Hemolytic disease of newborns due to Rh factor. Hemolytic jaundice in newborns

Hemolytic disease newborns and fetus - isoimmune hemolytic anemia, which occurs when the blood of mother and fetus is incompatible with erythrocyte antigens, while the antigens are the erythrocytes of the fetus, and antibodies to them are produced in the mother's body. Hemolytic disease of the newborn is diagnosed in approximately 0.6% of children. Perinatal mortality 2.5%.

ICD-10 code

P55 Hemolytic disease of the fetus and newborn

What causes hemolytic disease of the newborn?

The occurrence of an immune conflict underlying hemolytic disease of the newborn is possible if the mother is antigen-negative and the fetus is antigen-positive. With the development of HDPiN according to the Rh factor, the mother's red blood cells are Rh negative, and the fetus's red blood cells are Rh positive, i.e. contain O-factor. The implementation of the conflict (development of civil and non-government problems) is usually carried out when repeat pregnancies, since previous sensitization is necessary.

Hemolytic disease of newborns due to group incompatibility develops with 0(1) blood group in the mother and A(II) or, less commonly, B(III) blood group in the fetus. The realization of the conflict is possible already during the first pregnancy. GBPiN can also occur due to incompatibility for other rare antigenic systems: Kell, Lutheran, etc.

How does hemolytic disease of the newborn develop?

For the development of hemolytic disease of the newborn, it is necessary for antigen-positive erythrocytes of the fetus to enter the bloodstream of an antigen-negative pregnant woman. At the same time great value It is not so much the fact of transplacental transfer of fetal red blood cells that matters, but the amount of fetal blood entering the mother’s body. Factors contributing to isoimmunization, especially for the Rh factor, include:

• previous medical and non-medical abortions;
• previous spontaneous (one or more) miscarriages;
• previous ectopic pregnancy;
• previous births (premature and term);
• invasive diagnostic methods (amniocentesis, cordocentesis, chorionic villus biopsy);
• threat of miscarriage.

The disease is based on hemolysis (destruction) of red blood cells, caused by the incompatibility of the blood of the mother and fetus in terms of Rh factor, group and other blood factors, which occurs in the 3-4th month of intrauterine development and sharply increases after birth.

When antigen-positive red blood cells of the fetus enter the bloodstream of an antigen-negative woman, anti-Rhesus or group antibodies are produced in her body. If the antibodies belong to the IgG class, they pass transplacentally into the fetal bloodstream and bind to antigen-positive fetal red blood cells, causing their hemolysis.

The Rh antigen system consists of six main antigens: C, c, D, d, E and e. Rh-positive red blood cells contain the D factor, and Rh-negative red blood cells do not contain it, although other Rh antigens are often found in them. During the first pregnancy, fetal erythrocytes that have a D antigen that have entered the bloodstream of an Rh-negative pregnant woman initially lead to the synthesis of Rh antibodies, which are class M immunoglobulins, which do not penetrate the placenta. Class G immunoglobulins are then produced, which are able to cross the placental barrier. Due to the low number of fetal red blood cells and immunosuppressive mechanisms, the primary immune response in the pregnant woman is reduced. That is why conflict with Rh incompatibility practically does not occur during the first pregnancy, and the child is born healthy. With repeated pregnancies, the development of conflict is possible, and the child is born with hemolytic disease of the newborn.

A and B antigens are located on outer surface plasma membrane of the erythrocyte. Isoimmune anti-A and anti-B group antibodies belong to the IgG class, in contrast to natural group antibodies - calamus, which belong to the IgM class. Isoimmune antibodies can combine with the corresponding antigens A and B and become fixed to other tissues, including the tissues of the placenta. This is why hemolytic disease of the newborn according to the ABO system can develop already during the first pregnancy, but only in about 10% of cases.

When it is possible to implement both variants of a conflict, a conflict occurs more often according to the AB(0) system.

But not only the Rh factor is the cause of the development of the disease. It can occur due to blood incompatibility and other factors. In addition, hemolytic disease of the fetus can occur when the blood of the mother and fetus do not match the main blood groups of the ABO system. Antigens A and B, inherited from the father, can cause the formation of incomplete agglutinins in a mother with blood type 0, which, unlike ordinary α- and β-agglutinins, can pass through the placental barrier and cause hemolysis of fetal red blood cells. Conflict based on inconsistency according to the AB0 system occurs in 10% of cases and, as a rule, proceeds benignly. It should be noted that a mismatch between the blood of the fetus and mother does not always lead to the development of the disease. For example, Rh incompatibility occurs in 5-10% of pregnancies, and Rh conflict - in 0.8%.

Pathogenesis in the edematous form of hemolytic disease of the newborn

The edematous form, or fetal hydrops, occurs if hemolysis begins in utero, from approximately 18-22 weeks of pregnancy, is intense and leads to the development of severe fetal anemia. As a result, severe fetal hypoxia occurs, which causes profound metabolic disorders and damage to the vascular wall. Increased permeability of the vascular wall leads to the fact that albumin and water move from the fetal blood into the tissue interstitium. At the same time, the synthesis of albumin in the baby’s liver decreases, which aggravates hypoproteinemia.

As a result, a general edema syndrome is formed in utero, ascites develops, fluid accumulates in the pleural cavities, in the pericardial cavity, etc. Decreased drainage function lymphatic system aggravates the development of ascites and the accumulation of fluid in other cavities of the body. Hypoproteinemia, accumulation of fluid in the cavities in combination with damage to the vascular wall lead to the development of heart failure.

As a result of erythroid metaplasia in organs and severe fibrosis in the liver, hepato- and splenomegaly is formed. Ascites and hepatosplenomegaly cause a high position of the diaphragm, which leads to pulmonary hypoplasia. Formed during hemolysis increased amount indirect bilirubin is excreted from the blood and tissues of the fetus through the placenta into the mother’s body, so there is no jaundice at birth.

Pathogenesis in the icteric form of hemolytic disease of the newborn

The icteric form of the disease develops if hemolysis begins shortly before birth. As a result of the destruction of red blood cells, the concentration of indirect (unconjugated) bilirubin quickly and significantly increases, which leads to the following changes:

• the accumulation of indirect bilirubin in the lipid substances of tissues, which causes icteric staining of the skin and sclera - jaundice, as well as as a result of the accumulation of indirect bilirubin in the nuclei of the base of the brain, which leads to its damage with the development of neuronal necrosis, gliosis and the formation of bilirubin encephalopathy (kernicterus);
• increased load on liver glucuronyltransferase, which leads to depletion of this enzyme, the synthesis of which begins in liver cells only after birth, and as a result hyperbilirubinemia is maintained and intensified;
• increased excretion of conjugated (direct) bilirubin, which can lead to impaired bile excretion and the development of a complication - cholestasis.

As with the edematous form, hepatosplenomegaly develops.

Pathogenesis of the anemic form of hemolytic disease

The anemic form develops when small amounts of maternal antibodies enter the fetal bloodstream shortly before birth. At the same time, hemolysis is not intense, and the newborn’s liver quite actively removes indirect bilirubin. Anemia dominates, and jaundice is absent or minimally expressed. Hepatosplenomegaly is characteristic.

Symptoms of hemolytic disease of newborns

Hemolytic disease of the newborn and fetus has three clinical forms: anemic, icteric and edematous. Among them, the most severe and prognostically unfavorable is edematous.

General clinical signs all forms of hemolytic disease of the newborn: pallor skin and visible mucous membranes resulting from anemia, hepatosplenomegaly. Along with this, edematous, icteric and anemic forms have their own characteristics.

Edema form

The most severe form of hemolytic disease of the newborn. The clinical picture, in addition to the above symptoms, is characterized by a common edematous syndrome: anasarca, ascites, hydropericardium, etc. Possible appearance of hemorrhages on the skin, development of disseminated intravascular coagulation syndrome as a consequence of hypoxia, hemodynamic disturbances with cardiopulmonary failure. The expansion of the borders of the heart and the mutedness of its tones are noted. Often after birth, respiratory disorders develop against the background of pulmonary hypoplasia.

Jaundice form of hemolytic disease

This is the most common form of hemolytic disease of the newborn. In addition to general clinical manifestations, which include pallor of the skin and visible mucous membranes, as a rule, very moderate and moderate enlargement of the spleen and liver, jaundice of a predominantly warm yellow hue is also noted. At the birth of a child, amniotic fluid, umbilical cord membranes, and vernix may be stained.

Characteristic early development jaundice: it occurs either at birth or in the first 24-36 hours of a newborn’s life.

According to the severity of jaundice, there are three degrees of the icteric form of hemolytic disease of the newborn:

• mild: jaundice appears at the end of the first or at the beginning of the second day of the child’s life, the bilirubin content in cord blood does not exceed 51 µmol/l, hourly increase in bilirubin - up to 4-5 µmol/l, moderate enlargement of the liver and spleen - less than 2.5 and 1.0 cm, respectively;
• moderate: jaundice occurs immediately at birth or in the first hours after birth, the amount of bilirubin in the umbilical cord blood exceeds 68 µmol/l, the hourly increase in bilirubin is up to 6-10 µmol/l, liver enlargement is up to 2.5-3.0 cm and spleen up to 1.0-1.5 cm;
• severe: diagnosed according to ultrasound of the placenta, indicators of the optical density of bilirubin amniotic fluid obtained during amniocentesis, the amount of hemoglobin and the hematocrit value of blood obtained during cordocentesis. If treatment is not started in a timely manner or is inadequate, the icteric form may be accompanied by the development of the following complications.

Kernicterus

At the same time, symptoms indicating damage are noted nervous system. First, in the form of bilirubin intoxication (lethargy, pathological yawning, loss of appetite, regurgitation, muscle hypotonia, disappearance of phase II of the Moro reflex), and then bilirubin encephalopathy (forced body position with opisthotonus, “brain” cry, bulging of the large fontanel, disappearance of the Moro reflex , convulsions, pathological oculomotor symptoms - the “setting sun” symptom, nystagmus, etc.).

Bile thickening syndrome, when jaundice acquires a greenish tint, the liver is slightly enlarged compared to previous days, a tendency to acholia appears, and the color of urine increases in saturation.

Anemic form of hemolytic disease of the newborn

Least common and most light form diseases. Against the background of pallor of the skin, lethargy, poor sucking, tachycardia, hepatosplenomegaly are noted, and possible muffled heart sounds and systolic murmur.

Along with changes in the fetus’s body, there are changes in the placenta. This is expressed in an increase in its mass. If normally the ratio of the weight of the placenta to the weight of the fetus is 1: 6, then with Rh conflict it is 1: 3. The enlargement of the placenta occurs mainly due to its edema.

But the pathology of Rhesus conflict is not limited to this. In addition to the above, with Rh conflict, antenatal (prenatal) fetal death and repeated spontaneous abortions are observed.

Moreover, when high activity antibodies, spontaneous abortions can occur in the early stages of pregnancy.

Women who have had a Rhesus conflict are more likely to develop toxicosis of pregnancy, anemia, and impaired liver function.

Classification

Depending on the type of conflict, hemolytic disease of newborns is distinguished:

• in case of incompatibility of red blood cells of mother and fetus according to the Rh factor;
• in case of incompatibility according to the ABO system (group incompatibility);
• in case of incompatibility rare factors blood.

By clinical manifestations highlight:

• edematous form (anemia with dropsy);
• icteric form (anemia with jaundice);
• anemic form (anemia without jaundice and dropsy).

According to the severity, the icteric form is classified as mild, moderate and severe.

In addition, complicated ones are distinguished (kernicterus, bile thickening syndrome, hemorrhagic syndrome, damage to the kidneys, adrenal glands, etc.) and uncomplicated forms of hemolytic disease of the newborn.

Diagnosis of hemolytic disease of newborns

Diagnosis of hemolytic disease of newborns is based on an immunological examination of the pregnant woman, ultrasound, Doppler measurements of fetal-placental and uteroplacental blood flow, electrophysiological examination methods, examination of amniotic fluid (during amniocentesis), cordocentesis and fetal blood testing.

An immunological study allows you to determine the presence of antibodies, as well as changes in their quantity (increase or decrease in titer). Ultrasound allows you to measure the volume of the placenta, determine an increase in its thickness, detect polyhydramnios, an increase in the size of the fetal liver and spleen, an increase in the size of the fetal abdomen compared to the size of the head and chest, and ascites in the fetus. Doppler measurements can detect an increase in the systolic-diastolic ratio and resistance index in the umbilical cord artery and an increase in blood flow velocity in the middle cerebral artery of the fetus. Electrophysiological methods (cardiotocography with determination of the fetal condition indicator) make it possible to detect a monotonous rhythm in moderate and severe forms of the disease and a “sinusoidal” rhythm in the edematous form of HDP. The study of amniotic fluid (during amniocentesis) allows us to determine the increase in the optical density of bilirubin in the amniotic fluid. Finally, cordocentesis and fetal blood testing can detect a decrease in hematocrit, a decrease in hemoglobin, an increase in bilirubin concentration, conduct an indirect Coombs test and determine the fetal blood type and the presence of the Rh factor.

Since the prognosis for the disease depends on the content of bilirubin, in a child born with suspected hemolytic disease of the newborn, in order to develop further medical tactics, it is first necessary to do a biochemical blood test to determine the concentration of bilirubin (total, indirect, direct), protein, albumin, AST, ALT, and then conduct an examination to determine the etiology of hyperbilirubinemia. For this purpose, the newborn is given a general blood test, the Rh status is determined for possible Rh sensitization and the blood group for possible ABO sensitization, and the antibody titer is determined and the direct Coombs test is performed.

Differential diagnosis

Differential diagnosis of hemolytic disease of newborns is carried out with other anemias. These include hereditary anemia caused by the following disorders:

• disturbance of erythrocyte morphology (microspherocytosis, elliptocytosis, stomatocytosis);
• deficiency of erythrocyte enzymes (glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, pyruvate kinase);
• anomaly of hemoglobin synthesis (a-thalassemia).

To exclude these diseases, you should carefully collect anamnesis about the presence of other carriers of this pathology in the family and conduct the following studies:

• determination of erythrocyte morphology;
• determination of osmotic resistance and diameter of red blood cells;
• determination of erythrocyte enzyme activity;
• determination of hemoglobin type.

Treatment of hemolytic disease of newborns

First of all, if we are talking about Rh conflict, it is necessary to diagnose the disease during the period of intrauterine development of the fetus, assess its severity and, accordingly, the prognosis of the disease, and carry out treatment until the fetus reaches viability. All treatment and prophylactic methods used during this period of fetal life are divided into non-invasive and invasive.

Non-invasive methods

Non-invasive methods include plasmapheresis and administration of intravenous immunoglobulin to the pregnant woman.

Plasmapheresis of a pregnant woman is carried out for the purpose of detoxification, rheocorrection and immunocorrection.

Contraindications to plasmapheresis:

• severe damage to the cardiovascular system;
• anemia (hemoglobin less than 100 g/l);
• hypoproteinemia (less than 55 g/l);
• hypocoagulation;
• immunodeficiency state;
• history of allergic reactions to protein and colloid drugs, anticoagulants.

Immunoglobulin for intravenous administration is used to inhibit the production of one's own maternal antibodies and blockade of Rh-bound antibodies during their placental transport. Immunoglobulin is used for intravenous administration at a dose of 0.4 g per kilogram of the pregnant woman’s body weight. This dose is distributed over 4-5 days. Courses of administration must be repeated every 3 weeks until delivery. This method treatments are not considered generally accepted, because when severe course disease, the outcome for the fetus improves slightly.

Invasive methods

Invasive methods include cordocentesis and intrauterine red blood cell transfusion. These procedures are carried out only with Rh-sensitization, currently this is the only pathogenetic method treatment of hemolytic disease of the fetus.

Indications for cordocentesis:

• burdened obstetric history (death of previous children from severe forms of hemolytic disease of the newborn);
• high antibody titer (1:32 and above);
• Ultrasound shows signs of hemolytic disease of the fetus;
• high values ​​of the optical density of bilirubin in amniotic fluid obtained during amniocentesis (zone 3 of the Lily scale).

Timing during which cordocentesis is performed: from the 24th to the 35th week of pregnancy.

The indication for intrauterine transfusion of red blood cells when a positive Rh factor is detected in the fetus is a decrease in hemoglobin and hematocrit by more than 15% of the norm determined at a given stage of pregnancy. For intrauterine transfusion of red blood cells, only “washed” red blood cells of blood group 0(1) Rh-negative are used. Intrauterine transfusion of red blood cells is carried out according to indications 1-3 times.

Treatment of hemolytic disease of the newborn, in contrast to the treatment of hemolytic disease of the fetus, includes, first of all, treatment of hyperbilirubinemia, secondly, correction of anemia and, finally, syndromic therapy aimed at restoring functions various organs and systems. All newborns with this disease are not put to the breast, but are fed artificially in the first 5-7 days of life, since antibodies can pass through a woman’s breast milk and be absorbed in the intestines of newborns, which leads to increased hemolysis.

Treatment of hyperbilirubinemia

Treatment of hyperbilirubinemia involves the use of conservative and surgical therapy. Start with conservative treatment, and when bilirubin levels are critical, they are combined with operative exchange (exchange) blood transfusion (BCT).

Conservative therapy includes phototherapy (PT) and the use of intravenous immunoglobulin. Infusion therapy, on recommendation Russian Association perinatal medicine specialists (RASPM), are carried out in cases where it is impossible to adequately feed the child. Phenobarbital is currently practically not used due to the fact that the onset of the effect is significantly delayed from the start of its use and the use causes an increase in the syndrome of central nervous system depression.

Phototherapy

The mechanism of action of phototherapy is based on the fact that when it is carried out on irradiated areas in the skin and subcutaneous fat layer at a depth of 2-3 mm, as a result of the processes of photooxidation and photoisomerization, a water-soluble isomer of indirect bilirubin is formed - lumirubin, which then enters the bloodstream and is excreted in the bile and urine.

Indications for phototherapy:

• yellowness of the skin at birth;
• high concentration of indirect bilirubin.

Principles of phototherapy:

• radiation dose - not less than 8 μW/(cm2xnm);
• the distance from the source to the patient specified in the instructions for the device should be observed;
• the child should be placed in an incubator;
• the child’s eyes and genitals should be protected;
• The child’s position under the PT lamps should be changed every 6 hours.

Minimum values ​​of indirect bilirubin concentration (µmol/l), at which phototherapy is indicated

Phototherapy is carried out continuously with breaks for feeding the child for 3-5 days. PT should be discontinued when the level of indirect bilirubin decreases below 170 µmol/l.

During phototherapy, various reactions and side effects.

Complications and side effects of phototherapy

Manifestations	Development mechanism	Events
Tanned skin syndrome	Induction of melanin synthesis	Observation
Bronze Child Syndrome	Accumulation of direct bilirubin photooxidation products	Cancel TF
	Activation of intestinal secretory function	Observation
Lactase deficiency	Serous lesions of the villous epithelium
	Damage to circulating red blood cells due to photosensitivity	Cancellation of FT
Skin burns	Excessive lamp emission	Cancellation of FT
	Increased fluid loss	Increase the amount of fluid your child takes
Skin rashes	Increased formation and release of histamine during photosensitivity	Observation, if necessary - cancellation of FT

If signs of cholestasis appear, as evidenced by an increase in the direct bilirubin fraction by 20-30% or more, an increase in the activity of AST and ALT, alkaline phosphatase, cholesterol concentration, the time of phototherapy should be limited to 6-12 hours/day or completely canceled to avoid development "bronze child" syndrome.

Use of immunoglobulin

Immunoglobulin for intravenous administration is used to block Fc receptors, which prevents hemolysis. Early initiation of immunoglobulin administration is necessary (in the first 2 hours of life), which is only possible with antenatal diagnosis of the disease. Later administration of immunoglobulin is possible, but less effective.

Standard immunoglobulins for intravenous administration are used: sandoglobin, ISIVEN (Italy), polyglobin Np (Germany), etc.

Possible regimens for administering immunoglobulins:

• 1 g/kg every 4 hours;
• 500 mg/kg every 2 hours;
• 800 mg/kg daily for 3 days.

Regardless of the dose and frequency, proven results were obtained (95%) positive effect, which manifested itself in a significant reduction in the frequency of PCD and the duration of phototherapy.

Infusion therapy

Infusion therapy is carried out in cases where it is not possible to adequately feed the child during phototherapy. The daily volume of fluid administered to the child must be increased by 10-20% (in children with extremely low body weight - by 40%) compared to the physiological need.

When conducting infusion therapy, you should monitor the child’s body weight, evaluate diuresis, electrolyte levels, blood glucose, and hematocrit.

Infusion therapy primarily involves transfusion of a 10% glucose solution4. Infusion therapy is carried out intravenously or intragastrically through gastric tube. Intragastric fluid administration can begin from the 3-4th day of life; to prevent the development of cholestasis, a 25% solution of magnesium sulfate can be added to the dropper at the rate of 5 ml/kg, no-spa - 0.5 ml/kg, 4% potassium solution chloride - 5 ml/kg. With intragastric fluid administration, there is no need to reduce the volume of feedings.

Surgical therapy - replacement blood transfusion

There are early (in the first 2 days of life) and late (from the 3rd day of life) PCD.

The indication for late PCD is the concentration of indirect bilirubin equal to 308-340 µmol/l (for a full-term newborn).

Indications for late exchange blood transfusion in newborns depending on body weight at birth

1 * Minimum values ​​of bilirubin - an indication for the initiation of appropriate treatment in cases where the child’s body is affected by pathological factors, increasing the risk of bilirubin encephalopathy (anemia; Apgar score at 5 minutes less than 4 points; Pa02 less than 40 mm Hg lasting more than 1 hour; pH arterial blood less than 7.15 lasting more than 1 hour; rectal temperature less than 35 °C; albumin concentration less than 25 g/l; deterioration of neurological status due to hyperbilirubinemia; generalized infectious disease or meningitis).

When the first symptoms of bilirubin intoxication appear, immediate POC is indicated, regardless of the concentration of bilirubin.

Selection of drugs for replacement blood transfusion

In case of isolated Rh conflict, Rh-negative red blood cells and plasma of the same group as the child’s blood are used, but it is possible to use AB(IV) blood group plasma. In case of an isolated group conflict, red blood cell mass of group 0(1), which matches the Rh factor of the child’s red blood cells, and plasma AB(IV) or one group with the child’s blood group are used. If it is possible to develop both Rh-incompatibility and ABO incompatibility, as well as after intrauterine blood transfusions, Rh-negative red blood cells of the 0(1) blood group and AB(IV) plasma or one of the same group as the child’s blood group are used for PCD.

In case of hemolytic disease of a newborn with a conflict regarding rare blood factors, donor blood that does not have a “conflict” factor is used.

Calculation of the volume of drugs for exchange blood transfusion

The total volume is 1.5-2 bcc, i.e. for a full-term baby, about 150 ml/kg, and for a premature baby, about 180 ml/kg.

The ratio of red blood cells to plasma depends on the initial hemoglobin concentration before surgery. The total volume consists of the volume of red blood cells required to correct anemia, and the volume of red blood cells and plasma required to achieve the volume of the PCC. The volume of red blood cells required to correct anemia is calculated using the formula:

volume of erythrocyte mass (ml) = (160 - child’s hemoglobin in g/l) x 0.4 x child’s weight in kg.

The volume of red blood cells required to correct anemia should be subtracted from the total volume; the remaining volume is replenished with red blood cells and plasma in a ratio of 2:1. The above approximately corresponds to the following ratio of red blood cell mass depending on the hemoglobin concentration in the child.

Exchange transfusion technique

The PCA is carried out through one of the large vessels (umbilical vein, subclavian vein). Before POC, blood is drawn to determine the concentration of bilirubin and the compatibility of the blood of the donor and recipient. ZPK is carried out using the “pendulum method”, i.e. removing and introducing alternately a portion of blood at the rate of up to 5-7 ml per kilogram of the child’s weight. Before the start of PCD, it is possible to administer plasma at a rate of 5 ml/kg. ZPK begins with the removal of blood. Before the start of PCD and throughout it, the catheter is washed with sodium heparin solution.

When the initial hemoglobin concentration is below 80 g/l, PCP begins with the correction of anemia, i.e. with the introduction of only red blood cells under the control of hemoglobin content. After reaching a hemoglobin concentration of 160 g/l, red blood cells and plasma are administered. To do this, you can dilute the red blood cells with plasma, or you can alternately inject two syringes of red blood cells and one syringe of plasma.

At the end of the PCA, blood is taken again to determine the concentration of bilirubin. After PCO, conservative therapy is continued.

PCO may be accompanied by the development of immediate and delayed side effects.

Complications of exchange transfusion

Manifestations		Events
Heartfelt		Cardiac monitoring
	Volume overload
	Heart failure
Vascular	Thromboembosis, air embolism	Compliance with blood transfusion techniques
		Flushing the catheter with sodium heparin solution
Coagulation	Overdose of heparin sodium	Monitoring the dose of heparin sodium
	Thrombocytopenia	Platelet count control
Electrolyte	Hyperkalemia	For prophylaxis, for every 100 ml transfused (erythrocyte mass and plasma in total), administer 1-2 ml of 10% calcium gluconate solution
	Hypocalcemia
	Hypernatremia	Control
		WWTP control
Infectious	Viral	Donor control
	Bacterial	To prevent complications after PCP and while the catheter is in a large vessel, antibacterial therapy is prescribed
	Mechanical destruction of donor cells	Control
	Necrotizing enterocolitis	Surveillance, detection clinical symptoms, appropriate therapy
	Hypothermia	Body temperature control, warming
	Hypoglycemia	For prophylaxis, for every 100 ml transfused (erythrocyte mass and plasma in total), administer 2 ml of 10% glucose solution4
Graft versus host disease		Transfuse blood products exposed to irradiation
		Do not use large volumes for ZPK

Late anemia develops 2-3 weeks after PCO. Usually it is hyporegenerative and hypoerythropoietic in nature. To correct it, recombinant erythropoietin is used (epoetin alfa subcutaneously 200 IU/kg once every three days for 4-6 weeks).

If iron deficiency is detected during treatment with recombinant erythropoietin, iron supplements are included in the therapy at a dose of 2 mg/kg orally for utilized iron.

Prevention

Prevention is developed for women with Rh- negative blood. There is no prevention for group incompatibility.

To prevent the development of Rh sensitization, all women with Rh-negative blood should be given one dose of anti-Rhesus immunoglobulin.

To prevent all the negative consequences of Rh-conflict and conflict on other blood factors, it is necessary to determine the blood type of the expectant mother and, if it turns out that Rh-negative blood is present, then you should find out whether this woman has been transfused with Rh-positive blood (and in general, whether any blood was transfused); find out what kind of pregnancy there is (whether there have been artificial or spontaneous abortions, intrauterine fetal death, premature birth or death of a newborn soon after birth from jaundice). Information about the Rh status of the father of the unborn child is also important.

For the purpose of prevention, in addition to everything listed earlier, anti-Rhesus immunoglobulin is used. This is done either after the birth of an Rh-positive child, or after the first artificial abortion. It is administered intramuscularly to the postpartum woman, once, no later than 72 hours after birth. This specific prevention of Rh-conflict is possible only in non-sensitized women (sensitization - increased sensitivity), that is, in those who have not been transfused with Rh-positive blood, they have not had abortions or miscarriages, and, in general, this is the first pregnancy.

In addition to specific prevention, nonspecific prevention is also carried out. It includes various medications that reduce the sensitization of the body and increase its immunobiological protective forces. Sometimes, for the same purpose, the pregnant woman uses her husband’s skin graft.

During the neonatal period, the most important in terms of urgency of treatment (threat of kernicterus, severe consequences or death) is hemolytic disease of newborns, caused by biological incompatibility of the Rh factor, its subtypes, ABO blood groups and more rare factors. The red blood cells of 85% of people contain a special antigen, the Rh factor (people with a positive Rh factor). The remaining 15% of people do not have the Rh factor in their red blood cells. If the father has positive Rh factor(+Rh), and the mother does not have the Rh factor (-Rh) and the fetus inherited (+Rh) from the father, then the Rh factor of the fetus, entering the blood of the mother, who does not have this factor, causes the formation of antibodies in her. These antibodies, penetrating through the placenta from the mother's blood into the blood of the fetus, cause agglutination of red blood cells, hemolysis. The same is the pathogenesis of hemolytic disease of newborns with incompatibility of the blood of mother and child according to the ABO system and other factors. There are three forms of hemolytic disease of newborns:

• icteric;

  anemic.

Edema form of hemolytic disease of newborns (the most severe). Children are mostly born still, premature, or die in the first hours after birth.

Symptoms

The color of the skin is waxy, yellow, or cyanotic, general swelling, often with effusion in the abdominal, pleural cavities and pericardium, hepatosplenomegaly, severe anemia, high reticulocytosis (150% or more; leukocytosis with a left shift to myeloblasts and myelocytes). When differentiating, one should keep in mind an unfavorable obstetric history and the presence of Rh-negative blood in the mother. With congenital edema in children whose mothers suffer from diabetes, the anamnestic information is different (diabetes in the mother, absence of Rh conflict) and the fetus is usually heavy. With fetal ascites, there is isolated abdominal hydrops. In congenital neonatal edema due to cardiac decompensation, the newborn may experience physical changes in the heart.

The prognosis is unfavorable, but in view of the fact that, according to some authors, it was possible to save children even in the edematous form of hemolytic disease, it is necessary to immediately after birth carry out all the measures as in the severe icteric form.

The icteric form of hemolytic disease of the newborn is the most common form. There is an unfavorable obstetric history of the mother - spontaneous abortions, miscarriages, death of newborns from hemolytic disease in the first hours and days or maternal transfusion incompatible blood in the past (cause of hemolytic disease of the newborn in primiparous women).

Symptoms:

yellow color of vernix lubrication, amniotic sac and amniotic fluid;

jaundice from the first hours of the first day, sometimes at birth, quickly intensifying to a yellow-green, yellow-brown color;

severe general condition, lethargy, poor appetite, anxiety, muffled heart sounds;

there is a tendency to skin hemorrhages and bleeding;

the liver and spleen are enlarged;

the color of the stool is normal or dark yellow, sometimes from the 5th to 17th day the stool is discolored only as a result of “bile thickening syndrome” - bile blood clots (symptoms of mechanical obstruction);

early hyperbilirubinemia with a predominantly sharp increase in indirect bilirubin;

often anemia, increased reticulocytosis, hypoproteinemia;

there is bilirubinuria; urobilinuria is absent, it may appear later with impaired liver function and with kernicterus;

confirmation of Rh incompatibility between the blood of mother and child:

• the establishment of resistance antibodies in the mother’s blood (indirect Coombs reaction);

  in the blood of a newborn (umbilical cord), detection of sensitization of erythrocytes by incomplete antibodies (presence of maternal resusantibodies fixed on the child’s erythrocytes) - positive direct Coombs reaction.

Therefore, to make a diagnosis at the birth of a child with suspected Rh conflict, the following measures are necessary: ​​taking 10 ml of blood from the umbilical cord and 10 ml from the mother’s vein for urgent research in the laboratory:

determination of the group and Rh affiliation of the blood of the mother and child;

general clinical blood test of the child - hemoglobin percentage, number and nuclear forms of red blood cells, bilirubin;

determination of incomplete Rh antibodies in the mother’s blood serum (indirect Coombs reaction) and mainly in the child’s blood serum by direct Coombs reaction (presence of maternal Rh antibodies fixed on the child’s red blood cells).

A positive direct Coombs test with Rh-positive blood of the child and a characteristic clinical picture is an absolute indication for urgent treatment replacement blood transfusion.

But regardless of the result of serological reactions or if they cannot be made urgently, diagnosis and treatment without delay should be based on the clinical picture of the disease.

Confirmation of hemolytic disease due to ABO incompatibility is the detection of high-titer incomplete complement-fixing isoimmunoantibodies. The most common combination of blood groups in ABO incompatibility: O in the mother and A or less commonly B in the child.

With hemolytic disease of newborns due to ABO incompatibility, the symptoms are the same as for Rh incompatibility, but usually more mild form. Symptoms of the development of kernicterus are observed with a delayed diagnosis of hemolytic disease:

significant fluctuations in body temperature;

thirst, progressive malnutrition;

restlessness, twitching, yawning, lethargy;

high bilirubinemia;

breathing problems with pulmonary edema and pneumonia.

Differential diagnosis of the icteric form of hemolytic disease of newborns is sometimes very difficult. It is necessary to differentiate from “physiological” jaundice of premature infants, birth defects development biliary tract, hemolytic disease of the Minkowski-Choffard type, jaundice with sepsis, infectious hepatitis, toxoplasmosis, syphilis.

It is necessary to mention a number of medications that can increase bilirubinemia and, if left untreated, cause kernicterus. This has been proven for vitamin K when it is prescribed to premature babies at a dose of 10 mg, to full-term babies at a dose of 30 mg, as well as when mothers are given increased doses of vitamin K in the last days before childbirth. The same should be said for sulfonamides, especially long acting, prescribed to mothers shortly before childbirth or to newborns. It is possible for sulfonamides to pass into the fetal bloodstream, where they can remain unchanged for a long time and displace bilirubin from its compounds with protein, after which free bilirubin easily diffuses and, freely entering the spinal canal, can lead to kernicterus. Severe toxic hemolytic syndrome, dangerous in its consequences (including kernicterus), can also be caused by naphthalene when using diapers and blankets that have been kept in mothballs for a long time. Hemolytic syndrome can also be caused by the use of lotions and mash with resorcinol.

at severe forms hemolytic disease of newborns, the main method of treatment is early, in the first 12 hours, replacement blood transfusion (replacement transfusion on the 2nd day gives a worse result) of freshly citrate, single-group (or zero group), Rh-negative blood (in case of ABO incompatibility, transfusion is mandatory only group 0, compatible with the child’s blood regarding the Rh factor);

the amount of blood administered is 130-150 ml per 1 kg of the child’s weight, at least 300-00 ml (replacement of 75% of the child’s blood). In more severe cases, from 600 ml (replacement of 85% of blood) to 900 ml (replacement of 95% of blood) is administered. At the same time, 50-80 ml less is produced;

the infusion is carried out slowly, over ½-2 hours, alternating suction and infusion in fractional doses of 30-40 ml (according to instructions) while observing the rules of asepsis, protecting the child from cooling and continuously giving oxygen.

To prevent hypocalcemia, administer 1 ml of 10% calcium gluconate solution in 10 ml of 20 glucose solution after removing every 100 ml of blood from the newborn. The replacement blood transfusion is completed with the administration of 200,000-300,000 units of penicillin.

Absolute indications for urgent replacement blood transfusion:

poor obstetric history;

yellow staining of the umbilical cord, amniotic fluid, early jaundice;

anemia, hemoglobin from birth below 100 g/l (80% in venous blood and 95% in capillary), erythroblasts, significant reticulocytosis 1150% or more);

umbilical cord blood bilirubin 3 mg% or higher, serum bilirubin more than 15 mg% (especially an increase of 1 mg% per hour or higher);

positive direct Coombs test.

In the absence of freshly citrated blood, it is necessary, as an exception, to use canned Rh-negative single-group blood (in case of ABO incompatibility of group 0) no more than 3-4 days old. Negatives administration of preserved blood consists of a simultaneous undesirable increase in potassium, a change in the biochemical oxygenic properties of red blood cells and their lower viability. IN lately it was proposed to introduce erythroenriched and Rh-negative blood of type O instead of nitrate blood. Exchange transfusions of blood can be combined with intravenous administration gemodeza (6% polyvinylpyrrolidone) 5-15 ml per 1 kg of weight 1-2 times for 3-4 days, repeat as indicated. For replacement blood transfusion in the first hours and no later than 2 days, they use the umbilical cord method, later by injecting saphenous veins, mainly the head, with simultaneous bloodletting from the radial artery. Usually, after the transfusion, the child’s well-being and appetite improve with a decrease in jaundice and the size of the liver and spleen in the following days. Hematological indicators of effectiveness are a decrease in bilirubinemia, an increase in the number of red blood cells and hemoglobin, and the disappearance of erythroblasts. Lack of improvement and progressive increase in bilirubinemia are indications for repeated replacement blood transfusion.

Abundant administration of liquid peros, in severe forms 5% glucose solution, saline solution intravenously at the rate of 150 ml per day per 1 kg of weight, as well as transfusion of fractional doses of blood, dry plasma (30-40 ml). repeated administration of gamma globulin. Prescription of prednisone or prednisolone 0.5 1 mg per 1 kg per day for 5-10 days. Corticosteroids delay the formation of iso immune antibodies, hemolysins, regulate bilirubin metabolism, normalize the glucuronide enzyme system. Their use is also replacement therapy with postpartum adrenal damage. Vitamins C and B in age-related doses, B1 g 30-50 every other day, 8-10 injections, vitamin B6 1 ml of 1% solution for 8-10 days. Campolon or antianemin 1 ml every other day, methionine 0.2 g 2 times a day for 10 days as it improves liver function together with vitamin B6 with the regulation of the most important amino acids.

Feeding in the first 5-7-10 days with expressed milk from other women (depending on the content of Rh antibodies in the mother’s milk) or from the 5th day with expressed milk mother's milk, heated to 70° for 5 minutes or boiled. In milder cases, with bilirubinemia below 15 mg%, instead of replacement blood transfusion, hemotherapy with fractional blood transfusions of Rh-negative single-group or 0 group, 50-70 ml every 2-3 days. In addition to blood transfusions, therapeutic measures, indicated for severe forms (in accordance with clinical manifestations).

In case of kernicterus, it is necessary to repeat replacement blood transfusions 2-3 times, carry them out slowly with breaks of half an hour or more. These procedures promote diffusion (leaching) of bilirubin from tissues into the bloodstream. Other treatment measures are listed above.

The anemic form of hemolytic disease of newborns is the mildest and occurs without jaundice.

Symptoms

By the 7-10th day after birth, pallor of the skin is clearly visible, and in more severe cases, already in the first days of life. The amount of hemoglobin and red blood cells in the blood is reduced, microcytosis, anisocytosis, reticulocytosis, and sometimes erythroblastosis are observed. The spleen and liver are enlarged.

For proper targeted treatment, it is important to differentiate it from hyporegenerative anemia of newborns of another etiology, which is diagnosed based mainly on a negative Coombs reaction. Others need to be carried out serological reactions for ABO incompatibility and take into account anamnestic information.

Treatment: antianemic drugs, repeated, fractional blood transfusions, fortification (vitamins C, B complex, including B12, P).

Preventive measures during pregnancy:

examination of all pregnant women for the Rh factor, starting from the third month of pregnancy, again for women with an unfavorable obstetric history (miscarriages, stillbirths, hemolytic disease of the newborn), placing them under special observation;

3-4 weeks before giving birth, women with Rh-negative blood should be hospitalized;

periodic conduct preventive measures: three courses of treatment for 12-14 days at the beginning of pregnancy, in the middle and at the 33-34th week.

Course of treatment: intravenous infusion of 10% glucose solution, 20 ml per ascorbic acid, vitamin E solution 1 teaspoon per day, vitamin B1 10 mg, rutin 0.02 g and Vicasol 0.015 g 3 times a day, oxygen inhalation 2-3 pillows daily, general ultraviolet irradiation, eating lightly fried liver, taking methionine, campolone. In the maternity hospital, careful monitoring of the fetal heartbeat in the last days of pregnancy is necessary for timely adoption of the necessary therapeutic measures. As a last resort, obstetric surgical interventions are indicated.

vohistamines;

rehabilitation of purulent foci.

Hemolytic disease of the newborn (HDN) is a disease associated with incompatibility of fetal blood with maternal blood. The causes of this condition, diagnosis and treatment of the pathology will be discussed in this article.

Reasons

Incompatibility between maternal blood and fetal blood may be associated with the Rh factor and group incompatibility. It is known that there are 4 different groups blood: 0 (I), A (II), B (III) and AB (IV). 85% of Europeans have the Rh factor in their blood, and 15% of the European population are Rh negative.

HDN in 3-6% of cases develops with Rh incompatibility, when a Rh-negative mother develops a Rh-positive fetus: an Rh conflict occurs. Incompatibility with group antigens (ABO conflict) develops when the fetus has A (II) gr. blood (2/3 cases) or B (III) (about 1/3 cases) and 0 (I) gr. at the mother's. With group incompatibility, HDN is easier than with Rh conflict.

In all these cases, the red blood cells in the fetus have different antigenic qualities. If such red blood cells cross the placental barrier and enter the mother’s blood, the mother’s body begins to produce antibodies to these red blood cells.

When these specific antibodies enter the fetal body, the process of destruction of red blood cells (hemolysis) may begin, which will lead to the development of not only anemia, but also jaundice, which is dangerous for the fetus.

Maternal sensitization (acquisition hypersensitivity to a specific antigen) occurs not only during pregnancy: to a much greater extent, fetal red blood cells enter the maternal body during childbirth. Therefore the risk development of HDN for the first child less (antibodies have not yet been developed in the mother’s body) than for subsequent children.

It should be taken into account that sensitization can also occur during pregnancy termination (miscarriage or induced medical abortion), since the Rh factor is formed in the fetus already from the 5th week of pregnancy. Sensitization can occur when a woman is transfused with Rh-incompatible blood (even if the transfusion was performed in early childhood).

It is not always the case that when the spouses have Rh blood incompatibility, HDN develops in the child. An infant may or may not inherit the Rh factor from one of its parents.

Therefore, HDN due to Rh incompatibility develops in 0.5% of newborn babies, while Rh incompatibility in spouses is 20 times more common. In addition, at low birth rates, not every mother develops such severe sensitization that the fetus develops severe TTH. The degree of permeability of the placenta is also important for the development of the disease.

When TTH occurs in the ABO system, the number of previous pregnancies does not matter, since many factors can contribute to sensitization.

The mechanism of development of HDN

The destruction of red blood cells leads not only to anemia of the fetus or infant, but also to a significant increase in the level of bilirubin in the blood. Normally, indirect bilirubin binds to albumin (a type of blood protein) and turns into direct bilirubin. But too much large number indirect bilirubin released from destroyed red blood cells does not have time to bind to blood albumin and continues to circulate and build up in the blood.

Indirect bilirubin is toxic to the nervous system. When levels reach above 340 μmol/L in full-term infants and above 200 μmol/L in premature infants, it is able to penetrate the blood-brain barrier and affect the brain (primarily the cortex and subcortical nuclei). As a result, bilirubin encephalopathy, or kernicterus, develops.

Indirect bilirubin is dangerous not only for the nervous system: it is a tissue poison that causes degenerative changes in many organs, including cell death. When the liver is damaged, the level of direct bilirubin in the blood also increases, thickening of bile develops, its stagnation in bile ducts and reactive hepatitis.

As a result of the destruction of red blood cells, the child develops anemia, in response to which atypical foci of hematopoiesis appear. In internal organs breakdown products of red blood cells are deposited. A deficiency of microelements (copper, iron, etc.) develops.

Symptoms

Jaundice is one of the signs of HDN.

There are the following clinical forms of HDN:

• Edema (the most severe form, developing in 2% of cases), occurs in utero and can lead to miscarriage and stillbirth. In case of progression, it leads to hypoxia, severe impairment, decreased levels of blood proteins and tissue edema. This form is sometimes called “general hydrops fetalis.”

The fetus dies in utero, or the baby is born in very in serious condition, with pronounced swelling.

The skin is pale, with a jaundiced tint. The child is lethargic, muscle tone is sharply reduced, the spleen is significantly reduced, pulmonary symptoms are pronounced. Hemoglobin level is below 100 g/l. With this form, newborns die within 1-2 days after birth.

• Jaundice form develops most often, in 88% of cases. This is medium heavy clinical form diseases. Its main manifestations are: quickly and early (in the first day of life, rarely on the second) developing jaundice of the skin, anemia, enlargement of the liver and spleen. An orange tint of yellowness is characteristic. It grows literally by the hour. The earlier jaundice appears, the more severe the disease.

As the level of bilirubin increases, the child’s drowsiness and lethargy increases, and a decrease is noted. muscle tone, a monotonous scream appears. When the concentration of indirect bilirubin increases to critical levels (usually on days 3-4), signs of kernicterus appear: nagging convulsions, bulging of the large fontanel, tension in the muscles of the back of the head, monotonous crying, the symptom of “setting sun” appears (a small part of the iris is visible above the lower eyelid ).

Critical indicator of bilirubin level:

For 10% of full-term infants with TTH, the level exceeds 340 µmol/l;

For 30% of babies – over 430 µmol/l;

For 70% of newborns – over 520 µmol/l.

In rare cases, even this high level indirect bilirubin, as high as 650 µmol/l, does not lead to the development of kernicterus.

If left untreated, the child may die on days 3-6 of life. With kernicterus, surviving children may experience impaired intelligence, even idiocy, and impaired physical development.

By 7-8 days of life, against the background of the therapy, bile stagnation develops: the child develops a greenish tint to the skin, dark color urine and discolored feces, direct bilirubin increases in the blood. A blood test reveals anemia, which can persist for up to 2-3 months. The yellowness of the skin also persists for a long time. In the absence of damage to the nervous system, recovery, although long, is still complete.

• Anemic form occurs in 10% of cases of HDN. It has a benign course. Manifestations of the disease appear immediately after birth or in the first week of life. In some cases, the characteristic pallor of the skin is not immediately detected - at 2-3 weeks, already in severe anemia.

The child's general condition suffers little. Upon examination, an increase in the size of the liver and spleen is revealed. The concentration of indirect bilirubin sometimes increases slightly. The prognosis is usually favorable.

HDN, which arises as a result of a conflict in the ABO blood group, most often occurs in a mild form, but if diagnosed untimely, it can lead to bilirubin encephalopathy.

With a combination of Rh incompatibility and ABO incompatibility, that is, with double incompatibility, HDN occurs more easily than with an isolated Rh conflict.

Diagnostics

There are antenatal (prenatal) and postnatal (postpartum) diagnostics of the likelihood of tension-type headache.

Antenatal is carried out in case of Rh incompatibility of the blood of the spouses and taking into account the woman’s obstetric and gynecological history (miscarriages, abortions, stillbirths, blood transfusions). It determines the possibility of an immune conflict.

Antenatal diagnosis includes:

• During pregnancy, the blood of a Rh-negative woman is examined at least 3 times for the presence of anti-Rh antibodies. What is more important is not the magnitude of the antibody titer, but the nature of the changes in the titer, especially its sharp fluctuations.
• If a risk of an immune conflict is identified, amniotic fluid is examined to determine the level of protein, trace elements (copper, iron), glucose, and immunoglobulins.
• Ultrasound allows you to confirm the development of fetal HDN: this is evidenced by thickening of the placenta and its rapid growth (as a result of edema), polyhydramnios, increased size of the fetal liver and spleen.

Postnatal diagnostics of tension-type headache carried out taking into account:

• clinical symptoms of the disease at the first examination after the birth of the baby and over time (jaundice, enlarged spleen and liver, anemia);
• laboratory tests: increased indirect level and its increase, detection of young immature blood cells - erythroblasts, increase in the number of reticulocytes in the blood, decrease in the dynamics of the number of erythrocytes, decrease in hemoglobin level, positive result of the Coombs test (detection of anti-Rhesus and anti-erythrocyte antibodies using a serological blood test) . Laboratory studies are carried out in dynamics.

Treatment

In the treatment of severe forms of tension-type headache, an exchange transfusion of fresh (not more than 3 days old) is indicated. donated blood in order to prevent the level of bilirubin from increasing to a life-threatening concentration (20 mg%). Blood transfusions are carried out according to strict indications.

If there is a risk of developing HDN, a cord blood test is performed. If her bilirubin level is above 3 mg% and the Coombs test is positive, then a transfusion should be performed immediately.

If there is no cord blood test and there is a suspicion of HDN, a Coombs test is performed and the level of bilirubin in the baby’s blood is determined.

Rh-negative blood is injected through a catheter into the umbilical vein at the rate of 180-200 ml/kg of the newborn’s body weight (thereby replacing 95% of the baby’s blood). After infusion of every 100 ml of blood, 1-2 ml of calcium gluconate is injected. To prevent infection umbilical vein The baby is prescribed a 3-day course of antibiotics.

After 96 hours of the child’s life, blood transfusions are performed depending on general condition baby. With a bilirubin level of 20 mg%, severe anemia and positive result Coombs test - transfusion is performed. If the test is negative, then the further content of bilirubin in the blood is monitored.

After blood transfusion, bilirubin levels are monitored every 6 hours. If ongoing hemolysis is detected, the transfusion may be repeated.

Jaundice is a visual manifestation of hyperbilirubinemia. Bilirubin, one of the end products of catabolism of the heme protoporphyrin ring, accumulates in large quantities in the body and causes a yellow coloration of the skin and mucous membranes. The breakdown of 1 g of hemoglobin produces 34 mg of bilirubin. In adults it appears when the bilirubin level is 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. In approximately half of full-term and most premature infants, this is accompanied by the development of icteric syndrome. An important task A medical worker during the period of monitoring the health of a newborn child is to distinguish between physiological characteristics 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 size of the liver and spleen is not enlarged;

normal color of stool and urine.

Laboratory criteria:

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

the hemoglobin concentration in the blood is normal;

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

total blood bilirubin increases due to the indirect fraction;

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

Pathological hyperbilirubinemia

Present at birth or appear on the first day or second

week of life;

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

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

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

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

The level of NB in ​​umbilical cord blood serum is >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 NB values ​​on any day of life exceed 221 µmol/L

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

bin) - >25 µmol/l

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

Dark urine or discolored stools

Physiological jaundice is a diagnosis excluding pathological jaundice.

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

1. Hyperproduction of bilirubin due to hemolysis;

2. Impaired conjugation of bilirubin in hepatocytes;

3. Impaired excretion of bilirubin into the intestine;

4. Combined violation of conjugation and excretion.

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

1) hemolytic;

2) conjugation;

3) mechanical;

4) hepatic.

Hemolytic disease of newborns (HDN) is an isoimmune hemolytic anemia that occurs in cases of incompatibility between the blood of 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 GBN provides for the establishment of:

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

Clinical form (intrauterine death of the fetus with maceration, edematous, icteric, anemic);

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

Complications (bilirubin encephalopathy - kernicterus, 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 underlying conditions (prematurity, intrauterine infections, asphyxia, etc.)

Etiology. A conflict may arise if the mother is antigen-negative and the fetus is antigen-positive. There are 14 known main erythrocyte group systems, combining more than 100 antigens, as well as numerous private erythrocyte antigens and common erythrocyte antigens with other tissues. HDN usually causes incompatibility of the fetus and mother for Rh or ABO antigens. It has been established that the Rh antigen 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 (Fisher's terminology), or Rh", hr", Rho, hr0, Rh", hr" (Winner's terminology). Rh-positive red blood cells contain D-factor (Rho factor, in Winner's terminology), while so-called Rh-negative red blood cells do not. Incompatibility for ABO antigens, leading to HDN, usually occurs with the mother's blood group 0 (1) and the child's blood group A (II). If HDN develops due to double incompatibility of the child and mother, i.e. the mother is O (I) Rh(-), and the child is A (II) Rh(+) or B (III) Rh (+), then, as a rule, it is caused by A- or B-antigens. Rh-HDN is usually caused by sensitization of the Rh-negative mother to the Rh-O antigen prior to pregnancy. Sensitizing factors are, first of all, previous pregnancies (including ectopic ones and those ending in abortions), and therefore Rhesus HDN, as a rule, develops in children not born from the first pregnancy. In case of ABO-conflict, this pattern was not noted, and ABO-THB can occur already during the first pregnancy, but if the barrier functions of the placenta are impaired due to the presence of somatic pathology, gestosis, leading to intrauterine fetal hypoxia.

Pathogenesis.

Previous abortions, miscarriages, ectopic pregnancy, childbirth, etc. predispose the antigen-positive erythrocytes of the fetus to enter the bloodstream of the antigen-negative mother. In this case, the mother’s body produces anti-Rhesus or group antibodies. Incomplete anti-red blood cell antibodies, belonging to class G immunoglobulins, damage the erythrocyte membrane, leading to an increase in its permeability and metabolic disorders in the erythrocyte. These red blood cells, changed under the influence 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 eliminated by the liver, and hyperbilirubinemia develops. If hemolysis is not too intense with a small amount of incoming maternal antibodies, the liver quite actively removes NB, then in the child the clinical picture of HDN is dominated by anemia with the absence or minimal severity of jaundice. It is believed that if anti-erythrocyte alloimmune antibodies penetrate to the fetus for a long time and actively during pregnancy before the onset of labor, then intrauterine maceration of the fetus or an edematous form of HDN develops. In most cases, the placenta prevents the penetration of alloimmune antibodies to the fetus. At the time of birth, the barrier properties of the placenta are sharply disrupted, 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 passed to the baby through mother's milk, which increases the severity of HDN.

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

Features of pathogenesis in the icteric form of HDN. Hemolysis begins shortly before birth, the level of bilirubin quickly and significantly increases, 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 glucuronyltransferase and an increase in the excretion of conjugated (direct) bilirubin, which leads to impaired 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 bloodstream shortly before birth. At the same time, hemolysis is not intense, and the newborn’s liver quite actively removes bilirubin.

Although hyperbilirubinemia with NB leads to damage to a variety of organs and systems (brain, liver, kidneys, lungs, heart, etc.), damage to the nuclei of the base of the brain is of leading clinical importance. The staining of the basal ganglia, globus pallidus, caudal nuclei, putamen of the lenticular nucleus is maximally expressed; less often, the hippocampal gyrus, cerebellar tonsils, some nuclei of the thalamus optic, olives, dentate nucleus, etc. can be changed; this condition, according to the proposal of G. Schmorl (1904), was called “kernicterus”.

Clinical picture.

Edema form- the most severe manifestation of Rh-HDN. Typical is the mother's aggravated medical history - the birth of previous children in a family with HDN, miscarriages, stillbirths, prematurity, transfusions of Rh-incompatible blood, repeated abortions. During ultrasound examination of the fetus, the Buddha pose is characteristic - head up, lower limbs due to the barrel-shaped enlargement of the abdomen, they are bent at the knee joints, located unusually far from the body; "halo" around the cranial vault. Due to edema, the weight of the placenta is significantly increased. Normally, the weight of the placenta is 1/6-1/7 of the body weight of the fetus, but in the edematous form this ratio reaches 1:3 and even 1:1. The placental villi are enlarged, but their capillaries are morphologically immature and abnormal. Polyhydroamnion is characteristic. As a rule, mothers suffer from severe gestosis in the form of preeclampsia and eclampsia. Already at birth the child has: severe pallor (rarely with an icteric tint) and general swelling, especially pronounced on the external genitalia, legs, head, face; a sharply increased barrel-shaped belly; significant hepato- and splenomegaly (a consequence of erythroid metaplasia in organs and severe fibrosis in the liver); expansion of the boundaries of relative cardiac dullness, muffling of 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 fetal NP through the placenta. Very often, immediately after birth, respiratory disorders develop due to hypoplastic lungs or hyaline membrane disease. The cause of pulmonary hypoplasia is seen in an elevated diaphragm with hepatosplenomegaly and ascites. Hemorrhagic syndrome (hemorrhages in the brain, lungs, gastrointestinal tract) is common in children with the edematous form of tension-type headache. A minority of these children have decompensated DIC syndrome, but all have very low level in the blood plasma of procoagulants, the synthesis of which is carried out in the liver. Characteristic: hypoproteinemia (serum protein level falls below 40-45 g/l), increased levels of BDG in the umbilical 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 can be so severe that, in combination with hypoproteinemia, damage to the vascular wall can lead to heart failure. In survivors active treatment 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.

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

If treatment is not started in a timely manner or is inadequate, the icteric form of HDN may be complicated 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 rarely clinically 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 EB are manifestations of bilirubin intoxication - lethargy, decreased muscle tone and appetite up to the point of refusal to eat, a monotonous, unemotional cry, rapid depletion of physiological reflexes, regurgitation, vomiting. Then the classic signs of kernicterus appear - spasticity, stiff neck, forced body position with opisthotonus, stiff limbs and clenched hands; periodic excitement and a sharp “cerebral” high-frequency cry, bulging of a large fontanelle, twitching of facial muscles or complete amymia, large-scale tremors of the hands, convulsions; "setting sun" symptom; 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; mental retardation; 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, fasting, hypoalbuminemia, certain medications (sulfonamides, alcohol, furosemide , diphenin, diazepam, indomethacin and salicylates, methicillin, oxacillin, cephalothin, cefoperazone).

Anemic form diagnosed in 10-20% of patients. Children are pale, somewhat lethargic, suck poorly and gain weight. They have 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 hypogenerator 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 to diagnose tension-type headache are presented in Table 3.

Table 3.

Examination of the pregnant woman and fetus in case of suspected

hemolytic disease of the fetus.

Survey	Indicator	Characteristic changes in hemolytic disease of the fetus
Immunological examination of a pregnant woman	Determination of anti-Rhesus antibody titer	The presence of antibody titer, as well as their dynamics (increase or decrease in titer)
	Measuring the volume of the placenta	Increased thickness of the placenta
	Measuring the amount of amniotic fluid	Polyhydramnios
	Fetal size measurement	Increased size of the liver and spleen, increase in the size of the abdomen compared to the size of the head and chest, ascites
Dopplerometry of fetal-placental uterine blood flow	Umbilical artery	Increase in systole-diastolic ratio of resistance index
	Middle cerebral artery of the fetus	Increased blood flow speed
Electrophysiological methods	Cardiotocography with determination of fetal condition indicator	Monotonous rhythm in moderate and severe forms of hemolytic disease and “sinusoidal” rhythm in the edematous form of hemolytic disease of the fetus
Study of amniotic fluid (during amniocentesis)	The optical density of bilirubin	Increased optical density of bilirubin
Cordocentesis and fetal blood testing	Hematocrit
	Hemoglobin
	Bilirubin
	Indirect Coombs test	Positive
	Fetal blood type
	Fetal Rh factor	Positive

All women with Rh-negative blood are tested at least three times for the titer of anti-Rhesus antibodies. The first study is carried out upon registration at the antenatal clinic. It is optimal to further conduct a repeat study at 18-20 weeks, and in the third trimester of pregnancy, carry it out every 4 weeks. The mother's Rh antibody test does not accurately predict the future severity of HDN in the child, and determining the level of bilirubin in the amniotic fluid is of great value. If the titer of Rh antibodies is 1:16-1:32 or greater, then at 6-28 weeks. amniocentesis is performed and the concentration of bilirubin-like substances in the amniotic fluid is determined. If the optical density with a 450 mm filter is more than 0.18, intrauterine blood transfusion is usually necessary. It is not performed on fetuses older than 32 weeks. gestation. Another method for diagnosing the congenital edematous form of HDN is ultrasound examination, which reveals fetal edema. It develops when the hemoglobin level is 70-100 g/l.

Since the prognosis for HDN depends on the content of hemoglobin and the concentration of bilirubin in the blood serum, it is first 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 TTH:

1. Determination of the blood group and Rhesus status of the mother and child.

2. Analysis of the child’s peripheral blood with evaluation of the blood smear.

3. Blood test with reticulocyte count.

4. Dynamic determination of bilirubin concentration in blood serum

see the child.

5. Immunological studies.

Immunological studies. In all children of Rh-negative mothers, the blood type and Rh affiliation, and serum bilirubin level are determined in the umbilical cord blood. In case of Rh incompatibility, the titer of Rh antibodies in the mother’s blood and milk is determined, and a direct Coombs reaction (preferably an aggregate agglutination test according to L.I. Idelson) is performed with the child’s red blood cells and an indirect Coombs reaction with the mother’s blood serum, and the dynamics of Rh is analyzed. antibodies in the mother's blood during pregnancy and the outcome of previous pregnancies. In case of 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 (colloid) and salt media, in order to distinguish natural agglutinins (they have a large molecular weight and belong to immunoglobulins class M, do not penetrate the placenta) from immune ones (they have a small molecular weight, belong to class G immunoglobulins, easily penetrate the placenta, and after birth - with milk, i.e. are 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 saline medium. A direct Coombs test for ABO conflict in a child is usually weakly positive, i.e. slight agglutination appears after 4-8 minutes, whereas with Rh-conflict, pronounced agglutination is noticeable after 1 minute. When there is a conflict between the child and the mother regarding other rare erythrocyte antigenic factors (according to various authors, the frequency of such conflict ranges from 2 to 20% of all cases of HDN), the direct Coombs test is usually positive in the child and the indirect test in the mother, and incompatibility of the child’s erythrocytes and mother's serum in an individual compatibility test.

Changes in the child’s peripheral blood: 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 determinations 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 as indicated), platelet count, transaminase activity (at least once) and other studies depending on the characteristics of the clinical picture.

Table 4.

Examinations for suspected HDN.

Survey	Indicator	Characteristic changes in HDN
Biochemical blood test	Bilirubin (total, indirect, direct)	Hyperbilirubinemia due to an increase in the predominantly indirect fraction, an increase in the direct fraction with a complicated course - the development of cholestasis
	Protein (total and albumin)	Hypoproteinemia and hypoalbuminemia reduce bilirubin transport to the liver and uptake by hepatocytes, maintaining bilirubinemia
		Activity is moderately increased with complicated course - development of cholestasis
	Cholesterol	Increased in complicated course - development of cholestasis
	Gammaglutamyltransferase, alkaline phosphatase	Activity is increased with complicated course - development of cholestasis
General blood test	Hemoglobin		Hyperregenerative anemia, normochromic or hyperchromic
	Red blood cells	Quantity reduced
	Color index	Normal or slightly elevated
	Reticulocytes	Promoted
	Normoblasts	Promoted
	Leukocytes	The amount may be increased in response to prolonged intrauterine hypoxia with early onset hemolysis
	Platelets	Quantity may be reduced
Rhesus status with possible Rh sensitization	Rhesus belongs to the mother	Negative
	Rhesus affiliation of the child	Positive
Blood group with possible ABO sensitization	Mother's blood type	Mainly O(I)
	Child's blood type	Mainly A (II) or B (III)
Antibody titer determination	Anti-Rhesus
	Group  or 	Immune in any titer or natural in titer 1024 and above
Direct Coombs reaction	Rhesus conflict	Positive
	ABO conflict	Negative

Diagnostic criteria for tension-type headache:

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 with an AB0 conflict is usually bright yellow; with an Rh conflict it may 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 - normal coloring of stool and urine; against the background of phototherapy, there may be a green coloration of the stool and short-term darkening of the urine.

Laboratory criteria:

Concentration of bilirubin in umbilical cord blood (moment of birth) - in mild forms of immunological conflict for Rh and in all cases of A0 incompatibility -<=51 мкмоль/л; при тяжелых формах иммунологического конфликта по Rh и редким факторам – существенно выше 51 мкмоль/л;

The concentration of hemoglobin in umbilical 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 infants, >> 171 µmol/L in premature infants;

Total blood bilirubin increases mainly due to the indirect fraction,

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

decrease in hemoglobin level, red blood cell count and increase in reticulocyte count in clinical tests blood 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 umbilical cord blood (up to 150 g/l), a moderate increase in bilirubin in the umbilical cord blood (up to 85.5 µmol/l), hourly an increase in bilirubin to 4-5 µmol/l, a moderate enlargement of the liver and spleen of less than 2.5 and 1 cm, respectively, a slight pastiness of the subcutaneous fat.

b) 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, pasty subcutaneous fat, enlarged liver by 2.5 - 3.0 cm and spleen by 1.0 - 1.5 cm.

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

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

Examples of diagnosis formulation.

Hemolytic disease due to Rh conflict, edematous-icteric form, severe, complicated by bile thickening syndrome.

Hemolytic disease due to 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 are used with intrauterine transfusion of red blood cells ("washed" red blood cells of blood group 0(II), Rh-negative are used).

Management tactics for tension headaches.

An important condition for the prevention and treatment of hyperbilirubinemia in newborns is the creation of optimal conditions for the early neonatal adaptation of the child. In all cases of illness in a newborn, care must be taken to maintain optimal body temperature, provide his body with a sufficient amount of fluid and nutrients, and prevent metabolic disorders such as hypoglycemia, hypoalbuminemia, hypoxemia and acidosis.

In cases where there are clinical signs of a severe form of hemolytic disease at the time of 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, enlargement of the liver and spleen), an emergency PCD operation is indicated without waiting for laboratory tests. data. (In this case, the partial PCD technique is used, in which 45-90 ml/kg of the child’s blood is replaced with a similar volume of donor red blood cells of group 0(1), Rh-negative)

In other cases, the management tactics for such children depend on the results of the initial laboratory examination and dynamic observation.

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

The management tactics for children with tension-type headache over 24 hours of age depend 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.

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

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

The ordinate is the concentration of bilirubin in the blood serum (in µmol/l); on the x-axis - the child’s age in hours; dotted line - bilirubin concentrations at which PCA is necessary in children with no risk factors for bilirubin encephalopathy; solid lines - bilirubin concentrations at which BPC is necessary in children with the presence of risk factors for bilirubin encephalopathy (with ABO and Rh conflict, respectively)

Hemolytic disease of newborns (HDN): causes, manifestations, how to treat

Hemolytic disease of the newborn (HDN) is a very common disease. This pathology is registered in approximately 0.6% of children born. Despite the development various methods treatment, the mortality rate from this disease reaches 2.5%. Unfortunately, a large number of scientifically unsubstantiated “myths” are widespread about this pathology. For a thorough understanding of the processes occurring during hemolytic disease, knowledge of normal and pathological physiology, and also, of course, obstetrics.

What is hemolytic disease of the newborn?

TTH is a consequence of a conflict between the immune systems of mother and child. The disease develops due to the incompatibility of the blood of a pregnant woman with antigens on the surface of the fetal red blood cells (primarily this). Simply put, they contain proteins that are recognized by the mother’s body as foreign. That is why the processes of activation of her immune system begin in the body of a pregnant woman. What's going on? So, in response to the ingress of an unfamiliar protein, the biosynthesis of specific molecules occurs that can contact the antigen and “neutralize” it. These molecules are called antibodies, and the combination of antibody and antigen is called immune complexes.

However, in order to get a little closer to a true understanding of the definition of HDN, it is necessary to understand the human blood system. It has long been known that blood contains different types of cells. The largest number of cellular composition is represented by erythrocytes. On modern level development of medicine is known at least 100 various systems antigenic proteins present on the erythrocyte membrane. The most well studied are the following: rhesus, Kell, Duffy. But, unfortunately, there is a very common misconception that hemolytic disease of the fetus develops only according to group or Rh antigens.

The lack of accumulated knowledge about erythrocyte membrane proteins does not mean that incompatibility with this particular antigen in a pregnant woman is excluded. This is the debunking of the first and, perhaps, the most basic myth about the causes of this disease.

Factors causing immune conflict:

Video: about the concepts of blood group, Rh factor and Rh conflict

Probability of conflict if the mother is Rh-negative and the father is Rh-positive

Very often, a woman who is Rh negative worries about her future offspring, even without being pregnant. She is afraid of the possibility of developing a Rhesus conflict. Some are even afraid to marry an Rh-positive man.

But is this justified? And what is the likelihood of developing an immunological conflict in such a couple?

Fortunately, the Rh sign is encoded by the so-called allelic genes. What does it mean? The fact is that the information located in the same areas of paired chromosomes can be different:

• The allele of one gene contains a dominant trait, which is the leading one and manifests itself in the organism (in our case, the Rh factor is positive, let’s denote it capital letter R);
• A recessive trait that does not manifest itself and is suppressed by a dominant trait (in this case, the absence of the Rh antigen, let’s denote it with a small letter r).

What does this information tell us?

The bottom line is that a person who is Rh positive can contain either two dominant traits (RR) or both dominant and recessive (Rr) on their chromosomes.

Moreover, a mother who is Rh negative contains only two recessive traits (rr). As you know, during inheritance, each parent can give only one trait to their child.

Table 1. The probability of inheritance of a Rh-positive trait in a fetus if the father is a carrier of a dominant and recessive trait (Rr)

Table 2. Probability of inheriting a Rh-positive trait in a fetus if the father is a carrier of only dominant traits (RR)

	Mother (r) (r)	Father (R) (R)
Child	(R)+(r) Rh positive	(R)+(r) Rh positive
Probability	100%	100%

Thus, in 50% of cases, there may not be an immune conflict at all if the father is a carrier of the recessive trait of the Rh factor.

So, we can draw a simple and obvious conclusion: the judgment that an Rh-negative mother and an Rh-positive father must necessarily have immunological incompatibility is fundamentally wrong. This is the “exposure” of the second myth about the causes of the development of hemolytic disease of the fetus.

In addition, even if the child still has a positive Rh factor, this does not mean that the development of tension-type headache is inevitable. Don't forget about protective properties. During a physiological pregnancy, the placenta practically does not allow antibodies to pass from mother to child. Proof is the fact that hemolytic disease occurs only in the fetus of every 20th Rh-negative woman.

Forecast for women with a combination of negative Rh and first blood group

Having learned about the identity of their blood, women with a similar combination of group and Rhesus fall into panic. But how justified are these fears?

At first glance it may seem that the combination of “two evils” will create high risk development of HDN. However, ordinary logic does not work here. It's the other way around: the combination of these factors, oddly enough, improves the prognosis. And there is an explanation for this. In the blood of a woman with the first blood group there are already antibodies that recognize a foreign protein on red blood cells of a different group. This is how nature intended, these antibodies are called agglutinins alpha and beta, all representatives of the first group have them. And when a small amount of fetal red blood cells enter the mother’s bloodstream, they are destroyed by existing agglutinins. Thus, antibodies to the Rh factor system simply do not have time to form, because agglutinins are ahead of them.

Women with the first group and negative Rh have a small titer of antibodies against the Rh system, and therefore hemolytic disease develops much less frequently.

Which women are at risk?

Let us not repeat that negative Rh or first blood group is already a certain risk. However, It is important to know about the existence of other predisposing factors:

1. Blood transfusion in an Rh-negative woman during her life

This is especially true for those who have had various allergic reactions after a transfusion. Often in the literature one can find the judgment that those women who received a blood type transfusion without taking into account the Rh factor are at risk. But is this possible in our time? This possibility is practically excluded, since Rhesus status is checked at several stages:

• During blood collection from a donor;
• At the transfusion station;
• The hospital laboratory where blood transfusions are performed;
• A transfusiologist who conducts a three-time compatibility test between the blood of the donor and the recipient (the person receiving the transfusion).

The question arises: Where then is it possible for a woman to become sensitized (presence of hypersensitivity and antibodies) to Rh-positive erythrocytes?

The answer was given quite recently, when scientists found out that there is a group of so-called “dangerous donors” whose blood contains red blood cells with a weakly expressed Rh-positive antigen. It is for this reason that their group is defined by laboratories as Rh negative. However, when such blood is transfused, the recipient’s body may begin to produce specific antibodies in a small volume, but even their quantity is sufficient for the immune system to “remember” this antigen. Therefore, in women with a similar situation, even in the case of their first pregnancy, an immune conflict may arise between her body and the child.

2. Repeated pregnancy

It is believed that in During the first pregnancy, the risk of developing an immune conflict is minimal. And the second and subsequent pregnancies already occur with the formation of antibodies and immunological incompatibility. And this is true. But many people forget that the first pregnancy should be considered the fact of development ovum in the mother's body until any time.

Therefore, women who have had:

1. Spontaneous abortions;
2. Frozen pregnancy;
3. Medical and surgical termination of pregnancy, vacuum aspiration of the fetal egg;
4. Ectopic pregnancy (tubal, ovarian, abdominal).

Moreover, primigravidas with the following pathologies are also at increased risk:

• Chorionic detachment, placenta during this pregnancy;
• Formation of a retroplacental hematoma;
• Bleeding with low placenta previa;
• Women who have had invasive methods diagnostics (piercing the amniotic sac with sampling of amniotic fluid, taking blood from the fetal umbilical cord, biopsy of the chorion section, examination of the placenta after 16 weeks of pregnancy).

Obviously, the first pregnancy does not always mean the absence of complications and the development of an immune conflict. This fact dispels the myth that only the second and subsequent pregnancies are potentially dangerous.

What is the difference in hemolytic disease of the fetus and newborn?

There are no fundamental differences in these concepts. Simply hemolytic disease in the fetus occurs during prenatal period. HDN means the occurrence of a pathological process after the birth of a child. Thus, the difference lies only in the conditions under which the baby is staying: in utero or after birth.

But there is one more difference in the mechanism of this pathology: during pregnancy, maternal antibodies continue to enter the fetus’s body, which lead to a deterioration in the condition of the fetus, while after childbirth this process stops. That's why women who have given birth to a baby with hemolytic disease are strictly prohibited from feeding their baby breast milk. This is necessary in order to prevent the entry of antibodies into the baby’s body and not to aggravate the course of the disease.

How does the disease progress?

There is a classification that well reflects the main forms of hemolytic disease:

1. Anemic– the main symptom is a decrease in fetus, which is associated with the destruction of red blood cells () in the baby’s body. Such a child has all the signs:

2. Edema form. The predominant symptom is the presence of edema. Distinctive feature is the deposition of excess fluid in all tissues:

• In subcutaneous tissue;
• In the chest and abdominal cavity;
• In the pericardial sac;
• In the placenta (during the prenatal period)
• Hemorrhagic skin rashes are also possible;
• Sometimes there is a dysfunction of blood clotting;
• The child is pale, lethargic, weak.

3. Jaundice form characterized by, which is formed as a result of the destruction of red blood cells. With this disease there is toxic damage all organs and tissues:

• The most severe option is the deposition of bilirubin in the liver and brain of the fetus. This condition is called “kernicterus”;
• A yellowish coloration of the skin and sclera of the eyes is characteristic, which is a consequence of hemolytic jaundice;
• Is the most frequent form(in 90% of cases);
• Possible development diabetes mellitus with damage to the pancreas.

4. Combined (the most severe) - is a combination of all previous symptoms. It is for this reason that this type of hemolytic disease largest percentage lethality.

How to determine the severity of the disease?

In order to correctly assess the child’s condition, and most importantly, prescribe effective treatment, it is necessary to use reliable criteria when assessing severity.

Diagnostic methods

Already during pregnancy, it is possible to determine not only the presence of this disease, but even the severity.

The most common methods are:

1. Determination of the titer of Rh or group antibodies. It is believed that a titer of 1:2 or 1:4 is not dangerous. But this approach is not justified in all situations. Here lies another myth that “the higher the titer, the worse the prognosis.”

The antibody titer does not always reflect the real severity of the disease. In other words, this indicator is very relative. Therefore, it is necessary to assess the condition of the fetus using several research methods.

2. Ultrasound diagnostics is a very informative method. The most characteristic signs:

• Placenta enlargement;
• The presence of fluid in tissues: fiber, chest, abdominal cavity, swelling of the soft tissues of the fetal head;
• Increased blood flow speed in the uterine arteries and in the vessels of the brain;
• Presence of suspension in amniotic fluid;
• Premature aging of the placenta.

3. Increased density of amniotic fluid.

4. Upon registration - signs and disturbances of heart rhythm.

5. In rare cases, cord blood testing is performed(determine the level of hemoglobin and bilirubin). This method is dangerous due to premature termination of pregnancy and fetal death.

6. After the birth of a child, there are simpler diagnostic methods:

• Taking blood to determine: hemoglobin, bilirubin, blood group, Rh factor.
• Examination of the child (in severe cases, jaundice and swelling are evident).
• Determination of antibodies in the child's blood.

Treatment of tension-type headache

Treatment for this disease can begin now. during pregnancy, to prevent deterioration in the condition of the fetus:

1. Introduction of enterosorbents into the mother’s body, for example “Polysorb”. This drugs helps reduce antibody titer.
2. Drip administration of solutions of glucose and vitamin E. These substances strengthen the cell membranes of red blood cells.
3. Injections of hemostatic drugs: “Ditsinon” (“Etamzilat”). They are needed to increase blood clotting ability.
4. In severe cases it may be necessary intrauterine fetus. However, this procedure is very dangerous and is fraught with adverse consequences: fetal death, premature birth, etc.

Methods of treating a child after childbirth:

For severe disease, use following methods treatment:

1. Blood transfusion. It is important to remember that only “fresh” blood is used for blood transfusion, the date of collection of which does not exceed three days. This procedure is dangerous, but it can save the baby's life.
2. Blood purification using hemodialysis and plasmapheresis machines. These methods help remove from the blood toxic substances(bilirubin, antibodies, red blood cell destruction products).

Prevention of the development of immune conflict during pregnancy

Women at risk for developing immunological incompatibility You must adhere to the following rules, there are only two of them:

• Try not to have an abortion; to do this, you need to consult a gynecologist to prescribe reliable methods of contraception.
• Even if the first pregnancy went well, without complications, then after birth, within 72 hours it is necessary to administer anti-Rhesus immunoglobulin (“KamROU”, “HyperROU”, etc.). The completion of all subsequent pregnancies should be accompanied by the administration of this serum.

Hemolytic disease of the newborn is a serious and very dangerous disease. However, you should not unconditionally believe all the “myths” about this pathology, even though some of them are already firmly rooted among most people. A competent approach and strict scientific validity are the key to a successful pregnancy. In addition, it is necessary to pay due attention to prevention issues in order to avoid potential problems as much as possible.