Hemolytic disease of the newborn. What is this? Hemolytic disease of the fetus and newborn (HDN). Clinical guidelines Hemolytic disease of the newborn according to the AVO system

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

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

THE CONCEPT OF HEMOLYTIC DISEASE OF THE NEWBORN (HDN)

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

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

The mechanism of development of HDN

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

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

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

REASONS FOR THE DEVELOPMENT OF HEMOLYTIC DISEASE

Hemolytic disease: causes of conflict in the Rhesus system

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

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

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

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

Hemolytic disease: causes of conflict in the AB0 system

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

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

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

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

FORMS OF HDN AND THEIR CLINICAL FEATURES

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

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

Dropsy fetus

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

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

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

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

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

anemic form

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

edematous form

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

HDN according to the AB0 system: clinical features:

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

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

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

HEMOLYTIC DISEASE: CONSEQUENCES AND COMPLICATIONS

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

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

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

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

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

HEMOLYTIC DISEASE OF THE NEWBORN: TREATMENT AND PREVENTION

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

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

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

The prescribed infusion therapy (albumin, physiological saline, glucose solution) is aimed at removing bilirubin intoxication and promptly removing bilirubin from the body.

Medications (zixorin, etc.) are used that activate the enzyme system of the liver. Adsorbents are used (carbolene, agar-agar, etc.), choleretic (by electrophoresis), vitamins (E, ATP, A), stabilizing cell membranes, hepatoprotectors (Essentiale, etc.), antihemorrhagic agents (adroxon, etc.).

Zaluzhanskaya Elena, pediatrician

Hemolytic disease of the newborn is a severe condition in the fetus or newborn that occurs as a result of an immune conflict.

This conflict arises due to the incompatibility of the blood of the fetus and his mother for some antigens. Such antigens can be different blood types or the Rh factor of the fetus and mother.

As a result, fetal erythrocytes are attacked by maternal antibodies that cross the placental barrier, leading to their hemolysis (the cells burst).

Manifestations of hemolytic disease of newborns can be of varying degrees and forms, but are always dangerous for the health and life of the baby, up to his death in the womb.

Therefore, when risk factors and pathology of the course of pregnancy are identified, the fetus and mother are carefully monitored, and if the mother has a negative Rh factor, special preparations are administered to her - anti-Rh globulins.

Hemolytic disease of the newborn: causes

The causes of hemolytic disease of the newborn can be immunological conflicts that develop in the presence of:

• incompatibility of the blood of the mother and fetus by the Rh factor. This usually happens if the mother has Rh-negative blood, and the fetus inherits the father's positive Rh factor. This condition in medicine is called Rh-conflict. It usually occurs with repeated pregnancies, or if a woman has previously had blood or red blood cells transfused with a Rh factor that is not her own. The accumulation of antibodies goes from pregnancy to pregnancy (even if it was an abortion or miscarriage), and the risks increase if adequate therapy is not carried out.
• incompatibility of the blood of the mother and fetus by blood type, if the mother has the first blood type, and the fetus has any other. It does not proceed as hard as with Rh incompatibility, it can occur during the first pregnancy. Special antibodies of the mother, directed to the erythrocytes of the fetus, penetrate into the blood of the child.
• rare variants of incompatibility for different antigens on the surface of fetal erythrocytes that are not associated with a blood group or Rh factor.

How will it manifest?

During pregnancy, there are no special manifestations, symptoms similar to preeclampsia may appear. But for the fetus, hemolytic disease of the newborn can manifest itself in the following variants:

• intrauterine death after 20 weeks or more due to the attack of maternal antibodies on fetal tissues
• anemic form
• icteric form
• edematous form of the disease.

Hemolytic disease of newborns by blood type does not fundamentally differ from that by the Rh factor in the clinical course, but the manifestations will not be so bright and severe, and the prognosis will be more positive.

The main manifestations that occur with all forms of fetal hemolytic disease are severe anemia, an enlarged liver and spleen of the child, which significantly disrupts its normal metabolism.

In the edematous form of the disease, the liver and spleen, all glands and the heart are sharply enlarged, the amount of protein in the blood is reduced, the skin and subcutaneous tissue swell strongly, in the abdomen and chest, fluid also accumulates in the heart sac, which leads to an increase in the weight of the baby by two and a half. more times.

It is the edematous form that occurs most severely due to sharp disruptions in the functioning of all organs and systems, severe tissue hypoxia due to a very low number of red blood cells and hemoglobin, damage to the nervous system, which often leads to the death of the baby shortly after birth.

The icteric variant is easier, the child is born on time and with normal weight, the skin is also of normal color, but after a few hours the child begins to turn yellow sharply, congenital jaundice may be less common.

The spleen and liver, heart and lymph nodes increase, the level of toxic bilirubin in the blood increases sharply.

Such a level of bilirubin damages the cells of the liver and heart, kidneys, but it is especially dangerous for the brain, manifesting itself as encephalopathy and kernicterus.

The brain is literally saturated with bilirubin and stained yellow.

Children are lethargic and eat poorly, spit up heavily and do not gain weight, they have reduced reflexes, convulsions and vomiting are possible.

The critical level of bilirubin will be above 340 µmol, if the child is not full-term, the level of bilirubin that damages the brain will be even lower for him.

The consequences of such a condition can be dangerous - from the death of a baby to severe neurological disorders and developmental delays in the future.

The anemic form is the easiest, with pallor of the child, enlargement of the liver and spleen and poor suckling, weight gain and a lag in physical and mental development.

At the same time, it is worth remembering that the more antibodies to fetal erythrocytes in the mother's blood, the more serious the prognosis for the child will be. The diagnosis is sometimes made even at the stage of pregnancy, and they prepare in advance to help the baby immediately after his birth.

Hemolytic disease of the newborn: treatment

The main tasks in the treatment of hemolytic disease of the newborn is the removal from the blood of maternal antibodies that destroy the cells of the baby and metabolic products that are toxic - bilirubin and others.

In addition, you need to actively increase the level of hemoglobin and the number of red blood cells, support the work of internal organs.

Usually, if HDN is suspected:

• They decide on the date and method of delivery, in case of a serious condition of the fetus, an emergency caesarean section is performed to save his life. This is especially important with a large mass of the fetus due to edema, it simply cannot be born naturally.
• The baby is measured daily for hematocrit, bilirubin and hemoglobin levels.
• If necessary, enter the erythrocyte mass of only your blood group.
• put droppers with nutrients (glucose solution with B vitamins, saline solution, ringer's solution) and detoxification solutions (hemodez, polyglucin). An equally important part of the treatment in the presence of jaundice will be phototherapy under a lamp, which helps in the destruction and removal of bilirubin from the child's skin. The baby is placed under the lamp several times a day for a strictly limited time, watching for reactions. A special bandage is worn to protect the eyes from UV rays. Radiation breaks down toxic bilirubin in the skin and excretes it in the urine.
• In severe manifestations of hemolytic disease of the newborn, it will be necessary to conduct a probe drip of nutrient fluids (glucose, protein solutions, albumin, saline) into the child's tummy with an exchange transfusion. This is a complete replacement of the child's own blood with single-group blood for the entire volume through the vessels of the navel. In case of Rh-conflict, in case of exchange transfusion, single-group blood is used, Rh-negative, and in case of incompatibility by blood group, erythrocytes of the first blood group are transfused in accordance with the child's Rh and single-group blood plasma of the child.
• If the child is in serious condition, he is placed in a pediatric intensive care unit and connected to ventilators and all necessary measures for treatment and nursing are carried out.

Hemolytic disease of the newborn: consequences

The consequences of hemolytic disease of the newborn may be different depending on the severity of the pathology.

Severe forms of HDN can subsequently lead to severe physical and mental developmental delays, up to the development of cerebral palsy.

Mild forms of pathology can leave behind mental retardation or mental retardation, impaired movement function, strabismus and hearing loss.

Children with past TTH do not tolerate vaccines well, are prone to develop severe allergies, and often and for a long time can get sick with infectious diseases.

In order to reduce the risk of such complications during pregnancy, in women with a negative Rh factor, strict monitoring of the level of antibodies and the introduction of special anti-Rh immunoglobulins to them at certain stages of pregnancy (usually in the third trimester of pregnancy and immediately in childbirth) is necessary.

Hemolytic disease of the newborn is one of the most common causes of life-threatening jaundice and anemia in newborns. This diagnosis in the Russian Federation occurs in 0.83% of newborns. Even in our time, when this disease is thoroughly studied, the mortality rate in the occurrence of kernicterus against the background of HDN is 2.5%.

To prevent the development of severe complications, all pregnant women must be observed by a doctor without fail. Increased attention is paid to women with Rh-blood, 1st blood group and HDH in past births.

Hemolytic disease of the newborn is a severe, life-threatening pathology, manifested by isoimmune anemia with erythrocyte decay, which has developed due to the immune incompatibility of maternal blood and the child's blood.

For an incompatibility conflict to arise, the presence in the maternal blood of highly specific antibodies that work against the missing erythrocyte D-antigens (Rh-factor) is necessary. Incompatibility develops in a third of patients with HDN and is called Rh-erythroblastosis.

Hemolytic disease also occurs due to the incompatibility of maternal and fetal blood according to the ABO system. Conflict on antibodies to blood groups is called ABO-erythroblastosis and occurs in two-thirds of patients.

For reference. Incompatibility for other erythrocyte-antigen systems of Kell, Duffy, Kid, etc. rare and difficult to diagnose.

How is the D antigen inherited?

In order for hemolytic disease to occur, maternal blood must be Rh-negative, and paternal blood must be Rh+.

An Rh+ male can have a homozygous (DD) or heterozygous (DD) set of Rh system genes.

In a homozygous male, all children will have + Rh (100% heritability of the D-antigen).

In a heterozygous male, seventy-five percent of the children will be Rh + and twenty-five percent -.

Hemolytic disease of the newborn according to the Rh system

According to the presence of the Rh factor, all patients are divided into Rh + and -.

The Rh or D antigen is a lipoprotein with a complex structure of antigens. It is located only on the inner surface of the erythrocyte membrane. The presence of D-antigens on erythrocyte membranes indicates that the patient's blood is Rh +. Rh negative people do not have the D antigen.

D-antigen can only contain erythrocyte membranes, it cannot be in other cells and tissues of the body. Also, a person does not have his own, natural antibodies to the Rh antigen.

The processes of differentiation of the D-antigen begin in the fetus at the fifth week of development. The maximum activity of the Rh factor is observed by the fifth or sixth month. Immunization of the mother's Rh-negative blood (formation of anti-O-antibodies) occurs when Rh+ erythrocytes enter the Rh-blood.

However, several antigenic stimuli are required to generate an immune response. That is, isoimmunization (the formation of anti-O-antibodies) during the first pregnancy is possible only in 2% of cases.

As a rule, after birth from a Rh - mother Rh + child, the mother's body is initially sensitized. This occurs as a result of the process of micro-transfusion into the negative blood of the mother, the positive erythrocytes of the child.

Micro-transfusion is enhanced by abortions, placental abruption, preeclampsia of pregnancy, inflammatory diseases accompanied by impaired placental permeability, etc. All these factors increase the penetration of Rh+ erythrocytes into the maternal blood and increase the formation of anti-O-antibodies directed against them.

Fetal damage develops when a sufficient amount of anti-O-antibodies enter the fetal blood, causing hemolysis (destruction).

Each subsequent pregnancy increases the maternal specific immune response and increases the risk of Rh hemolytic disease of the newborn.

During the 1st pregnancy, a Rh conflict is possible if the woman is already immunized as a result of a transfusion of Rh- or ABO-incompatible blood.

Hemolytic disease of the newborn is the result of a mother's immune response to her own fetus.

How does hemolysis happen?

After erythrocytes are damaged by antibodies, they are broken down in the liver and spleen.

Primary hemolysis is extravascular. As a result of this process, hemoglobin from decayed erythrocytes does not enter the bloodstream, but is transformed by tissue macrophages into a bile pigment - bilirubin.

Important! Intravascular hemolysis begins with severe HDN and is considered an extremely poor prognostic indicator.

HDN in Rh conflict. Causes

The risk of Rh incompatibility increases with each subsequent pregnancy.

The occurrence of HDN contributes to the presence of a woman:

• one or more abortions;
• spontaneous interruptions (miscarriages);
• pregnancy and childbirth Rh + fetus;
• blood transfusions;
• placental abruption, gestosis and severe infectious and inflammatory pathologies in the history of the mother;
• infection of amniotic fluid;
• organ and tissue transplants;
• HDN during previous births.

Hemolytic disease of the newborn by blood group

For the development of group incompatibility, the mother must have group 0 (1st blood type), and the baby has the second (A) or third (B) group.

Most often, incompatibility occurs in mothers with the first (0) and fetus with the second (A) group. Antigen B and β-agglutinins of the third group have significantly less antigenic activity than antigen A and α-agglutinins.

Hemolytic disease of the newborn is detected in 0.6% of newborns. The disease belongs to the immunological pathology, since it is associated with an antigenic conflict between the blood of the mother and the fetus.

It has been established that the main antigens are found in erythrocytes. One of them - the Rh factor (Rh factor) - was called the D-antigen. It causes incompatibility in 1/3 of cases. In other cases, the disease is determined by the antibodies of the AB0 system, which are responsible for the formation of the blood group.

Causes

Incompatibility of maternal Rh-negative blood with the fetal erythrocyte antigen occurs when Rh-positive properties are transferred to him through the father's line. The mother's body perceives them as foreign and aggressively reacts with the formation of antibodies. Another name is Rh-erythroblastosis. In total, there are about 15% of Rh-negative people on the globe. The trait is inherited by girls and boys. It is dangerous only for the female and the fetus during pregnancy, provided that the father of the child is in the Rh-positive group.

A stronger immune response develops with a second pregnancy, even if the first ended in an abortion

During a second pregnancy with a Rh-positive fetus, a small amount of antigens causes complications in the form of preeclampsia, placental abruption, and inflammatory diseases. Foreign antibodies penetrate the placental barrier with the destruction of red blood cells, hemolysis.

The role of the AB0 group system matters if the mother has the first blood group (0), and the fetus has formed the second (A in 90% of cases) or the third (B in 10%), rarely in the fourth group (AB). Immunization is different:

• Individuals with group I always have antibodies to A and B-immunoglobulins, but in this case they acquire aggressive properties for unclear reasons. The conflict manifests itself already during the first pregnancy. Premature infants do not have RBC hemolysis because A and B antigens mature later.
• Communication with fetal erythrocytes is established in the prenatal period. Hemolysis threatens only part of the cells, so the manifestation is less aggressive for the newborn.

A conflict on other antigenic structures is possible, but it is rarely determined and with great difficulty.

What changes occur in the child's body?

The pathogenesis (development) of the disease is caused by the retention of damaged erythrocytes in the cells of the liver and spleen, their hemolysis in these organs. Insufficient maturity of the liver tissue is expressed in the absence of the necessary enzyme (glucuronyl transferase). It is responsible for neutralizing the toxic bile pigment indirect bilirubin and converting it to bilirubin-glucuronide (indirect).

As a result, the released hemoglobin does not enter the bloodstream, but is processed to the level of direct bilirubin and accumulates in the blood. This type of destruction of red blood cells is called extravascular. An intravascular reaction is possible in severe hemolytic disease in the fetus.

Classification

The existing forms of the disease are divided depending on the time of occurrence into:

• congenital;
• postnatal (appeared after childbirth).

By severity, depending on the need for replacement blood transfusions:

• easy - treatment does without transfusions;
• moderate - it is possible to normalize the indicators after one replacement transfusion;
• severe - 2 or more replacement transfusions are needed.

Depending on the nature of the flow:

• acute - the disease occurs after a short period (hours, days) after the penetration of antibodies from the mother to the fetus;
• subacute - more often observed immediately 3 days before childbirth;
• subchronic - with congenital intrauterine damage, occurs in the early stages of pregnancy.

What determines the severity of the reaction?

The severity of fetal damage depends on the period of introduction of antibodies through the placenta:

• if they were received during pregnancy, congenital forms of the disease appear in the form of a macerated fetus, the birth of a child with an already existing clinical variant of the disease;
• with a reaction during childbirth - a typical postpartum jaundice develops.

The baby has a high degree of prematurity with maceration of the skin, a possible cause is incompatibility with maternal antibodies

In addition, the aggressiveness and severity of immune damage differ in:

• different amounts of antibodies that have penetrated from the mother's body to the fetus, the concentration is determined by the presence of acute and chronic diseases in the mother, contributing to the increase in the permeability of the placental barrier;
• high or low compensatory ability of the fetus (premature babies suffer more from severe forms).

Probable clinical manifestations

Options for signs of hemolytic disease can be:

• fetal death in the period from the twentieth to the thirtieth week of pregnancy due to a violation of intrauterine development;
• the birth of a baby with general edema;
• early development in the newborn period of severe jaundice or anemia.

There are three main forms of hemolytic disease in newly born children:

• anemic,
• icteric,
• edematous.

For all forms, a common symptom is the development of normochromic anemia (anemia), the appearance in the blood of early forms of erythrocytes (normoblasts, erythroblasts), reticulocytosis, enlargement of the liver and spleen.

The periods of the course of the disease are divided into:

• acute - the first days of a newborn;
• restorative - after normalization of the level of bilirubin in the blood;
• residual events.

Usually, the course of AB0 incompatibility is milder than with Rh incompatibility. The edematous form is very rare, and the anemic and icteric forms are not severe. But with AB0-hemolytic disease, a variant of the development of intravascular hemolysis in combination with DIC is possible.

Anemic form and its clinic

The anemic option is the easiest of all possible. It is observed in one fifth of children. Its cause is the minimum amount of penetrating antibodies with a short effect on the fetus. The damage caused is small, the placenta returns the products of processing of erythrocytes to the mother's body.

After birth, the baby may not have jaundice if his liver is functioning well. The main symptoms appear at the end of the first week of life:

• pale skin;
• enlarged liver and spleen;
• in the blood test, in addition to general manifestations, a low amount of hemoglobin, erythropenia, the appearance of erythrocyte cells of various sizes and shapes are found.

Recovery is quickly achieved by fractional portions of transfusion of Rh-negative blood.

A sick baby has lethargy, loss of facial expressions

Features of the icteric form

It has been proven that the icteric form appears when antibodies act on the fetus at the end of pregnancy. The body weight of the newborn is not disturbed, the birth takes place on time, the skin color of the newborn begins to change in the first day of life. Rarely, a baby is born with yellow skin, colored amniotic fluid and lubrication.

Symptoms:

• jaundice is rapidly increasing;
• an enlarged liver and spleen are determined;
• enlarged lymph nodes are palpated;
• the expansion of the boundaries of the heart is rarely determined;
• the content of bilirubin in the blood from the umbilical cord rises to 51 µmol/l and above (at a normal level of about 28 µmol/l), for every hour its concentration increases by 3.4 µmol/l.

Indirect bilirubin primarily damages liver cells (hepatocytes), myocardial muscle tissue, and selectively destroys neurons. Without treatment, intoxication will reach its maximum damaging level in a day or two. Neurological symptoms of bilirubin encephalopathy (brain damage) appear:

• lethargy increases;
• the baby sucks poorly, refuses to eat, often burps;
• vomit;
• less often, from the fourth day of life, tonic convulsions are noticed;
• the symptom of rigidity in the occipital muscles is determined;
• disorders of the oculomotor muscles, downward deviation of the eyeballs, the appearance of a strip of sclera between the upper edge of the eyelid and the cornea (a symptom of the "setting sun");
• changes in respiration of a central nature (decrease, rhythm disturbance, asthma attacks with cyanosis of the skin);
• decreased innate reflexes.

Bilirubin affects the nervous system at a level of indirect fraction in a full-term baby of 306-340 µmol/l, in case of prematurity - 170-204. It has been established that blood plasma albumins are involved in the development of severe icteric form. They are able to bind excess bilirubin, significantly increase the critical level of exposure to the brain. In case of albumin deficiency, the lesion easily spreads to different organs and tissues.

Excess bilirubin is deposited in the renal tubules and blood vessels. This contributes to the development of kidney infarction.

The affected liver interferes with the production of protein, blood clotting factors. Therefore, there is a drop in the level of prothrombin and an increase in bleeding time. Increased secretion of bilirubin into bile makes it thicker, which contributes to the development of obstructive jaundice. The stool becomes discolored. Bile pigments are determined in the urine.

Bilirubin encephalopathy is detected on the third or sixth day after birth.

It is customary to distinguish between the phases of the flow:

• with predominant signs of intoxication - loss of appetite, lethargy, loss of muscle tone, inactivity, yawning, vomiting and profuse regurgitation;
• signs of jaundice inside the nuclei of the brain - spastic convulsions, tension of the occipital muscles, bulging of a large fontanel above the surface of the skull, trembling of the hands, loss of the sucking reflex, nystagmus of the eyeballs, short-term cessation of breathing, a tendency to bradycardia, lethargy;
• imaginary well-being - in the second week of life, spastic tension in the muscles disappears, neurological symptoms are less pronounced;
• complications - possible at the age of three to five months, the child manifests paralysis, paresis, deafness, convulsions.

Death due to bilirubin encephalopathy occurs 36 hours after birth. Surviving children are physically and mentally retarded, have depressed immunity, which is why they often suffer from infectious diseases, pneumonia, and suffer from sepsis when the infection spreads.

Edema form and its manifestations

For the formation of an edematous form, the effect on the fetus of the mother's antibodies must be long-term. The fetus does not die immediately, because it adapts to the removal of antibodies back to the mother's body, forms foci of additional hematopoiesis. The spleen and liver are significantly enlarged, cardiac hypertrophy is observed, endocrine glands are activated. Hypoalbuminemia leads to increased vascular permeability and the release of plasma into the intercellular space.

This leads to fluid accumulation in:

• subcutaneous tissue;
• pleural cavity;
• abdominal cavity;
• pericardium.

At the same time, the mass of the fetus and placenta increases sharply (almost 2 times). Anemia is significantly pronounced: hemoglobin drops to 35–50 g/l, and erythrocytes decrease to 1 x 10 12/l, there are many blast forms in the blood. These violations are the cause of fetal death before the onset of labor or immediately after. The edematous form is considered the most severe manifestation of hemolysis.

How to detect fetal disease?

To determine the risk of having a child with signs of hemolytic disease, analyze:

• the condition of the expectant mother, the presence of chronic diseases;
• compatibility with the father of the child by Rhesus;
• the course of previous pregnancies;
• information about previous blood transfusions.

In diagnosis, it is important to know and take into account information about:

• aggravated course of previous pregnancies;
• miscarriages;
• the birth of a dead child;
• mental and physical retardation in the development of existing children.

Women with risk factors are taken to a special account in antenatal clinics, they are recommended special studies before the expected pregnancy

Be sure to determine the antibodies in Rh-negative women. When they are detected, prophylaxis is carried out with the help of a specific anti-Rhesus gamma globulin, which weakens the aggressive properties.

The disease of the fetus is determined by the study of amniotic fluid extracted by amniocentesis (puncture of the uterus). The diagnosis is assumed by the increased specific gravity, the presence of bilirubin.

For the treatment of a newborn, it is important to make a diagnosis immediately after birth.

When suspected, the following are carried out:

• tests for antibodies in a Rh-negative mother by Rh and blood groups (if the mother has the first group);
• determination of the group and Rh of the newborn.

About hemolytic disease they say:

• type of baby
• coloration of the skin, amniotic fluid and lubrication;
• enlarged liver and spleen of a newborn.

In an unclear state, umbilical cord blood is most valuable for the study of a child, changes are detected in it before other signs

If the cord blood was not taken, then in the first 24 hours the hourly increase in bilirubin is estimated. A rapid increase indicates the severity of the disease.

With negative tests of the mother for Rh and group incompatibility, if there are signs of hemolytic disease in the child, treatment of the baby is started, and other possible antibodies are examined in the mother.

What diseases should be distinguished from hemolytic disease?

In differential diagnosis, it is necessary to compare symptoms, biochemical and clinical manifestations with possible diseases accompanied by jaundice and elevated bilirubin:

• congenital disorders of the erythrocyte structure;
• insufficiency of liver enzymes;
• thalassemia;
• disseminated intravascular coagulopathy;
• endocrine hyperbilirubinemia (congenital family syndromes), decreased function of the thyroid gland, pituitary gland.

The diagnosis necessarily takes into account the intake by the nursing mother of drugs that block the functioning of the child's liver:

• sulfonamides,
• antibiotic novobiocin,
• vitamin K.

Contribute to the jaundice of the child:

• maternal diabetes mellitus with acidosis;
• any kind of hypoxia;
• increase in indirect bilirubin without hemolysis;
• cytomegaly;
• toxoplasmosis;
• congenital hepatitis;
• sepsis;
• syphilis.

Modern treatment

Treatment of hemolytic disease of the newborn requires the speedy removal of toxic products of hemolysis and antibodies that caused the reaction from the child's body. In addition, the baby needs protection of organs and systems, stimulation and support for the functioning of the liver and kidneys.

The most effective method is the transfusion of fresh blood, 150–180 ml per 1 kg of body weight. In case of Rh incompatibility, one-group Rh-negative blood is shown. In the event of a conflict in the AB0 system, group I erythrocytes diluted with group IV plasma are transfused. The sooner a transfusion is started, the greater the chance of removing the affected red blood cells and limiting hemolysis with damage to the liver, brain, and spleen.

In the case of a severe anemic form (with a hematocrit of up to 35%), transfusion through the umbilical vein begins half an hour after birth. A catheter is installed in a vein, 10 ml of blood is taken from it and the same amount of donor blood is infused. The procedure lasts up to three hours. After every 100 ml of replacement, the child is given a solution of calcium chloride, 10 ml of glucose.

At the same time, detoxification is required: liquid inside through the esophageal tube, intravenous administration of glucose, plasma, albumin.

Without the support of the acid-base composition of the blood, the introduced preservatives (citrates) can cause cardiac arrest. Therefore, it is better to use donor blood with alkalizing solutions.

Pediatricians during treatment monitor the baby's blood coagulation. The attitude to the use of Heparin is different. Some authors believe that an undesirable consequence of this drug is an increased level of fatty acids, which can act like bilirubin.

To improve the function of liver cells, Phenobarbital, a solution of magnesium sulfate, xylitol, sorbitol, ATP, Methionine are used. Prednisolone is used in a course of 7 days.

The child is given duodenal sounding to eliminate bile stasis.

Feeding is carried out using donor milk that does not contain antibodies. Be sure to intramuscularly injected vitamins E, B, C. Symptoms of damage to the nervous system require the use of vitamin B 12.

The phototherapy technique (exposure to a blue light lamp) allows you to enhance the oxidation of bilirubin and turn it into a non-toxic compound. Sessions are held 12 hours a day for no longer than a week.

In phototherapy, eye protection, measurement of body temperature, excretion and administration of fluid, determination of hematocrit are mandatory

Monitoring of blood parameters should be carried out after the child is discharged from the maternity hospital up to two months of age every 2 weeks.

Forecast and consequences

With timely treatment of children with hemolytic disease, their development does not suffer. If the content of bilirubin in the blood was at a critical level and no complete treatment was carried out, then death occurs in the first days of life. Surviving children have negative consequences in the form of:

• disturbed psyche;
• lag in physical and mental development;
• impaired speech;
• hearing loss.

Further treatment was unsuccessful. Children from time to time undergo a course of rehabilitation in the departments of nursing care.

Disability is established, the child needs constant care

With residual focal disorders of the brain, course restorative therapy is carried out: massage, B vitamins, Aminalon and other nootropic drugs inside.

Prevention options

If a high risk is detected by history and the content of antibodies in the blood, a woman is observed by specialists from the perinatal center. It is possible to remove or reduce the state of sensitization:

• in the last decade of pregnancy - with the help of "replanting" the skin of the father of the child;
• immediately after delivery (in the first 72 hours) - the introduction of anti-rhesus gamma globulin.

This prophylaxis should also be carried out in case of unsuccessful childbirth, abortion.

An increase in the content of antibodies in the blood is an indication for hospitalization of a woman and early delivery (2 weeks earlier).

Modern centers have the ability to carry out intrauterine blood replacement of the fetus. Prevention methods are possible only with a conscious approach of the mother and father to the health of their offspring. Any unwillingness of the future mother to take blood tests, come to the obstetrician-gynecologist or go to the hospital is fraught with stillbirth, severe complications in the development of children.

Hemolytic disease of the newborn (another name for erythroblastosis) occurs against the background of incompatibility of maternal blood with the blood of the fetus for a number of factors. The disease is very serious, since it often develops even in the prenatal period and can take on various forms, but the result of a neglected state is the same - hemolysis of red blood cells and death of the fetus (or newborn).

Hemolysis of erythrocytes is the destruction of the membrane of red blood cells with the release of hemoglobin into the plasma. By itself, this process is normal, because after 120 days it ends the life cycle of the erythrocyte. However, if, under certain circumstances, pathological destruction occurs, the entire mechanism of the circulatory system goes astray. Released hemoglobin in large quantities when released into the plasma is a poison, because it overloads the body with a high content of bilirubin, iron, etc. In addition, it leads to the development of anemia.

If too much bilirubin is released in a toxic form, the organs involved in its conversion and excretion suffer.

Free bilirubin from the blood enters the liver, where it is conjugated, in other words, neutralized. But when there is a lot of it, the liver simply does not have time to process a large amount. As a result, the neurotoxic form of this special pigment migrates from one organ to another, slowing down oxidative processes and causing destructive changes in tissues and organs at the cellular level, up to their destruction.

At concentrations above 340 µmol/l, bilirubin passes through the blood-brain barrier, changing brain structures. For premature babies, a concentration of 200 µmol / l is sufficient. This is how bilirubin encephalopathy develops, poisoning the brain and leading to subsequent disability.

The so-called extramedullary hematopoiesis is also inherent in the disease - processes in which blood is formed not in the tissues of the bone marrow, but in other organs: the liver, spleen, and lymph nodes. Because of this, there is an increase in the aforementioned organs, along with a lack of such important trace elements as zinc, cobalt, iron and copper. Erythrocyte decay products "settle" in the cells of the pancreas, kidneys and other organs.

Reasons for the development of hemolysis

The cause of the progression of hemolytic disease of the newborn, as a rule, is the incompatibility of the blood of the mother and baby due to the Rh factor or due to the ABO conflict. But even with such established genetic combinations (we will now consider the essence of the problem in detail), hemolysis of erythrocytes occurs in no more than 6 cases out of 100. This means that it makes sense to fight for the life of a child, and effective methods of treatment exist. Let's talk in more detail about common blood incompatibilities.

ABO conflict

As you know, according to the ABO system, there are 4 combinations that make up 4 blood groups. So, if the mother has O (I) blood type, and the unborn child has II or III, an “antigen-antibody” immunoconflict is possible. Although it is generally accepted that "hostility" according to the ABO system occurs more often than Rh conflict, hemolytic disease of the newborn in this case is much easier, and sometimes barely noticeable, so it is not always diagnosed.

Rh conflict

The Rh factor can be either positive or negative and is designated Rh+ and Rh- respectively. The presence or absence of this factor (some antigen D on the surface of erythrocytes) does not affect the health of its owner and life itself, with the exception of the only situation: if we are not talking about a woman with a negative Rh who has married and wants to have children from a Rh-positive father. Then the risk of complicated pregnancies and gestation increases.

Rh-conflict manifests itself when a woman has Rh-negative blood, and her unborn child has Rh-positive blood. Why such enmity? The moment Rh-positive fetal blood enters the bloodstream of an Rh-negative mother, the woman's immune system sets off an alarm about the intrusion of "strangers" because her body is not familiar with the Rh system protein. Antibodies are produced, aimed at destroying the "enemy", which turns out to be ... the blood of your own child!

The first pregnancy is usually uneventful, because the mother's immune system is not yet sensitized and antibodies are produced in small quantities. But there are situations in which the risk of Rhesus conflict is high. These include:

• second and subsequent births (each time the risk of conflict increases);
• ectopic pregnancy;
• the first pregnancy ended in miscarriage or abortion;
• transfusion of previously Rh-positive blood, and the statute of limitations does not play any role.

There are situations when mother and child become "blood enemies"

The consolation is that 85% of white people are Rh positive.

The nature of the disease and symptoms

There are several forms of hemolytic disease of the newborn:

1. anemic. The most favorable in relation to the severity of the disease, since it has a minimal damaging effect on the fetus. Anemia, as a rule, is not diagnosed immediately, but only 15-20 days after birth. The skin turns pale, the level of unbound bilirubin is increased, but in general the child's condition is satisfactory and responds well to treatment.
2. edematous. The most severe variant of the course of the disease, occurring in 2% of cases. Development begins in the womb and often ends with the death of the child. If he manages to survive, the condition is very serious: anemia is pronounced, the boundaries of the heart, spleen, liver and other organs are enlarged, there is a deficiency of albumin. The body weight of the newborn is 2 times higher than the norm. Subcutaneous fat is edematous, a child is often born with pleurisy, pericarditis, ascites.
3. icteric. Occurs against the background of bilirubin intoxication and is characterized by a rich icteric skin tone, which is visible immediately at birth or after 24 hours. By how quickly the jaundice manifested itself, the severity of the disease is judged. The birth of a baby most often occurs from premature birth. In the case of the formation of nuclear jaundice, convulsions, vomiting, frequent regurgitation are observed, the newborn is lethargic, the sucking reflex is poorly developed. With bilirubin encephalopathy, the central nervous system suffers, which subsequently affects the mental development of the baby.

Diagnostics

When registering a pregnant woman, her blood type and Rh factor are first determined. Future mothers with a negative Rh are under special, close attention of obstetricians. The same examination is carried out by the future father. The woman is asked in detail about previous pregnancies, how they proceeded, whether there were miscarriages, abortions, etc.

A pregnant woman must be examined on time and take the necessary tests.

In Rh-negative mothers, blood is taken at least three times during pregnancy to determine the titer of anti-Rh antibodies. If there is a suspicion of an immunoconflict, an amniocentesis is performed (a method for examining amniotic fluid), thanks to which data are obtained on the optical density of fetal bilirubin and the concentration of other elements). Sometimes they resort to cordocentesis.

When conducting an ultrasound examination, special attention is paid to the possible thickening of the placenta, the rate of its growth, the presence of polyhydramnios, ascites, expansion of the boundaries of the liver and spleen. All this together may indicate swelling of the placenta and the development of hemolytic disease. And conducting cardiotocography allows you to assess cardiac activity and identify possible hypoxia.

After birth, the diagnosis of the disease is based on visible manifestations (jaundice of the integument, anemic conditions) and on these test results over time. For example, the content of bilirubin and hemoglobin in cord blood, the presence (or absence) of erythroblasts are assessed.

Treatment

The main goal for hemolytic manifestations is antitoxic therapy, that is, the removal of toxic substances from the baby's body, in particular, free bilirubin.

Phototherapy is very effective. The method is based on observations that under the influence of daylight, yellowness of the skin (a sign of hyperbilirubinemia) is significantly reduced due to the breakdown and excretion of unconjugated bilirubin.

For the procedure, fluorescent lamps with blue, white and blue-white light are used. When prescribing phototherapy sessions, not only the bilirubin level is taken into account, but also the body weight, as well as the age of the newborn. During the session, the baby is either in a special heated bed or in an incubator. Every 8-12 hours, blood is taken for laboratory control of bilirubin.

After the start of the widespread use of phototherapy, the need for exchange blood transfusion decreased by 40%, the time for nursing children with jaundice was reduced, and complications became an order of magnitude smaller.

Treatment also includes the normalization of the liver by introducing vitamins of group B, E, C, cocarboxylase. They improve metabolic processes. Cholagogue drugs help fight bile thickening, and cleansing enemas and the use of activated charcoal slow down the absorption of bilirubin in the intestine. General detoxification infusion therapy is carried out.

Phototherapy is a very effective method in the fight against neonatal jaundice.

In severe situations (the development of anemia), treatment is carried out promptly, with the help of an exchange transfusion of blood or its components, for example, erythrocyte mass. This takes into account the Rh-affiliation of the fetus.

Can I breastfeed?

Previously, breastfeeding of children in the presence of a Rh conflict or hemolytic disease was prohibited, later the child was allowed to breastfeed only 2 weeks after birth. It was believed that anti-Rhesus antibodies contained in milk could harm the baby. Now it has been proven that when they enter the gastric tract, they are destroyed by hydrochloric acid and enzymes, therefore they cannot enter the bloodstream, and, therefore, they cannot harm.

Forecasts

It is difficult to say how hemolytic manifestations will affect the child in the future, it all depends on the severity of the development of the disease. In the most unfavorable cases, there is a subsequent developmental delay, cerebral palsy in various manifestations. In simpler situations, the hepatobiliary system suffers due to the high load on it, the baby is prone to allergies, special reactions to vaccination, strabismus, and hearing problems may develop.

Prevention

Preventive measures can be divided into two stages.

When a woman is not sensitized

That is, her Rh-negative blood had not previously encountered Rh-positive antigens. Such a mother should be in awe of her first pregnancy, as she has the highest chances of a favorable outcome. She is strongly discouraged from having abortions and blood transfusions. In the third trimester, a blood test is done several times to detect antibodies.

When a woman is sensitized

During the first 24 hours after the first birth and the birth of an Rh-positive baby, immunoglobulin is injected, the purpose of which is to prevent the formation of Rh antibodies in the mother's blood. A similar procedure is also done after:

• ectopic pregnancy;
• abortion;
• transfusions of Rh-positive blood;
• specific diagnosis in the fetus: amniocentesis, chorionic biopsy, cordocentesis.

Another option for prevention is specific hyposensitization. Its essence is as follows: a skin flap from the husband (Rh +) is transplanted to the wife (with Rh -) and then the antibodies “switch” their attention to the graft, thereby reducing the likelihood of hemolysis of the fetal erythrocytes.

As you can see, hemolytic disease has serious consequences. For this reason, it is extremely important for a woman with Rh-negative blood to remember her Rh status and take a responsible approach to motherhood and childbearing. If the obstetrician-gynecologist says that you need to pass additional tests, it is better to do this so that the situation does not get out of control. Equally important is timely treatment. Then the risk of developing erythrocyte hemolysis with all the ensuing consequences will be minimized.