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Intrauterine blood transfusion to the fetus: how is the procedure performed and why is it dangerous for the child? Indications for phototherapy are. Can risk be avoided?

Fetal Blood Transfusion (Intrauterine Transfusion; IUT; Intraperitoneal Transfusion; IPT)

Description

A blood transfusion is performed when a baby who is still in the womb suffers from severe anemia. Anemia is a lack of red blood cells (erythrocytes). When the child's blood test shows too low of them, a blood transfusion will be required. A transfusion means giving a child red blood cells from a donor.

There are two types of blood transfusion for the fetus:

intravascular blood transfusion(VSPK) is carried out through the mother's abdomen into the umbilical cord of the fetus - the most common procedure;
intraperitoneal blood transfusion(VBPK) is carried through the mother's abdomen and uterus in abdominal cavity fetus - usually performed only if VSPK cannot be done due to the position of the baby and the umbilical cord.

Reasons for fetal blood transfusion

A fetal blood transfusion is done if the baby in the womb suffers from severe anemia and could die without a blood transfusion. Anemia can be caused by:

Rh incompatibility - the mother and child have a different type of blood, the mother's antibodies lyse (destroy) the blood cells of the fetus;
Parvovirus B19 - viral infection at mother.

Purpose of blood transfusion:

Prevention or treatment of fetal hydrops before childbirth. Dropsy causes severe anemia in the fetus, and he develops heart failure. This leads to the accumulation of fluid in the skin, lungs, abdomen or heart area;
To prevent premature birth.

Possible complications of intrauterine blood transfusion

Possible complications for the mother and fetus include:

The need for an urgent caesarean section after the procedure;
premature rupture membranes and/or premature birth
graft-versus-host disease in the fetus (a rare disorder in which the donor's blood cells attack the baby's cells);
bruising or tenderness in the abdomen;
Bleeding, spasms, or leakage of fluid from the vagina;
Infection;
fetal injury;
Injection of too much blood;
Fetal bleeding.

You should discuss these risks with your doctor before the procedure.

How is intrauterine blood transfusion performed?

Preparation for the procedure

To make sure the fetus has severe anemia or hydrops fetalis, the doctor may order some tests:

Amniocentesis - a sample of amniotic fluid is taken;
Cordocentesis - collection of blood from the umbilical cord;
Ultrasound examination - a test that uses sound waves to study the internal organs;
If dropsy is found in the fetus, a blood transfusion will be done immediately.

Before transfusion, it may be prescribed:

The introduction of an anesthetic;
Intravenous injection of muscle relaxants.

Anesthesia

Applies local anesthesia, which will anesthetize a small area of \u200b\u200bthe abdominal cavity.

Description of the intrauterine blood transfusion procedure

During the VSPK, the fetus will be paralyzed for a short time. This is necessary to ensure access to the fetal vessels and reduce harm to the fetus. During both WSP and PBP, the doctor will monitor the fetus with an ultrasound. Ultrasound will be used to:

Show the position of the fetus;
Guide the needle through the amniotic cavity to the vessel in the umbilical cord;
Show fetal heart rate.

The doctor inserts a needle into the abdomen. Using an ultrasound, the doctor will verify that the needle is inserted correctly. The needle will be passed through the mother's abdomen and inserted into the umbilical cord or into the abdomen of the fetus. The fetus is then given a blood transfusion.

Before the needle is removed, the doctor will take a blood sample from the fetus. This is necessary to determine the fetal hematocrit. The doctor will determine if one transfusion was enough or if the procedure needs to be repeated.

The transfusion may need to be repeated every 2 to 4 weeks until the doctor determines the baby is safe.

How long will intrauterine blood transfusion take?

An intravascular transfusion of 10 ml of blood will take 1-2 minutes. Usually during one procedure 30-200 ml of blood is transfused.

Will transfusion harm mother and baby?

You will feel pain and muscle spasm where the doctor inserts the needle. If childbirth is coming soon, or if the procedure takes a long time, then the uterus will be inflamed.

Average time in hospital

This procedure is carried out in a hospital. After the transfusion, you can go home. If complications arise, a caesarean section may need to be performed.

Care after fetal blood transfusion

The doctor may provide:

antibiotics to prevent infection;
Medicines to prevent uterine contractions or childbirth.

Be sure to follow your doctor's instructions.

When your baby is born, he immediately needs to do a blood test. The doctor will monitor the child closely to prevent:

Anemia
liver damage;
congestive heart failure;
Respiratory failure;
Other complications if the baby was born prematurely.

Communication with a doctor after a fetal blood transfusion

After discharge from the hospital, you should consult a doctor if the following symptoms appear:

signs of infection, including fever or chills;
redness, swelling, increased pain, bleeding, or discharge from the needle insertion site;
You do not feel that the child is moving normally;
waste amniotic fluid(a sign of childbirth);
Other signs of labor onset:
Uterine contractions;
Back pain that comes and goes
Vaginal bleeding.

Hyperbilirubinemia does not have a significant effect on the condition of the fetus, since the mother's liver takes on the function of neutralizing the resulting bilirubin. Hyperbilirubinemia is dangerous for the newborn.

According to autopsies of fetuses who died from hemolytic disease, a characteristic dropsy with abdominal distention and severe subcutaneous edema is observed. Severe anemia is always noted with a predominance of immature forms of erythrocytes. At autopsy, ascites, excessively enlarged liver and spleen are found; their lower poles may reach the iliac crest. In both organs, pronounced extramedullary erythropoiesis is noted, a large number of erythroblasts. All this leads to a violation of normal anatomy. The cavities of the heart are usually dilated, the muscular wall is hypertrophied. Along the coronary vessels, foci of erythropoiesis can be found. Hydrothorax is often detected. In the lungs, plethora is found and big number erythroblasts. The kidneys may have marked erythropoiesis, but they are usually normal sizes. The bone marrow shows polycythemia. characteristic view and in the placenta: pronounced edema, an increase in size. Its mass often reaches 50% of the mass of the fetus. The placenta and membranes are more or less stained in yellow due to bile pigments secreted by the kidneys of the fetus. In the villi of the chorion - edema, stromal hyperplasia, an increase in the number of capillaries.

Despite the well-known picture pathological changes, the chronology of the process is not entirely clear. At first it was believed that dropsy was a consequence of heart failure that developed against the background of severe anemia and hypervolemia of the fetus, but now it has become known that liveborn children with dropsy have neither significant ventricular failure nor hypervolemia. More new point view is that fetal ascites is the result of hypertension in the portal and umbilical veins due to enlargement and anatomical changes in the liver. Due to erythropoiesis, hypoproteinemia develops in the liver tissue as a result of liver failure and the inability of the edematous placenta to ensure the normal transfer of amino acids and peptides. This, in turn, leads to an increase in ascites and subsequent generalized edema. With the development of the cordocentesis technique, it became possible to understand the pathophysiology of dropsy. Indeed, hypoproteinemia and hypoalbuminemia are often found in affected fetuses, and in fetuses with dropsy this is an obligatory finding. These data prove that hypoproteinemia plays a major role in the genesis of fetal dropsy. It was revealed that dropsy does not develop until the level of hemoglobin in the fetus decreases to less than 40 g/l. The average level of hematocrit in dropsy is 10.2%.

The breakdown of red blood cells, damage to the function of the kidneys, liver and brain of the fetus occur as a result of exposure to incomplete antibodies passing to the fetus from the mother. When exposed to incomplete antibodies, capillary thrombosis and ischemic tissue necrosis develop. In the fetal liver, protein synthesis decreases, hypo- and dysproteinemia occurs, as a result, plasma oncotic pressure decreases, vascular permeability increases, swelling and anasarca increase. When erythrocytes are destroyed, thromboplastic factors are released, DIC develops, microcirculation is disturbed, and deep metabolic disorders in the fetus occur.

Hemolytic disease often develops in a newborn due to the massive influx of maternal antibodies into his bloodstream during birth, before the umbilical cord is cut.

In the first hours after birth, toxic indirect bilirubin accumulates in the tissues of the child. In cages nervous system the processes of cellular respiration are disrupted (bilirubin encephalopathy), resulting in the death of a child or persistent neurological disorders (deafness, blindness) that persist for life.

Diagnosis of hemolytic disease of the newborn

Immediately after the birth of a child, he is determined:

blood group;

Rh factor;

hemoglobin (normal - 38.4 g / l);

the number of erythrocytes (normal - 6.0 10 | 2 / l);

To determine the blocking (complete) antibodies, an indirect Coombs test is performed, which makes it possible to identify the newborn's erythrocytes associated with antibodies; an hourly increase in bilirubin, an increase in its content over 5.13 μmol / l in 1 hour indicates an increase in the severity of jaundice.

Hemolytic disease of the newborn is characterized by a rapid increase in anemia, jaundice, the content of indirect toxic bilirubin and its rapid hourly increase. The newborn has lethargy, hyporeflexia, decreased tone, decreased sucking reflex, and apnea.

The essence of hemolytic disease of the fetus is hemolysis of red blood cells, anemia, bilirubin intoxication. Due to the breakdown of erythrocytes under the influence of anti-rhesus antibodies of the mother, there is an increase in toxic indirect bilirubin. The liver loses the ability to convert indirect bilirubin into direct bilirubin, which dissolves in water and is excreted from the body by the kidneys. Hypoxia develops, severe intoxication.

Forms of hemolytic disease of the newborn

There are three forms of hemolytic disease:

hemolytic anemia.

Hemolytic anemia associated with jaundice.

Hemolytic anemia with jaundice and dropsy.

Let us briefly consider these clinical forms, which reflect the severity of the disease.

Hemolytic anemia- most mild form diseases. The newborn has a reduced hemoglobin level and the number of red blood cells. The skin is pale, there is a slight increase in the liver and spleen. The content of hemoglobin and bilirubin may be at the lower limit of the norm or slightly lower.

The anemic form of hemolytic disease is the result of exposure to a small amount of Rh antibodies on a full-term or almost full-term fetus (37-40 weeks).

Isoimmunization of the fetus occurs more often in childbirth. Anemia is the leading sign of mild injury.

Hemolytic anemia associated with jaundice- more frequent and severe form of the disease. The main symptoms are: hyper- or normochromic anemia, jaundice and hepatosplenomegaly. In these cases, icteric staining of the amniotic fluid occurs, skin, primordial lubricant, umbilical cord, placenta and fetal membranes. The content of indirect bilirubin is more than 50-60 µmol/L. The condition of the newborn gradually worsens, convulsive twitches, nystagmus, and hypertonicity appear.

At rapid rise an hourly increase in bilirubin by 5-10 times develops "nuclear jaundice", indicating damage to the central nervous system, when blindness, deafness, and mental disability can occur. The hemoglobin content is below 38 g/l.

The icteric form occurs when antibodies act on mature fruit short time. Decompensation of protective and adaptive mechanisms does not occur, the fetus is born viable.

After birth, jaundice and intoxication with indirect bilirubin develop rapidly. Often join infectious complications(pneumonia, respiratory distress syndrome, omphalitis). After 7 days of life, the pathogenic effect of antibodies that have penetrated into the blood of the fetus stops.

Hemolytic anemia associated with jaundice and dropsy- the most severe form of the disease. Newborns are usually either stillborn or die in the early neonatal period. Clinical symptoms diseases are: anemia, jaundice and general edema (ascites, anasarca), severe splenomegaly. Often hemorrhagic syndrome develops.

The penetration of maternal antibodies through the placenta does not always occur, the severity of the fetal lesion does not always correspond to the titer (concentration) of Rh antibodies in the blood of a pregnant woman.

part Rh negative women due to the pathology of pregnancy and placental insufficiency, Rh antibodies enter the fetus during pregnancy. In this case, fetopathy occurs: a congenital form of hemolytic disease of the newborn (edematous, icteric), the birth of macerated fetuses. In full-term fetuses hemolytic disease newborns occurs ten times more often than in preterm infants. This indicates an increase in the transport of isoantibodies through the placenta before and during childbirth.

With the edematous form of hemolytic disease of the newborn, there are pronounced signs of immaturity even in full-term newborns. In the abdominal, pleural cavities, in the pericardial cavity contains a large amount of fluid, in the tissues of the liver, kidneys, spleen, various hemorrhages. The spleen is enlarged by 5-10 times, the thymus gland is reduced by 50%, the liver is enlarged by 2 times, signs of hypoplasia are expressed in the lungs.

The immediate cause of death of newborns in the edematous form of hemolytic disease is severe dystrophic changes in vital organs, the impossibility of spontaneous breathing.

Edematous form of hemolytic disease of the newborn develops with repeated exposure during pregnancy moderate amount Rh antibodies. The main sign of tissue reactions is the development of compensatory-adaptive processes, the variety and severity of which increase with time. intrauterine life fetus (increase in the size of the heart, liver, spleen, lymph nodes).

In this regard, despite the ongoing re-penetration of isoantibodies, the fetus survives, but it develops dystrophic processes in organs and tissues, and the development of the lungs and kidneys is impaired. Due to the high vascular permeability, edema appears, the weight of the fetus does not correspond to the gestational age and is increased by 1.5-2 times. A fetus born alive most often dies.

Intrauterine fetal death with maceration during isoimmunological conflict occurs in sensitized women with a massive breakthrough of the placental barrier to antibodies at 26-28 weeks of gestation. The immaturity of the organs and systems of the fetus causes the rapid development of dystrophic processes and necrotic changes, and the fetus dies. At a later date (34-36 weeks), the action of a very large amount of antibodies leads to the same outcome.

Treatment of fetal hemolytic disease

Currently, for the treatment of hemolytic disease of the fetus, intrauterine blood transfusions under ultrasound control. Fetal blood transfusions can be performed from 18 weeks of gestation. Intrauterine blood transfusion creates preconditions for prolongation of pregnancy. There are intra-abdominal and intravascular methods of blood transfusion.

The technique of intra-abdominal transfusion consists in puncturing the abdominal wall of the mother, the wall of the uterus, the abdominal wall of the fetus and introducing into its abdominal cavity a single-group and Rh-negative erythrocyte mass, which is adsorbed by the lymphatic system and reaches vascular system fetus.

Preference is given to intravascular blood transfusion to the fetus, the indications for which in case of Rh sensitization are severe anemia and a hematocrit of less than 30%.

In order to conduct intravascular hemotransfusion, cordocentesis is performed. The vein of the umbilical cord is punctured in the immediate vicinity of its entry into the placenta. The conductor is removed from the needle and blood is taken to determine the hematocrit of the fetus. The erythrocyte mass is slowly injected through the needle, after which a second blood sample is taken to determine the final fetal hematocrit and assess the adequacy of the therapy. To stop the movements of the fetus, as a result of which the needle can be pushed out of the vein of the umbilical cord, the fetus is injected with arduan (pipecuronium) intravenously or intramuscularly. Determination of the need and timing of subsequent blood transfusions to the fetus is based on the results of ultrasound, post-transfusion hemoglobin and hematocrit in the fetus.

The transfused components enter directly into the bloodstream of the fetus, which can save his life in case of a serious illness.

Intra-abdominal transfusion should be performed only if the gestational age is less than 22 weeks or intravascular transfusion is difficult. In the plasma taken during cordocentesis, the concentration of fetal hemoglobin, blood type and fetal karyotype are determined. It is clear that the fetus Rh negative blood hemolytic disease associated with incompatibility for antigens of the Rhesus group will not develop.

Treatment of hemolytic disease of the newborn

To date, from the standpoint of evidence-based medicine, methods of treating hemolytic disease of the newborn are effective:

replacement blood transfusion;

phototherapy;

intravenous administration of standard immunoglobulins.

Exchange transfusion. Exchange transfusion of blood to a newborn is based on the removal of Rh antibodies and bilirubin. An increase in the titer of antibodies in the mother during pregnancy to 1:16 and above should alert the neonatologist regarding hemolytic disease in the newborn. A particularly unfavorable fact is the decrease in antibody titer before childbirth, which indicates the risk of their movement to the fetus.

A severe form of hemolytic disease can be assumed in the presence of icteric staining of the skin, cheesy lubrication, placenta, amniotic fluid, swelling and enlargement of the fetal liver.

Risk factors for bilirubin encephalopathy include:

low body weight of the newborn (less than 1500 g);

hypoproteinemia (content total protein less than 50 g/l);

hypoglycemia (glucose content less than 2.2 mmol/l);

anemia (hemoglobin less than 140 g/l);

the appearance of jaundice in the first 12 hours of life; intrauterine infection fetus.

Indications for replacement blood transfusion:

the appearance of jaundice immediately after childbirth or in the first hours of life;

rapid hourly increase in bilirubin in the first hours of life 6.8 mmol / l);

low hemoglobin level (below 30 g/l). For exchange transfusion, one-group or 0(1) group Rh-negative red blood cells and plasma [single-group or AB(IV)] are used.

In case of conflict in the AB0 system, the erythrocyte mass should be 0 (1) of the group, suspended in the plasma of the AB (IV) group. In case of blood incompatibility due to rare factors, individual selection donors.

In a newborn, 40-50 ml of blood is removed and the same amount of erythrocyte mass is injected. With repeated replacement transfusion, the dose is reduced by 2 times. Thus, the total volume of erythrocyte mass is 70 ml per 1 kg of the child's body weight.

Exchange transfusion is effective way removal from the body of a newborn of toxic products of hemolysis, namely indirect bilirubin, antibodies and incompletely oxidized products of interstitial metabolism. Nonetheless possible complications: heart failure, air embolism, infection, anemia, hemorrhagic syndrome, etc.

Phototherapy. In 1958 Cremer et al. found that light destroys indirect bilirubin. Therefore, a method of phototherapy was proposed - irradiation of the body of a newborn with a fluorescent lamp.

The yellow color of bilirubin is associated with the presence of a light absorption band in it in the blue region of the spectrum at a wavelength of 460 nm.

Phototherapy promotes the conversion of free bilirubin in the skin and capillaries into non-toxic metabolites (biliverdin), which are excreted in the urine and bile of the fetus. In this case, albumins lose their ability to bind bilirubin.

Light penetrates the skin of a newborn to a depth of 2 cm.

Indications for phototherapy are:

conjugative jaundice in full-term newborns with serum indirect bilirubin levels up to 170-188 µmol/l or more;

hemolytic disease of the newborn according to the Rh factor and group incompatibility;

condition after replacement blood transfusion in severe hemolytic disease;

prevention in newborns at risk for the development of hyperbilirubinemia (perinatal hypoxia, immature and premature newborns, impaired thermoregulation).

With phototherapy, the development of toxic effects in newborns is possible (erythema, dyspepsia, burns, hypohydration, "bronze baby syndrome"). At values of direct bilirubin in blood serum more than 85 µmol/l, phototherapy should be discontinued.

Therapy with intravenous immunoglobulins. Immunoglobulins (in high doses) block Fc receptors that are involved in the cytotoxic antigen-antibody reaction and thereby reduce hyperbilirubinemia.

Newborns are injected intravenously with ImBio-immunoglobulins at a dose of 800 mg/kg per day for 3 days in combination with phototherapy.

Thus, the complex therapy for hemolytic disease of the newborn, including exchange transfusion, phototherapy, and intravenous immunoglobulin, can reduce the frequency and severity of this pathology, as well as improve the health and prognosis of children's development.

It is believed that after the first pregnancy with an Rh-positive fetus, sensitization occurs in 10% of Rh-negative women. With each subsequent pregnancy, 10% are immunized with an Rh-positive fetus.

It is important to make an approximate calculation of the number of doses of immunoglobulin for obstetric institutions. Taking into account the literature data, it should be considered that out of 1000 giving birth, 170 will have Rh-negative blood. Of these, 100 women will have an Rh-positive child. Therefore, 100 doses of the drug are needed per 1000 births if it is administered to all women with Rh-negative blood who have given birth to children with Rh-positive blood.

With the strict implementation of the method of specific prevention of Rh sensitization, it is possible to practically solve the problem of Rh-conflict pregnancy.

KYIV. January 31st. AMN. Recently, specialists from the Interregional Center for Medical Genetics and prenatal diagnosis in Krivoy Rog, a unique operation was performed - intrauterine blood transfusion. This is a rare operation that saves the lives of unborn children with severe anemia and prevents further development illnesses after childbirth. He spoke about the features of the procedure chief physician Interregional Center for Medical Genetics and Prenatal Diagnosis Nikolay Veropotvelyan.

How long ago did intrauterine blood transfusion appear in Ukraine?

In Ukraine, the treatment of hemolytic disease was usually carried out mainly with the help of plasmapheresis, and a skin graft was also done. And after birth, the baby was given replaceable blood transfusions. But today the gold standard in the world is intrauterine blood transfusion. It should be carried out already when the fetus shows signs of anemia. This can be determined by assessing the blood flow in the average cerebral artery using dopplerometry. If the blood flow indicators are normal, then the fetus is doing well. And if he has no other pathological manifestations, but blood flow indicators are higher than normal values, we predict what severity of anemia and hemoglobin level. And then the question arises how to effectively treat.

In both of the women we operated on, in previous pregnancies, the children died immediately after childbirth from a severe hemolytic disease. In the current pregnancies, these women also showed early fetal disease. Even unborn children were doomed to death. The only way to save them life before birth and health after it was a transfusion of donor erythrocyte mass of the first group with a negative Rh factor.

In total, we did 4 transactions in 1 month. The first one took place on December 23rd. The last one is January 23rd. Each pregnant woman undergoes such an operation with an interval of 2-3 weeks, both of them underwent 2 operations.

How is the procedure performed?

Through the mother's abdomen under the control of ultrasound, a thin needle must be inserted directly into the vein of the umbilical cord. It is not easy to get into the umbilical cord vessel, even when a child is born. And here the task is to do this when we see it only under ultrasound control on the screen. This can take 5-10 and sometimes 20-30 minutes because during this time the fetus and umbilical cord float and move. And it is necessary to get into the vein. If you hit an artery, it can cause cardiac arrest. If you pierce a vein through and through, there will be bleeding, if you insert the needle in the wrong place, a hematoma may form that will pass the vessel, and the child may die in the womb. This is not so easy and very responsible. And here you first need to get the blood of the fetus, and inject the fetus with a drug that will allow him to temporarily immobilize and get the result of a blood test of the fetus in order to identify what his indicators are and calculate the amount of transfusion. After that, it is necessary to slowly and carefully, without moving the needle, carry out a transfusion, which lasts from about 30 minutes to one hour. In general, the duration of the procedure takes 1-2 hours, and even more with preparation.

What medical staff is involved in the operation?

10 involved in the operation medical workers. That is, it is a well-functioning team work.
The operating team includes me as an operator and a doctor for ultrasound diagnostics, which helps display the image and controls the position of the needle. Operating nurse gives instruments. Also anesthesiology team: doctor and nurse. The transfusion team includes a doctor and two nurses who prepare the blood for transfusion and directly supply blood to the system. I insert and hold a needle, to which a special elastic tube is attached, and the nurses inject blood through it at a certain speed. A laboratory group is also working, immediately doing hemoglobin, hematocrit and other tests at the beginning and end of the transfusion.

Tell us about the women who had such operations
In one of the women, when she came to us, the fetus already had a severe hemorrhagic disease, there was already free fluid in his stomach. Hemoglobin was 45 units, hematocrit - 12%, after the first transfusion, in a week, this liquid practically disappeared. Then we performed a second transfusion. The day before yesterday, this woman had a caesarean section in a specialized city maternity hospital No. 1 in Dnepropetrovsk. The child was delivered with good blood counts. We gave another woman a fetal blood transfusion a few days ago. She will give birth in a week or two.

What other unique operations do you do at the Center?

At one time, in 1980, we were the first in Ukraine and in the Soviet Union to start making invasive prenatal or prenatal diagnostics of chromosomal pathology. In our center, we perform amniocentesis, chorion biopsy, placentocentesis, cordocentesis - but they have long been routine intrauterine interventions.

There are things that we alone do in Ukraine and the CIS. Since 1995, we aspirate the contents of the cyst in utero from the fetus, if it is large and dangerous because it can twist, tear, squeeze internal organs. This allows the child to survive until childbirth, to avoid complications during childbirth, and after them to avoid the traditional surgical intervention. But this does not happen every day and depends on when such patients with serious situations come to us.
Over the past 20 years, only 30 to 40 such operations have been performed worldwide.

ISOSEROLOGICAL INCOMPATIBILITY OF MOTHER AND FETUS BLOOD

basis isoserological incompatibility of maternal and fetal blood is the heterogeneity of their antigenic factors of erythrocytes, more often according to the Rh system, less often according to the ABO system. Due to the penetration of fetal blood factors with antigenic properties into the bloodstream of a mother who does not have them, alloimmune antibodies are produced in her body, which penetrate the placenta to the fetus, and an antigen-antibody reaction occurs in his body. Such a reaction leads to agglutination and hemolysis of fetal erythrocytes, anemia, the formation of indirect bilirubin - to hemolytic disease of the fetus and newborn (GBP and HDN).

With isoserological incompatibility of the blood of the mother and fetus, the disease can manifest itself both during pregnancy (GBP) and after the birth of a child (GBN).

Hemolytic disease (synonym: erythroblastosis) is often cause of fetal and neonatal death, increased morbidity in the postnatal period and subsequent years of life.

A significant reduction in perinatal mortality and morbidity in children was achieved through the use of replacement blood transfusion in newborns with HDN, as well as the introduction of the mother of anti-Rh immunoglobulin (Rh IgG) after termination of pregnancy in any way (abortion, ectopic pregnancy, childbirth). The injected Rh IgG binds Rh antigens, which can enter the mother's bloodstream during pregnancy termination, and thereby prevents the production of maternal antibodies and Rh immunization.

Obstetricians have long known about diseases ( familial jaundice,erythroblastosis) newborns, accompanied by jaundice, often fatal. However, the cause and pathogenesis of hemolytic disease became known only in 1940, when American scientists K. Landsteiner and A.Wiener found a protein factor in erythrocytes, which had antigenic properties. These scientists in the experiment showed that the erythrocytes of monkeys ( rhesus monkey) when administered to rabbits caused the production of antibodies in the latter. Reaction antigen-antibody(immunized rabbit serum and human erythrocytes), expressed in agglutination, was found in 15% of people. In the rest of the population, a similar antigen, called the D-factor, Rh factor (Rh), is found in red blood cells, and may also be in white blood cells, platelets and other tissue cells. Subsequently, it was proved that, in addition to the Rh factor, other antigens that are qualitatively different from each other, C (Rh ") and E (Rh "), can be found in erythrocytes. Antigen C (Rh") is found in the blood of 70% of people, antigen E (Rh") - 30%. Essentially, blood can be considered Rh-negative only when it lacks all 3 varieties of the Rh factor. Rh-negative blood is not devoid of antigenic properties, it contains alleles of antigens C, D, E: c, d, e (Hg system) associated with erythrocytes, of which only antigen c can be important in the development of immunoconflict in the mother-fetus system.

The complexity of the Rh system is due to the large number mutations every gene.

The inheritance of Rh antigens is determined by a series of allelic genes located on the same chromosome, and the genes D and d, Cie, Eie are in mutually exclusive relationships. The presence of the D-antigen on erythrocytes is due to the D gene, which has the d allele. Thus, 3 genotypes are possible: DD - homozygous, Dd- heterozygous and dd- homozygous. All 3 genes on the same chromosome are inherited simultaneously.

Hemolytic disease of the fetus and newborn can also develop with incompatibility of the blood of the mother and fetus according to the ABO system. Antigens A and B of the fetus can enter the mother's bloodstream during pregnancy, leading to the production of immune a- and p-antibodies, respectively, and the development of an antigen-antibody reaction (Aa, BP) in the fetus. In this case, immunological incompatibility manifests itself if the mother has 0 (1) blood type, and the fetus has A (P) or B (Sh).

Maternal and fetal blood group incompatibility is more common (1 case per 200-256 births), but HDP and HDN are milder. This is explained protective function amniotic membranes and amniotic fluid. Much less often, HDP and HDN occur when the blood of the mother and fetus is incompatible for other erythrocyte antigens: Kell (K, k), Duffy (Fy a -Fy b), Kidd (Ik a), MNSs, PP, Lutheran (Lu a -Lu b ), Lewis et al.

Hemolytic disease of the fetus . Etiology and pathogenesis. HDP and HDN develop when the mother's blood is Rh-negative and the fetus's blood is Rh-positive. However, the disease can also Rh positive blood mother and Rh-negative blood of the fetus, with sensitization to antigen c.

As a rule, HDP and HDN occur after previous Rh immunization, which can occur after even a small amount of Rh-containing red blood cells enter the mother's bloodstream: blood transfusion without taking into account the Rh-affiliation, intramuscular injection of blood, as well as the entry of Rh-positive red blood cells into maternal blood flow during previous or real pregnancy accompanied by a violation of the integrity of the chorionic villi or the placenta.

Rh factor formed in early dates pregnancy (according to some sources, starting from the 3-8th day of pregnancy), fetal erythrocytes in the blood of pregnant women may appear at a period of 6-8 weeks. The duration of circulation of fetal erythrocytes in the mother's bloodstream has not been precisely established, however, it is known that early abortions and ectopic pregnancy contribute to immunization - the production of antibodies in maternal organism. Particularly often, childbirth is the cause of antigens entering the mother's bloodstream with subsequent sensitization. The risk of sensitization increases with operative delivery, especially during caesarean section and manual removal of the placenta. To a lesser extent, fetal erythrocytes are likely to enter the mother's bloodstream during pregnancy, but this is not excluded if there are factors that contribute to the violation of the integrity of the chorionic villi and placenta: amniocentesis, threatened miscarriage,placenta previa, placental abruption, outer turn fetus, intrauterine fetal death. Even a small amount of antigen that enters the mother's bloodstream can have a pronounced sensitizing effect, cause the production of antibodies. Immunization can also occur during the first pregnancy, since fetal erythrocytes can enter the mother's bloodstream starting from the first trimester (6.7%). In the II trimester of gestation, fetal erythrocytes are found in 15.9%, in the III - in 28.9% of pregnant women. For immunization, it is enough to administer 0.1 ml of Rh-positive blood to a woman with Rh-negative blood (this fact was proved by G.K. Cohen et al. in 1964 in experiments on volunteers). Once arisen, antibodies do not disappear, and the sensitivity to re-entering the body of Rh-positive erythrocytes is high.

After the first pregnancy, 10% of women are immunized, but in subsequent pregnancies, the same number of women can be immunized if it did not occur after the first pregnancy.

The severity of the course of GBP largely depends on the type of antibodies produced immune system mother. The main role in the development of HDP is played by incomplete antibodies related to IgG, which easily cross the placental barrier. Complete antibodies related to IgM have a large molecular weight and practically do not penetrate the placental barrier.

Maternal anti-rhesus antibodies, entering the bloodstream of the fetus, cause agglutination of his erythrocytes or at first their blockade, and then agglutination. Subsequently, regardless of the exposure option, the erythrocyte complexes are destroyed, a large amount of indirect bilirubin is released, anemia and hyperbilirubinemia occur. If erythrocytes are not destroyed in the bloodstream, they accumulate in the spleen and there they undergo hemolysis under the influence of phagocytes.

Usually, if indirect bilirubin appears in the body, it is quickly converted to direct bilirubin by attaching two molecules of glucuronic acid produced in the liver. Direct bilirubin is excreted by the kidneys. Indirect fetal bilirubin can be excreted transplacentally in a certain amount, and then pass into direct bilirubin in the mother's body. However, part of the indirect bilirubin circulates in the body of the fetus, which is facilitated by the functional immaturity of its liver. In addition, an increase in the foci of erythropoiesis in the liver, the expansion of the bile ducts with bile that has undergone thickening, lead to a change in the liver parenchyma and a violation of its architectonics. The consequences of this are a decrease in the production of proteins in the liver, hypoproteinemia,portal hypertension, ascites and generalized edema. In the fetus with hemolytic disease, along with hyperbilirubinemia, anemia occurs and, consequently, tissue hypoxia with acidosis. Indirect bilirubin is fat-soluble, therefore it easily penetrates lipid-rich tissues, inhibiting enzymatic processes. In this regard, hyperbilirubinemia often affects the brain tissue, especially the nuclei of the brain.

Depending on the degree of immunization, HBP can develop at different stages of pregnancy, sometimes very early, starting from 22-23 weeks. At any stage of pregnancy, the most severe manifestations of the disease can be observed - general dropsy, edematous form of GBP. More often, the disease occurs in the first hours and days after birth. Depending on the severity of the disease, the disease can manifest itself in an anemic, icteric form and in the form of a universal edema. Anemia is expressed in all forms.

With GBP due to anemia, hyperbilirubinemia, tissue hypoxia, acidosis, disorders of cardiac activity and the state of the central nervous system are often observed. With GBP, pregnancy throughout its entire length can be complicated by the threat of its interruption (late miscarriage, premature birth).

Diagnostics is based on the identification of a number of signs associated with maternal immunization, the development of hyperbilirubinemia, anemia and fetal hypoxia.

When determining the doctor's tactics during pregnancy, choosing the method and timing of delivery, in addition to detecting GBP, it is very important to assess the severity of the disease.

An important sign is the detection of antibodies in the mother's blood. This diagnostic test is not absolute, as antibodies do not disappear after they are produced in the mother's body, even if the fetus does not subsequently develop disease or if the fetus has Rh-negative blood. However, in combination with other signs, the presence of antibodies makes it possible to assume GBP with some degree of probability.

Dynamics matter antibody titer. The antibody titer reflects the highest dilution of blood serum (1:2, 1:4, 1:8, 1:16, etc.), at which hemolysis of the Rh-positive erythrocytes added to it still occurs. During pregnancy, antibody titer may increase, decrease somewhat and fluctuate. Increase in antibody titer is not always determined by an increase in the degree of immunization, sometimes this is due to their entry into the bloodstream from other cells, and a decrease, on the contrary, by binding them to cells. Nevertheless, an increase in antibody titer, especially significant (by 3-4 orders of magnitude), is taken into account as indirect sign worsening of the course of GBP.

Hyperbilirubinemia and anemia are one of the main signs of GBP, therefore it is extremely important to determine the degree of their severity, which can be judged with a certain degree of probability by the optical density of bilirubin (OPB) in the amniotic fluid. OPB increases as the concentration of bilirubin excreted by the fetal kidneys increases. Amniotic fluid is obtained by puncturing the anterior wall of the abdomen, uterus, amniotic membranes (see. Amniocentesis).

In the amniotic fluid, the OPB, antibody titer, and, if necessary, the fetal blood type are determined. During the last amniocentesis before delivery, amniotic fluid is examined for the degree of maturity of the fetal lungs (foam test according to the Clemence method or determination of the ratio of lecithin and sphingomyelin content).

OPB set using spectrophotometry at a wavelength of 450 nm in relation to distilled water. In this case, the normal value of the bilirubin peak, as a rule, does not exceed 0.1. With OPB from 0.1 to 0.15, the presence of GBP can be assumed mild degree. In the event that the OPB is from 0.15 to 0.2, the birth of a child with moderate and severe hemolytic disease can be expected. OPP from 0.2 and above, as a rule, indicates the development of a severe form of GBP in the fetus or its intrauterine death. False-positive results may be obtained when evaluating the ROP due to the ingestion of maternal blood (during the production of amniocentesis), meconium, urine, or fetal ascitic fluid into the needle. OPP can be reduced by diluting bilirubin with a large amount of amniotic fluid in polyhydramnios, which is often observed in GBP. A more accurate assessment of the severity of the hemolytic process can be obtained by examining the OPB of the amniotic fluid with various lengths light waves - from 300 to 700 nm. In such cases, LE is calculated, applied to a graph divided into 3 zones depending on the severity of hyperbilirubinemia and gestational age. The further tactics of the doctor depends on which zone the set value of the OPB falls into. Ultrasound has an important role in the diagnosis of GBP, which is advisable to perform at the following gestational ages: 20-22, 24-26, 30-32, 34-36 weeks and immediately before delivery. Ultrasound can detect changes in both the placenta and the fetus. Depending on the severity of the disease, an increase in the thickness of the placenta is observed (normally, it depends on the gestational age, averaging 34-36 mm in the III trimester). Exceeding the normal thickness of the placenta for gestation by 0.5-1.0 cm or more indicates a possible disease of the fetus, and therefore a second ultrasound is required. With edematous GBP form the thickness of the placenta can reach 60-80 mm.

In hemolytic disease, ultrasound can detect an increase in the size of the liver and spleen in the fetus. Signs of the edematous form of hemolytic disease are pronounced hepatosplenomegaly, ascites, polyhydramnios. With severe dropsy of the fetus, there are, in addition, cardiomegaly and pericardial effusion, hydrothorax, increased echogenicity of the intestine due to edema of its wall, edema of subcutaneous fatty tissue in the head and limbs of the fetus. Additional ultrasound criteria for assessing the severity of fetal disease can be expansion of the vein of the umbilical cord(up to 10 mm or more), increased blood flow velocity in the descending fetal aorta(the rate is inversely proportional to the content of hemoglobin in the fetus).

Due to the fact that the fetus with GBP suffers from hypoxia, the severity of which increases with the severity of the disease, it is important to obtain information about its functional state. For this purpose, the definition biophysical profile modified Vintzileos scale(1983). Unlike oligohydramnios, which is an unfavorable factor in pregnant women without isoserological incompatibility, if there is one, the degree of polyhydramnios is taken into account, and instead of the degree of maturity of the placenta, its thickness. Other criteria of the scale (cardiac activity, respiratory movements, physical activity, tone) are evaluated according to the standard scheme (see. Additional Methods research. It is possible to determine the presence and severity of GBP by analyzing the fetal blood obtained from the vessels of the umbilical cord by its puncture ( cordocentesis; cm. Additional research methods).

Cordocentesis allows you to make a direct study of cord blood with the determination of the blood group and Rh affiliation of the fetus, the level of hemoglobin, bilirubin, serum protein and hematocrit, direct Coombs test. Most important criterion GBP is considered hematocrit (Ht), which, on the one hand, indicates the degree of hemolysis, and, on the other hand, is an indicator of the compensatory possibilities of hematopoiesis. A decrease in Ht by 10-15% indicates a severe form of GBP (normal Ht up to 26 weeks is 35%, later - from 38 to 44%).

Management of pregnancy and childbirth

In all pregnant women, at the first visit to the doctor, they determine (or check) the group and Rh blood affiliation.

In pregnant women with blood type 0 (1), if the husband has a different group, it is necessary to examine the blood for the presence of group immune antibodies. In patients with Rh-negative blood, it is necessary, starting from the early stages, to conduct a blood test for the presence of antibodies and determine their titer: up to 20 weeks of pregnancy, 1 time per month, then 1 time in 2 weeks. To establish the alleged Rh affiliation of the fetus, the presence of the Rh factor in the father is detected. It is also necessary to carry out an indirect Coombs reaction, which allows you to determine which antibodies circulate in the blood, bound or free.

In the absence of antibodies before 28 weeks of gestation, many researchers recommend that pregnant women with Rh-negative blood administer 300 mg of Rh Ig intramuscularly as a preventive measure, which can block Rh antibodies. It is important that the preparation containing antibodies does not pass through the placenta.

Determination of the state of the fetus based on the results of the assessment of the biophysical profile and ultrasound is carried out weekly, starting from 31-32 weeks. In the pregnant group high risk development of GBP (presence in anamnesis in pregnant women with Rh-negative blood late miscarriages, premature births, stillbirths, HDN, blood transfusions, excluding Rh-affiliation). Ultrasound should be performed daily or at intervals of 1-2 days.

In order to reduce maternal sensitization by fetal erythrocytes to all pregnant women with Rh-negative blood, even in the absence of Rh antibodies, as well as in the presence of ABO sensitization it is recommended to conduct 3 courses of non-specific desensitizing therapy for 10-12 days with a period of 10-12, 22-24, 32-34 weeks. Women who have a complicated pregnancy ( threat of interruption, toxicosis, preeclampsia), should be hospitalized in the department of pathology of pregnant women, where, along with the treatment of the underlying disease, a course of desensitizing therapy is carried out. Nonspecific desensitizing therapy includes intravenous administration of 20 ml of 40% glucose solution with 2 ml of 5% ascorbic acid solution, 2 ml of 1% solution of sigetin and 100 mg of cocarboxylase. Inside appoint rutin 0.02 g 3 times, teonikol 0.15 g 3 times or methionine 0.25 g each and calcium gluconate 0.5 g 3 times, iron preparations (ferroplex 1-2 tablets 3 times, etc. .), tocopherol acetate (vitamin E) 1 capsule. At night, it is recommended to use antihistamines (0.05 g of diphenhydramine, 0.025 g of suprastin).

Pregnant women with a history of spontaneous miscarriages and childbirth with an edematous or severe icteric form of hemolytic disease, with a high titer of Rh antibodies in a specialized institution, plasmapheresis can be performed, which consists in the removal of a certain volume (250-300 ml) of plasma containing antibodies from pregnant women , using various devices ( RK-0,5 "AMINKO" and etc.). The replacement of the withdrawn plasma is carried out with colloid, crystalloid and protein preparations and at the same time the blood cells of the pregnant woman are returned to the bloodstream. Plasmapheresis perform 1 time per week under the control of antibody titer, starting from 23-24 weeks of pregnancy until delivery; Plasmapheresis can also be performed before pregnancy as a preparation for it.

In order to reduce the degree of Rh sensitization, hemosorption using activated carbon for sorption of free antibodies (see fig.). The use of hemosorption is justified in pregnant women with an extremely burdened obstetric history ( repeated miscarriages , stillbirth). The most optimal time for starting hemosorption is 20-24 weeks of pregnancy. Hemosorption carried out in a hospital. In one session of hemosorption, 8-12 liters of blood (2-3 BCC) are perfused through the hemosorbent. The interval between sessions is 2 weeks. The course of sorption therapy must be completed 1 week before the expected date of delivery.

Scheme of connecting the device for carrying out hemosorption: 1 - catheters inserted into vessels (into a vein or into a vein and artery); 2 - tubular line for blood sampling; 3 - blood pump; 4 - bubble chambers; 5 - heparin delivery device; 6- pressure gauges with dividing chambers separating them from direct contact with blood; 7 - sorbent column; 8 - magnetic valve to protect the patient from air embolism; 9 - blood return tubing. The arrows show the direction of blood flow through the system.

Currently, the treatment of HDP is widely carried out by intrauterine blood transfusions under ultrasound control. Fetal blood transfusions can be performed from 18 weeks of gestation. Intrauterine blood transfusion creates preconditions for prolongation of pregnancy. There are intra-abdominal and intravascular methods of blood transfusion. Technique of intra-abdominal transfusion consists in puncturing the abdominal wall of the mother, the wall of the uterus, the abdominal wall of the fetus and introducing into its abdominal cavity a single-group and Rh-negative erythrocyte mass, which is adsorbed by the lymphatic system and reaches the vascular system of the fetus.

AT last years preference is given to intravascular blood transfusion to the fetus, the indications for which in case of Rh sensitization are severe anemia and a hematocrit of less than 30%.

In order to conduct intravascular blood transfusion, cordocentesis is performed, while the umbilical cord vein is punctured in the immediate vicinity of its entry into the placenta. The conductor is removed from the needle and blood is taken to determine the pre-transfusion hematocrit of the fetus. The erythrocyte mass is slowly injected through a needle, after which a second blood sample is taken to determine the final fetal hematocrit and assess the adequacy of the therapy. To stop the movements of the fetus, as a result of which the needle can be pushed out of the vein of the umbilical cord, the fetus is injected arduan (pipecuronium) intravenously or intramuscularly. Determining the need and timing of subsequent blood transfusions to the fetus is based on the results of ultrasound, post-transfusion hemoglobin and hematocrit in the fetus. Amniocentesis after intrauterine transfusion does not make sense, since the amniotic fluid after this procedure is usually stained with blood, which can lead to false positive results determination of optical density. The effectiveness of treatment of severe forms of GBP with intravascular blood transfusion is 85-91%, with intra-abdominal - 66%.

Pregnant women with Rh sensitization should be sent to the maternity hospital at 34-36 weeks of gestation, with AB0 sensitization - at 36-37 weeks for additional examination and the issue of delivery. In the presence of GBP, early delivery is necessary, since by the end of pregnancy, the supply of Rh antibodies to the fetus increases. Optimal term delivery - 37-38 weeks. pregnancy, since with an earlier delivery due to the functional immaturity of the organs (especially the liver), hemolytic disease is more severe, the child often suffers from respiratory distress syndrome. However, if objective evidence indicates severe fetal distress, if the woman has burdened obstetric history, delivery is possible in earlier periods of pregnancy. At the same time, it is necessary to take measures aimed at acceleration of maturation of the lungs of a premature fetus. Appoint dexamethasone 2 mg 4 times a day for 2-3 days before the expected birth.

With a pronounced edematous form of GBP, pregnancy is interrupted at any time. If by the time of delivery, ultrasound determines very big sizes fetal abdomen, it is advisable to release ascitic fluid by puncturing the anterior abdominal wall of the mother, uterus and anterior wall of the fetal abdomen.

As a rule, delivery is carried out through natural birth canal. Caesarean section is performed in the presence of additional obstetric complications ( placenta previa, malposition, scar on uterus,cord prolapse etc.).

Labor induction should begin with the creation of a glucose-vitamin-hormonal-calcium background for 2-3 days (depending on the condition of the cervix). When the cervix is ready for childbirth, an amniotomy is performed. If generic activity will not develop, 5-6 hours after amniotomy, labor induction with oxytocin or prostaglandins begins according to the generally accepted method.

In childbirth, careful monitoring of the condition of the fetus is carried out, hypoxia is prevented. Immediately after the birth of the child, it is quickly separated from the mother in order to avoid massive entry of Rh antibodies into the bloodstream of the newborn. Blood is taken from the umbilical cord to determine the content of bilirubin, hemoglobin, the child's blood type, and its Rh affiliation. An indirect Coombs test is carried out, which makes it possible to detect the newborn's erythrocytes associated with antibodies (an agglutination reaction of the child's blood with specific Coombs' serum). Given the tendency of the fetus and newborn with hemolytic disease to hemorrhages, the second stage of labor should be carefully managed. Epidural anesthesia and perineal incision are advisable. With ABO sensitization, the management of labor does not have any features.

Subsequently, if replacement blood transfusion is necessary for newborns with hemolytic disease, umbilical vessels are used, so the umbilical cord is not stapled. The umbilical cord is tied at a distance of 2-3 cm from the umbilical ring.

Prevention of Rh sensitization. Preventive measures are as follows: any blood transfusion should be performed taking into account the Rh-belonging of the blood of the recipient and donor; it is necessary to save the first pregnancy in women with Rh-negative blood; prevention and treatment of pregnancy complications; conducting desensitizing therapy; implementation of specific prevention of Rh sensitization in women with Rh-negative blood by administering anti-Rh immunoglobulin after any termination of pregnancy.

Immunoglobulin-antirhesus is administered in one dose intramuscularly once. The indicated dose is prescribed to the puerperal within 48 hours after childbirth, and preferably 24 hours, in case of abortion - at the end of the operation. After caesarean section and manual separation of the placenta, the dose of the drug should be doubled.

With the strict implementation of the method of specific prevention of Rh sensitization, it is possible to practically solve the problem of Rh-conflict pregnancy.

intrauterine blood transfusion and with the use of ultrasonic control today - the most effective method in the treatment of hemolytic disease or Rh conflict. it necessary procedure if mom and future child have blood incompatibility.

Types of intrauterine transfusion

There is intravascular and intraperitoneal transfusion. Of course, the first is preferable, but it is carried out after 22 weeks of pregnancy. Until this time, or if difficulties arise, intraperitoneal is used. As a rule, the indication for transfusion is a 15% or more decrease in total erythrocytes. The procedure is repeated every two to three weeks, since hemolytic disease of the fetus reduces its hematocrit by 1% every day. After 34 weeks, with a progressive or complicated form, a decision is made on early delivery.

How is the transfusion procedure carried out?

The procedure itself assumes the following. Applying ultrasound control, the doctor, using a catheter, penetrates the umbilical cord vein through the anterior abdominal wall of the woman and transfuses 20-50 ml of blood with Rh negative factor. If the blood type of the fetus is known, use the same, if not - blood I (0) . The procedure weakens the body's immune response future mother, as it reduces the relative number of Rh-positive erythrocytes and maintains the fetal hematocrit above critical values. Intrauterine blood transfusion is a rather dangerous procedure. It must be remembered that intrauterine blood transfusion is a rather dangerous procedure for both the fetus and the expectant mother, so it is carried out an experienced doctor and with strict indications. Rarely, but sometimes complications of an infectious nature, umbilical vein squeezing, feto-maternal transfusion, premature birth, and even intrauterine fetal death can occur.

How to avoid blood transfusion?

Is it possible to avoid the possibility of encountering this procedure if the pregnancy is only planned? The answer is yes. First you need to find out the Rh factors and blood groups in yourself and your husband. If it turns out that the expectant mother is Rh-negative, and the father is Rh-positive, you will have to undergo a set of preventive measures.

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