Pregnancy with Rh conflict: when a child needs an intrauterine blood transfusion. New blood

Today, intrauterine blood transfusion to the fetus is the most effective method of treating fetal hemolytic disease, which occurs due to incompatibility of the blood of the mother and child.

According to statistics, Rh incompatibility occurs in 9.5-13% of all marriages, the frequency of hemolytic disease is about 1.5%. Of all Rh-sensitized women, 40-50% will have a fetus with mild or no hemolytic disease, 25-30% will have hemolytic disease requiring treatment in the early neonatal period, and only 20-25% will develop severe anemia. requiring invasive methods therapy and early delivery.

Today, many married couples with a history of fetal loss with a severe form of hemolytic disease have the opportunity to carry and give birth to a child. Thanks to modern diagnostic methods and the latest equipment, specialists from the Republican Clinical Hospital annually perform intrauterine blood transfusions to the fetus. More details about the method in the interview Liliana Efimovna Teregulova.

— What is the method, and in what cases is its use advisable?

— Intrauterine blood transfusion to the fetus is the transfusion of blood products (erythrocytes and platelets) into the fetal umbilical cord vein. To do this, under ultrasound guidance, a puncture of the fetal umbilical cord vein is performed through the anterior abdominal wall and the wall of the uterus with a special, especially strong, rigid, atraumatic needle to determine the level of hemoglobin in the blood. After we receive a blood test, a transfusion of 100 to 250 ml is carried out under ultrasound guidance. freshly washed red blood cells. During the entire operation, fetal cardiac activity is constantly monitored. In addition, transfusion of a blood product helps to weaken the immune response of the pregnant woman by reducing the relative number of Rh-positive red blood cells and helps maintain the total volume of fetal red blood cells above the critical level, which can significantly improve the condition of the fetus.

Intrauterine blood transfusion to the fetus is carried out in cases where the pregnant woman has a Rhesus conflict; monthly we perform an ultrasound, which assesses the condition of the fetus, placenta and blood flow speed in the middle narrow artery. It is the speed of blood flow in the middle narrow artery that is a criterion for anemia. After making this diagnosis, we prepare the patient for intrauterine fetal blood transfusion.

It is worth noting that in a number of diseases, such as anemia, various forms of immune conflict, including Rh conflict, anemia of non-immune origin, for example, parvovirus infection, as well as alloimmune thrombocytopenia, blood transfusion is the only method of treatment and saving the fetus. Before the introduction of intrauterine blood transfusion, most fetuses with such anemia died, or, in best case scenario, became severely disabled as a result of the need for premature delivery. Most women with Rh conflicts, having given birth to several stillborn children, remained childless as a result.

— At what stage of pregnancy should this procedure be performed?

— It all depends on the specific case. The moment a fetus is diagnosed with severe anemia, we immediately perform this operation. We typically perform intrauterine blood transfusions for the fetus between 18 and 33 weeks of pregnancy.

— After an intrauterine transfusion, how much time does the mother and fetus need to recover?

— Usually the postoperative period is 1-2 days.

— When carrying out this treatment, there is a need for parallel administration medicines?

- No, there is no such need.

— In what cases is repeated intrauterine transfusion necessary?

— The number of repeat transfusions depends on the stage of pregnancy. There was a case in our practice where we performed this procedure on one patient 8 times. Regarding the duration of pregnancy, intrauterine blood transfusions can be performed repeatedly up to 34 weeks of pregnancy. This is due to the fact that it is at this time that the fetus becomes quite viable. For example, if after 34 weeks hemolytic disease of the fetus develops or its course becomes aggravated, the issue of early birth is decided. It could be like natural childbirth, and caesarean section - it all depends on the situation in each specific case.

- Can there beAre there any complications?

— Intrauterine blood transfusion is a procedure that is dangerous for both the mother and the fetus, so it must be carried out by an experienced doctor according to strict indications. For example, a mother may develop a complication such as placental abruption, the fetus may experience large blood loss due to thrombocytonemia that often accompanies Rhesus conflict, and in rare cases intrauterine fetal death. It is also worth considering that after this procedure there may be premature birth.

Of course, it is difficult to say unambiguously what complications may develop in a particular case, but if the procedure is carried out in a qualified manner, everything usually goes well. If the intrauterine transfusion was successful and the desired result was achieved, all children grow and develop normally after birth. Deviations from normal development are observed only in severely premature babies with hemolytic disease and they are caused by prematurity.

— Is there a possibility that this treatment will not work? positive results?

— In my practice, there have been no such cases. If the diagnosis is made correctly, we always get an adequate result.

Liliya Turullina

TsPSiR, being the leading obstetric hospital city, has been providing specialized care to patients with immunocompromised pregnancies for 20 years.

As part of the CPSR there is a consultative and diagnostic department, where highly qualified obstetricians and gynecologists receive consultations, to which antenatal clinics pregnant women with Rh sensitization are sent to the city of Moscow, the Moscow region, as well as various regions of the country. Most of these patients develop hemolytic disease of the fetus (HDF). Diagnosis of hemolytic disease of the fetus is based on the results of a comprehensive examination of the condition of the mother and fetus, which includes anamnesis, determination of the titer of Rh antibodies, echography with feto-and placentometry, study of cardiac activity and biophysical profile fetus (FFPP), amniotic fluid, fetal blood obtained by cordocentesis. The tactics of pregnancy management in case of immunological incompatibility of the blood of mother and fetus is aimed at early diagnosis GBP, identifying the degree of sensitization, conducting therapeutic measures and determining the optimal timing of delivery.

Konoplyannikov Alexander Georgievich

Chief obstetrician-gynecologist of the city of Moscow. Doctor of Medical Sciences, Professor of the Department of Obstetrics and Gynecology, Russian National Research Medical University named after. N.I. Pirogova, doctor of the highest category

Cordocentesis

It is advisable to begin examination of pregnant women with the specified obstetric pathology at the Center for Pregnancy and Rehabilitation at 20 weeks of gestation. However, patients with aggravated obstetric history(antenatal death of children from hemolytic disease, birth of children with severe forms of this disease) it is necessary to contact the center as early as 18 weeks. It is during this period that the center’s specialists, using ultrasound scanning, can identify the first signs of hemolytic disease of the fetus and make a timely diagnosis. However, a more accurate method for identifying HDP and determining its severity is to study fetal blood obtained by cordocentesis - umbilical cord puncture. This diagnostic procedure is performed by doctors at the Center for Pregnancy and Rehabilitation in a day hospital from 24 weeks of pregnancy. Indications for cordocentesis are the presence of ultrasound markers of HDP, antibody titer of 1:16 or higher, and a complicated medical history. The resulting fetal blood is examined to determine the blood type and Rhesus, the level of hemoglobin and hematocrit, red blood cells and bilirubin, and acid-base balance. Based on the data obtained, further pregnancy management tactics are determined. If the fetus has Rh-negative blood, further monitoring of the pregnant woman continues on an outpatient basis as a non-sensitized patient and hospitalization in a specialized hospital is not required for her delivery. With rhesus positive blood fetus and the presence of data indicating the presence of HDP, it is necessary to begin pathogenetic treatment of this disease.

Unfortunately, traditional methods therapies for this pathology (desensitizing therapy, hemosorption and plasmapheresis, intravenous administration of immunoglobulin solutions) are ineffective, and their use often leads to loss of time for pathogenetic treatment and the development of severe incurable forms of the disease. Currently, the only effective method of treating severe forms of hemolytic disease of the fetus is the operation of intrauterine blood transfusion, which has been successfully performed by specialists from the Center for Pregnancy and Rehabilitation for many years. To perform this operation, the pregnant woman is hospitalized in the pathology department of the center. The purpose of this manipulation is to increase the hematocrit level, reduce the risk of developing the edematous form of HDP, and further prolong the pregnancy by 2-3 weeks (the functioning time of the injected red blood cells). Indications for intrauterine blood transfusion to the fetus are a decrease in cord blood hemoglobin and hematocrit indicators by 15% or more compared to the gestational norm. Often this manipulation is carried out several times during pregnancy. The need for repeated blood transfusions to the fetus is determined by the duration of pregnancy and the level of post-transfusion hematocrit, since with HDP the rate of decrease in hematocrit is on average 1% per day. Intrauterine blood transfusions can be performed up to 32 weeks of pregnancy. After this period, the issue of early delivery is decided.

The CPSR has accumulated extensive experience in performing this operation: every year the center performs from 70 to 80 intrauterine blood transfusions. This method of treating hemolytic disease is unique and in the city of Moscow is performed only by specialists from the Center for the Treatment of Hemolytic Diseases.

Premature birth is a problem that often accompanies immunocompromised pregnancy. In the structure of the Center for Children's and Rehabilitation, an important place is occupied by the pediatric intensive care unit, which has the ability to care not only for children with extremely low body weight, but also for premature children with severe forms of hemolytic disease of the newborn. These children receive complex treatment for hypertension, including blood transfusion in the operating room immediately after their mothers had a cesarean section, then replacement blood transfusion in pediatric intensive care, as well as infusion and phototherapy.

The algorithm for examination and treatment of patients with Rh sensitization, developed and implemented at the Center for Pregnancy and Resuscitation, allowed to reduce perinatal losses by 1.5 times, reduce the number of prematurely born children, the number of children with severe forms of hemolytic disease, reduce the frequency and frequency of use of exchange transfusions in newborns with HD, and also made it possible to achieve the birth of healthy children from patients with a large number of perinatal losses caused by Rh sensitization and HD.

However, the problem of Rh sensitization has not yet been solved. Doctors of the Consultative and Diagnostic Department of the Center for Pregnancy and Rehabilitation every day accept new patients suffering from this obstetric pathology. This is due to the lack of preventive measures in other medical institutions, despite the fact that preventive measures are known to everyone and have long been introduced into the practice of medical work of the Center for Rehabilitation and Rehabilitation.

In the CPSR all patients with Rh negative blood and the absence of Rh antibodies in the blood serum at a gestational age of 28 weeks, with a threat of miscarriage accompanied by bloody discharge from the genital tract, regardless of gestational age, after invasive procedures (chorionic villus biopsy, amniocentesis, cordocentesis), spontaneous or artificial termination of pregnancy, ectopic pregnancy, as well as after the birth of a Rh positive fetus, anti-Rhesus immunoglobulin is administered.

Bugerenko Andrey Evgenievich

Candidate of Medical Sciences. Associate Professor, Department of Obstetrics and Gynecology, Faculty of Fundamental Medicine, Moscow State University

Feto-fetal transfusion syndrome

A desired pregnancy is a joy for future parents. Pregnancy with twins is double the joy. But for an obstetrician, these are not even double problems, but problems squared. This is especially true for monochorionic twins. Although the frequency of such pregnancies is low, in addition to the problems inherent in multiple pregnancies as such, there are serious complications inherent exclusively in the monochorionic type of placentation.

One of these severe complications of monochorionic twins is feto-fetal transfusion syndrome (FTTS). The occurrence of this complication, as a rule, ends in the death of both fetuses before the time in which prematurely born children can be nursed.

Feto-fetal transfusion syndrome, also known as twin-to-twin transfusion syndrome (TTTS), occurs due to the presence of vascular placental anastomoses connecting the circulatory systems of the fetuses. The incidence of TTFT, according to different authors, ranges from 5 to 25% of the number of pregnancies with a monochorionic type of placentation. An imbalance of blood exchange along the anastomoses leads to an outflow of blood from one twin (donor) to the other (recipient). This is a severe pathology in which the probability of intrapartum fetal death reaches 80-100%.

SFFT was first described in 1882 by the German obstetrician Friedrich Schatz. But despite such a long history, for the vast majority of outpatient healthcare doctors, both diagnosis and management tactics for patients with manifestations of TTFT are “terra incognita”, which results in an unfavorable end of pregnancy.

Briefly about the pathogenesis of the development of TTFT:

An imbalance of blood exchange along the anastomoses leads to an outflow of blood from one twin (donor) to the other (recipient). The donor twin develops hypoxia (due to insufficiency of placental circulation), hypovolemia with a decrease in blood pressure. As a result of these factors, intrauterine development is delayed, the volume of amniotic fluid decreases, and severe anemia often develops with a hemoglobin level of less than 80 g/l. The most common consequence of severe antenatal hypoxia is the formation of so-called latent heart failure, when stroke and cardiac output do not change significantly, but a number of diastolic function indices indicate damage to the fetal myocardium. The recipient fetus, on the contrary, receives too much blood and develops hypervolemia, which increases pre- and afterload on the heart, which can further lead to heart failure. Under conditions of hypervolemia, edema appears in the recipient fetus, blood pressure rises, and myocardial hypertrophy develops. The fetal body, in response to an increase in circulating blood volume (CBV), releases an excess amount of water through the organs of the urinary system, which leads to severe polyhydramnios. Due to the high content of red blood cells in the blood, there is a high risk of developing thrombosis. Polycythemia in the recipient twin causes an elevated hematocrit of 60% or more or a hemoglobin level greater than 220 g/L at any time during the first week of life of the newborn. A twin with polycythemia is at risk for breathing problems, cardiac problems, and damage to the central nervous system.

If there is intrauterine death of one fetus during TTTS, there is a 25% chance of complications developing in the other fetus. Such complications in the form of necrosis of the brain and parenchymal organs are considered to be a consequence of acute ischemia and hypotension arising from shunting blood from a living fetus to a dying one. Perinatal mortality of the recipient fetus after the death of the donor fetus is about 50% for gestational age up to 34.

For timely diagnosis of TTFT, it is necessary, first of all, to correctly determine the type of placentation in the early stages of pregnancy, when this does not present any difficulties. The presence of the T-sign (as opposed to the λ-sign in bichorionic pregnancy) is a reason for close ultrasound monitoring of this pregnancy during the manifestation of TTFT (from 14 weeks). Characteristic ultrasound signs of the development of TTTS are: increasing polyhydramnios in the amniotic cavity of the recipient, defined as the vertical size of the largest water pocket from 8 cm or more until 20 weeks of gestation, and exceeding 10 cm from 20 to 26 weeks; The donor is characterized by oligouric oligohydramnios or ahydramnios and the absence of an echo-shadow of the bladder. Difficulties may arise in the differential diagnosis of TTFT with another serious complication of monochorionic twins - isolated fetal growth restriction syndrome (iFGR), but this is already the prerogative of a specialized obstetrics and gynecology hospital.

The only pathogenetically justified treatment method for SFFT is fetoscopic laser coagulation of anastomoses (FLCA). The technique consists of fetoscopic (through a small-diameter optical system) transabdominal introduction of a laser light guide into the amniotic cavity of the recipient fetus under ultrasound control. Endoscopic laser coagulation allows for examination of the placenta along the entire interfetal septum, identification and coagulation of anastomosing vessels. Thus, the flow of blood from one twin to the other is stopped, the balance of blood flow to both fetuses is restored, and the twins subsequently develop normally. The operation ends with drainage of amniotic fluid until its quantity normalizes. The effectiveness of endoscopic laser coagulation therapy for SFFT (the birth of at least one living child) ranges from 80 to 90%; it is possible to prolong pregnancy by an average of 10-12 weeks, which leads to a decrease in intrauterine fetal death.

At the Center for Family Planning and Reproduction of the Moscow Health Department, fetoscopic operations have been carried out since 2005; to date, more than 100 interventions have been performed. The availability of special equipment makes it possible to perform FLCA during pregnancy from 15 to 25 weeks at stage FFTS up to 4.

We perform the intervention under regional anesthesia. The fetuses, the amniotic septum and especially the vessels crossing it on the fetal surface of the placenta are carefully examined. Such vessels can be traced to their terminal branches, which, in fact, can connect with similar branches on the side of the second fruit. Not only the quantity is assessed, but also the nature, and most importantly, the diameter of the anastomoses. This is very important for correct order coagulation. First, the blood flow in large arterio-venous and arterio-arterial anastomoses is “blocked”. Then, smaller and minute anastomoses are coagulated. During the operation, part of the blood returns to the donor, improving his prognosis.

It is important to identify and coagulate absolutely all anastomoses, even the smallest ones, otherwise, as pregnancy progresses, their diameter will increase and by 28-30 weeks of pregnancy a relapse of fetofetal syndrome may occur.

When laser coagulation of anastomoses is performed correctly and without complications, the prognosis is favorable in the vast majority of patients. Currently, the effectiveness of our fetoscopic operations is similar to the data in the world literature (favorable pregnancy outcome in 80-85% of cases).

480 rub. | 150 UAH | $7.5 ", MOUSEOFF, FGCOLOR, "#FFFFCC",BGCOLOR, "#393939");" onMouseOut="return nd();"> Dissertation - 480 RUR, delivery 10 minutes, around the clock, seven days a week and holidays

Ivanova Anastasia Viktorovna. Health status and dynamics of hematological parameters in infants who have undergone intrauterine blood transfusion for hemolytic disease due to the Rh factor: dissertation... Candidate of Medical Sciences: 01/14/08 / Ivanova Anastasia Viktorovna; [Place of defense: Federal State Budgetary Educational Institution of Higher Education Ural State Medical University Ministry of Health of the Russian Federation], 2017.- 138 p.

Introduction

Chapter 1. Modern representations about HDN according to the Rh factor and its impact on the health of young children (literature review).

13

1.1 HDN by Rh factor: epidemiology, etiology, pathogenesis, clinical picture, diagnosis, treatment 13 1.2. Intravascular intrauterine blood transfusion to the fetus modern method

providing assistance to children with HDN and preventing severe forms of HDN. 27

1.3. Clinical and laboratory characteristics of the health status of children who received VPC in the neonatal period and in the first year of life. thirty

Chapter 2. Materials and research methods 35 Chapter 3. 43

Clinical characteristics of observed patients

3.1. Clinical and anamnestic characteristics of mothers of newborns who received intrauterine blood transfusion 43

3.2. Features of the neonatal period in newborns who received intrauterine blood transfusion

3.3 Results of laboratory examination of children who have undergone VPC in the neonatal period 54

3.4 Results of instrumental examination of children who underwent VOC for HDP 68

CHAPTER 4. Health status and results of laboratory and instrumental examination of children in the first year of life who received VPC for hemolytic disease according to the Rh factor 75

4.1. Health status and indicators of physical development of children in the first year of life who received military training. 75

4.2 Results of laboratory and instrumental examination of children in the first year of life who received military training

4.3. Prediction of severe anemia requiring blood transfusion in the first six months of life and an algorithm for monitoring children who have undergone VPC in the first year of life. 100

Conclusion 104

References 119

Introduction to the work Relevance of the problem. The incidence of hemolytic disease of newborns (HDN) in the Russian Federation during recent years

Currently promising in the prevention of severe forms
disease is early detection of signs of hemolytic disease
fetus (FBP). Modern method of treating hemolytic disease
as anemia progresses in the fetus, intrauterine

intravascular blood transfusion (IVT). The technology for conducting military-industrial complexes has not been implemented everywhere in the Russian Federation.

In our country, starting from the 60-70s, the problem of hemolytic
Much work has been devoted to the disease of the fetus and newborn. Thanks to
Numerous studies have improved diagnosis and treatment

hemolytic disease.

But in modern literature There is no data on the relationship between the multiplicity of the VPC and the dynamics of hemogram parameters and the oxygen transport function of erythrocytes. The timing of normalization of these indicators after transfusions of foreign blood has not been identified. At the same time, assessing the participation of erythrocytes in the early adaptation reactions of a newborn who has undergone VPC is of undoubted interest.

The duration of detection of fixed

anti-erythrocyte antibodies, possible timing restoration of one's own blood type in children who have undergone VPC.

No follow-up studies have been conducted that would make it possible to assess the impact of military-industrial complex on the formation of the somatic and neurological status of the child in the first year of life.

No algorithm has been developed for monitoring children who have undergone VPC in the first year of life.

All of the above determines the relevance of the presented research.

Goal of the work

Based on the results of a comprehensive clinical and laboratory examination, study the structure of morbidity, the dynamics of hematological

indicators, to evaluate the physical, neuropsychic development in children of the first year of life who underwent intrauterine intravascular blood transfusion for hemolytic disease of the fetus according to the Rh factor, to optimize the tactics of dispensary observation of children with hemolytic disease in an outpatient setting.

Research objectives

To study the anamnestic data and features of the course of the neonatal period in children who received VPC.

To study the features of the morphological state and transport function of erythrocytes, the levels of erythropoietin and ferritin in newborns who received VPA.

To establish the structure of morbidity, the dynamics of hematological parameters, to assess the physical, neuropsychic development of children in the first year of life who received military training.

To determine the timing of the appearance of their own blood type and the duration of circulation of anti-erythrocyte antibodies in children in the first year of life who received VPC.

To establish patterns of changes in hematological parameters during the first year of life in children who received VPC.

To identify informative signs that make it possible to predict the development of anemia requiring blood transfusion in the first half of life, and to develop an algorithm for monitoring children who received VPC in the first year of life.

Scientific novelty

For the first time, it has been established that in children who have undergone VPC, during the first year of life there is a change in the morphological characteristics of erythrocytes in the form of a decrease in the total volume of erythrocytes and the average hemoglobin content in erythrocytes, which indicates the presence of donor (adult) erythrocytes in the population of circulating erythrocytes in the child. It was shown for the first time that red blood cells received from a donor as a result of VPC cannot ensure complete utilization of oxygen from maternal blood, which contributes to the development intrauterine hypoxia in the fetus. However, after birth, with the onset spontaneous breathing donor red blood cells, which have a lower affinity for oxygen, help improve oxygen transfer to tissues, preventing the development of severe tissue hypoxia under conditions of reduced hemoglobin content.

An increased level of erythropoietin at birth was revealed, which is a compensatory-adaptive reaction of the body in response to long-term hypoxia associated with hemolytic disease of the fetus.

High levels of ferritin in blood serum have been established in children in
the neonatal period, which indicates oversaturation of the body
child with iron as a result of multiple blood transfusions,

ongoing hemolysis of red blood cells.

For the first time, follow-up observation of children was carried out,

who have undergone a military infection during the first year of life. It has been shown that the circulation of anti-erythrocyte antibodies in children who received VPC No. 1-2 persists for up to 9 months, and in those who received VPC 3 or more times - up to 12 months of life. It has been revealed that the “true”, i.e. Children who received VPC No. 1-2 appear to have their own blood type by 3 months of life, and after multiple VPCs - by 9 months of life.

It has been established that changes in morphological characteristics

red blood cells persist throughout the first half of life.

A relationship was found between the multiplicity of VPC and the dynamics of erythropoietin and ferritin in the first year of life.

High levels of ferritin were revealed throughout the first year of life in children who received VPC, which indicates the absence of iron deficiency, in contrast to premature children without hemoconflict.

It has been shown that during the first year of life there is a decrease and normalization of erythropoietin levels, which indicates the adequacy of hematopoiesis by the end of the first year of life.

Informative signs have been identified that make it possible at the preclinical stage to predict the development of severe anemia, requiring additional blood transfusion in the first half of life.

Practical significance

A method for predicting the development of severe anemia, requiring additional blood transfusion in the first half of life in children who received VPC, has been proposed for practical healthcare.

Based on the developed forecasting method, an algorithm for monitoring children in the first year of life in an outpatient setting who received VPC was proposed.

Main provisions submitted for defense

1. The neonatal period in children who received VPC requires

carrying out intensive therapy, including replacement surgeries

blood transfusions and blood transfusions. The hemogram of children is characterized by changes in the morphological characteristics and oxygen transport function of erythrocytes, increased levels of erythropoietin and ferritin in the blood serum.

During the first year of life, children who received VPC maintain long-term circulation of anti-erythrocyte antibodies, changes in the morphological characteristics of erythrocytes, increased ferritin content, a decrease in the relatively increased level in the neonatal period and normalization of erythropoietin levels. Normalization of erythropoiesis is observed by the end of the first year of life.

A method has been developed for preclinical prediction of severe anemia with the need for additional blood transfusion in the first half of life based on laboratory tests (hematocrit level and average erythrocyte volume) in the neonatal period.

Implementation of research results

The results of the research carried out were introduced into the work of the department of pathology of newborns and the department of young children of the Federal State Budgetary Institution "Ural Research Institute of Maternal and Infant Care", are used when giving lectures and conducting practical classes with clinical residents and advanced training cycles for doctors.

A manual for doctors has been prepared: “Tactics for monitoring children in the first year of life who have undergone intrauterine blood transfusion for hemolytic disease of the fetus due to the Rh factor.”

Patent application No. 2016128420 dated July 12, 2016, “Method for predicting the risk of developing severe secondary anemia requiring blood transfusion in the first half of life in children who have undergone intrauterine blood transfusion for hemolytic disease of the fetus according to the Rh factor,” has been submitted.

Approbation of work

The main provisions of the work were presented at the V Russian-German Congress of Obstetricians and Gynecologists “Reproductive health in the spotlight of the medical community” (Ekaterinburg, 2013), at the scientific and practical conference “Unresolved issues in obstetrics, gynecology and perinatology” (Ekaterinburg, 2014). In 2015, at the International Congress “Family Reproductive Health – a Guarantee of State Security,” a report on the topic of the work was awarded a 1st degree diploma for participation in the competition for young scientists. 6 printed publications have been published on the research topic.

Scope and structure of the dissertation

The dissertation is presented on 135 pages of text, contains 27 tables, 7 figures, 5 clinical examples. Consists of introduction, literature review, 3 chapters of own research, conclusion, conclusions, practical recommendations, a list of references, including 171 sources, including 138 domestic and 33 foreign literature.

Intravascular intrauterine blood transfusion to the fetus as a modern method of providing care to children with HDN and preventing severe forms of HDN

Under fluoroscopy control, after 8 hours, 75-185 ml of donor O(I)Rh(-) negative erythrocyte mass was injected into the fetal abdominal cavity, from where this blood penetrated into the fetal bloodstream within 7 days. Several methods of intrauterine intravascular transfusion have been developed using in various ways access: hysterotomy, under fetoscopy control, cases of intrahepatic, intracardiac administration of donor erythrocytes are described.

Since 1982, intrauterine intravascular blood transfusion (into the umbilical cord vein) under ultrasound control has been the “gold” standard for intrauterine correction of fetal anemia. Currently, 236 erythrocyte antigens have been discovered, which are located in 29 genetically independent systems. In most cases, headache occurs as a result of maternal sensitization with antigens of the Rh system - 92% or ABO - 7%, rarely others (Kell, Kidd, MNS MN, Lutheran, etc. - 1%).

Hypertension most often occurs and progresses severely due to Rhesus conflict. The Rh system is based on 6 antigens - C, c, D, d, E, e. If at least one of the antigens D, C, E is detected on red blood cells, human blood is considered Rh-positive; if d, c, e are present, it is Rh-negative. The D gene is of greatest importance, since it is considered the most immunogenic and is found in the blood of 85% of people.

Rh antigen is a complex complex of polypeptides that is located on inner surface erythrocyte membranes, insoluble in body fluids and takes part in ensuring normal hydration of erythrocytes.

Antigens of the Rh system are detected in the fetus at 7-8 weeks of gestation; by the 20th week of intrauterine development, the degree of Rh activity is 16

antigen is higher than that of an adult. Natural antibodies to the Rh factor are absent in human blood. Immune anti-Rh antibodies are formed in the body in response to the penetration of the Rh antigen; their presence is a marker of the body’s sensitization to the Rh system.

Most often, sensitization is a consequence of fetal-maternal transplacental transfer of fetal red blood cells into the maternal bloodstream during pregnancy or childbirth.

During physiological pregnancy, fetal red blood cells penetrate

through the placenta. The volume of fetal blood in the mother's bloodstream increases with increasing gestational age and reaches about 30–40 ml at birth. Violation of the integrity of the chorionic villi (threat of miscarriage, premature detachment placenta, gestosis, extragenital pathology, invasive procedures - chorionic villus biopsy, amniocentesis, cordocentesis) during pregnancy contributes to Rh immunization. Sensitization can occur after spontaneous and artificial abortion, ectopic pregnancy. Transplacental transfusion is most often observed during childbirth, especially during surgical interventions (caesarean section, manual separation of the placenta).

The development of sensitization is influenced by the blood type and Rh factor of the fetus, the sex of the fetus, the immunological tolerance of the mother’s body, a decrease in immune reactivity during pregnancy, and genetic factors.

The occurrence of sensitization is explained by the clonal-selective theory of F. Burnet. The antigen, entering the mother's bloodstream, interacts with T-lymphocytes. Lymphocytes sensitized by an antigen undergo several stages of proliferation and form a clone of lymphoid cells. However, lymphocyte differentiation does not occur. Proliferating lymphoid cells act as “cellular memory.” As a result of a repeated encounter with the antigen, they activate short-lived lymphocytes located in the lymph nodes, which turn into plasma cells and begin to produce specific antibodies.

The production of IgM is the primary response to the entry of the Rh antigen into the mother's bloodstream. IgM have a large molecular weight, so they do not cross the placental barrier and do not play a role in the development of HDP. Rapid and massive production of IgG, which, due to its low molecular weight, easily penetrates the placenta, occurs when the Rh antigen re-enters the sensitized mother’s body and is the main cause of the development of headache.

Simultaneous detection of two subclasses of antibodies: IgG1 (predominantly mediates phagocytosis of D-positive erythrocytes) and IgG3 (causes their cytolysis) is an additional prognostically significant criterion for the development of severe and edematous forms of HDP.

The antibody titer indicates the patient's level of immunization. The antibody titer corresponds to the highest serum dilution at which it is still able to agglutinate Rh-positive erythrocytes. During pregnancy, the antibody titer may increase or remain unchanged. The prognostic factor for the development of severe forms of HDP is the early (before 20 weeks) detection of a high antibody titer (1:16 or more) and its increase during pregnancy. However, the titer and biological activity of antibodies do not necessarily coincide: the titer characterizes the recorded amount of antibodies in the reaction with red blood cells and does not indicate the amount of free antibodies in the solution, it depends on the binding ability

Features of the neonatal period in newborns who received intrauterine blood transfusion

The gestational age of the observed children did not differ. All newborns of group 1 at birth had average physical development indicators corresponding to their gestational age. In children from group 2, anthropometric indicators were significantly lower than in children from group 1, which may be due to more early onset and severe hemolytic disease of the fetus, prolonged exposure to intrauterine tissue hypoxia, but did not differ from the children of the comparison group. The distribution of observed newborns according to the Apgar score is presented in the table (Table 5). Table 5 Distribution of observed newborns according to the Apgar score (M±). Apgar score Group 1 (n=25) Group 2 (n=21) Comparison group (n=23) Significance level (p) 1 minute 5.76±0.62 5.14±0.9 5, 16±0.83 р1-2=0Д6рі-з=0.09 р2-з= 0.44 5 minutes 6.92±0.4 6.5±0.61 6.75±0.44 рі-2 = 0.19 рі-з=0.29 р2-з= 0.39 Note: p 1-2 level of significance of differences between the main groups, p 1-3, 2-3 level of significance of differences with the comparison group. The Apgar score allows you to assess the condition of the newborn immediately after birth, and also allows you to judge the severity of perinatal asphyxia. All observed children were born premature. They were affected to varying degrees by unfavorable factors during pregnancy and prolonged intrauterine suffering of the fetus, therefore, no significant differences in Apgar scores were found at the 1st and 5th minutes of life. In the structure of the severity of asphyxia in all groups, moderate asphyxia prevailed (in the 1st group - 61%, in the 2nd group - 58%, in the comparison group - 61%, p1-2 = 0.48, p1-3 = 0, 94, р2-3=0.62). In isolated cases, severe asphyxia was detected (in the 1st group - 7%, in the second group - 14%, in the comparison group - 9% of children, p1-2 = 0.32, p1-3 = 0.86, p2- 3=0.71). 4 (16%) children of group 1 had no signs of asphyxia at birth.

All children who underwent VPC were born with signs of severe HDN and after birth, due to the need for intensive observation and treatment, were transferred from the operating room to the neonatal intensive care unit. Children in the comparison group were mostly (69%) admitted to the intensive care unit; the remainder (31%) were admitted to the intensive care unit due to their severe condition at birth. Subsequently, all children of the main group and the comparison group were transferred to the neonatal pathology department.

The duration of stay of children who received VPC in the neonatal intensive care unit was on average 3.81±1.58 days. The average length of stay of children in the comparison group in the neonatal intensive care unit was 4.66±2.5 days (p=0.2).

In the main group, no differences were found in the incidence of anemic and icteric forms of HDN. The anemic form in the 1st group was 23% (6 children), in the 2nd group - 25% of cases (5 children). The icteric form occurred in 77% (19 children) and 75% (16 children) of cases in the first and second groups, respectively (p1-2=0.49).

In the icteric form, high levels of bilirubin were noted already at birth (icteric staining of amniotic fluid, umbilical cord, mucous membranes, skin). With the predominance of anemic syndrome, attention was drawn to the pronounced pallor of the skin and mucous membranes. During the observation of children with HDN who received VPC, it was found that a single replacement blood transfusion was more often performed in newborns of group 1 (68%) than in group 2 (47.6%), p1-2 = 0.005. Repeated blood transfusion surgery was required in 12% of children in group 1 and 24% of children in group 2 (p = 0.61). Every fifth newborn received only blood transfusions without OPC (group 1 - 20%, group 2 - 28.5%, p = 0.19). The frequency of blood transfusions performed after birth is presented in the table (Table 6).

Frequency of blood and plasma transfusions performed in the neonatal period in observed children (abs.,%) Indicators 1st group (n=25) 2nd group (n=21) Significance level (p) abs. % abs. % Operation of exchange-replacement blood transfusion Once 17 68 10 47.6 pi-2 =0.005 Twice 3 12 5 24 pi-2 =0.61 Hemotransfusion without OPC 5 20 6 28.5 pi-2 =0.19 Hemotransfusion in the neonatal period after OPC 7 26 5 24 pi-2 =0.39 Plasma transfusion in the neonatal period after OPC 5 20 2 9 pl-2 =0.13 Note: p 1-2 level of significance of differences between the main groups, p 1-3, 2 -3 level of significance of differences with the comparison group. The multiplicity of blood transfusions performed without acute urolithiasis in both groups is the same, which is associated with an equal frequency of registration of the anemic form of HDN. The need for repeated blood transfusions after OPC also does not differ between groups. The structure of the pathology concomitant with TTH in the observed children is presented in the table (Table 7). Children who underwent VOC for HDP do not differ in the development of concomitant pathology from the group of premature infants. Some children were diagnosed with pneumonia and diseases of the ENT organs. Newborns of the study groups were born prematurely, which in most cases was the reason for their development of type II RDS, which required respiratory support using mechanical ventilation and CPAP. Hemolytic anemia (normochromic, microcytic) was detected in 100% of children in the main group, and in the comparison group, anemia of premature infants (normochromic, normocytic) was detected in 26%.

Results of laboratory examination of children who have undergone VPC in the neonatal period

In the first half of life, 17.3% (8) of children in the main group required additional blood transfusions. In 10.8% of cases (5 children), one blood transfusion was sufficient. These are 2 children from the 1st group, who received 1 and 2 VPC; after birth, they underwent DPK, after which no additional blood transfusions were performed in the neonatal period. And 2 children from the 2nd group who received VPC three times, who did not undergo VPC after birth, but only blood transfusion in the neonatal period in one case once, in another - twice. In 6.5% of cases (3 children), two blood transfusions were performed. These are children of the 2nd group, who underwent VPC 4 or more times, who in the neonatal period received only blood transfusions in one case once, in two or two times. Thus, children of the 2nd group, who did not undergo OPC after birth, but only underwent blood transfusion, are at high risk for developing severe anemia, requiring additional blood transfusions in the first half of life.

Some of the children in the main group (58%) were followed up by a hematologist in the first year of life. On his recommendation, we received iron supplements, folic acid, and vitamin E up to 3 courses per year.

To illustrate the case of a severe anemic form of hemolytic disease in a newborn who has undergone VPC, we give a clinical example.

Newborn Z. (case history No. 53265). Child from a 35 year old mother. The first pregnancy is over medical abortion without complications at 8 weeks. After this pregnancy, the woman was not given anti-Rhesus immunoglobulin. The second pregnancy ended in antenatal death of the fetus at 26 weeks due to the development of immune hydrops. Regarding this pregnancy, I registered at 11-12 weeks. The titer of anti-Rhesus antibodies was first detected at 12 weeks of pregnancy and amounted to 1:16 (32). An ultrasound scan at 26 weeks revealed ultrasound signs of fetal anemia. After additional examination, 3 intrauterine intravascular transfusions of blood and albumin were performed to the fetus at 27, 30, 32 weeks of gestation. The pregnancy was completed at 33-34 weeks by cesarean section. The titer of anti-Rhesus antibodies at the time of delivery was 1:8192. The baby's weight at birth was 2220 g, length 46 cm, head circumference 32 cm, chest circumference 31 cm. Apgar score 6/7 points. Due to the presence of severe HDN, the child was transferred to the intensive care unit.

Starting hematological parameters: red blood cells 3.361012/l, hemoglobin 94 g/l, hematocrit 27.1%, leukocytes 6.3109/l, platelets 240109/l, total bilirubin 43 µmol/l, total protein 40 g/l, glucose 3 .7 mmol/l, AST 42 IU, ALT 12 IU. Blood group after multiple intrauterine transfusions O (I) Rh (-) negative. Fixed anti-erythrocyte antibodies were not detected. During the first day of life, progression of anemia was noted, and therefore blood transfusion No. 1 was performed. On the 4th day of life, the child was transferred to the neonatal pathology department, where standard therapy was carried out: phototherapy, antibacterial, antihemorrhagic, infusion, cerebroprotective therapy, rational feeding.

An ultrasound examination of the abdominal organs revealed an increase in the size of the liver, which was leveled out by the time of discharge. Ultrasound of the thymus gland revealed grade I thymomegaly. Echocardiography revealed a patent foramen ovale and accessory chordae of the left ventricle. Neurosonography revealed cerebral ischemia of II–III degree and hemorrhage in the choroid plexus of the left lateral ventricle. Upon discharge from the hospital, cerebral ischemia of grade II-III is in the resolution stage; At the site of hemorrhage, a subcyst of the choroid plexus of the lateral ventricle on the left formed.

According to the hemogram, during the entire observation period the tendency towards leukopenia remained, and anemia increased over time.

The child was discharged home with recommendations on the 17th day of life. Hematological parameters at discharge: red blood cells 3.781012/l, hemoglobin 106 g/l, hematocrit 29.9%, leukocytes 6.2109/l, platelets 246109/l, total bilirubin 94.6 µmol/l, total protein 54 g/l l.

Diagnosis: Hemolytic disease of the newborn according to the Rh factor, anemic form, severe course (VPK No. 3, blood transfusion No. 1). Ischemic-hypoxic damage to the central nervous system of severe severity. Prematurity 33-34 weeks.

In an outpatient setting at the place of residence, the CBC was taken 10 days after discharge from the hospital. The following data were obtained: red blood cells 3.641012/l, hemoglobin 102 g/l, hematocrit 29.5%, leukocytes 6.8109/l, platelets 254109/l, leukocyte count within normal limits.

Results of laboratory and instrumental examination of children of the first year of life who received military training

At the age of 6 months of life, no significant differences were found between the groups in the number of red blood cells, hemoglobin levels, hematocrit, and reticulocytes. In groups 1 and 2, the MCH (average hemoglobin content in an erythrocyte) and MCHC (average hemoglobin concentration in an erythrocyte) indicators were significantly higher than in the comparison group, which is associated with an increased iron content (after numerous blood transfusions), which in turn turn favorable for the formation of hemoglobin. The level of leukocytes did not differ in all groups. Platelets remained significantly elevated in groups 1 and 2, relative to the comparison group, without going beyond age norm. By 6 months of life, there was a steady trend towards normalization of hematopoiesis.

At the ages of 9 and 12 months of life, no significant differences in the groups in the number of red blood cells, hemoglobin levels, hematocrit, or reticulocytes were also revealed. The platelet level remains elevated and does not go beyond the age norm. No significant differences in biochemical parameters were found in children of the main and comparative groups in the first year of life.

During the first year of life, the level of ferritin in children who received VPC gradually decreases, however, it remains significantly higher than the indicators of children in the comparison group. Thus, iron deficiency, characteristic of premature infants in the first year of life without hemoconflict, is not observed in children who received VPC.

The level of erythropoietin at the age of 3 months remains significantly high compared to children in the comparison group, which is associated with ongoing hemolysis of erythrocytes and anemia in children who received VPA. By the ages of 6 and 12 months, the level of erythropoietin decreases and does not differ significantly from the children in the comparison group.

In our study, in the first year of life, dynamic ultrasonography internal organs. In children who received VPC, hepatomegaly (p = 0.013) and diffuse changes in the liver parenchyma (p = 0.016) were detected significantly more often at the age of 6 months of life than in children in the comparison group. Stagnant contents of the gallbladder were detected in 3 children (6.5%) of the main group. By 12 months of life, pathological changes in the liver and gall bladder were leveled out.

Based on mathematical processing of the research results using discriminant analysis, a method has been developed for predicting the development of severe anemia, requiring additional blood transfusion in the first half of life in children who received VPC. The basis of the method is the determination of hematocrit in peripheral blood at birth and mean erythrocyte volume (MCV) at the age of 14-21 days of life, followed by calculation of the discriminant function using the developed formula. The sensitivity of the method is 89.2%, the specificity of the method is 82%. The proposed method allows, even in the neonatal period, among children with tension-type headache who received VPC, to identify a group at risk for the development of severe anemia at the preclinical stage, requiring blood transfusion in the first half of life. This will allow us to begin preventing this condition and narrow the circle of children requiring frequent research hemograms. The method is minimally invasive, does not require special expensive equipment and can be used in a clinical laboratory of any level. Based on the research carried out and the forecast method developed, we proposed an algorithm for monitoring children in the first year of life who received military training. The algorithm involves calculating a discriminant function based on the results of a hemogram at birth and discharge from the hospital and classifying the patient as a high or low risk group for the development of severe anemia in the first half of life. If the risk of developing severe anemia is low, the child should be monitored according to existing clinical recommendations. At high risk development of severe anemia in the first 3 months of life, the child should be observed together with a hematologist with the prevention of anemia, drugs that improve erythropoiesis ( folic acid, 10% vitamin E solution, recombinant erythropoietin). Hemogram monitoring is recommended every 10 days. If the hemoglobin level decreases to less than 85 g/l (order of the Ministry of Health of the Russian Federation dated April 2, 2013 No. 183n), it is recommended to send the child to the hospital to resolve the issue of blood transfusion.

At the age of 3-6 months of life, it is recommended to continue monitoring the child together with a hematologist, examining the hemogram once every 14 days, as well as conducting an ultrasound examination of the organs of the hepatobiliary system, given the high frequency of changes in these organs during the neonatal period. To compile individual calendar preventive vaccinations, an immunologist is involved in the monitoring of children who have had a military infection.

In the second half of life, hemogram monitoring is carried out monthly. According to indications, the child is observed by a hematologist, and an ultrasound examination of the organs of the hepatobiliary system is performed. Thus, a severe form of hemolytic disease of the fetus and newborn, accompanied by intrauterine blood transfusions, contributes to the formation of deviations in the state of health and disorders of hematological parameters in the first year of life of children. This dictates the need for a multidisciplinary approach to assessing the health status of such children, predicting the risk of developing severe anemia at the preclinical stage and differentiated tactics for monitoring children who received VPC during the first year of life.

Intrauterine blood transfusion using control is the most effective method to date in the treatment of Rh conflict or hemolytic disease. This procedure necessary when the unborn child and mother have blood incompatibility.

There are intra-abdominal and intravascular transfusions. Intravascular is preferable, but it is performed after the twenty-second week of pregnancy. When difficulties arise before this period, intraperitoneal transfusion is used. The indication for transfusion is, as a rule, a fifteen percent or even more decrease in the total number of red blood cells. The procedure is repeated every three weeks, since hemolytic disease of the fetus reduces the hematocrit by one percent per day. In case of a complicated or progressive form, after the thirty-fourth week, a decision is made to carry out an early birth.

The procedure uses ultrasound guidance, when the doctor, using a catheter, penetrates the umbilical cord vein through the anterior abdominal wall, and then transfuses from twenty to fifty milliliters of blood containing Rh negative factor. When the fetal blood type is known, the same is used, and when it is unknown, blood 1(0) is used. This procedure weakens the immune response from the expectant mother’s body, since it reduces the number of Rh-positive red blood cells and will maintain the fetal hematocrit above critical levels.

You should know that intrauterine blood transfusion is quite dangerous procedure, both for the expectant mother and the fetus, so it is carried out under exceptional indications and only by an experienced doctor. Sometimes complications of an infectious nature, feto-maternal transfusion, compression of the umbilical vein, premature birth and possible fetal death fetus

When pregnancy is just being planned, this procedure can be avoided by finding out the blood type, as well as the Rh factors of the woman and man. When the father is Rh positive and the mother is Rh negative, you need to undergo a set of preventive measures.

If you are undergoing such a complex procedure, you should not panic. Often the procedure goes well, and subsequently the children who have undergone it develop physically and psychologically normally.

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, characteristic dropsy with abdominal bloating and pronounced subcutaneous edema are observed. Severe anemia with a predominance of immature forms of red blood cells is always noted. At autopsy, ascites and an excessively enlarged liver and spleen are found; their lower poles can reach the iliac crest. In both organs, pronounced extramedullary erythropoiesis and a large number of erythroblasts are noted. All this leads to disruption of normal anatomy. The cavities of the heart are usually dilated, the muscular wall is hypertrophied. Foci of erythropoiesis can be found along the coronary vessels. Hydrothorax is often detected. The lungs show plethora and a large number of erythroblasts. There may be significant erythropoiesis in the kidneys, but they are usually normal sizes. Polycythemia is noted in the bone marrow. The placenta also has a characteristic appearance: pronounced swelling, increased size. Its weight often reaches 50% of the weight of the fetus. The placenta and membranes are more or less yellow due to bile pigments secreted by the fetal kidneys. In the chorionic villi - edema, stromal hyperplasia, increased number of capillaries.

Despite the good famous painting pathological changes, the chronology of the process is not entirely clear. At first it was believed that hydrops was a consequence of heart failure that developed against the background of severe anemia and hypervolemia of the fetus, but it has now become known that in live-born children with hydrops there was no significant ventricular failure or hypervolemia. A newer view is that fetal ascites is the result of hypertension in the portal and umbilical veins due to liver enlargement and anatomical changes. As a result of erythropoiesis, hypoproteinemia develops in the liver tissue as a result of liver failure and the inability of the edematous placenta to ensure 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 has become possible to understand the pathophysiology of hydrops. Indeed, hypoproteinemia and hypoalbuminemia are often found in affected fetuses, and in fetuses with hydrops this is a mandatory finding. These data prove that hypoproteinemia plays a major role in the genesis of hydrops fetalis. It has been revealed that dropsy does not develop until the hemoglobin level in the fetus decreases to less than 40 g/l. Average level hematocrit number for dropsy is 10.2%.

The breakdown of red blood cells and 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 red blood cells are destroyed, thromboplastic factors are released, disseminated intravascular coagulation syndrome develops, microcirculation disorders and profound metabolic disorders occur in the fetus.

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 baby’s tissues. In the cells of the nervous system, the processes of cellular respiration are disrupted (bilirubin encephalopathy), which may result in the death of the child or persistent neurological disorders(deafness, blindness), lasting for life.

Diagnosis of hemolytic disease of the newborn

Immediately after the birth of the child, the following is determined:

blood type;

Rh factor;

hemoglobin (normal - 38.4 g/l);

number of red blood cells (normal - 6.0 10|2/l);

To determine blocking (complete) antibodies, an indirect Coombs test is performed, which allows the detection of newborn red blood cells associated with antibodies; An hourly increase in bilirubin, an increase in its content above 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 develops lethargy, hyporeflexia, decreased tone, decreased sucking reflex, and apnea.

The essence of fetal hemolytic disease is hemolysis of red blood cells, anemia, and bilirubin intoxication. Due to the breakdown of red blood cells under the influence of the mother's anti-Rh antibodies, toxic indirect bilirubin increases. 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 and severe intoxication develop.

Forms of hemolytic disease of the newborn

There are three forms of hemolytic disease:

Hemolytic anemia.

Hemolytic anemia in combination with jaundice.

Hemolytic anemia in combination with jaundice and dropsy.

Let's look briefly at these clinical forms, which reflect the severity of the disease.

Hemolytic anemia- the mildest form of the disease. The newborn's hemoglobin level and red blood cell count are reduced. The skin is pale, there is a slight enlargement of the liver and spleen. The content of hemoglobin and bilirubin may be at the lower limit of normal or slightly lower.

The anemic form of hemolytic disease is a consequence of exposure to large quantity Rh antibodies for a full-term or almost full-term fetus (37-40 weeks).

Isoimmunization of the fetus occurs more often during childbirth. The leading sign of mild damage is anemia.

Hemolytic anemia in combination with jaundice- a 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, skin, vernix lubrication, umbilical cord, placenta and fetal membranes occurs. The content of indirect bilirubin is more than 50-60 µmol/l. The condition of the newborn gradually worsens, convulsive twitching, nystagmus, and hypertonicity appear.

With a rapid increase in the hourly increase in bilirubin by 5-10 times, “kernicterus” develops, indicating damage to the central nervous system, when blindness, deafness, and mental disability may occur. The hemoglobin content is below 38 g/l.

The icteric form occurs if antibodies act on a mature fetus for a short time. Decompensation of protective-adaptive mechanisms does not occur, the fetus is born viable.

After birth, jaundice and intoxication with indirect bilirubin quickly develop. Infectious complications (pneumonia, respiratory distress syndrome, omphalitis) are often associated. After 7 days of life, the pathogenic effect of antibodies entering the fetal blood ceases.

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

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

In part Rh negative women in connection with the pathology of pregnancy and placental insufficiency Rh antibodies penetrate into 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 of the newborn occurs tens of times more often than in premature fetuses. This indicates increased transport of isoantibodies across the placenta before and during childbirth.

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

The immediate cause of death in newborns with the edematous form of hemolytic disease is severe degenerative changes in vital organs and the inability to breathe independently.

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

In this regard, despite the continued re-penetration of isoantibodies, the fetus survives, but it develops degenerative processes in organs and tissues, and the development of the lungs and kidneys is disrupted. Due to 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 due to an isoimmunological conflict occurs in sensitized women with a massive breakthrough of the placental barrier to antibodies at 26-28 weeks of pregnancy. The immaturity of the organs and systems of the fetus causes the rapid development of dystrophic processes and necrotic changes, and the fetus dies. In more later(34-36 weeks) the action of a very large number of antibodies leads to the same outcome.

Treatment of hemolytic disease of the fetus

Currently, for the treatment of hemolytic disease of the fetus, intrauterine blood transfusions under ultrasound control. Blood transfusions to the fetus can be performed starting from 18 weeks of pregnancy. Intrauterine blood transfusion creates the prerequisites for prolonging pregnancy. There are intraabdominal and intravascular methods of blood transfusion.

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

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 number less than 30%.

In order to carry out intravascular blood transfusion, cordocentesis is performed. The umbilical cord vein is punctured in the immediate vicinity of its entry into the placenta. The guidewire is removed from the needle and blood is drawn to determine the hematocrit number of the fetus. The red blood cell mass is slowly injected through the needle, after which a second blood sample is taken to determine the final fetal hematocrit number 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 umbilical cord vein, the fetus is administered Ardoin (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 levels and hematocrit number in the fetus.

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

Intraperitoneal transfusion should only be performed if gestation is less than 22 weeks or if intravascular transfusion is difficult. In the plasma taken during cordocentesis, the concentration of fetal hemoglobin, blood type and fetal karyotype are determined. Obviously, a fetus with Rh-negative blood will not develop hemolytic disease associated with incompatibility of Rh antigens.

Treatment of hemolytic disease of the newborn

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

exchange blood transfusion;

phototherapy;

intravenous administration of standard immunoglobulins.

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

A severe form of hemolytic disease can be assumed in the presence of icteric discoloration of the skin, cheese-like lubricant, placenta, amniotic fluid, swelling and enlargement of the fetal liver.

Risk factors for bilirubin encephalopathy include:

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

hypoproteinemia (total protein content 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 exchange blood transfusion:

the appearance of jaundice immediately after birth 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 replacement blood transfusion, single-group or 0(1) group Rh-negative red blood cells and plasma [single-group or AB(IV)] are used.

In case of conflict according to the AB0 system, the red blood cell mass must be 0(1) group, suspended in plasma of the AB(IV) group. In case of blood incompatibility due to rare factors, individual selection of donors is carried out.

40-50 ml of blood is removed from the newborn and the same amount of red blood cells is injected. When repeating replacement transfusions, the dose is reduced by 2 times. Thus, the total volume of red blood cells 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 under-oxidized products of interstitial metabolism. Nevertheless possible complications: heart failure, air embolism, infection, anemia, hemorrhagic syndrome, etc.

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

The yellow color of bilirubin is due to the presence of a light absorption band 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 newborn's skin to a depth of 2 cm.

Indications for phototherapy are:

conjugation jaundice in full-term newborns with the level of indirect bilirubin in the serum up to 170-188 µmol/l or more;

hemolytic disease of the newborn due to 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, toxic effects may develop in newborns (erythema, dyspepsia, burns, hypohydration, “bronze baby syndrome”). If serum direct bilirubin values ​​exceed 85 µmol/L, phototherapy should be discontinued.

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

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

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

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 immunoglobulin doses for maternity institutions. Taking into account the literature data, it should be assumed that out of 1000 people giving birth, 170 will have Rh-negative blood. Of these, 100 women will have a child who is Rh positive. Therefore, 100 doses of the drug are needed per 1000 births if it is administered to all women with Rh-negative blood who give birth to children with Rh-positive blood.

If the method is strictly followed specific prevention Rh sensitization can practically solve the problem of Rh conflict pregnancy.