Hemolytic disease of the newborn obstetrics. Hemolytic disease of the fetus and newborn (HDN). Clinical guidelines. How does hemolytic disease manifest?

One of the most severe childhood pathologies is hemolytic disease of the newborn (HDN), which occurs when the immune systems of the mother and the child conflict, which is accompanied by massive destruction of red blood cells. Therefore, this disease of the fetus and newborn is also known as erystoblastosis - this is a sad result of categorical differences in the blood of mother and baby according to the Rhesus or ABO system.

The main cause of infant erythroblastosis is the opposite difference between the blood of mother and baby, more often by the Rh factor. More rarely, blood group antigens (in the ABO system) are the culprits, and they are less likely to encounter opposition of a different nature.

What is the predisposition to the Rhesus conflict of mother and baby? When a mother with a minus rhesus is pregnant with a baby with a plus rhesus. Most often, this is why hemolytic disease of the newborn manifests itself, starting development already in the womb.

The cause of the clash of immunities in the ABO system is a mismatch in blood types: O (1) -blood group in the mother and A (2) or B (3) in the fetus.

It is worth noting that not always a child is born sick. And only when the mother had previously experienced the so-called sensitization, that is, increased sensitivity to foreign blood components that she encountered for one reason or another.

Maternal sensitization can have different sources. For example, an Rh-negative mother becomes sensitized after she receives an Rh-positive blood transfusion (this could have happened a long time ago, even when she was a child). In addition, sensitization occurs during a miscarriage, and if there was an artificial abortion. Also, the main culprits of maternal sensitization are childbirth. Therefore, with each subsequent child, the risk increases.

If we are talking about immune incompatibility according to the ABO system, it does not matter what kind of pregnancy a woman has, because we are faced with sensitization to antigens every day - when eating, with vaccinations, during certain infections.

In addition to the aforementioned discrepancies in the Rh factor and the ABO system, the placenta occupies a special place, since it provides direct contact between the organisms of the mother and the baby when he is in the womb. If the barrier itself is violated, it is easier to exchange antibodies and antigens in the bloodstreams of mother and baby.

In the prenatal period, together with erythrocytes, hostile blood bodies penetrate inside. These bodies (Rh factor, antigens A and B) contribute to the formation of antibodies in the blood, and they then penetrate through the protective barrier into the bloodstream of the baby to be born. The result of this exchange is the combination of antigens and antibodies that cause pathological destruction of red blood cells.

The consequences of such destruction, with the participation of hostile bodies, have a detrimental effect on the development of the fetal organism. As one of the consequences of this decay is an increase in the concentration of toxic bilirubin and the development of anemia (anemia).

Bilirubin that has not passed through the liver is toxic to humans, and even more so to an infant. It has the ability to overcome the obstacle separating the circulatory system and the central nervous system, and also causes damage to the subcortical nuclei and the cerebral cortex, which is the cause of "nuclear jaundice".

If it has developed, then as a result of the destruction of red blood cells, new blood cells are formed - erythroblasts. Therefore, this disease is also called erythroblastosis.

Forms

Depending on the type of immunological conflict, the following forms are distinguished

• Hemolytic disease of the newborn due to a conflict on the Rh factor;
• Hemolytic disease of the newborn due to a blood type conflict (ABO incompatibility);
• More rare forms (conflict over other antigenic systems).

Clinical forms:

• edematous;
• icteric;
• Anemic.

According to the severity, the following forms of the disease are distinguished:

• Mild: Symptoms are mild or only laboratory findings are present.
• Moderate: bilirubin in the blood is increased, but intoxication and complications have not been identified. In the first 5–11 hours after the birth of a baby, it manifests itself (depending on the Rh conflict or ABO conflict), in the 1st hour of life less than 140 g / l, bilirubin in the blood from the umbilical cord exceeds 60 μmol / l, the liver and spleen are enlarged.
• Severe: edematous form of the disease, symptoms of nuclear jaundice, respiratory disorders and cardiac function.

Symptoms

Clinical symptoms are different in some form of pathology: edematous, anemic or icteric.

edematous

The edematous form, similarly called dropsy of the fetus, is the rarest, while the severity of the course of the disease surpasses all others. Here are its signs and symptoms:

• The beginning of development is intrauterine;
• High probability of miscarriage in the first trimester of pregnancy;
• Less often - later death of the fetus or birth in an aggravated position with edema characteristic of this form, a deep deficiency of hemoglobin and red blood cells in the bloodstream, with oxygen starvation and heart failure;
• Great, almost waxy, pallor of the skin of an infant;
• Sharp strengthening of muscles, reflex oppression;
• Large abdomen due to enlargement of the liver and spleen;
• Extensive tissue swelling.

anemic

The anemic form is the mildest possible. Her symptoms:

• Can be recognized in the near future (up to four to five days) after the birth of a child;
• Anemia progressively develops, the skin and mucous membranes turn pale, the abdomen increases;
• In general, it does not greatly affect the well-being of the child.

icteric

The icteric form is the most common. Her symptoms:

• The tissues acquire a pronounced yellow tint due to the hyperaccumulation of the bilirubin pigment and its derivatives in the bloodstream;
• Deficiency of coloring pigment and red cells per unit volume of blood;
• Significant enlargement of the spleen and liver in size.

The development of jaundice occurs soon after the birth of the baby, sometimes - after 24 hours. It progresses over time.

The skin and mucous membranes of the child become yellow, even orange. The severity of the course of the disease depends on how early it manifested itself. The more bilirubin accumulates in the blood, the more lethargy and drowsiness manifest in the child. There is an inhibition of reflexes and a decrease in muscle tone.

On days 3-4, the concentration of toxic bilirubin becomes critical - more than 300 micromoles per liter.

Jaundice acquires a nuclear form when the subcortical nuclei of the brain are affected. This can be understood by stiff neck and opisthotonus, a symptom of the "setting sun", a piercing brain cry. By the end of the week, the skin becomes greenish, the feces become colorless, and the rate of direct bilirubin increases.

Diagnostics

It is necessary to carry out prenatal diagnosis of the conflict between the immune system of the mother and the fetus. At risk are women with miscarriages, stillbirths, children who died on the first day from jaundice, if mothers did a blood transfusion without taking into account the Rh factor.

• It is necessary to determine the Rh and ABO group of the child's parents. The mother with a negative, and the fetus with a positive Rh are at risk. The genotype of the father is checked with the prognosis of the Rh of future children. Women with I blood group are also in a dangerous position.
• Check the dynamics of the titer of anti-Rhesus antibodies, if a woman has a negative Rh, at least three times during the gestation period.
• Do a sampling of amniotic fluid at the 34th week, if there is a risk.
• Be sure to conduct an ultrasound examination for thickening of the placenta and polyhydramnios.

Postpartum diagnosis is also carried out on the basis of clinically manifested symptoms during childbirth and immediately after them, as well as laboratory indicators of the disease. A consultation with a pediatric hematologist is appointed, who will oversee the treatment if a pathology is detected.

Treatment

In severe forms of the disease, treatment is as follows:

• Carry out a blood transfusion with replacement (they release "bad" blood and carry out a donor transfusion);
• Hemosorption is carried out - blood is passed through or resins capable of absorbing toxic substances;
• A certain amount of blood is taken and plasma containing toxic components is removed from it.

A replacement transfusion helps to get rid of indirect bilirubin and harmful antibodies from the baby's blood and increase the number of red blood cells.

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To carry out such a transfusion, blood with a negative Rh and the same ABO group as in an infant is used. Now they try not to transfuse whole blood, so as not to reduce the risk of transmitting HIV or hepatitis, but to use a mass of red blood cells with a negative Rh or plasma, depending on the group of the ABO system.

If the disease has a mild form or surgical treatment was performed, do the following:

• Intravenous glucose and protein-based preparations are infused;
• Assign inducers of microsomal liver enzymes;
• Vitamins C, E, group B, cocarboxylase, which improve the functioning of the liver and normalize metabolic processes.

If there is a syndromic thickening of bile, cholagogues are prescribed inside. If anemia is severe, an erythrocyte transfusion is done. In parallel, phototherapy is prescribed, that is, the child's body is irradiated with a fluorescent lamp of white or blue light. Indirect bilirubin, located in the skin, is oxidized, water-soluble components are formed from it, which are excreted naturally.

Complications and consequences

If the disease is severe, complications can be the most disappointing, despite treatment:

• The fetus may die during pregnancy or in the first week after birth;
• The child may become disabled, including cerebral palsy;
• May become completely deaf or blind;
• Psychomotor disturbances can be observed;
• May develop due to stagnation of bile;
• Psychiatric disorders are often observed.

The red blood cells of the child may have differences in properties with those of the mother. If the placenta passes such red blood cells, they turn into foreign antigens, and the response is the production of antibodies by the mother's body. The penetration of antibodies into the body of the fetus can cause:

• Hemolysis (breakdown of red blood cells);
• Extremely dangerous jaundice.

Prevention

Prevention of hemolytic disease is divided into specific and non-specific:

• In case of non-specific prophylaxis, transfusion is carried out taking into account the group and the Rh factor and pregnancies are preserved;
• With specific prophylaxis, anti-D immunoglobulin is administered on the first or second day immediately after childbirth (if there is a Rh conflict between mother and child) or abortion.

In the event that during pregnancy the concentration of antibodies in the blood increases, apply:

• hemosorption;
• 3–4 times intrauterine exchange transfusion at the 27th week using washed erythrocytes of the O(I) group with negative Rh and subsequent delivery from the 29th week of pregnancy.

Hemolytic disease of the fetus and newborn is a dangerous disease that can and must be prevented in time, even in the first stages of pregnancy, to be observed by specialists.

- a disease characterized by hemolysis of fetal erythrocytes due to isoserological incompatibility of the mother and fetus according to the Rh system (less often according to AB0, Kell-cellano, Lutheran, HLA Lewis, etc.)

Pathogeny of HDN

Entering the mother's bloodstreamRh Hypertension (with ectopic pregnancy; spontaneous and artificial termination of pregnancy, childbirth; preeclampsia; PORN, abdominal trauma, operative delivery; invasive procedures in the uterine cavity; history of incompatible blood transfusion)

Working outIgM

Re-hitRhAG

Sensitization of the mother's body

Massive productionIgG

Passage from the mother's bloodstream to the fetus

Interaction with AH of fetal erythrocytes

Hemolysis→ formation of indirect bilirubin

↓ ↓

Anemia Accumulation of bilirubin→ GM defeat

↓ ↓ ↓

Increased synthesis of erythropoietin Jaundice Encephalopathy

The occurrence of extramedullary bleeding in the liver, spleen, adrenal glands, placenta, intestines

Obstruction of the portal and umbilical veins

portal hypertension

Impaired liver function

Hyperbilirubinemia, hypoproteinemia

↓colloidal osmotic blood pressure

Ascites, edema in the fetus

Compensatory increases in cardiac output and MOS

Formation of hyperdynamic type of blood circulation

Myocardial hypertrophy

Progressive tissue hypoxia and acidosis

Thus, anemia and hyperbilirubinemia are the main symptoms of GBP, and in severe forms, dropsy of the fetus.

Clinic: There is no specific clinic, it is diagnosed on the basis of laboratory and instrumental examinations.

Diagnostics:

• Studying the anamnesis
• Determination of the titer of erythrocyte antibodies in the peripheral blood of the mother from the initial stages of pregnancy: 1 time per month until 32 weeks, 1 time in 2 weeks from 32-35 weeks, after 35 weeks 1 time per 1 week. AT are detected using the indirect/direct Coombs reaction.

The titer of antibodies during pregnancy may be unchanged, may be increased or decreased.

Management of pregnant women with isoimmunization:

• Early diagnosis of GBP.
• Determination of the term and method of delivery.
• From early pregnancy, the determination of Rh AT and their titer throughout pregnancy.
• If there is a history of OAH and a titer above 22 at 22-23 weeks, decide on an invasive diagnostic procedure.

Ultrasound:

• An increase in the thickness of the placenta from the gestational age by 0.5-1 cm
• Enlargement of the fetal liver and spleen
• Polyhydramnios
• Extension of the veins of the umbilical cord, more than 10 mm
• Ascites in the fetus
• Cardiomegaly, pericardial effusion
• hydrothorax, hydrocephalus

In pregnant women up to 32 weeks, 1 time every 4 weeks. After 32 weeks, every 2 weeks, if a severe form is suspected, 1-3 days between each ultrasound, so as not to miss the time for delivery.

UZDG - the leading method in the diagnosis of fetal anemia, this is the study of cerebral blood flow in the middle cerebral artery and the functional state of the fetus. A speed of more than 1.5 indicates the development of a hyperdynamic type of blood circulation - a severe form.

Amniocentesis - examination of amniotic fluid taken with a thin needle through a puncture in the abdomen.

Indications: death of children from GBP in previous births; the presence of children who underwent replacement blood transfusion; the presence of a titer; history of stillborns.

With GBP, due to hemolysis of erythrocytes, an increase in the optical density of bilirubin in the amniotic fluid occurs.

Cordocentesis - Puncture of the umbilical cord of the fetus. Fetal blood is examined for group and Rh affiliation, hemoglobin and hematocrit levels, bilirubin.

Cardiotocography - Daily fetal monitoring.

Intrauterine intravascular blood transfusion to the fetus. Indications: hemoglobin and hematocrit 15% or more in relation to the gestational norm. Use erythrocyte mass 0 (I) group Rh - with a shelf life of not more than 24 hours.

Often in the first few days after birth, the baby's skin begins to rapidly turn yellow. This phenomenon is familiar to neonatologists, who immediately prescribe an examination of the baby and appropriate treatment.

However, not all young parents know how to properly respond to such a symptom and why it is dangerous for the child. Consider what the diagnosis of hemolytic disease means, what are the causes of jaundice and what should parents of a newborn do?

What is hemolytic disease and why is it dangerous?

Hemolytic disease is a rather serious condition of a newborn, in which a massive breakdown of red blood cells called hemolysis is noted in the baby's blood. Scientists explain this phenomenon by the difference in the composition of the blood of mother and child.

There are several varieties of this disease, but the most dangerous condition is caused by the incompatibility of the blood according to the Rh factor. This problem occurs in almost one hundred percent of cases in women who have a negative Rh. If the disease develops due to the difference in the blood groups of the mother and baby (according to the AB0 system), its course is less complicated.

More often, hemolytic disease of the newborn is manifested by a change in skin color - it acquires a yellow tint. However, this is only one of the symptoms of the development of the disease. The most dangerous manifestations can only be determined by the results of laboratory tests, ultrasound, dopplerography, reflex disorders.

A mild form of the disease can pass without consequences, however, it also requires the intervention of a specialist. If moderate to severe hemolytic jaundice in newborns is not treated, the baby may die. To date, there is a fully developed mechanism for the prevention and treatment of this dangerous condition, and therefore the scenario of the disease is favorable in most cases.

Causes of the disease in newborns

Why does pathology occur? Consider its main reasons. All people have a certain blood group. There are four of them - 0, A, B and AB (in domestic medicine, the designations I, II, III, IV are used). The group is assigned based on the composition of the blood in which antigens are present.

In addition to antigens, in the blood of most of the Caucasian population of the planet (about 85%) there are special erythrocyte proteins (D antigens) that determine the Rh factor. If this protein is not found in a patient, his blood belongs to the Rh-negative group.

The composition of the blood in a newborn may differ from the parent (according to genetic probability). If the mother and fetus have a different group or Rh factor, prerequisites for an immunological conflict arise.

What is this contradiction? The woman's body perceives the blood cells of the fetus as alien to him and begins to fight them, producing antibodies. These particles enter the baby's bloodstream through the placenta.

The described process can begin as early as the 8th week of pregnancy, when the Rh factor and blood type are formed in the fetus. However, more often the mass penetration of antigens through the placenta occurs at the time of delivery. As a result, the baby in the blood begins the process of disintegration of red blood cells - hemolysis.

Such a breakdown of red blood cells causes the accumulation in the tissues of the child's body of a bile pigment - bilirubin, which provokes damage to vital organs - the liver, spleen, and bone marrow. This component of bile is especially dangerous because it can penetrate the blood-brain barrier and disrupt the brain.

In addition, hemolysis significantly reduces the level of hemoglobin in the blood, and the baby develops anemia. Anemia is a rather dangerous condition for a newborn, as it contributes to oxygen starvation of tissues and organs.

The mismatch of blood according to the ABO system (that is, according to the group) usually does not lead to serious consequences. However, if during pregnancy a woman had ARVI, influenza or other infectious diseases, this increases the permeability of the placenta, which leads to the development of dangerous forms of the disease.

According to statistics, the disease often occurs in babies who do not match the Rh factor with maternal blood. However, some experts are sure that the immunological conflict in the ABO system is not a rare phenomenon, only its symptoms can be blurred and the diagnosis is often not made.

Classification and symptoms of hemolytic disease of the newborn

As we mentioned, hemolytic disease has several varieties. More precisely, there are four of them.

Let's take a closer look at these types:

1. The icteric form of hemolytic disease is especially common in newborns. This is a moderate severity type of the disease. It is characterized by the appearance of initial symptoms only on the next day after birth. The child is born with normal skin color and no visible pathologies. Then the skin of the baby acquires a yellowish tint, which gradually becomes brighter. The child may have depressed reflexes, enlarged liver, spleen.
2. Nuclear jaundice or bilirubin encephalopathy is a dangerous intoxication of the brain. The disease occurs with delayed therapy of the icteric type of the disease. Nuclear jaundice occurs in two stages. The initial phase is characterized by a relaxed posture of the baby, weak reactions to stimuli. The skin becomes bluish, convulsions occur, the baby's eyes are wide open (we recommend reading:). The next stage is spastic. The child is screaming, his muscles are tense, his breathing is ragged. This disease can lead to cerebral palsy, deafness, speech disorders.
3. The anemic form is the most harmless. In this condition, the child has reduced hemoglobin in the blood, the baby is lethargic, weakened, and sucks poorly at the breast. This type of disease occurs in every 10 sick newborn and has a favorable scenario.
4. The edematous variety is the most dangerous case of the disease. A child is born with characteristic edema in all cavities of the body - the heart sac, the pleural region, and the abdominal cavity. The skin has a yellow tint, with pronounced pallor. The liver and spleen are enlarged, a blood test shows deep anemia (we recommend reading:). These symptoms can lead to heart failure and death while still in the womb or immediately after birth.

All varieties of the disease have similar symptoms - yellowing of the skin, dark urine, lethargy of the child. However, the most accurate diagnosis can be made only on the basis of laboratory tests.

Diagnostic methods

Diagnosis of the disease is carried out at the stage of intrauterine development of the fetus and after birth. Consider the methods of natal and postnatal diagnosis.

If the mother's blood is Rh negative, even during pregnancy, the doctor collects data to draw up a picture of possible pathologies. A lot of information is taken into account: incompatibility of the blood of parents, abortions, miscarriages, previous births of the mother.

At least three times during pregnancy, a woman has a titer of anti-Rhesus antibodies. Alarming symptoms - spasmodic values, their stable growth, as well as a decrease in levels shortly before delivery - may indicate the penetration of antibodies through the placenta.

If there is a risk of immune conflict, the doctor prescribes a study of amniotic fluid (bilirubin, protein, iron, glucose levels, etc. are determined). The results of ultrasound and Dopplerography are certainly taken into account - thickening of the placenta, polyhydramnios, blood flow velocity in the cerebral artery, etc.

Postnatal diagnosis is made on the basis of an examination of the infant after birth. This is the presence of jaundice, control of bilirubin in dynamics, erythroblastosis, hemoglobin levels in the blood, etc. All indications are considered as a whole. The immunological conflict in the ABO system, despite a favorable prognosis, also requires the attention of a doctor.

Differential diagnosis is carried out with conditions such as hereditary hemolytic jaundice, sepsis, hemorrhages, which can cause anemia. Cytamegalovirus infections and toxoplasmosis are also screened out.

Jaundice in newborns can be purely physiological in nature. Its occurrence is due to insufficient maturity of liver enzymes and the replacement of hemoglobin cells. As soon as the enzymes begin to be produced in the right amount, the baby's skin color takes on a normal shade. The described condition does not require treatment.

In difficult cases, blood transfusion is indicated, which is done to the fetus in utero or after birth. Other ways to eliminate symptoms are hemosorption (passing blood through special filters) and plasmapheresis (removal of plasma containing toxins from a limited volume of blood). However, exchange transfusion and other interventions have clear indications:

• if indirect bilirubin in the cord blood exceeds 60 µmol / l or grows at a rate of more than 10 similar units per hour;
• the hemoglobin level in the baby is critical - less than 100 g / l;
• jaundice appeared immediately after birth or in the first 12 hours.

It should be remembered that blood transfusions often carry complications, most of which are associated with a violation of the technique of the procedure. Only fresh blood, stored for no more than 2 days, and a low transfusion rate are used. In addition, it is important that the red cell mass is close to body temperature in order to avoid cardiac arrest.

Also, newborns who are in serious condition are given glucocorticoids. This therapy is possible within a week after childbirth.

Babies with milder symptoms are treated conservatively. As a rule, this is:

• in / in the introduction of glucose, protein;
• the use of liver enzyme activators;
• the appointment of absorbents that help bind and remove toxins from the body;
• the use of vitamins and drugs that stimulate the liver and accelerate metabolic processes in the baby's body.

All children with signs of yellowing of the skin are prescribed phototherapy. This procedure involves exposing the skin to crumbs of fluorescent light (white or blue). Such activities remove indirect bilirubin from the body, transforming it into water-soluble substances.

Also, phototherapy is carried out in order to prevent the occurrence of hyperbilirubinemia, if there was fetal hypoxia, and violations of thermoregulation. Often the procedure is prescribed for premature babies.

You can start lactation with hemolytic disease only after the permission of the attending physician. As a rule, attachment to the breast is carried out only three weeks after birth. During this period, antibodies are completely removed from the mother's milk, but for now the baby is fed with a mixture or donor milk.

Vaccinations, which are customary to do in the hospital, with jaundice can be postponed. In particular, BCG is done a little later.

Consequences of hemolytic disease for a child

The consequences of hemolytic disease of the newborn may be absent altogether, and may be quite significant. It all depends on the form of the disease, as well as on the timeliness and adequacy of therapy. When diagnosing a mild form of hemolytic disease, by the end of the second week, all indicators of the child's health return to normal. Subsequently, the baby will grow and develop well according to his age.

If the level of bilirubin exceeded the critical values ​​​​of 340 μmol / l, negative consequences are possible in the future. The short-term include the development of a nuclear form of the disease, when the baby's brain suffers from toxins. This form can lead to various mental disorders, the development of cerebral palsy, hearing loss.

The development of the nuclear form can be judged by the rigidity of the muscles at the back of the head, the protrusion of the fontanel, muscle twitching, and signs of suffocation. There are also other symptoms of this condition that neonatologists are aware of.

High levels of bilirubin may affect later. According to statistics, every third child with similar symptoms is diagnosed with neuropsychiatric disorders. In this regard, babies with a severe form of hemolytic disease after stabilization of the condition are registered with a neurologist, ophthalmologist and pediatrician.

Some of the children require a long period of rehabilitation, while others need only a couple of months for the final recovery. However, the observation of specialists is shown by both.

Preventive actions

Preventive measures include special monitoring of the condition of a pregnant woman who is at risk.

Patients with a negative Rh factor are subject to separate registration in the antenatal clinic.

The following events are being held:

1. History taking - previous pregnancy blood transfusions, miscarriages, stillborn babies, abortions. This information will help assess the likely level of antigens in the patient's blood. The most vulnerable of them are those who have already given birth or with a history of abortions, since in these cases the body is already ready to “resist” and the likelihood of an immune conflict is high.
2. In critical cases, the doctor recommends an injection of anti-Rhesus immunoglobulin to suppress the production of antibodies. Such an injection will prevent problems with a new pregnancy.
3. Systematic monitoring of the blood of a pregnant woman for the presence of Rh antibodies. If their concentration increases, the patient is referred for preventive treatment.
4. Often the doctor prescribes the stimulation of labor after the 36th week of pregnancy. Premature birth is caused due to the high risk of hemolytic disease of the newborn, since it is in the last month of bearing a child that the permeability of the placenta increases and the exchange of blood cells between mother and child is activated.

- an intrauterine immunological conflict caused by the incompatibility of the blood of the fetus and mother for a number of antigens, which leads to hemolysis of the child's erythrocytes under the influence of maternal antibodies that overcome the placental barrier. Hemolytic disease of the fetus can occur in edematous, icteric, anemic form and even lead to intrauterine death of the fetus. In the diagnosis, a study of amniotic fluid (amniocentesis), cord blood, bilirubin and hemoglobin in a newborn is carried out. Treatment of hemolytic disease of the fetus requires phototherapy, intravenous infusion of solutions, exchange transfusion.

General information

The pathogenetic basis of hemolytic disease is the processes caused by immunological (antigen-antibody) incompatibility of the blood of the fetus and mother. In this case, the antigens present in the blood of the fetus are inherited from the father, and there are no antigens in the mother's blood. Most often (1 case per 250 pregnancies), fetal hemolytic disease develops with a conflict over the Rh factor; can also occur with group incompatibility of blood and other less studied antigens. Hemolytic disease of the fetus in 3.5% of cases leads to perinatal mortality.

With hemolytic disease of the fetus, under the influence of maternal antibodies that are formed to fetal antigens and penetrate the placenta, the child develops hemolysis of erythrocytes and inhibition of hemipoiesis. The toxic effect of the breakdown products of erythrocytes on the body of the fetus (newborn) leads to the development of anemia, an increase in bilirubin and blast (immature) erythrocytes.

Causes of fetal hemolytic disease

An immunological conflict leading to hemolytic disease of the fetus most often develops with isoserological incompatibility of blood according to the Rhesus (Rh) system, when the mother has Rh-negative blood, and the fetus is Rh-positive. In this case, it is called the Rhesus conflict. Isoimmunization in this case can occur in two ways: iatrogenic (when a woman was sensitized by transfusions of Rh (+) blood in the past) or with the fetal-maternal transplacental transfer of fetal erythrocytes into the maternal circulation during pregnancy and childbirth. In the case of Rh incompatibility, hemolytic disease of the fetus is rarely associated with the first pregnancy; more often develops from the 2nd or 3rd pregnancy with increasing risks with each subsequent gestation.

Another possible cause of hemolytic disease is the incompatibility of the blood of the fetus and mother according to the AB0 system, that is, with the mother's blood type 0 (I), and the fetus has any other. At the same time, antigens A and B from the fetus cross the placenta into the maternal circulation and cause the production of immune α- and β-antibodies, followed by an antigen-antibody conflict. Hemolytic disease of the fetus with ABO incompatibility has a milder course than with Rh incompatibility. With AB0 incompatibility, hemolytic disease of the fetus may develop already during the 1st pregnancy.

In relatively rare cases, fetal hemolytic disease can be associated with immunological conflicts in the Duffy, Kell, MNSs, Kidd, Lutheran, etc. systems or P, S, N, M antigens.

Manifestations of fetal hemolytic disease

In pregnant women, a specific pattern of pathology is not observed; sometimes an increase in intrauterine reactions can cause a symptom complex in a woman similar to preeclampsia. Hemolytic disease of the fetus can manifest itself in the following ways: intrauterine fetal death in the period from 20 to 30 weeks of pregnancy; edematous, icteric or anemic forms. Common manifestations characteristic of all forms of fetal hemolytic disease are the presence of normochromic anemia with an increase in erythroblasts in the blood, hepatomegaly and splenomegaly.

With the edematous variant of hemolytic disease in the fetus, the size of the spleen, liver, heart, glands increases, hypoalbuminemia increases. These changes are accompanied by a pronounced swelling of the subcutaneous fat, ascites, pericarditis, pleurisy, an increase in the weight of the child by 2 times compared to the norm. With the edematous variant of hemolytic disease of the fetus, there is a pronounced anemia (Er -1-1.5 x 1012 / l, Hb 35-50 g / l), erythroblastemia, an increase and swelling of the placenta. Severe metabolic disorders can cause intrauterine fetal death or death of the child shortly after birth. The edematous form of hemolytic disease of the fetus is distinguished by an extremely severe course, which in most cases leads to death.

With the icteric variant of hemolytic disease of the fetus, the child is more often born from urgent delivery, full-term, more often with normal skin color. In this case, fetal hemolytic disease manifests itself several hours after birth - the child's icteric coloration of the skin rapidly increases; less commonly, jaundice is congenital. In newborns with an icteric form of hemolytic disease, the spleen, liver, lymph nodes, and sometimes the heart are enlarged, and there is an intense increase in indirect bilirubin in the blood.

Hyperbilirubinemia is dangerous with the possibility of damage to hepatocytes, cardiomyocytes, nephrons, neurons with the development of bilirubin encephalopathy. With nuclear jaundice (bilirubin intoxication), the child is lethargic, sucks poorly, often burps, he develops hyporeflexia, vomiting, convulsions. The critical level of indirect bilirubin, which is dangerous in terms of CNS damage, is more than 306-340 µmol/l in full-term babies and 170-204 µmol/l in premature babies. The consequence of bilirubin encephalopathy may be the death of a child or a subsequent lag in mental development.

In the anemic form of hemolytic disease, the damaging effect on the fetus is usually small. Anemia, pallor of the skin, hepatomegaly and splenomegaly come to the fore. The severity of manifestations of hemolytic disease of the fetus is determined by the antibody titer in the pregnant woman and the degree of maturity of the newborn: the disease is more severe in premature babies.

Diagnosis of hemolytic disease of the fetus

Given that hemolytic disease is often accompanied by hypoxia, cardiotocography is performed with an assessment of fetal cardiac activity. In the case of obtaining data for hemolytic disease of the fetus, invasive studies are required - cordocentesis and amniocentesis under ultrasound control. At the birth of a child, its Rh and group affiliation are immediately determined, the content of Hb and bilirubin in the umbilical cord blood is examined.

Treatment of fetal hemolytic disease

Therapeutic tasks for hemolytic disease of the fetus are the rapid removal of toxic factors of hemolysis from the child's blood - indirect bilirubin and antibodies, as well as an increase in the functions of suffering systems and organs. The choice of delivery method for women with isoimmunization is determined by the condition of the fetus, gestational age, and the preparedness of the birth canal. In the absence of data for a severe form of hemolytic disease of the fetus, at a gestational age of more than 36 weeks, the maturity of the cervix, natural childbirth is possible. In severe condition of the fetus, a caesarean section is preferable 2-3 weeks before the expected date.

In newborns with hemolytic disease of the fetus, Hb, Ht, and bilirubin are monitored daily. If necessary, correction of anemia with erythrocyte mass, infusion detoxification therapy is carried out. An important component of the treatment of hemolytic disease of the fetus is phototherapy, which contributes to the destruction of indirect bilirubin in the skin of the child. Light therapy is carried out in pulsed or continuous mode using fluorescent or blue light lamps.

With more severe manifestations of fetal hemolytic disease, intragastric drip and exchange transfusion are indicated. In case of fetal hemolytic disease caused by Rh-conflict, single-group Rh (-) blood is used for exchange transfusion. In case of incompatibility according to ABO, the erythrocyte mass of group 0 (I) is transfused in accordance with the Rh-belonging of the newborn and single-group plasma. The development of pulmonary edema and severe respiratory failure requires mechanical ventilation; the presence of ascites dictates the need to perform laparocentesis under ultrasound control.

Prevention of fetal hemolytic disease

It consists in the prevention of Rh-immunization of women - careful blood transfusion, taking into account Rh-affiliation. Women with Rh (-) blood are categorically not recommended to terminate a pregnancy that has come for the first time. The method of specific prevention of Rh-conflict in women with Rh (-) blood is the introduction of immunoglobulin anti-Rhesus Rho human after abortion, delivery of Rh (+) fetus, ectopic pregnancy, as well as after invasive prenatal diagnosis - chorion biopsy, amniocentesis, cordocentesis.

Hemolytic disease of the fetus and newborn (HDN)

ICD 10: P55

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

ID: KR323

Professional associations:

• Russian Association of Perinatal Medicine Specialists

Approved

Russian Association of Specialists in Perinatal Medicine 2016

Agreed

Scientific Council of the Ministry of Health of the Russian Federation __ __________ 201_

newborn

phototherapy

blood transfusion surgery

kernicterus

fetal dropsy

rhesus - isoimmunization of the fetus and newborn

ABO - isoimmunization of the fetus and newborn

List of abbreviations

AG? antigen

HELL? arterial pressure

ALT? alanine aminotransferase

AST? aspartate aminotransferase

AT? antibody

BE? bilirubin encephalopathy

HDN? hemolytic disease of the newborn

GGT? gamma-glutamyl transpeptidase

ICE? disseminated intravascular coagulation

KOS? acid-base state

ICD? international classification of diseases -10

ABOUT? total bilirubin

OZPK? exchange transfusion surgery

NICU? neonatal intensive care unit

bcc? circulating blood volume

PITN - resuscitation and intensive care unit for newborns

FFP - fresh frozen plasma

FT? phototherapy

BH? breathing rate

heart rate? heart rate

AP? alkaline phosphatase

hb? hemoglobin

IgG? immunoglobulin G

IgM? immunoglobulin M

Terms and Definitions

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

1. Brief information

1.1 Definition

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

1.2 Etiology and pathogenesis

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

Prior isosensitization due to abortion, miscarriage, ectopic pregnancy, childbirth, in which the mother's immune system produces antibodies to erythrocyte antigens, predisposes to the entry of fetal erythrocytes into the mother's bloodstream and the occurrence of an immunological conflict in cases of antigenic incompatibility for blood factors. If antibodies belong to class G immunoglobulins (subclasses IgG1, IgG3, IgG4)? they freely cross the placenta. With an increase in their concentration in the blood, the likelihood of developing hemolytic disease of the fetus and newborn increases. Antibodies of the IgG2 subclass have a limited ability of transplacental transport, antibodies of the IgM class, which include α- and β-agglutinins, do not cross the placenta.

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

1.3 Epidemiology

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

1.4 ICD 10 codes

Hemolytic disease of the fetus and newborn(P55):

P55.0 - Rhesus isoimmunization of fetus and newborn

P55.1 ABO fetal and newborn isoimmunization

P55.8 Other hemolytic disease of fetus and newborn

P55.9 Hemolytic disease of fetus and newborn, unspecified

1.5 Classification

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

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

1.5.2 According to clinical manifestations, the forms of the disease are distinguished:

edematous (hemolytic anemia with dropsy);

icteric (hemolytic anemia with jaundice);

anemic (hemolytic anemia without jaundice and dropsy).

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

medium severity;

severe degree.

1.5.4 According to the presence of complications:

bilirubin encephalopathy: acute damage to the central nervous system;

kernicterus: irreversible chronic damage to the central nervous system;

bile thickening syndrome;

hemorrhagic syndrome.

2. Diagnostics

2.1 Complaints and medical history

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

Rh - affiliation and blood type of the mother;

infections during pregnancy and childbirth;

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

the presence of jaundice in parents;

the presence of jaundice in a previous child;

weight and gestational age of the baby at birth;

feeding the baby (underfeeding and/or vomiting).

2.2 Physical examination

Edematous form of HDN

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

Icteric form of HDN

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

Anemic HDN

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

Complications of HDN

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

2.3 Laboratory diagnostics

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

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

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

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

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

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

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

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

2.4 Instrumental diagnostics

• An abdominal ultrasound is recommended;

• Neurosonography is recommended.

2.5 Other diagnostics

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

blood for ELISA (for the presence of infection);

blood for PCR (for the presence of infection);

coagulogram;

bacteriological examination of blood.

3. Treatment

3.1 Conservative treatment

Comments:Features of PT in HDN:

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

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

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

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

Eyes and genitals should be protected with opaque material;

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

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

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

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

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

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

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

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

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

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

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

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

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

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

3.2 Surgical treatment

Comments:Indications for OZPK:

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

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

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

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

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

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

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

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

Volume calculation for OZPK

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

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

Example: a child weighing 3 kg.

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

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

Actual volume of EM

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

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

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

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

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

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

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

4. Rehabilitation

• It is recommended to carry out rehabilitation measures:

neonatal care;

exclusive breastfeeding;

medical withdrawal from preventive vaccinations for 1 month.

5. Prevention and follow-up

5.1 Prevention

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

• Recommended:

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

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

Additional factors that increase the risk of developing bilirubin encephalopathy:

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

Criteria for assessing the quality of medical care

Bibliography

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Annex A1. Composition of the working group

Antonov A.G. ?

Aronskind E.V. ?

Baybarina E.N. ?

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

Degtyarev D.N. ?

Degtyareva A.V. ?

Kovtun O.P. ?

Mukhametshin F.G. ?

Parshikova O.V. ?

Doctor - Neonatology;

Physician-Anesthesiology-Resuscitation;

Doctor-Pediatrics.

Methods used to collect/select evidence:

search in electronic databases.

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

Methods used to assess the quality and strength of evidence:

expert consensus;

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

Table P2 - Levels of persuasiveness of recommendations

Good Practice Points (GPPs):

Economic analysis:

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

External peer review;

Internal peer review.

Annex A3. Related Documents

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

Nomenclature of medical services (Ministry of Health and Social Development of the Russian Federation) 2011.

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

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

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

Appendix B. Patient Management Algorithms

Management of children with HDN over 24 hours of age:

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

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

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