Prenatal diagnosis

Prenatal diagnosis

Prenatal diagnosis is a set of diagnostic measures aimed at identifying pathology in the fetus in utero.

Sometimes children are born with genetic, chromosomal abnormalities, developmental defects. This can be prevented by early detection of the pathology in the early stages.

What is prenatal fetal diagnosis?

Prenatal diagnosis of the fetus can be non-invasive (through the mother's blood) or invasive (penetrating the body). Invasive methods carry risks for both the mother and the fetus, and therefore are carried out only when indicated.

The procedures used:

• cordocentesis - fetal cord blood sampling;
• amniocentesis - the collection of amniotic fluid;
• chorionic biopsy - taking the cells of the outer embryonic membrane for analysis.

The biomaterial obtained in this way (blood, amniotic fluid or chorionic villi) is subject to study in a genetic laboratory.

Due to the emergence of new, reliable methods for determining the pathology of the fetus from the mother's blood, it is possible not to resort to invasive methods at the slightest suspicion from the doctor by ultrasound. Today, invasive methods are used only if the threat of detecting malformations is higher than the risk of complications (infection, miscarriages, etc.) after such a diagnosis.

Prenatal diagnosis during pregnancy

During pregnancy, some non-invasive prenatal diagnostic methods are prescribed for all women, while others are performed when indicated or the couple wishes.

1. Screening, which is performed for all pregnant women in accordance with the order of the Ministry of Health of the Russian Federation, includes:

Ultrasound. Ultrasound examination can detect many abnormalities from 12 weeks of gestation. The doctor can visualize a violation of the anatomical structure of organs and parts of the fetal body (head, limbs), as well as suspect malformations by indirect signs: the state of amniotic fluid, the location of the placenta, fetal heartbeat.

Blood test for serum factors. Blood is taken from the mother's vein. It measures the concentration of β-hCG, alpha-fetoprotein, free estriol. Thus, many diseases (Down and Edwards syndromes, defects in the development of the neural tube, defects in the anterior abdominal wall closure, abnormalities of the fetal kidneys) can be detected at a period of 16-20 weeks, however, there is a fairly high probability of both false-positive and false-negative results. Therefore, positive results are rechecked using other diagnostic methods.

The purpose of screening during pregnancy is to identify the risk group of pregnant women with possible fetal malformations.

Until recently, there were 2 mandatory screenings - at 9-13 weeks and at 16-20 weeks. Currently, in Russia, only the second screening is included in the mandatory examination during pregnancy.

2. Non-invasive prenatal genetic test (NIPT).

It is an alternative to invasive methods of prenatal diagnosis, but does not carry any risks. Blood is taken from the mother, and then the DNA of the fetus is examined in it.

Patients of VitroKlinik have the option of conducting a non-invasive prenatal test .. Your blood will be taken for analysis in Moscow, and then delivered for analysis to the laboratory of Natera, in pieces. California, USA.

The information content of such a study is very high, therefore its price is higher than that of other non-invasive methods of prenatal diagnostics.

With its help, you can find:

• Down syndrome;
• Shereshevsky-Turner syndrome;
• Edwards syndrome;
• Klinefelter's syndrome;
• Patau syndrome;
• polyX syndrome;
• XXYY syndrome;
• polyY syndrome;
• deletion of 22q11.2 and 1p36;
• maternal 5q11.2 deletion;
• Prader-Willi syndrome;
• cat cry syndrome.

All these syndromes and chromosomal abnormalities significantly worsen the quality of life of children and are not treatable. They do not depend on the age of the couple and are found all over the world.

For whom is prenatal diagnosis indicated?

Ultrasound and a blood test for serum factors are screening studies that are shown to all pregnant women without exception.

A non-invasive prenatal genetic test is carried out either according to indications or at the request of a woman who wants to be confident in the good health of her child.

Indications for the study:

• suspicion of chromosomal abnormalities (based on the results of screening studies);
• a history of the birth of children with chromosomal abnormalities or developmental defects (in one of the spouses or their relatives);
• history of stillbirth;
• habitual miscarriage.

There are also a number of situations that are not direct indications, but in which a woman is recommended to do this research:

• age after 35 years;
• the onset of pregnancy with IVF;
• history of infertility.

Before donating blood to the NIPT, a consultation with an obstetrician-gynecologist is required to confirm the presence of a progressive pregnancy and a fresh ultrasound result.

Genetic diagnosis of spouses when planning pregnancy

Already at the planning stage of pregnancy, it is possible to assume the likelihood of chromosomal abnormalities in the fetus.

For this purpose, genetic diagnosis of the spouses is performed. Used cytogenetic (study of the karyotype - the number and quality of chromosomes) and molecular genetic (to determine gene mutations) research methods.

Performing genetic diagnostics at the stage of pregnancy planning is indicated for spouses who have:

• genetic diseases;
• age after 35 years;
• cases of miscarriage, infertility, history of stillbirth;
• relatives with genetic pathology.

At VitroKlinik you have the opportunity to protect yourself from the negative consequences of having children with developmental disabilities.

In our clinic you can do:

• At the stage of preparation for pregnancy - analysis for the karyotype and molecular genetic studies to assess the risk of genetic pathology in the child.
• As part of the IVF program with PGD (a diagnostic procedure that allows you to examine the genetic material of the embryo before it is placed in the woman's uterus).
• During pregnancy, screening tests (biochemical test, ultrasound) and

Methods for prenatal diagnosis of hereditary diseases

The development of methods for prenatal diagnosis of hereditary diseases turned out to be the largest achievement of medical genetics and so significantly changed the attitude of families to the risk of having a sick child that this section has become an integral and often very important part of medical genetic counseling.

Prenatal diagnostic methods are divided into 2 groups:

Non-invasive methods.

Invasive methods.

Non-invasive methods:

Ultrasound procedure. The method is based on the ability of high-frequency vibrations to spread in the body's environments with different frequencies and depths of penetration. During pregnancy, the following is carried out:

with mass screening at 15-16 and 23-24 weeks

in the pathological course of pregnancy, ultrasound in the 1st trimester is performed to determine the term, multiple pregnancy, cystic drift, localization of the placenta. In the 2nd and 3rd trimesters of pregnancy, ultrasound can diagnose the following pathological conditions of the fetus:

16 weeks of pregnancy anencephaly, hydrocephalus, microcephaly, spinal hernia;

20 weeks of pregnancy - malformations of the gastrointestinal tract, malformations of the kidneys;

26-27 weeks of pregnancy - heart defects.

The ultrasound method allows you to identify polyhydramnios, which is often a consequence of intrauterine infection, as well as oligohydramnios, characteristic of autosomal trisomies.

Determination of alpha-fetoprotein in the serum of a pregnant woman.

Alpha-fetoprotein (AFP)- a specific protein produced by the cells of the yolk sac, and at the subsequent stages of intrauterine development by the cells of the liver of the fetus. AFP crosses the placenta and is detected in the mother's blood. In adults, AFP is not synthesized. Each week of pregnancy has its own AFP level. The maximum concentration of AFP is determined at 16-18 weeks of gestation. It is during this period that the serum of pregnant women is examined. Normal AFP values for this gestational age = 0,5-2,5 mom.

The AFP level is increased in the following diseases:

neural tube defects (anencephaly, hydrocephalus, spinal hernia, cranial hernia)

spontaneous intrauterine fetal death;

omphalocele;

Shereshevsky-Turner syndrome;

congenital nephrotic syndrome;

sacrococcygeal teratoma;

bladder exstrophy;

focal hypoplasia of the dermis;

Meckel's syndrome;

AFP level decreased with anomalies of autosomes (Down's disease, Patau's syndrome, Edwards, etc.).

When the level of AFP in the serum of a pregnant woman changes, the question of the use of invasive methods of prenatal diagnosis is decided.

Invasive methods of prenatal diagnosis

Transabdominal amniocentesis. Duration 16-17 weeks of pregnancy. After an ultrasound scan, in which the localization of the placenta, the gestational age are determined, a direct puncture of the uterus is performed under local anesthesia and 10-12 ml of amniotic fluid is removed. The resulting material is used as follows:

a) direct study of the obtained cells: to determine the sex of the fetus (X and Y chromatin); identification of morphological changes in cells.

b) direct study of amniotic fluid: to determine the level of alpha-fetoprotein, biochemical markers of monogenic diseases, biochemical indicators characterizing the state of the fetus (level of surfactant, bilirubin, etc.).

c) cultivation of the resulting fetal cells for 2-3 weeks. Subsequently, the karyotype of the fetus, the level of cell metabolism for the diagnosis of many metabolic diseases, in the presence of molecular genetic methods, genetic defects are examined for cell culture.

Hereditary diseases diagnosed on the basis of a direct study of enzymes in the cells of the amniotic fluid: adrenogenital syndrome, cystinosis, Fabry disease, galactosemia, glucose-6-phosphate dehydrogenase deficiency, hemophilia A and B, mucopolysaccharidosis, Tay-Sachs disease.

Monogenic diseases that can be diagnosed using molecular genetic methods: and -thalassemia, phenylketonuria, Lesch-Nayyan syndrome, adrenogenital syndrome, hemophilia A and B, cystic fibrosis, Duchenne myopathy, Huntington's chorea, polycystic kidney disease, Duchenne myotonia, Recklinghausen's disease, retinitis pigmentosa, ectodermal dysplasia insufficiency.

Complications of amniocentesis make up 1% of all operations and consist in trauma to the fetus and placenta, damage to the great vessels, infection, bleeding, termination of pregnancy.

Lack of amniocentesis- late (at 19-20 weeks of gestation) the term for obtaining the results of the study.

Choriocentesis. This method consists in obtaining chorionic cells by biopsy. Chorion is formed from the cells of the zygote and has the same chromosomal composition as the fetus. Biopsy is performed by transcervical cell aspiration, or transabdominal centesis.

Duration: 7-9 weeks of pregnancy.

Cordocentesis. The method involves obtaining fetal blood from the vessels of the umbilical cord. The material obtained during cordocentesis is the most reliable and informative for carrying out cytogenetic and biochemical diagnostics. The disadvantage of this method is the technical complexity of the implementation.

Fetal skin biopsy.

Fetoscopy.

Indications for the use of invasive prenatal diagnostic methods:

Mother's age: absolute indication - more than 40 years, relative - more than 35 years;

The presence in the family of patients with chromosomal pathology;

Carriage of a balanced chromosomal translocation in parents;

Determination of the sex of the fetus with X - linked monogenic diseases;

At the risk of monogenic diseases, if prenatally it is possible to determine the biochemical or molecular genetic markers of this disease;

If an elevated or decreased serum alpha-fetoprotein level is detected in a pregnant woman.

NON-INVASIVE PRENATAL DIAGNOSTIC METHODS
Method name	Dates of pregnancy	Indications for	Object of study	Methodology	Method capabilities	Advantages of the method
Screening for maternal serum factors	Between 15 and 20 weeks of gestation. In some cases, an earlier analysis is possible, but after 20 weeks the diagnostic value of the method is low.		Venous blood of a pregnant woman.	Blood serum is tested for the content of three substances: alpha-fetoprotein (AFP); chorionic gonadotropin (Hg); unconjugated estriol (NE)... Sometimes the "triple test" is supplemented with a study of the level of neutrophilic alkaline phosphatase (NSCF).	Diagnostics 2 : Down syndrome; some deformities of the brain or spinal cord (anencephaly, craniocerebral or spinal hernia) and a number of other severe malformations in the fetus.	Quite high efficiency: 70% of all cases of Down syndrome and neural tube closure defects can be detected at 15-22 weeks of gestation. With additional research NSCF the identification of fetuses with Down syndrome reaches 80%. This makes it possible, when the family makes the appropriate decision, to terminate the pregnancy without any particular complications for the woman's body. The risk of complications for the fetus is negligible.	The test results are influenced by various factors - multiple pregnancy, features of the female body, obstetric problems, etc. The consequence of this can often be false negative or false positive results of the study. In all suspicious cases, an ultrasound scan, amniocentesis, placentocentesis or cordocentesis is prescribed.
Ultrasound (US) screening of the fetus, membranes and placenta	Standard obstetric ultrasound screening of fetal malformations is carried out in two stages: at 11-13 weeks of gestation and 22-25 weeks of pregnancy.	Indicated for all pregnant women.	Fetus and placenta	1 way. A transducer (transducer) is installed on the surface of the woman's abdomen, which emits high-frequency sound waves. Reflecting from the fetal tissue, these waves are again captured by the sensor. Computer processing of waves forms a sonogram - an image on a monitor screen, which is assessed by a specialist. 2 way(more often used in the early stages). A specially designed transducer, protected by a latex condom, is inserted into the woman's vagina.	Diagnostics of dozens of varieties of congenital malformations in the fetus (defects of the brain and spinal cord, heart, kidneys, liver, intestines, limbs, facial structures, etc.). Early (up to 12 weeks gestation) detection of specific signs of Down syndrome in the fetus. In addition - clarification: the nature of pregnancy (uterine / ectopic); the number of fetuses in the uterus; the age of the fetus (gestational age); the presence of a lag in the development of the fetus; position of the fetus in the uterus (head or breech presentation); the nature of the fetal heartbeat; the sex of the fetus; location and condition of the placenta; the state of amniotic fluid; violations of blood flow in the vessels of the placenta; the tone of the uterine muscles (diagnosis of the threat of termination of pregnancy).	The potential harmful effects of ultrasound scanning on the fetus are much less than the harmful effects of X-rays (a WHO expert group has officially recognized four-fold ultrasound of the fetus during pregnancy as safe).	Technical limitations and relative subjectivity in interpreting scan results. The diagnostic value of ultrasound screening can significantly decrease with weak technical capabilities of the apparatus and low qualifications of a specialist.
Sorting fetal cells	Between 8 and 20 weeks of gestation.	Similar to those for chorionic biopsy, placentocentesis and cordocentesis.	Erythroblasts or fetal lymphocytes contained in the venous blood of a pregnant woman.	For sorting (separation of fetal cells contained in a woman's blood from her own cells), highly specific monoclonal antibodies and flow-through laser sorting are used. The resulting fetal cells are subjected to molecular genetic studies.	Virtually similar to chorionic biopsy, placentocentesis and cordocentesis	An negligible risk of complications for the fetus due to the low invasiveness of the procedure in combination with diagnostic capabilities identical to those in highly invasive procedures (chorionic biopsy, etc.)	Large labor and technical intensity of the method, leading to a high cost of research. Insufficient verification in terms of reliability - this technique is currently mainly experimental and is rarely used in routine practice.

INVASIVE PRENATAL DIAGNOSTIC METHODS
Method name	Dates of pregnancy	Indications for	Object of study	Methodology	Method capabilities	Advantages of the method	Disadvantages of the method, risk during the procedure
Chorionic biopsy	10-11 weeks.	High probability of hereditary diseases (the probability of detecting a serious illness in the fetus, comparable to the risk of miscarriage after a biopsy).	Chorionic cells (outer embryonic membrane).	1 way. A small amount of chorionic tissue is aspirated with a syringe through a catheter inserted into the cervical canal. Method 2. The tissue sample is sucked into a syringe using a long needle inserted into the uterine cavity through the abdominal wall. Both options for chorionic biopsy are performed on an outpatient basis or with a short-term hospitalization of a pregnant woman. The manipulation is performed under ultrasound control. Depending on the practice of the particular healthcare facility, the biopsy is performed either under local or general anesthesia (anesthesia). Before the procedure, a woman needs to undergo a laboratory examination (blood tests, smears, etc.).	Determination of Down syndrome in the fetus, Edwards syndrome, Patau and other chromosomal diseases, accompanied by gross deformities or mental retardation. Diagnosis of genetic diseases (the range of diagnosed hereditary diseases depends on the capabilities of a particular laboratory and can vary from isolated genetic syndromes to dozens of different disabling diseases). Determination of the sex of the fetus. Establishment of biological relationship (paternity).	Rapid receipt of results (within 3-4 days after taking the material). It is possible to diagnose a severe disabling disease in the fetus in the period up to the 12th week, when the termination of pregnancy occurs with fewer complications for the woman, in addition, the stress load on family members is reduced.	For a number of technical reasons, it is not always possible to conduct a qualitative analysis of tissue samples. There is little risk of false positive and false negative results due to the so-called phenomenon. "Placental mosaicism" (non-identity of the genome of chorionic and embryonic cells). Prolonged exposure of the fetus to ultrasound, the harmlessness of which has not been proven. Risk of accidental damage to the membranes. The risk of an adverse effect on the course of pregnancy in Rh-conflict. The risk of miscarriage (from 2 to 6% depending on the condition of the woman). Risk of fetal infection (1-2%). The risk of bleeding in a woman (1-2%). Risk (less than 1%) of some abnormalities in the development of the fetus: cases of gross deformities of the extremities in newborns undergoing chorionic biopsy have been described. In general, the risk of complications with chorionic biopsy is low (no more than 2%).
Placentocentesis (late chorionic biopsy)	II trimester of pregnancy.	These are the same indications for a chorionic biopsy.	Placental cells.	Similar to the method described above for the 2nd method of chorionic biopsy. It is carried out under local or general anesthesia, on an outpatient basis or with a short-term hospitalization of a woman. The requirements for examining a pregnant woman before placentocentesis are identical to those for a chorionic biopsy.	Similar to Chorionic Biopsy.		The cultivation of cells obtained during placentocentesis may be less effective than the cultivation of chorionic cells, therefore sometimes (very rarely) there is a need to repeat the procedure. This risk is absent in laboratories practicing modern methods of cytogenetic diagnostics. Conducting an examination at a sufficiently long period of pregnancy (if a serious pathology is detected, termination of pregnancy during this period requires lengthy hospitalization and is fraught with complications).
Amniocentesis	15-16 weeks.	The same as for chorionic biopsy and placentocentesis. Suspicion of the presence of certain congenital diseases and pathological conditions in the fetus.	Amniotic fluid and fetal cells in it (desquamated fetal skin cells, epithelial cells from the urinary tract, etc.).	The amniotic fluid is drawn into a syringe with a needle inserted into the uterine cavity through the abdominal wall. The manipulation is performed under the control of an ultrasound machine, on an outpatient basis or with short-term hospitalization. Local anesthesia is used more often, but it is quite possible to carry out the procedure under general anesthesia. Before the procedure, a pregnant woman undergoes a laboratory examination similar to that of a chorionic biopsy and placentocentesis.	Diagnostics of various chromosomal and gene diseases. Determination of the degree of maturity of the lungs of the fetus. Determination of the degree of oxygen starvation of the fetus. Determination of the severity of the Rh-conflict between mother and fetus. Diagnosis of certain fetal malformations (for example, gross deformities of the brain and spinal cord, anencephaly, exencephaly, spinal hernia, etc.).	A wider (in comparison with chorionic biopsy and other invasive methods of prenatal diagnosis) range of detected pathologies. The risk of miscarriage is slightly less than with a chorionic biopsy. This risk is only 0.5-1% higher than in pregnant women who have not undergone invasive examinations at all.	Technological problems. Since there are very few fetal cells in the collected sample, it is necessary to give them the opportunity to multiply in vitro. This requires special nutrient media, a certain temperature, reagents, and sophisticated equipment. Quite a long time (from 2 to 6 weeks) for the analysis of chromosomes. Results are obtained on average by 20-22 weeks. When the diagnosis is confirmed, termination of pregnancy at this time is accompanied by a greater number of complications than, for example, at the 12th week. Stronger and moral trauma of family members 1 ... Prolonged exposure of the fetus to ultrasound, the harmlessness of which has not been proven. The risk of having a small baby is slightly increased. There is a low (less than 1%) risk of respiratory distress in the newborn.
Cordocentesis	After the 18th week of pregnancy.	Similar to those for chorionic biopsy and placentocentesis.	Umbilical cord blood of the fetus.	A fetal blood sample is obtained from an umbilical cord vein, which, under ultrasound control, is punctured with a needle inserted into the uterine cavity through a puncture of the woman's anterior abdominal wall. The procedure is performed under local or general anesthesia, on an outpatient basis or with a short-term hospitalization of a woman. The requirements for examining a woman before cordocentesis are identical to those for a chorionic biopsy.	They are similar to the possibilities of chorionic biopsy and placentocentesis, partly amniocentesis. The possibility of therapeutic manipulations (administration of drugs, etc.).	The minimum likelihood of complications.	Examination during a long period of pregnancy (in case of detection of a serious pathology, termination of pregnancy during this period requires lengthy hospitalization and is fraught with complications).

Mass screening of newborns (neonatal screening) is one of the most effective ways to identify the most common congenital and hereditary diseases in newborn children.

Allows to ensure early detection of diseases and their timely treatment, to stop the development of severe manifestations of diseases ( phenylketonuria, cystic fibrosis, congenital hypothyroidism, adrenogenital syndrome, galactosemia) leading to disability.

As part of the implementation of the priority national project "Health" (order of the Ministry of Health and Social Development of Russia dated March 22, 2006 No. 185 "On mass examination of newborn children for hereditary diseases"), since 2006, the introduction of diagnostics of such diseases as adrenogenital syndrome, galactosemia and cystic fibrosis.

Since 2007, audiological screening of children in the first year of life has been included in the list of detected diseases, which will allow timely diagnosis of hearing impairment in a child and subsequent rehabilitation of hearing loss.

Since 2012, in the Sverdlovsk region, neonatal screening has been expanded to 16 diseases (order of the Ministry of Health of the SB dated 02.03.2012 No. 166-p "On improving the mass examination of newborn children for hereditary diseases in the Sverdlovsk region"). The study is carried out on a dry blood spot by tandem mass spectrometry (MS-MS). List of additional 11 diseases:

leucinosis

tyrosinemia (type 1)

citrullinemia

multiple carboxylase deficiency

deficiency of very long chains of acyl-CoA fatty acid dehydrogenase

insufficiency of the middle chains of acyl-CoA dehydrogenase of fatty acids

deficiency of mitochondrial trifunctional protein / deficiency of long-chain hydroxyl-CoA fatty acid dehydrogenase

glutaric aciduria (type 1)

isovalerian acidemia

methylmalonic acidemia

propionic acidemia

When choosing diseases for neonatal screening, in accordance with the recommendations of the World Health Organization, factors such as the severity of disease manifestations, the frequency of spread of these diseases, as well as the simplicity and reliability of the diagnostic methods used, and the availability of affordable and effective treatments were taken into account.

In the United States, mass neonatal screening has been carried out since 1963.

Neonatal screening is carried out at: - 4th day of life in a full-term baby; - 7th day of life in a premature baby.

A blood sample is taken from the heel of a newborn baby 3 hours after feeding. Blood samples are taken on special filter paper test blanks from the heel of the newborn. Before taking a blood sample, the heel of a newborn baby must be washed, wiped with a sterile napkin moistened with 70-degree alcohol, then moistened with a dry sterile napkin. The puncture of the heel of a newborn child is carried out with a disposable scarifier, the first drop of blood is removed with a sterile dry swab. To accumulate a second drop of blood, gently press on the heel of the newborn baby. The test blank is applied perpendicularly and soaked in blood completely and through in accordance with the circle dimensions indicated on the test blank. The appearance of the blood stains must be the same on both sides of the test blank.

Hypothyroidism... Thyroid gland pathology, which can lead to a delay in physical and mental development. To date, timely diagnosed hypothyroidism responds well to hormone therapy. The prevalence of the disease is 1 in 5 thousand. Androgenital syndrome. Pathology of the adrenal cortex, in which the normal production of the hormone cortisol is disrupted. It can manifest itself in the form of a delay in the development of the reproductive system, problems with blood vessels and heart. This syndrome cannot be completely cured, but it can be controlled with hormone therapy. The prevalence of the disease is 1 in 15 thousand.

Cystic fibrosis... The disease is manifested by a noticeable thickening of secretions in the digestive tract and lungs, which leads to damage to the liver, gastrointestinal tract, respiratory system and other organs. Treatable. The prevalence of the disease is 1 in 3 thousand.

Phenylketonuria... A disease characterized by a violation of the production of certain enzymes. The consequences are quite serious. First of all, these include lesions of the central nervous system. However, they can be avoided with a special diet. The prevalence of the disease is 1 in 15 thousand.

Galactosemia... This is the name of the lack of an enzyme that breaks down galactose - one of the sugars found in lactose and other substances. The consequences of a lack of this enzyme appear after a few weeks of life. The child begins to have jaundice, vomiting, loss of appetite. Over time, severe liver pathologies develop, mental and physical development slows down, vision deteriorates. This congenital pathology is dangerous, while it is quite rare. The prevalence is 1 in 30 thousand.

Prenatal diagnosis is associated with solving a number of biological and ethical problems before the birth of a child, since this is not about curing the disease, but about preventing the birth of a child with a pathology that cannot be treated (usually by terminating a pregnancy with the woman's consent). At the current level of development of prenatal diagnostics, it is possible to establish a diagnosis of all chromosomal diseases, most congenital malformations, enzymopathies, in which a biochemical defect is known. Some of them can be established at almost any stage of pregnancy (chromosomal diseases), some - after the 12th week (reduction defects of the limbs, atresia, anencephaly), some - only in the second half of pregnancy (heart and kidney defects).

Indications for prenatal diagnosis: presence of a well-established hereditary disease in the family; the mother is over 37 years old; carriage by the mother of the X-linked recessive disease gene; a history of spontaneous abortions in pregnant women in early pregnancy, stillbirths of unknown origin, children with multiple malformations and chromosomal abnormalities; the presence of structural rearrangements of chromosomes (especially translocations and inversions) in one of the parents; heterozygosity of both parents for one pair of alleles in pathology with an autosomal recessive type of inheritance; pregnant women from the zone of high radiation background.

Currently applied indirect and direct methods of prenatal diagnosis.

At indirect methods examine the pregnant woman (obstetric and gynecological methods, blood serum for alpha-fetoprotein); with straight lines - the fruit.

To direct non-invasive(without surgery) methods include ultrasonography; NMR tomography of the fetus,

To direct invasive(with violation of tissue integrity) include: chorionic biopsy, amniocentesis, cordocentesis and fetoscopy.

Ultrasonography (echography)- This is the use of ultrasound to obtain an image of the fetus and its membranes, the state of the placenta. From the 5th week of pregnancy, you can get an image of the membranes of the embryo, and from the 7th week - and the embryo itself. By the end of the 6th week of pregnancy, the cardiac activity of the embryo can be recorded. In the first two months of pregnancy, ultrasound still does not detect fetal abnormalities, but it is possible to determine its viability. In the 2nd trimester of pregnancy, the possibilities of ultrasound diagnostics increase significantly. At 12-20 weeks of pregnancy, it is already possible to diagnose twin pregnancy, localization of the placenta, anencephaly, defects in the skeletal system and closure of the neural tube, atresia of the gastrointestinal tract.

In recent years, has become widespread NMR tomography of the fetus, allowing to identify structural abnormalities that are not detected by ultrasound (small brain anomalies, tuberous sclerosis, polycystic kidney disease, etc.).

Direct invasive methods of prenatal diagnosis

Chorion biopsy - taking the epithelium of the chorionic villi for research - it is carried out transcervically (through the cervical canal) or transabdominal under the control of ultrasonography between the 8th and 10th weeks of gestation. The resulting tissue is used for cytogenetic and biochemical studies and DNA analysis. With this method, all types of mutations (gene, chromosomal and genomic) can be detected. A significant advantage of chorionic villus sampling is that this method of prenatal diagnosis can be used already in the early stages of fetal development. If any abnormalities in the development of the fetus are detected and the parents decide to terminate the pregnancy, then termination of pregnancy at the 12th week (the period of the chorionic villus biopsy) is less dangerous than at the 18-20th week, when the results of amniocentesis become known

Amniocentesis - obtaining amniotic fluid and fetal cells for later analysis. This study became possible after the development of the technology of transabdominal or transvaginal amniocentesis, carried out under the guidance of ultrasound. Obtaining the test material (cells and fluid) is possible at the 16th week of pregnancy. The main indications for amniocentesis are:

1) the age of the pregnant woman is more than 35 years old;

2) exceeding the threshold values ​​of the levels of alpha-fetoprotein, chorionic gonadotropin and a decrease in free estriol in the blood of a pregnant woman:

3) the presence of several serious risk factors for pregnancy complications;

Cordocentesis - taking blood from the umbilical cord, whose cells and serum are used for cytogenetic, molecular genetic and biochemical studies. This procedure is carried out in the period from the 18th to the 22nd week of pregnancy under the supervision of ultrasound I. Cordocentesis can also be carried out during embryopetoscopy. The procedure is successful on the first try in 80-97% of cases. The advantage of cordocentesis over amniocentesis is that lymphocytes are cultured much faster and more reliably than amniocytes. For example, the determination of virus-specific DNA or RNA (by reverse transcription) in the blood of the fetus is crucial for the diagnosis of intrauterine infections - HIV, rubella, cytomegaly, parvovirus B19. However, indications for cordocentesis are limited due to the high risk of complications, such as intrauterine fetal death (up to 6%), miscarriage (9%).

Fetoscopy - examination of the fetus with a fiberoptic endoscope inserted into the amniotic cavity through the anterior wall of the uterus... The method allows you to examine the fetus, umbilical cord, placenta and make a biopsy. Fetoscopy is accompanied by a high risk of termination of pregnancy and is technically difficult, therefore, has limited application.

Modern technologies make it possible to carry out biopsy of the skin, muscles, liver of the fetus for the diagnosis of genodermatosis, muscular dystrophies, glycogenosis and other severe hereditary diseases. The risk of termination of pregnancy when using invasive methods of prenatal diagnosis is 1-2%.

Vesicocentesis, or puncture of the fetal bladder, is used to obtain its urine for research in cases of serious diseases and malformations of the organs of the urinary system.

Pre-implantation diagnostics

serious hereditary diseases became possible in the last decade thanks to the development of in vitro fertilization technology and the use of polymerase chain reaction (PCR) to obtain multiple copies of embryonic DNA. At the stage of cleavage of a fertilized egg (blastocyst), when the embryo consists of 6-8 individual cells, one of them is separated by micromanipulation methods for DNA extraction, its multiplication and subsequent analysis using DNA probes ( primer polymerase chain reaction, Sauthern-blot, study of polymorphism of DNA restriction fragments, etc.). This technology is used to detect hereditary diseases - Tay-Sachs, hemophilia, Duchenne muscular dystrophy, fragile X-chromosome and a number of others. However, it is available to a few large centers and has a very high research cost.

Are being developed fetal cell isolation methods(erythroblasts, trophoblasts, etc.), circulating in the blood of a pregnant woman, for carrying out cytogenetic, molecular genetic and immunological analyzes for diagnostic purposes. So far, such a diagnosis is possible only in cases when the blood cells (erythroblasts) of the pregnant woman have chromosomes or fetal genes, for example, the Y chromosome, the Rh factor gene in a Rh negative woman, and HLA antigens inherited from the father.

Further development and dissemination of methods for prenatal diagnosis of hereditary diseases will significantly reduce the incidence of hereditary pathology in newborns.

Carrying a baby is a process in which it is important to monitor your well-being and health. Doctors often prescribe different types, but do not explain how each works. That is why it is worth understanding the features of prenatal diagnosis.

What it is

Prenatal fetal diagnosis is a comprehensive prenatal diagnostic method for determining the period. With its help, violations of the heart can be detected in a child.

Prenatal diagnosis also allows you to determine the baby's father. If the child is sick, the doctor and the parents consider all possible drug treatment options. As a result, the spouses decide whether to leave the child or.

Invasive methods and indications for the procedure

There are invasive and non-invasive methods of prenatal diagnosis. With the help of invasive techniques, diagnostics can be carried out by invading in order to obtain biological material. Techniques aimed at penetrating the body of a pregnant woman are quite dangerous, as they can cause various complications. For this reason, the doctor can only prescribe them in difficult cases. The purpose of the invasive examination is to obtain tissue samples that belong to the fetus.

The procedure is shown if:

• mother of a child over thirty-five years old;
• the baby has a chromosomal abnormality;
• a relative of the baby with a chromosomal abnormality has been identified;
• any monogenic disease was found in the parents of the baby or close relatives;
• if at the beginning or before her, the woman drank pharmacological drugs (against tumors);
• the woman was sick with rubella;
• someone from a married couple had previously received radiation up to the moment;
• pregnant in the past suffered spontaneous.

Important! An invasive examination can be carried out only if the family of the pregnant woman gives their consent to this. The doctor may recommend this procedure only if the risk of a severe child is higher than the risk of complications after an invasive examination technique.

Chorionic biopsy is an invasive procedure in which chorionic tissue samples are obtained to determine and prevent chromosomal diseases, chromosomal abnormalities, monogenic diseases. To obtain chorionic tissue, you need to take a puncture of the uterus.

This action can be done through the wall in the abdomen, vagina, or cervix using biopsy forceps or a suction catheter. The doctor selects a method depending on the specifics of the location of the chorion in the uterine cavity.

Did you know? The baby is able to hear sounds from the sixth month of pregnancy. He hears the mother's circulation, the digestion of the food she has consumed. The baby can hear the mother's voice, as it arises inside her body. Also, the child manages to feel the beating of his own and his mother's heart.

The main advantage of chorionic biopsy is that it can be done early in gestation. The test result can be obtained in three days.

It consists in the study of amniotic fluid, which is taken with a needle and a microscopic puncture in the abdominal cavity of a pregnant woman. That is, this is a simple surgical intervention in which the doctor takes amniotic fluid for further research.

Amniocentesis invasive prenatal diagnosis makes it possible from the fifteenth week to learn about the child's chromosome set and possible abnormalities. Amniocentesis is prescribed after a blood test or blood test, when the doctor suspects the presence of abnormalities in the chromosome set or hereditary diseases in the fetus.

From the twenty-second to the thirty-second week, such a survey is carried out if the expectant mother needs to find the causative agent of the infection, to find out at what stage of development the child's lungs are, to assess the protein concentration in the fetal blood.

Cordocentesis

Important! Be careful when choosing this procedure for examination, since such a diagnosis is still only experimental in nature and is used in rare cases.

Having discovered any problems with a woman or a baby, they can be effectively eliminated. Therefore, in the modern world, women can be calm about themselves and their child, provided that they consult a doctor in a timely manner.

Prenatal Diagnosis Facts

Most babies are born genetically and clinically healthy.

According to the European Registry of Congenital Malformations, the incidence of developmental anomalies in the prenatal period does not exceed 2.5-3%.

Chromosomal abnormalities (CA) in newborns are recorded only in 7-8 cases per 1000, i.e. less than 1%.

The frequency of gross pathology of chromosomes - chromosomal syndromes (mainly trisomies) - 2-3 cases per 1000. Among children born with stigmas of dysembryogenesis - 12%.

According to the WHO, only 4-6% of newborns suffer from VND.

Only 2% of congenital malformations are the result of exposure of a pregnant woman to medications, harmful substances, X-rays or viruses; in 98% of all cases, the formation of congenital malformations is caused by random mutations and heredity of the parents.

The immediate causes of CMF in 15-20% of cases are hereditary (genetic) factors, in 8-10% - environmental factors or maternal disease (diabetes), in 65% of all cases, the causes of CMF remain unknown.

In the same time:

Congenital malformations of the fetus in most regions of Russia occupy a leading place in the structure of the main causes of perinatal mortality;

Infant mortality rates from congenital malformations in Moscow and the Moscow region vary from 4.3 to 5.0%;

Up to 5-7% of stillbirths are due to VNZ, and their share in the structure of causes of infant mortality reaches 20-25%;

Surviving children, as a rule, become deeply disabled, treatment, special care, upbringing and social adaptation of which requires significant efforts from the family and the state, large economic costs;

The detection rate of congenital malformations remains low: according to the European Registry of Congenital Malformations, the incidence of congenital malformations in newborns is on average 21.8 per 1000, and the frequency of those detected antenatally is 5.8 per 1000. According to different authors, the rates of prenatal detection of congenital malformations vary widely - from 0.14% to 2.53%.

Research methods

Ultrasound (screening and selective).

Biochemical (determination of levels of serum blood markers).

Invasive (chorionic villus aspiration, amniocentesis, cordocentesis, placentocentesis).

Laboratory genetics methods (cytogenetics, molecular genetics, etc.).

Functional assessment of the state of the fetus (CTG, dopplerometry).

Diagnosis verification methods (pathological and syndromological studies).

Ultrasound procedure.

Among all modern methods of prenatal diagnostics, ultrasound takes the first place due to a unique combination of qualities: high information content, safety and the possibility of mass use.

Security:

In diagnostic devices, ultrasound is used with an intensity in the range of 1-40 milliwatts / cm2;

Tissue damage occurs at an ultrasound intensity of 4 watts / cm2, and the ultrasound intensity used in clinical practice is approximately 100-1000 times less energy in energy;

Due to the pulsating mode of radiation, the time of exposure to ultrasound is less than 1% of the time of the entire study;

Currently, there is not a single confirmed official report on the harmful effects of ultrasound on the development of the fetus.

It is important to emphasize:

1. Thorough assessment of the anatomy of the fetus, the ratio of the sizes of individual parts of its body and organs, allow to identify CMF in 60-70% of cases.

2. The effectiveness of ultrasound diagnostics of congenital malformations of the fetus increases with the use of a two-level examination of pregnant women.

Level I - screening of pregnant women in antenatal clinics, maternity hospitals.

Level II - diagnostic centers, departments of prenatal diagnostics of regional centers. Pregnant women with suspected congenital malformations are sent to these institutions after a level I examination.

3. Ultrasound diagnostics of congenital malformations is possible in the first trimester of pregnancy.

4. The problem of early diagnostics of congenital malformations cannot yet be effectively solved within the framework of practical health care. The main goal of an ultrasound scan in the first trimester is to form a risk group for VNZ.

Ultrasound examination in the first trimester

1. Allows you to set the gestational age as accurately as possible by measuring the coccygeal-parietal size (CTE) of the embryo / fetus.

2. Accuracy of diagnostics is achieved by performing ultrasound with a transvaginal transducer with a frequency of at least 5-7.5 MHz.

3. The details of all organs and anatomical structures during these periods are indistinguishable, therefore it is recommended to assess the following anatomical formations:

Bones of the cranial vault: an assessment of the bones of the skull reveals such defects as acrania, ecencephaly, anencephaly, inioncephaly, cranial hernia;

The vascular system of the lateral ventricles of the brain in the form of a “butterfly”: a distinct M-echo and a “butterfly” pattern allows one to suspect many severe cerebral defects in the early stages of pregnancy - proencephaly, holoprosencephaly, atelencephaly;

Spine: possible identification of spina bifida;

Stomach: Esophageal atresia may be suspected;

Anterior abdominal wall: gastroschisis, omphalocele can be diagnosed (not to be confused with physiological umbilical hernia observed up to 12 weeks!);

Bladder: Megacystic can be diagnosed;

Limb bones: identify phocomelia.

4. Assessment of the structures of the ovum and embryo is used as a selection criterion for the risk group for the chromosomal pathology of the fetus:

The thickness of the collar space (TVP) 3 mm or more at 10-14 weeks is a marker not only of CA (Down, Turner, Edwards syndromes), but also of a wide range of various congenital malformations (heart, musculoskeletal system) and other complications of pregnancy (spontaneous abortion, intrauterine fetal death, early neonatal mortality);

The diameter of the yolk sac: with abnormal values ​​of the diameter: more than 6.4 mm in the period of 10 -11 weeks, deformation of its structure and increased echogenicity, or absence, the likelihood of a non-developing pregnancy increases significantly;

Cardiac activity of the embryo: normal average heart rate values ​​are 170 beats / min at 10 weeks, and 157 beats / min at 14 weeks of gestation. The increase in frequency and, especially, the slowing down of the rhythm during these periods is an indication for dynamic monitoring of the pregnant woman.

Ultrasound examination in the II trimester

1. Detection of congenital malformations by ultrasound: the most optimal time should be considered 20-24 weeks.

2. Assessment of fetal development must necessarily include the measurement of the main fetometric parameters: biparietal and frontal-occipital dimensions (BPR and LZR), head and abdominal circumference (OH and OB), thigh length (DB) of the fetus:

All fetometric parameters set forth in numerous tables and existing in the programs of ultrasound devices correspond to the gestational age calculated by the date of the last normal menstruation;

The most commonly used fetometric tables are F. Hadlock, M. Hansmann and S. Campbell. At present, in many regions of Russia and in the Yaroslavl region, their own normative parameters of fetometry have been developed;

The use of regional standards (see Appendix) for fetometric indicators of the size of fetal body parts and its weight allows standardizing the results of prenatal examination, ensuring a correct assessment of the dynamics of fetal growth, and reducing the number of erroneous diagnoses of IUGR.

Diagnosis of congenital malformations

1. The study of the anatomy of the fetus is important to carry out sequentially according to a single scheme (head, face, spine, lungs, heart, abdominal organs, kidneys and bladder, extremities).

2. Some congenital malformations at the beginning of the second trimester are not yet detected by ultrasound (Dandy-Walker syndrome, some forms of hydrocephalus, aneurysm of the Galen's vein, arachnoid and porencephalic cysts) and can be diagnosed only in the third trimester, which requires additional ultrasound during these periods.

Central nervous system defects

Anomalies in the development of the central nervous system are the most frequently detected congenital malformations.

The frequency ranges from 1: 1000 live births (hydrocephalus) to 1: 25000-35000 live births (Dandy-Walker syndrome).

The main congenital malformations of the central nervous system include: anencephaly, cephalocele, hydrocephalus and ventriculomegaly, microcephaly, agenesis of the corpus callosum, vascular plexus cysts, holoproencephaly, spina bifida.

Anencephaly and acrania can be detected already in the first trimester. Anencephaly is established by the absence of the bones of the cerebral skull and brain tissue. Acrania - when the fetal brain is not surrounded by a bony vault. Anencephaly and acrania are developmental defects that are incompatible with life.

Cephalocele occurs with a frequency of 1: 2000 live births and represents the exit of the meninges outward through a defect in the bones of the skull. The term encephalocele means that the hernial sac contains brain tissue. With ultrasound, a cephalocele is defined as a hernial formation presenting to the bones of the skull. The prognosis for the life and health of the child is unfavorable; abortion is recommended.

Spina bifida is an anomaly in the development of the spinal column resulting from a violation of the closure of the neural tube. Exiting through a defect in the lining of the spinal cord is called a meningocele. If the hernial sac contains nerve tissue, the formation is called meningomyelocele. Most often, the defect is located in the lumbar and sacral spine. The frequency depends on the geographic region: in the UK 4: 1000, in the US 0.5: 1000 newborns. Ultrasound diagnostics is possible from the end of the first trimester. In the presence of spina bifida, the spinous processes of the vertebrae during transverse scanning do not close, but form a U- or Y-shaped configuration. In the presence of meningocele or meningomyelocele in the area of ​​the defect, a thin-walled hernial sac is determined. It can be an isolated anomaly, but is often associated with Arnold-Chiari syndrome, as well as more than 40 syndromes of multiple malformations. There is an increase in this pathology with monozygous twins. Tactics. If meningomyelocele is found before fetal viability, termination of the pregnancy is recommended. With isolated spina bifida, postpartum surgery (closure of the defect or bypass grafting) is possible. Any open neural tube defect must be closed within 24 hours of life (risk of infection). The prognosis for life and health depends on the level of location, the magnitude and nature of the combined anomalies.

Neural tube defects is a term that combines all of the above anomalies in the development of the central nervous system. The frequency ranges from 1-2: 1000 to 6: 1000 newborns, and depends on the place of residence, the time of year at the time of conception and the fact of taking anticonvulsants, both by the mother and the father of the child. Most of the defects occur in women without risk factors.

The probability of recurrence of this type of CDF in offspring is:

4-5% at the birth of one child with congenital malformations

10% at the birth of two children with congenital malformations

3-5% in the presence of congenital malformations in one relative of the first line

5-7% if two first-line relatives have congenital malformations

10% in the presence of two consecutive analyzes of alpha-fetoprotein in maternal serum with values ​​above 2.5 MoM (exceeding the average value)

Hydrocephalus is an increase in the size of the ventricles of the brain, in most cases accompanied by an increase in the size of the head. Ventriculomegaly is an isolated expansion of the ventricles of the brain, which is not accompanied by an increase in the size of the head. In most cases, it develops as a result of impaired outflow of cerebrospinal fluid. Chromosomal defects are found in 25% of cases of hydrocephalus detected before childbirth. Combined anomalies are diagnosed in 70-80% of cases, while half of them are extracranial and cannot always be detected prenatally:

Meningoencephalocele with the formation of Arnold-Chiari syndrome, which occurs in 1/3 of fetuses with hydrocephalus;

Dandy-Walker syndrome (partial or complete agenesis of the cerebellum, cystic enlargement of the IV ventricle and enlargement of the posterior cranial fossa);

Holoprosencephaly (violation of the division of the brain into hemispheres);

Agenesis of the corpus callosum;

Arachnoid cysts

Galen's vein aneurysm.

Tactics: if hydrocephalus is detected before the period of fetal viability, it is advisable to discuss the issue of termination of pregnancy with the parents. If the pregnancy has not been interrupted, in the future, with an increase in ventriculomegaly, bypass surgery is possible. The effectiveness of bypass surgery and the outcome of the operation depend on the presence of combined pathology.

Microcephaly occurs with a frequency of 1.6: 1000 live births and can be primary, as well as be part of various syndromes: encephalocele and spina bifida. Microcephaly has been described in more than 125 CA, 400 monogenic diseases. Factors contributing to the formation of microcephaly also include infections (cytomegalovirus, toxoplasmosis, rubella), alcohol, retinic acid, cocaine and phenylketonuria in the mother.

The diagnosis based only on the biparietal size values ​​is unreliable; it is necessary to assess the reduction in head size in relation to the length of the femur and / or gestational age by 3 weeks or more without any deviations from the normal development of individual brain structures. The prognosis for life and health depends on the cause of the abnormality.

Cysts of the choroid plexus of the lateral ventricles in the second trimester are found in 1-2% of pregnant women, more often in the period from 14 to 24 weeks. The diameter of the cysts, as a rule, does not exceed 10 mm. If cysts are present, the fetal anatomy must be carefully examined. In the presence of abnormalities, prenatal karyotyping is indicated. With single isolated cysts, the tactics of pregnancy management does not have any special features. In most fetuses, choroid plexus cysts spontaneously disappear by 28-30 weeks of gestation.

Important to remember:

The risk of a pathological karyotype of the fetus with isolated cysts reaches 2.4% (trisomy 18);

The risk of fetal aneuploidy is higher with bilateral cysts;

The probability of a pathological karyotype reaches 10.5% when cysts are combined with additional risk factors: maternal age, congenital malformations revealed by ultrasound, burdened obstetric and family history. Amniocentesis and fetal karyotyping are recommended.

Agenesis of the corpus callosum, complete or partial, occurs in 0.4 to 0.7% of all pregnancies. The incidence of fetal aneuploidy is 10%. Agenesis of the corpus callosum is possible with more than 40 chromosomal aberrations, 120 monogenic diseases and syndromes accompanied by malformations. Holoproencephaly, Dandy-Walker and Arnold-Chiari syndromes are most often combined with agenesis. Diagnosis before 20 weeks of pregnancy is almost impossible.

2. When studying the anatomy of the brain, the size and shape of the fetal head, it is important to pay attention to visualization of the fetal face:

Profile assessment allows diagnosing a number of defects (bilateral or large median cleft of the face) and identifying echographic markers of CA (smoothed profile, reduced length of the nasal bones, microgenia);

Examination of the nasolabial triangle makes it possible to diagnose or suspect the presence of clefts of the lip and palate, which are visualized as hypo- or anechoic defects;

Clear visualization of the eye sockets is necessary to exclude anophthalmia, microphthalmia, cyclopia, and neoplasms.

1. The most optimal time for the study of the anatomy of the fetal heart is considered to be 24-26 weeks of pregnancy. When conducting ultrasound in a time less than optimal and the impossibility of clear visualization of the anatomical structures of the heart, it is recommended to repeat the study after 4 weeks.

2. Currently, the mandatory screening protocol includes only the assessment of a 4-chamber section of the fetal heart. Any deviation from the classic image of a 4-chamber heart section should be a reason for referring the patient to the prenatal diagnostic center (level II) for extended echocardiography with the obligatory use of the Doppler method.

3. Compliance with a certain sequence in the stages of assessing the heart of the fetus allows you to conduct a high-quality echocardiographic study and identify from 60% to 80% of CHD.

Is the fetal heart in a normal position?

Is the size of the heart normal?

How is the axis of the heart located?

Are the atria and ventricles the same size?

Are there any defects of the interventricular septum?

Are the atrioventricular valves in their normal position?

Are there any changes in the endocardium, myocardium, pericardium?

5. When a fetal heart disease is detected, a study of its karyotype is shown, since aneuploidy is possible in 30% of such fetuses. The risk of CA increases to 50% when CHD is combined with other congenital malformations.

6. Fetuses with cardiac arrhythmias have a high risk of CHD: with supraventricular tachyardia - 10%, with ventricular arrhythmias - 1-2%, with complete blockade - 50-60%.

To improve the quality of echocardiographic examination of the fetus, in addition to studying the 4-chamber section, it is advisable to use in practice a section through 3 vessels, including the image of 3 main vessels - the pulmonary trunk, ascending aorta and superior vena cava. In this case, the duration of the ultrasound of the fetus increases by no more than 40-50 seconds. Particular attention should be paid to assessing the size of the vessels and their relative position. Any disproportion indicates pathology:

Hypoplasia of the left heart - the pulmonary trunk is significantly expanded, the diameter of the aorta is significantly reduced;

Pulmonary artery stenosis - a sharp decrease in the size of the pulmonary artery trunk, the diameter of the aorta and superior vena cava is normal;

Coarctation of the aorta - a decrease in the diameter of the aorta with a normal 4-chamber cut;

Common arterial trunk - only 2 vessels are visualized (the arterial trunk itself and the superior vena cava);

Transposition of the main vessels - there is a violation of the normal interposition of the main arteries: the aorta is displaced anterior to the trunk of the pulmonary artery and is located to the right of it;

Fallot's tetralogy - a decrease in the diameter of the pulmonary artery trunk, expansion of the diameter of the aorta and its displacement anteriorly from the line connecting the pulmonary trunk and the superior vena cava.

The most commonly diagnosed congenital heart diseases are:

Ventricular septal defect (VSD), small (up to 4 mm) and large, accounts for 20% of all CHD. It can be combined with other abnormalities, chromosomal defects: VSD occurs in more than 40 chromosomal defects, including trisomies 13, 18 and 21, as well as in more than 90 syndromes of multiple malformations. The frequency of small, non-hemodynamic VSD in its muscle part reaches 53 cases per 1000 live births. About 90% of such defects close on their own by 10 months of age and do not affect the prognosis for life and health. The risk of developing VSD in the fetus increases to 9.5% in the presence of VSD in the mother.

DIAGNOSTICS:

Most small VSDs are not detected during prenatal ultrasound.

The majority (73%) of CHD in the fetus, not detected by ultrasound at level I, belong to VSD.

Color Doppler mapping (CDM) is an essential aid in the diagnosis of CHD.

Even with large VSD defects, the disease can be asymptomatic up to 2-8 weeks of life.

DRIVING TACTICS:

The identification of a small isolated fetal VSD does not require a change in the management of pregnancy and childbirth.

The management of a pregnant woman is in agreement with pediatric cardiac surgeons, with whom the prognosis and possibilities of surgical treatment are discussed.

In 50% of cases, minor defects spontaneously close before the age of 5 years, 80% of the remaining ones - in adolescence.

Left heart hypoplastic syndrome (LHSS) is a spectrum of abnormalities characterized by underdevelopment of the left ventricle with atresia or severe hypoplasia of the mitral and / or aortic valves. The frequency is 7-9%, or the fourth place among all CHD. It is the most common cause of neonatal death from congenital malformations. Diagnostics is possible when a 4-chamber section is obtained, while the small size of the left heart is visualized in comparison with the normal or enlarged right heart. To exclude hypoplasia or atresia, it is necessary to assess the anatomy of the mitral and aortic valves. The optimal period for diagnosing a defect is 22-24 weeks of pregnancy. Forecast. Children with HSFS rarely survive: 15% of newborns die in the first day, 70% - in the first week, and 91% - in the first month of life. Surgical treatment of the defect consists in carrying out a multi-stage operation (according to Norwood), is accompanied by a high mortality rate and does not allow to avoid severe disability of the child.

A single ventricle of the heart is a severe defect in which the ventricles of the heart are represented by a single chamber in combination with a common atrioventricular junction containing two valves. Easily diagnosed using a standard 4-chamber cut. Often combined with trisomy 18 and 21, Turner syndrome. The survival rate of patients without surgical treatment is 30%.

Ebstein's anomaly is a congenital heart disease in which the septal and posterior cusps of the tricuspid valve develop directly from the endocardium of the right ventricle, which leads to the valve displacement deep into the right ventricle and the division of the ventricle into two sections: distal (subvalvular) - active, and proximal (supravalvular) - passive ... The supravalvular section, connecting with the right atrium, forms a single functional formation. The defect is rarely combined with chromosomal aberrations and multiple malformations. The incidence of Ebstein's anomaly is 0.5% of all CHD. Diagnosis is based on the detection of a significantly enlarged right heart due to the right atrium. It is diagnosed by examining a 4-chamber cut. Almost always accompanied by cardiomegaly. Ultrasound diagnostics is possible from 20 weeks. The prognosis mainly depends on the severity of the anatomical changes. Surgical treatment is indicated for patients with severe symptoms of the disease. After the operation, the majority of patients remain disabled in groups I or II.

Tetralogy of Fallot is a complex defect that includes several anomalies: ventricular septal defect, aortic dextraposition (rider aorta), pulmonary outlet obstruction, and right ventricular hypertrophy. In 30% of newborns with tetralogy of Fallot, extracardiac developmental anomalies are found. Often combined with chromosomal abnormalities (trisomies 13, 18 and 21). The pathological karyotype can be observed in 18-22% of cases. The frequency ranges from 4 to 11% of all CHD. It is very difficult to diagnose a defect when examining a 4-chamber section of the fetal heart, and it is often overlooked in screening tests performed before 22 weeks of gestation. It is imperative to use sections through the outlet sections of the main arteries and a section through 3 vessels. Recommended by CDK. The prognosis for life largely depends on the degree of obstruction of the right ventricular outflow tract. Surgical treatment of the defect is possible at any age. The early mortality rate in cases of complete surgical correction of Fallot's tetrad is less than 5%. In the long-term period, 80% of patients feel satisfactory and have normal functional parameters.

Major artery transposition is a heart defect in which the aorta, or most of it, exits the right ventricle and the pulmonary artery exits the left ventricle. 8% of newborns have a combined extracardiac pathology. The frequency is 5-7% of all CHD. Diagnostics is possible only when studying 3 vascular sections and sections through the great vessels: normally, the main arteries intersect, and during transposition they leave the ventricles in parallel: the aorta from the right ventricle, the pulmonary artery from the left ventricle. Vice is incompatible with life.

The arterial trunk is a malformation in which one arterial vessel leaves the heart. With this defect, VSD is always present. Large extracardiac defects are noted in 30% of newborns. Among chromosomal abnormalities, trisomies 13, 18 and 21, triploidy and various deletions and duplications are described. An abnormal karyotype is detected in 17% of fetuses. Frequency: occurs in 1-4% of patients with diagnosed CHD. Diagnostics: a 4-chamber cut does not allow diagnosing a defect; it is necessary to use a cut through 3 vessels. A useful addition is the CDC, which allows the assessment of the function of the arterial trunk valve. Ultrasound diagnostics is possible from 20 weeks. Prognosis: lethal defect - in the absence of surgical treatment, death can occur within 1-6 months of life.

Pulmonary stenosis and atresia. The defect has been described in many CAs and in 60 syndromes of multiple malformations. An abnormal karyotype is detected in 33% of fetuses. The risk of developing a defect in the presence of stenosis of the pulmonary artery in the mother is 4%. Frequency: about 20% of all CHF. Diagnostics. With atresia, the vessel is often invisible or significantly reduced in diameter; with stenosis, there is often a poststenotic expansion of the pulmonary artery and the small size of the right ventricle with hypertrophied walls. If there is no VSD, then the size of the right ventricle and atrium increases. Treatment. After birth, newborns with severe hemodynamic disturbances should undergo balloon valve repair or reconstructive surgery. The prognosis is often favorable.

Aortic stenosis. It occurs in some chromosomal aberrations and hereditary diseases (trisomy 13, 18 and Turner syndrome). The frequency is 3-6% of all CHD. Diagnosis: with aortic stenosis, there is a pronounced predominance of the diameter of the pulmonary artery over the aorta. Forecast. Outcome depends on the severity of the left ventricular outflow tract obstruction. Surgical treatment is often required (balloon plastic, Norwood plastic), because stenosis usually progresses with age.

Fetal lung examination

1. The study of echogenicity underlies the assessment of fetal lung maturity, which is carried out when comparing the echostructure of the lungs and its liver:

If the echostructure of the lungs is darker than the liver, the lungs are considered “immature” (high risk of SDR of the newborn);

If the echostructure of the lungs and the liver are the same, the lungs are considered “ripening” (the risk of SDR is 50%);

If the echostructure of the lungs is lighter than the liver, the lungs are considered “mature” (there is no risk of SDD).

2. Dimensions: width and anteroposterior dimension are measured in the plane perpendicular to the axis of the spine above the dome of the diaphragm by 2-3 mm, and the length - along the midclavicular, axillary or scapular lines.

3. Assessment of the presence in the chest cavity of free fluid or pathological formations (diaphragmatic hernia), as well as the features of the location of the ribs, which can help in the diagnosis of anomalies of the skeletal system. Among the congenital malformations, the most commonly diagnosed cystic-adenomatous malformation of the lung.

Examination of the abdominal organs

1. Most of the malformations of the gastrointestinal tract are combined with multiple malformations, chromosomal and hereditary diseases (10-40%), therefore, when they are detected, prenatal karyotyping of the fetus is recommended.

2. Obstructive gastrointestinal defects are often diagnosed only at the end of the second, beginning of the third trimesters of pregnancy. Almost always accompanied by polyhydramnios, often requiring therapeutic amniocentesis to prevent premature labor, and characteristic ultrasound signs: absence of stomach echo, “double bubble”, multiple dilated loops of the small and large intestines, hyperechoic intestines.

Omphalocele is an expansion of the umbilical ring with the formation of a hernial sac containing the abdominal organs. Combines with other abnormalities and chromosomal defects in 70% of cases. CA occur in 20% of cases. Frequency: 1: 3000-6000 newborns. Diagnosis: visualized as a rounded formation, directly adjacent to the anterior abdominal wall, filled with abdominal organs. It should be borne in mind that up to 10-13 weeks, a physiological umbilical hernia can be observed. Treatment is prompt. With small sizes of omphalocele, the operation is performed in one stage. The prognosis is favorable in the absence of associated anomalies.

Gastroschisis is an occurrence of the abdominal organs (more often the intestines) through a defect in the anterior abdominal wall (more often to the right of the navel). It occurs more often in isolation (up to 79%). The probability of a CA is 10%. The incidence of the defect is 1-7: 10,000 newborns. Diagnosis is based on ultrasound imaging of intestinal loops in the amniotic fluid near the anterior abdominal wall of the fetus. Hernial organs do not have a membrane. The prognosis is favorable: more than 90% of children survive after surgical treatment in the first day of life.

Study of the urinary system

Kidneys: it is necessary to assess their shape, size, localization, the state of the parenchyma and the PLC.

Pyelectasis is established by the anteroposterior size of the pelvis, which normally does not exceed 4 mm within 20-24 weeks. Pyelectasis disappears on its own during this pregnancy in 4.7 - 31% of cases. Moderate pyelectasis has a good prognosis: the need for surgical treatment after childbirth is rare. In most cases, there is spontaneous resolution of pyelectasis after childbirth.

In the infantile type of polycystic disease (Potter I syndrome, "large white kidneys"), there is a bilateral increase in the echogenicity of the kidneys and an increase in their size.

Polycystic kidney dysplasia can be unilateral and looks like an enlarged kidney with multiple anechoic inclusions. Bilateral polycystic kidney dysplasia, like polycystic kidney disease, is a fatal condition. If they are found, termination of pregnancy is indicated.

Bladder: Size is not critical given its ability to empty regularly. An exception is its pronounced increase (megacystic, Prune-belly syndrome) or decrease (renal agenesis), which remain unchanged during dynamic observation.

Estimation of the length of tubular bones

For prenatal diagnosis of skeletal dysplasias, the size, shape and echogenicity of both femurs and humerus, bones of the legs and forearms are studied. The shortening of the length of the tubular bones (mainly the hip and shoulder) can be a marker of a chromosomal abnormality: it is quite specific for Down's syndrome, where it is observed in 17.4-47.2% of cases.

Examination of the placenta and umbilical cord

The localization of the placenta, its thickness, structure and degree of maturity are assessed according to the generally accepted method.

The only artery of the umbilical cord (EAP). Normally, the umbilical cord contains 3 vessels: one vein and two arteries, in some cases only two: a vein and an artery. EAP is combined with various developmental anomalies in 20-67% of cases, with chromosomal pathology - in 5-20%. The most likely cytogenetic finding is chromosome 18 trisomy (Edwards syndrome), but trisomy 21 (Down syndrome) is not typical for EAP. The most common perinatal pathology is fetal growth retardation (8-50%), and the risk of fetal death in childbirth reaches 20%. Frequency: 1% in live births (more often in boys). Diagnosis: The most stable results can be obtained after 18 weeks of pregnancy. Management: in combination with other developmental anomalies, prenatal karyotyping of the fetus in the II trimester of pregnancy is indicated. With an isolated EAP, karyotyping is considered advisable, since congenital malformations combined with this pathology and reliably detected prenatally make up 37%, difficult to diagnose prenatally - 32%, and not diagnosed prenatally - 31%.

Assessment of the amount of amniotic fluid (AF)

If you suspect high or low water, you must use the definition of the amniotic fluid index (AFI), which is calculated as the sum of the vertical pockets of the AF in four (two upper and two lower) quadrants of the pregnant woman's abdomen. In terms of 20-24 weeks - in the two lower quadrants. AFI is expressed in centimeters with normal values ​​of 5-25 cm.

Low water is most often found in congenital malformations of the kidneys of the fetus (agenesis), with placental insufficiency and IUGR. Polyhydramnios - with congenital malformations of the central nervous system (anencephaly, spinal hernia), atresia of the esophagus, immune and non-immune dropsy of the fetus.

Verification of the diagnosis, i.e. pathological examination of the fetus should be carried out in all cases of prenatal detection of VNZ and termination of pregnancy for medical reasons, regardless of the weight of the fetus (including weight less than 500.0).

Should be considered:

Some echographic findings require special preparation of the material for the section and the use of certain autopsy techniques (fetal brain). The structures of the brain are among the first to undergo autolysis, therefore, if the material is improperly prepared, it is impossible to confirm or refute the data of ultrasound diagnostics;

About 35% of diagnoses made by ultrasound are impossible to prove (ventriculomegaly, pyelectasis, initial forms of non-immune dropsy of the fetus);

In 5-10% of postmortem examinations, congenital malformations are detected that are not subject to ultrasound diagnostics;

The best time for detecting congenital malformations in the first trimester is 10-14 weeks, in the second - 20-24 weeks, in the third - 32-34 weeks. Compliance with these rules reduces the number of unnecessary examinations, improves the quality of ultrasound examinations.

Echographic signs of chromosomal abnormalities of the fetus

1. Many VNZ, including chromosomal ones, are not accompanied by gross changes and do not have a pronounced echographic picture in the prenatal period.

2. One of the tasks of ultrasound is the early detection of echographic markers (EGM) of CA in order to form a group of patients for prenatal karyotyping of the fetus.

3. The frequency of detection of CA in the fetus depends on the number of ultrasound signs found: with a single echographic marker, the frequency of CA does not exceed 8%, in the presence of several it can be 53%, and with 8 or more it reaches 92%.

4. “Mild” signs: hyperechoic intestine, ventriculomegaly, abnormal head shape, hyperechoic focus in the heart, vascular plexus cysts, occur not only in CA, but also in the absence of any abnormalities in fetal development.

5. The study of the karyotype of the fetus allows you to draw up a rational plan for the management of pregnancy and decide on its continuation.

Terminate pregnancy upon detection of CA in the fetus, despite the absence of gross malformations, due to a poor prognosis for life and health;

Terminate pregnancy for medical reasons in case of diagnostics of abnormalities incompatible with life;

In the presence of malformations compatible with life (omphalocele, duodenal atresia, diaphragmatic hernia, facial cleft), perform karyotyping of the fetus, since a normal karyotype means a good prognosis and is an indication for full surgical correction.

Echographic markers XA

Expansion of the collar space within 10-14 weeks.

1. The detection rate of this marker ranges from 0.5 to 6.0%.

2. The most common chromosomal abnormalities during EP expansion: trisomies 13 (Patau's syndrome), 18 (Edwards syndrome) and 21 (Down's syndrome), Turner's syndrome. Of the other anomalies and VNZ, which are most common in the expansion of EP, it is necessary to note the Smith-Lemli-Opitz, Meckel-Gruber, Zellweger syndromes, fetal transfusion syndrome, anomaly in the development of the body stem, hydroletal syndrome, spinal muscular atrophy.

3. Expansion of the collar space is noted not only in CA, but also in cases of congenital malformations, the diagnosis of which is possible only in the later stages of pregnancy.

4. Normally, the TVP within 10-14 weeks should not exceed 3 mm.

5. The frequency of CA and CDF of the fetus increases with the increase in TBP:

With a thickness of up to 3.4 mm, fetal congenital malformations are detected in 2.4%, with 6.5 mm - in more than 35.6% of fetuses, with 7 mm and more unfavorable perinatal outcomes are recorded in 64.3% - 100% of cases;

The frequency of pronounced CHD is 17.3: 1000 fetuses, which is 2 times higher than in the population. The risk of EPS is 10% at 3mm TVP and 75% at a thickness of more than 4mm;

Diaphragmatic hernia is observed 7.5 times more often;

The frequency of omphalocele is 7: 4000-4200, and in the population 1: 3000;

In 40% of cases, there is an increase in the bladder (megacystic);

In pregnant women over the age of 35 with an expansion of CAP, the risk of chromosomal abnormalities can reach 90% with 5-9% of false-positive results.

6. With EP expansion, prenatal karyotyping of the fetus is indicated. Even with a normal karyotype, the incidence of unfavorable perinatal outcomes is 32%, while with a normal EP thickness it is 7%.

Hyperechoic focus (HF) in the ventricles of the fetal heart:

The frequency is on average 2.5 - 5.1%;

It is seen as a hyperechoic inclusion (one or more) in one (more often in the left) or both ventricles;

In most cases (up to 95%), HF disappears before delivery;

Can be regarded as EGM CA only when combined with extracardiac abnormalities and / or risk factors. In the absence of other EGMs, it is not a CA marker.

The frequency of detection of CA in the fetus with various echographic changes

microcephaly 30 - 66%

anomalies of the posterior cranial fossa 33 - 44%

abnormal skull shapes 27 - 81%

facial pathology 40 - 45%

cystic hygroma of the neck 68 -75%

congenital heart defects 29 - 56%

duodenal atresia 30 - 57%

hyperechoic intestine 20 - 66%

hand / foot anomalies 37 - 42%

umbilical cord pathology 40 - 44%

fetal growth retardation 19 - 39%

The most frequent echographic changes in fetuses with CA

DOWN'S SYNDROME:

ventriculomegaly 8.5 - 13.5%

neck pathology 2.6 - 50.9%

congenital heart defects 7.2 - 56%

shortening of the femur 33.3 - 47.5%

abnormal amount of AF 25 - 60.9%

EDWARD'S SYNDROME:

abnormal skull shapes 28.6 - 45%

increase in TVP 39 - 82.1%

vascular plexus cysts 29.6 - 80%

increase in the large tank 32.1 - 92.3%

congenital heart defects 39 - 82.2%

anomalies of the urinary system 15 - 42.9%

deformation of the hands and fingers 30 - 80%

fetal growth retardation 69 - 75%

polyhydramnios 32 - 53.8%

Biochemical methods of prenatal diagnosis

From the earliest stages of pregnancy, the fetal-placental complex (FPK) begins to produce substances specific to pregnancy, mainly proteins, which enter the mother's blood. If the fetus has malformations, chromosomal aberrations, the content of proteins changes significantly, which makes it possible to use these substances as markers of various pathological conditions of the fetus. With the development of ultrasound diagnostics, the importance of biochemical screening for detecting congenital malformations of the fetus has significantly decreased.

Alpha-fetoprotein (AFP)

It is a protein specific to the fetus. Its production begins in the syncytiotrophoblast and yolk sac, and from 11-12 weeks, the fetal liver becomes the source of secretion. AFP enters AFP through the fetal kidneys, and into the mother's blood through placental diffusion (94%) or transmembranous transport from AF (6%).

1. In different laboratories, due to the use of different equipment and reagents, there are significant differences in the quantitative indicators of the AFP content in the mother's blood serum. Therefore, since 1977, the level of AFP content has been recommended to be measured according to a unified system in units of MoM (multiples of median, or a multiple of the average value in normal pregnancy).

2. The concentration of AFP increases both with open defects of the neural tube and with teratomas, cystic-adenomatous malformation of the lungs, omphalocele, gastroschisis, kidney agenesis, obstructive lesions of the urinary tract, duodenal atresia, diaphragmatic hernia and other malformations.

3. An increase in AFP concentration in the absence of congenital malformations indicates an increased risk of pregnancy complications: premature birth, preeclampsia, fetal growth retardation or death, placental abruption. The risk increases from 19% at a concentration of 2.5-2.9 MoM to 67% at a concentration of more than 6 MoM.

4. In a normal pregnancy in the II trimester, the AFP concentration changes with an increase in the term: from 15 to 20 weeks, the AFP level increases linearly by 15% weekly, on average from 25 to 52 IU / ml. The optimal period for determining the AFP level is 15-22 weeks.

5. The AFP level is significantly influenced by:

Mother's body weight (dependence - inverse);

Number of fruits;

Some somatic diseases of the mother: with diabetes mellitus, AFP values ​​are below normal by 20%;

Race: an increase of 10-15% for the black and yellow races;

WGRP, lack of water;

The presence of CA in the fetus: a significant decrease in the AFP level in mothers with a fetus with Down syndrome (DM).

PRINCIPALLY IMPORTANT:

Determine your own standards for each biochemical marker, depending on the duration of pregnancy;

Definitions of markers in MoM;

The median for healthy fetuses is 1 MoM, for fetuses with diabetes - 0.75 MoM;

In each case, an individual risk calculation is required;

Determining only AFP as a screening method is not cost-effective, since about 55% of pregnant women with its pathological levels give birth to healthy newborns, but undergo additional studies (ultrasound, amniocentesis).

Human chorionic gonadotropin (hCG)

A glycoprotein that is produced by syncytiotrophoblast and enters the maternal bloodstream shortly after implantation of the ovum into the uterine wall. Several fractions of hCG are found in the mother's blood serum: the biologically active form of hCG, the inactive form, free and bound a and b - fractions. The metabolite of the b-fraction is detected in the urine.

In normal pregnancy, with an increase in its duration, the hCG values ​​decrease sharply and nonlinearly: from 30 to 18 IU / ml.

Numerous factors influence the synthesis and secretion of hCG during pregnancy: gonadotropin-releasing hormone, estradiol, epidermal growth factor, activin stimulate the production of hCG, and progesterone suppresses its secretion.

There are reports of a significant (two-fold or more) increase in the level of hCG in the maternal blood serum with trisomy 21 in the fetus.

Unconjugated estriol (NE)

In normal pregnancy, the content of NE in the mother's blood depends on its duration and increases linearly on average from 0.6 to 2.0 ng / ml, or by 20-25% weekly in the interval of 15-22 weeks.

Smoking has a significant negative effect on the content of NE in the blood: the level of NE is 15% below normal.

The age and body weight of a pregnant woman do not affect the level of NE in the blood.

A close relationship was proved between the level of NE in the mother's blood and diabetes in the fetus: the median for fetuses with diabetes was 0.75 MoM, which significantly differs from the median of healthy fetuses - 1.0 MoM.

Biochemical screening for Down syndrome

A significant decrease in AFP was noted in 20% of pregnancies with diabetes with 5% of false-positive results.

A significant increase in the level of hCG, two or more times, is recorded in 35-40% of cases of diabetes.

The sensitivity of the test for diabetes using NE was 35%.

In practical medicine, for screening for diabetes, it is recommended to use a combination of AFP and hCG (double test): the sensitivity of the double test, taking into account the age of the mother, varies within 56-70% with 5% of false positive results.

With a combination of AFP, hCG and NE (triple test), taking into account the age of the mother, the sensitivity of the test in relation to diabetes increases to 60 - 70% with 5% of false-positive results.

New biochemical markers of diabetes

PAPP-A (Plasma Protein A Associated with Pregnancy) is a high molecular weight glycoprotein. It is produced by syncytiotrophoblast and appears in the mother's blood from 5 weeks of pregnancy. With an increase in gestational age, the concentration of PAPP-A normally constantly increases. In various pathological conditions (non-developing pregnancy, chromosome abnormalities, including diabetes), the content of PAPP-A in the mother's blood is significantly reduced. The greatest changes in the levels of this marker, both in normal conditions and in fetal pathology, were noted in the first trimester of pregnancy.

SP 1 is a pregnancy-specific glycoprotein produced by syncytiotrophoblast and its derivatives. In the mother's blood, it is recorded already from the 7th day after ovulation. During physiological pregnancy up to 35 weeks, its concentration increases, and then remains constant. With diabetes in the first trimester, there is a decrease in the concentration of SP1 in the mother's blood, and in the second trimester, its level exceeds the standard values. The difference in medians for healthy fetuses and fetuses with diabetes is small: 1.0 and 1.28 MoM, which limits its use for screening for diabetes.

Inhibin A is a glycoprotein characterized by the ability to suppress the secretion of follicle-stimulating hormone. The inhibin A level in normal pregnancy decreases with increasing gestational age, and increases in the presence of diabetes mellitus. The median inhibin A for fetuses with diabetes in the first trimester is 1.41 MoM, in the second trimester - 1.85 MoM.

SOD (Superoxide Dismutase) belongs to the family of metalloproteins. The SOD gene is located on the long arm of chromosome 21. It was found that the SOD activity in maternal serum with diabetes is higher than in the control group (3.12 + 0.73 and 2.2 +0.7 ml). The SOD method is not used as the only test for diabetes due to its low sensitivity.

HCG hyperglycosylate is one of the HCG fractions, which accounts for about 3% of all HCG molecules. It is a product of cytotrophoblast cells and can be detected in the blood and urine of pregnant women. Determination of hyperglycosylate in the mother's blood reveals 60% of fetuses with diabetes, which is comparable to the effectiveness of the standard triple test.

Protein S100 is a low molecular weight protein that is found in many tissues of the body. The genetic code of this protein is registered in the long arm of chromosome 21 in the region 22.2-22.3, which is responsible for the phenotypic manifestations of diabetes. With diabetes, the concentration of S100 in the blood of the fetus increases sharply. However, S100 does not pass the placental barrier, which does not allow its use as a marker of diabetes mellitus.

It should be noted:

The effectiveness of early biochemical screening for 4 markers (AFP, hCG, NE, PAPP-A) without ultrasound is lower than that of ultrasound screening for TVP in early pregnancy: 70.1 and 72.7%, respectively.

The highest sensitivity (88.3%) has a method that combines screening for TVP with three biochemical markers: free b-hCG, NE, PAPP-A.

The best in terms of price / quality ratio is a combination of TVP assessment with the definition of PAPP-A (sensitivity 81.2%) or TVP with the determination of PAPP-A and free b-hCG (sensitivity 86.4%).

Edwards and Patau syndromes are the most common trisomies after Down syndrome:

In the first trimester of pregnancy, a decrease in the level of free b-hCG, PAPP-A and inhibin A is characteristic. At the same time, the concentration of PAPP-A decreases to a greater extent than b-hCG and estriol.

In the first trimester of pregnancy, determining the levels of b-hCG and PAPP-A in combination with the assessment of TVP can reveal 84-90% of cases of trisomy 13 (Patau) with 0.1-0.5% of false-positive results, and from 58 to 89% of trisomy 18 (Edwards).

With trisomy 18, all indicators of the “triple” test decrease: AFP - 0.6 MoM, NE - 0.5 MoM, hCG - 0.3 MoM. The test is 80% accurate, with 0.5% false positives.

In Turner syndrome in early pregnancy, the level of b-hCG does not change, and the concentration of PAPP-A and inhibin A decreases. For Turner syndrome, the sensitivity of the test in combination with the TBP score is about 90%.

General conclusion: the effectiveness of prenatal examination for the detection of CA significantly increases with the combined assessment of biochemical markers with ultrasound data, the most sensitive of which is the measurement of the thickness of the collar space within 10-14 weeks.

Prenatal diagnosis of gene diseases

General remarks:

The share of genetic disorders in total accounts for up to 5% of all congenital pathology.

More than half of the cases of monogenic pathology requiring prenatal diagnosis are relatively frequent and severe diseases such as cystic fibrosis, Duchenne myodystrophy, fragile X-chromosome syndrome, hemophilia A, phenylketonuria, polycystic pulmonary disease, Friedreich's ataxia, Werdnig-Hoffman syndrome and Charcot-Marie syndrome -Tus.

Molecular (DNA) diagnostics is carried out at the level of individual genes, and even at the level of DNA fragments of the genes themselves or nearby DNA sequences.

The advantages of molecular diagnostics:

Versatility, the ability to use any DNA-containing cells of the body for analysis;

Possibility of analysis at any stage of ontogenesis, starting from the zygote stage;

The optimal period for prenatal diagnosis by molecular methods is the first trimester of pregnancy, which requires a detailed DNA analysis of the family even before it occurs.

Material for analysis

Examination of high-risk families and patients with gene diseases: cystic fibrosis, phenylketonuria, is carried out using blood stains applied to filter paper, which greatly facilitates the transportation and storage of samples from districts remote from diagnostic centers;

For some other gene diseases: hemophilia A, Duchenne muscular dystrophy, diagnostics is carried out on pure DNA preparations isolated from the blood of the fetus, whose cells are obtained using standard invasive methods.

The basis of DNA diagnostics is the polymerase chain reaction of DNA synthesis (PCR). The method allows you to selectively multiply the number (aplicate) of relatively small DNA regions, from several tens to several thousand base pairs in length, using any DNA samples containing the required nucleotide sequence as a template.

Direct diagnosis is based on the direct identification of mutations in a particular gene. The reliability of molecular diagnostics by the direct method is very high and approaches absolute.

Indirect (indirect) diagnosis is based on the labeling of a mutant gene (diseased chromosome) using molecular markers. The misdiagnosis rate can be as high as 2%.

Combination of DNA diagnostics with other techniques:

In the case of hemophilia A, it is possible to directly determine the level of coagulation factor VIII in the umbilical cord blood of the fetus after 20 weeks of pregnancy;

In adrenogenital syndrome - a direct study of the content of 17-OH progesterone in the amniotic fluid;

Diagnosis of a fragile X chromosome is supplemented by an analysis of the culture of fetal cord blood lymphocytes;

In the case of cystic fibrosis, additional information about the state of the fetus can be obtained from a biochemical study of the activity of AF enzymes at 17-19 weeks of pregnancy.

Invasive research methods in prenatal diagnosis

Invasive diagnostic methods (IDM): aspiration of chorionic villi (chorionic biopsy), puncture of the placenta, umbilical cord or amniotic cavity in order to obtain biological material for further research (cytogenetic, molecular, biochemical). The most commonly used are transabdominal chorionic villus aspiration, amniocentesis and cordocentesis, which are most effective at relatively low economic costs. Therapeutic invasive methods: operations for the prenatal correction of certain fetal malformations, as well as interventions aimed at the treatment of certain fetal diseases (anemia).

Remember:

1. All invasive interventions are performed under ultrasound guidance

2. Any intrauterine intervention carries the risk of termination of pregnancy:

It is necessary to carefully assess the risk of having a baby with VND and the risk of losing pregnancy after IDM;

Within 10-14 days after the examination with the use of IDM, an average of 2.5% of pregnancies are interrupted: the frequency of complications depends on the type of intervention, duration of pregnancy, doctor's experience;

The lowest risk is observed with amniocentesis: 0.2-2.0%, the highest - with cordocentesis: up to 5.4%;

The indices of perinatal losses in IDM do not exceed the indices of fetal loss among all pregnant women in the population.

Indications (after consulting a geneticist):

The age of the pregnant woman is over 35 years old;

Complicated history: the birth of a child with CA or monogenic pathology;

The presence of a familial chromosomal translocation or an identified gene mutation;

A mother with any inherited disease associated with the X chromosome;

Any parent with a hereditary metabolic disorder;

Pregnancy after three or more spontaneous abortions;

Changes identified during pregnancy: echographic and biochemical markers of CA.

Amniocentesis:

EARLY AMNIOCENTESIS IS CONDUCTED IN 9-14 WEEKS

Is accompanied by a higher risk of spontaneous abortion compared to abdominal chorionic biopsy;

Ineffective for prenatal diagnosis, because AF contains few cells suitable for cultivation, which requires more than 40 days. Moreover, a successful result can be obtained in no more than 40% of cases.

AMNIOCENTESIS IN TERMS OF 14-18 WEEKS (GENETIC AMNIOCENTESIS):

The risk of spontaneous abortion is no more than 0.5-0.7%;

Errors due to cell mosaicism are possible: about 2.5% of AF cell cultures give a second cell culture;

Measurement of AFP and acetylcholinesterase content in AF (with AFP more than 2 MoM) increases the accuracy of diagnosing fetal neural tube defects up to 97% with 0.5% false-positive results.

Chorionic villus aspiration:

Chorionic villus sampling contains trophoblast material with full fetal chromosomes;

The fetal karyotype can be determined directly from the chorionic villi by a direct method, which is the fastest and most cost-effective;

Cultivation of cells is also possible, most often together with direct analysis.

INDICATIONS FOR ASPIRATION OF VORSIN CHORION:

The birth of a child with chromosomal diseases in the family;

Translocations and inversions of chromosomes in one of the spouses;

Sex-linked diseases;

Some monogenic diseases;

Ultrasound markers of chromosomal aberrations.

CONTRAINDICATIONS:

Inflammatory diseases with an increase in body temperature;

Bloody discharge from the genital tract;

Previous laparotomies and operations on the uterus and cervix;

Multiple nodes of uterine fibroids;

III-IV degree of cleanliness of the vagina.

The optimal duration of the procedure is 9-11 weeks.

METHOD:

Transcervical or transabdominal access. Transcervical manipulation can be prevented by genital herpes, cervical scars, polyps, uterine hyperretroflexion. Transabdominal aspiration is more commonly used.

An ultrasound scan is performed before and during the procedure.

Special 20G needle with mandrel.

No more than 10-20 mg of material is required, which is less than 1% of the functional chorionic tissue.

The procedure is performed on an outpatient basis, followed by observation of the patient in a day hospital for 2 hours.

OBTAINED MATERIAL.

Chorionic villus consists of: the outer layer - hormonally active syncytiotrophoblast, the middle layer - cytotrophoblast, the inner layer - mesodermal. The cytotrophoblast has a high mitotic index with many spontaneous mitoses suitable for immediate chromosomal analysis. Chromosomal preparations suitable for analysis can be obtained from 95 to 98%.

COMPLICATIONS:

Bleeding or bleeding: 1-4% for transabdominal access and 20% for transcervical;

Retrochorial hematoma;

Rupture of membranes in 0.3-0.5% of cases;

According to domestic data, the frequency of spontaneous abortions averages 3.3%: with transcervical access - 4.8%, with transabdominal access - 2.2%;

The frequency of spontaneous abortions according to foreign data is 0.6-0.8%;

Intrauterine infections: 0.2% - 0.5%

Fetal-maternal transfusion.

DISADVANTAGES OF THE METHOD:

Possibility of contamination of the taken sample with maternal decidual tissue;

The presence of mosaicism and pseudo-mosaicism in the material obtained: 1% and 0.4%, respectively.

Placentocentesis - aspiration of tissue from the placenta.

INDICATIONS

Same as for chorionic biopsy.

METHOD

It is performed in the II trimester under ultrasound control using an 18-20 G needle with a mandrel. The mass of the aspirate should be at least 20-50 mg.

BENEFITS

Before chorionic biopsy:

A negative effect on the morpho- and organogenesis of the fetus is excluded;

The place of sampling of the aspirate is located much further from the decidua than with aspiration of the chorion, therefore, contamination of the samples with mother cells is less common;

In the second trimester, careful ultrasound monitoring of the fetus is possible, which, in some cases, allows you to refuse manipulation in the presence of contraindications and reduce the number of complications;

Can be used with low water;

The direct method of obtaining chromosomal preparations from the tissue of the placenta is much faster than others, and the result can be known on the day of sampling, which makes it possible to make a quick decision when detecting fetal abnormalities during ultrasound;

Successful sampling of material with subsequent cytogenic or DNA analysis is 99%.

COMPLICATIONS

The same as for chorionic villus aspiration. The frequency of spontaneous abortions with placentocentesis is slightly lower: 0.9-2.2%.

CORDOCENTESIS

Taking blood from the vessels of the umbilical cord.

POSSIBILITIES

Prenatal karyotyping, diagnosis of monogenic diseases, intrauterine infection, study of the acid-base state, hematological and biochemical parameters of the fetus.

BENEFITS

Blood, in comparison with other biological material, gives much more information about the state and development of the fetus;

With prenatal karyotyping, obtaining a cytogenetic response is possible after 48-72 hours, since fetal blood lymphocytes are capable of rapid division;

Revealing all the structural features of chromosomes, since with a high mitotic activity of lymphocytes, it is possible to study a large number of metaphase plates and use various methods of differential staining of chromosomes, which is not always available when studying chorion preparations;

Unlike fetal blood, true fetal tissue, chorionic and amnion cells are derivatives of extraembryonic ectoderm and, in some cases, have a set of chromosomes that is different from fetal cells.

INDICATIONS

Diagnostic cordocentesis

1. Rapid karyotyping:

Fetal malformations;

Echographic markers of chromosomal aberrations;

Mosaicism, identified in the study of water / placenta;

Failure of the previous cytogenetic analysis.

2. Traditional indications:

The age of the pregnant woman is over 35 years old;

History of birth of a child with chromosomal abnormalities;

Chromosomal translocation in one of the spouses;

The possibility of CA according to the serum markers of the mother's blood.

3. Diagnosis of monogenic fetal diseases:

Metabolic disorders;

Fermentopathy;

Congenital blood diseases.

4. Diagnosis of intrauterine infections:

Toxoplasmosis;

Cytomegalovirus;

Rubella;

Parvovirus B19;

Chickenpox (varicella).

5. 5. Alloimmunization and autoimmunization:

Rhesus conflict;

Idiopathic thrombocytopenic purpura.

6. 6. Study of the intrauterine state of the fetus:

Acid-base state of fetal blood

Curative cordocentesis

Intrauterine transfusions of blood products for anemia

Intrauterine drug administration

CONTRAINDICATIONS:

Absolute:

Does not exist.

Relative:

The threat of termination of pregnancy;

Acute inflammatory processes of any localization;

Obesity;

Polyhydramnios and low water;

Multiple uterine fibroids.

Optimal term

The second half of the II trimester of pregnancy: on average at 24 (20-29) weeks, which is due to the diameter of the umbilical cord vessels, which during these periods reaches the optimal sizes for cordocentesis.

Methodology:

Puncture of the umbilical cord is performed with a spinal needle (with a mandrel) 9 to 16 cm long with a diameter of 20 to 25G under ultrasound guidance. It is possible to use special needles coated with a compound that improves the visualization of the needle on the screen.

It is preferable to puncture the free loop of the umbilical cord using the “free hand” technique. A puncture of the umbilical cord root is possible, but in this case it is easy to obtain mixed blood.

In cytogenetic studies, blood is taken into a syringe washed with heparin. DNA diagnostic material requires EDTA solution. For virological tests, blood serum is needed, so the addition of special solutions is not required.

The prenatal examination requires 1 to 4 ml of blood, depending on the type of further research, which is 4 to 16% of the total fetoplacental blood volume at the beginning of the second trimester of pregnancy.

In most cases, the procedure lasts no more than 5-7 minutes.

On the first attempt, blood is obtained in 63-87% of cases; in experienced hands, the success rate on the first attempt reaches 92-97%.

Complications:

1. Transient bradycardia - a decrease in heart rate up to 100 beats or less per minute.

Observed from 1.5 to 13.2%;

More often occurs in fetuses with IUGR, anemia, non-immune dropsy;

As a rule, it lasts a little more than a minute and recovers on its own, without any medication.

2. Bleeding from the puncture site.

It is noted on average at 31.3 (29-62)%;

The frequency increases with the duration of the procedure;

In 78-86% of cases, bleeding lasts less than a minute, it is mild and stops on its own;

The minimum recorded volume of blood loss is 0.25 ml, the maximum is up to 15 ml;

In pregnant women with Rh-negative blood, isosensitization prophylaxis is required by the administration of anti-D-immunoglobulin.

3. Hematomas of the umbilical cord.

The frequency does not exceed 0.5%;

They are small and do not affect perinatal outcomes.

4. Inflammatory complications (chorioamnionitis).

The frequency is 0.6-2.9% immediately after the procedure;

In 28-40% of cases of termination of pregnancy associated with cordocentesis, inflammatory changes in the ovum are subsequently detected;

Within a few days after the invasive intervention, it is possible to carry out prophylactic antibiotic therapy.

5. Termination of pregnancy.

It occurs more often within 10-14 days after the procedure;

The frequency of interruption, directly related to cordocentesis, is 2% -2.5%, interruption, which occurred 2 weeks after the procedure, up to 1.5%;

Perinatal losses are no more than 2-2.5%;

The highest perinatal losses are recorded in fetuses with developmental abnormalities (13.1%) and with developmental delay (8.9%);

In 23% of cases, the cause of termination of pregnancy is chorioamnionitis, in 15% - a severe form of placental insufficiency and fetal growth retardation, in 30% - increased contractile activity of the uterus, in 32% - the immediate cause cannot be established;

The incidence of perinatal loss increases with the number of attempts at cordocentesis.

Management tactics for patients at risk of giving birth to children with CA:

"Passive"

IDM is performed for all pregnant women with risk factors, which gives a relatively low frequency of CA detection, since the largest risk group is distinguished among the patients.

In the presence of equipment for ultrasound with low resolution, which does not allow for high-quality echographic studies;

With an average level of training of specialists in ultrasound diagnostics;

In the absence of the possibility of ultrasound in dynamics.

"Active"

Formation of a narrower risk group, which makes it possible to increase the detectability of CA and reduce both the number of invasive interventions and the number of pregnancy losses associated with IDM.

In the presence of equipment for ultrasound of the middle and expert class;

With high qualifications of ultrasound diagnostics specialists, which allows to reliably assess the presence of markers of chromosomal pathology in the fetus;

If possible, ultrasound in dynamics during pregnancy and the provision of the necessary assistance to newborns in full.

Applications

Normal parameters of fetometry of the fetus in Yaroslavl

	Biparietal size (cm)				Abdominal circumference (cm)			Thigh length (cm)
	Percentiles
Term (weeks)

Normal indicators of fetal weight in Yaroslavl

Pregnancy period (weeks)	Fruit weight (g)
	Percentiles

Limits of acceptable values ​​of AFP and hCG for pregnant women

(according to the Federal Center for Prenatal Diagnostics, St. Petersburg)

STANDARDS FOR AFP CONTENT IN BLOOD SERUM

	Median, ng / ml	Tolerant limits, ng / ml	Median, IU / ml	Tolerance limits, IU / ml

STANDARDS FOR THE CONTENT OF HCG IN BLOOD SERUM

Pregnancy period (weeks after conception)	Median, mIU / ml	Tolerance limits, mIU / ml
			Without dilution

Attention! MOM is calculated as the ratio of the AFP and hCG levels in IU / ml to the median in IU / ml. Normal values ​​of Mohm during physiological pregnancy are 0.5-2 Mohm.

Algorithm of indications for prenatal karyotyping

Conventional abbreviations:

• RF - risk factor
• EGM HA - echographic markers of chromosomal abnormalities
• AKV - abnormal amount of water (little and high water)
• PC - prenatal karyotyping