out rehabilitation measures:

neonatal care;

exclusive breastfeeding;

medical withdrawal from preventive vaccinations for 1 month.

5. Prevention and follow-up

5.1 Prevention

Prophylaxis of Rh-immunization after childbirth is recommended for Rh-negative puerperas who do not have anti-Rh antibodies who have given birth to a Rh-positive baby. It is performed in the first 72 hours after childbirth by introducing 300 mcg of anti-D (Rh)-immunoglobulin.

• Recommended:

1. supervision of a local pediatrician, general practitioner;
2. monthly control of the UAC;
3. at 6 months for children after OZPK - blood for HIV;
4. the issue of preventive vaccinations is decided after 6 months of life.

6. Additional information affecting the course and outcome of the disease

Additional factors that increase the risk of developing bilirubin encephalopathy:

• Factors that increase the permeability of the BBB for bilirubin: blood hyperosmolarity, acidosis, cerebral hemorrhages, neuroinfections, arterial hypotension.
• Factors that increase the sensitivity of brain neurons to the toxic effect of unconjugated bilirubin: prematurity, severe asphyxia, starvation, hypoglycemia, anemia.
• Factors that reduce the ability of blood albumin to firmly bind unconjugated bilirubin: prematurity, hypoalbuminemia, infection, acidosis, hypoxia, increased levels of non-esterified fatty acids in the blood, the use of sulfonamides, furosemide, phenytoin, diazepam, indomethacin, salicylates, semi-synthetic penicillins, cephalosporins.

Criteria for assessing the quality of medical care

Bibliography

1. Neonatology. National leadership. Brief edition / ed. acad. RAMN N.N. Volodin. ? M. : GEOTAR-Media, 2013. ? 896 p.
2. New technologies in the diagnosis, treatment and prevention of hemolytic disease of the fetus and newborn, Konoplyannikov A.G. Abstract for the degree of Doctor of Medical Sciences, Moscow 2009
3. Edematous form of hemolytic disease of newborns (diagnosis, treatment, long-term results), Chistozvonova E.A. Abstract for the degree of Candidate of Medical Sciences, Moscow 2004
4. Order of the Ministry of Health of Russia dated November 1, 2012 N 572n “On approval of the Procedure for providing medical care on the profile "obstetrics and gynecology (with the exception of the use of assisted reproductive technologies)".
5. Order of the Ministry of Health of Russia of November 15, 2012 N 921n "On approval of the Procedure for the provision of medical care in the profile" neonatology ".
6. Order of the Ministry of Health of Russia dated April 2, 2013 N 183n "On approval of the rules for the clinical use of donated blood and (or) its components."
7. Shabalov N.P. Neonatology / N.P.Shabalov. ? 5th ed., rev. and additional, in 2 volumes. ? Moscow: MEDpress-inform, 2009. ? 1504 p.
8. ABM Clinical protocol 22: Guidelines for management of jaundice in the breastfeeding infant equal to or greater than 35 weeks gestation // Breastfeeding medicine. ? 2010.? Vol. 5. ? N 2.? P. 87-93.
9. Alcock G.S., Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
10. Altunyurt S., Okyay E., Saatli B., Canbahishov T., Demir N., Ozkan H. Neonatal outcome of fetuses receiving intrauterine transfusion for severe hydrops complicated by Rhesus hemolytic disease // Int. J. Gynaecol. obstet. ? 2012.? Vol. 117.? N 2.? P. 153-156.
11. Barrington K.J., Sankaran K. Canadian Pediatric Society Fetus and Newborn Committee Abridged version // Paediatr Child Health. ? 2007.? Vol. 12. ? P. 1-12.
12. Buonocore G., Bracci R., Weindling M. Neonatology: A Practical Approach to Neonatal Management, 2012
13. Christensen RD, Henry E. Hereditary spherocytosis in neonates with hyperbilirubinemia // Pediatrics. ? 2010.? Vol. 125.? N 1.? P. 120-125.
14. Gleason C.A., Devaskar S.U. Avery's diseases of the newborn // 9th Ed. Elsevier Saunders. ? 2011.? 1520 p.
15. Gomella T.L. Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs // 7th edition; Medical Publishing Division. ? 2013.? 1113 p.
16. Hudon L., Moise K.J.Jr., Hegemier S.E., et al. Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease // Am J Obstet Gynecol. ? 1998.? Vol. 179.? N 4.? R. 858-863.
17. Kaplan M., Na "amad M., Kenan A., et al. Failure to predict hemolysis and hyperbilirubinemia by IgG subclass in blood group A or B infants born to group O mothers // Pediatrics. ? 2009. ? Vol. 123. ?N 1. ?e132-137.
18. Maisels M.J.,Watchoko J.F. Neonatology: A Practical Approach to Neonatal Management/ Treatmen of Hyperbilirubinemia- 2012- P 629
19. Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation // Pediatrics. ? 2004.? Vol. 114.? P. 297-316.
20. Mary Beth Ross, Pedro de Alarcon. Hemoliytic Disease of Fetus and Newborn. NeoReviews Vol.14 No.2 February 2013
21. Matthews D.C., Glader B. Erythrocyte disorders in infancy // In: Avery’s diseases of the newborn. Ninth edition. Elsevier Saunders. ? 2012.? P. 1087-1092.
22. Miqdad A.M., Abdelbasit O.B., Shaheed M.M., Seidahmed M.Z., Abomelha A.M., Arcala O.P. Intravenous immunoglobulin G (IVIG) therapy for significant hyperbilirubinemia in ABO hemolytic disease of the newborn // J Matern Fetal Neonatal Med. ? 2004.? Vol. 16. ? P. 163-166.
23. Moise K.J. Jr. Management of Rhesus alloimmunization in pregnancy // Obstet Gynecol. ? 2008.? Vol. 112.? P. 164-176.
24. Smits-Wintjens V.E.H.J., Walther F.J., Lopriore E. Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome // Seminars in Fetal & Neonatal Medicine. ? 2008.? Vol. 13. ? P. 265-271.
25. Steiner L.A., Bizzarro M.J., Ehrenkranz R.A., Gallagher P.G. A decline in the frequency of neonatal exchange transfusions and its effect on exchange-related morbidity and mortality // Pediatrics. ? 2007.? Vol. 120.? N 1.? R. 27-32.
26. Wagle S., Deshpande P.G., Itani O., Windle M.L., Clark D.A., Wagner C.l. Rosenkrantz T. Hemolytic Disease of Newborn. Updated: Sep 26, 2014. http://emedicine.medscape.com/article/974349
27. Oxford handbook of Neonatology Ed. Fox G., Hoque N., Watts T // Oxford, New York, Oxford University Press, 2010. - 523.

Annex A1. Composition of the working group

Antonov A.G. ?

Aronskind E.V. ?

Baybarina E.N. ?

Volodin N.N. ? Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, President of the Russian Association of Perinatal Medicine Specialists, Dmitry Rogachev Federal Scientific Clinical Center for Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia.

Degtyarev D.N. ?

Degtyareva A.V. ?

Kovtun O.P. ?

Mukhametshin F.G. ?

Parshikova O.V. ?

Doctor - Neonatology;

Physician-Anesthesiology-Resuscitation;

Doctor-Pediatrics.

Methods used to collect/select evidence:

search in electronic databases.

Description of the methods used to collect/select evidence: the evidence base for recommendations are publications included in the Cochrane Library, MEDLINE and EMBASE databases. The depth of the search was 25 years.

Methods used to assess the quality and strength of evidence:

expert consensus;

Table P1 - Levels of certainty of evidence according to international criteria

Table P2 - Levels of persuasiveness of recommendations

Good Practice Points (GPPs):

Economic analysis:

cost analysis was not performed and publications on pharmacoeconomics were not analyzed.

External peer review;

Internal peer review.

Annex A3. Related Documents

International Classification of Diseases, Injuries and Conditions Affecting Health, 10th Revision (ICD-10) (World Health Organization) 1994.

Nomenclature medical services(Ministry of Health and social development Russian Federation) 2011.

Federal Law "On the fundamentals of protecting the health of citizens in the Russian Federation" dated November 21, 2011 No. 323 F3.

List of vital and essential medicines for 2016 (Decree of the Government of the Russian Federation of December 26, 2015 No. 2724-r.)

The procedure for providing medical care in the neonatology profile (Order of the Ministry of Health of Russia dated November 15, 2012 N 921n).

Appendix B. Patient Management Algorithms

Management of children with HDN over 24 hours of age:

depends on the absolute values ​​of bilirubin (Table 1) or the dynamics of these indicators.

with the appearance of jaundice during the first 24 hours of life - an urgent study of ABOUT, further management tactics depend on the magnitude of the hourly increase in bilirubin;

order the necessary blood products (plasma + ermassa), stabilize the vital functions of the body.