Under pseudo-mosaicism understand mosaicism, which does not reflect the true chromosomal constitution of the individual and is due to the presence of individual cells with a chromosome set that differs from the karyotype of the main cell population. In this case, a single cell can have a chromosomal anomaly (single-cell pseudomosaicism) or various chromosomal anomalies can occur in several cells (multicellular pseudomosaicism).
On preparations from cultured cells fixed by the in situ method, pseudomosaicism is recorded if abnormal karyotype demonstrates a cell in one area of the colony, or all metaphase plates of one colony, or several colonies. In the flask method, pseudomosaicism refers to the presence of numerous cells with the same type of chromosomal abnormality within one flask.
Frequency of pseudomosaicism, according to the total data of different laboratories, varies within 0.6-1.0%.
Mosaicism limited to the placenta
As noted above, PD chromosomal abnormalities carried out on the cells of either the fetus or provisional organs. For the interpretation of PD results, the features of the origin of the analyzed material can be of fundamental importance. Thus, the chorionic cytotrophoblast, being a derivative of the trophectoderm, as well as the mesodermal stroma of the chorionic/placental villi, separate from the inner cell mass at the blastocyst stage, i.e. have an ex-straembryonic origin. The amnion, which develops from the primary ectoderm, is an embryonic structure. All have an embryonic origin. epithelial cells AF, as well as cord blood lymphocytes.
At the post-implantation stages human development chromosome set in the cells of the membranes, as a rule, corresponds to the karyotype of the fetus. However, in some cases, discordance of karyotypes in the cells of extraembryonic tissues and the fetus is possible. In this case, the mismatch of chromosome sets can be complete or have a mosaic form. Cell lines with an abnormal karyotype can be localized in the tissues of both the extraembryonic membranes and the fetus. The presence of an abnormal cell clone in the tissues of the fetus when it is present in the placenta (i.e. true or generalized mosaicism) is confirmed in 10% of cases of placental mosaicism, or 0.1% of all developing pregnancies. According to the generalized results of PD, cases of mosaic aneuploidy in the tissues of the fetus, which has a normal karyotype in cells of provisional organs, are rare. In approximately 2% of advanced pregnancies, cytogenetic abnormalities, more commonly mosaic trisomies, are confined to the placenta.
Type classification placental-limited mosaicism is given in table. It is assumed that placental mosaicism is an unfavorable factor for fetal development. risk of intrauterine growth retardation, spontaneous miscarriage, antenatal death or premature birth is typical for cases of placental mosaicism with a fairly high proportion of aneuploid cells in the cytotrophoblast, in the extraembryonic mesoderm, or in all tissues of the placenta at once (types 1, 2 and 3 of placental mosaicism, respectively). However, various approaches to assessing the obstetric and clinical manifestations of placental mosaicism do not currently allow us to consider its effect on fetal development as absolutely proven.
It is obvious that it is essential question about the type of mosaicism can only be solved in the case of parallel analysis of the cytotrophoblast and mesoderm, i.e. combining the direct method of preparation of preparations with the cultivation of samples of the chorion or placenta. Necessary steps diagnosis in cases of mosaicism should also be the establishment of the origin of the trisomic line (stage and mechanism of occurrence), as well as the exclusion of uniparental disomy. These studies are especially important when chromosomes are involved in mosaicism, for which the phenomenon of chromosomal imprinting has been established.
Modern medicine has reached such a level that it has become quite real and everyday for doctors to examine unborn babies and identify some serious pathologies fetal development long before the baby is born. Moreover, doctors today can even perform certain medical procedures in utero. Prenatal diagnosis and therapy - this is how these methods are called. These include cordocentesis. Many expectant mothers are afraid of the prospect of undergoing such a procedure. What is cordocentesis? And is it worth worrying about this analysis?
Description of the method
Cordocentesis is a puncture of the vessels of the umbilical cord of the fetus to collect cord blood and then study it for the presence of chromosomal abnormalities of the fetus and other pathologies of pregnancy.
To determine fetal diseases associated with heredity and chromosomal pathologies, it is best to take cord blood for analysis - blood from the umbilical cord connecting the placenta and the fetus. It is this examination that obstetricians and gynecologists consider the most informative and accurate. This diagnosis is called cordocentesis (puncture of the vessels of the umbilical cord).
A prerequisite for its implementation is the presence in your antenatal clinic (or in a medical center) of an ultrasound machine and, of course, specially trained highly qualified personnel.
Cord blood sampling is carried out under continuous ultrasound control.
Fetal pathologies, syndromes detected by cordocentesis:
- Patau syndrome (trisomy on chromosome 13);
- Edwards syndrome (trisomy on chromosome 18);
- Down syndrome (trisomy on chromosome 21);
- monosomy on the X chromosome - Shershevsky-Turner syndrome;
- polysomy on X chromosomes, polysomy on Y chromosomes - Klinefelter's syndrome;
- cystic fibrosis;
- Duchenne disease;
- thalassemia;
- hemophilia and other genetic diseases;
- intrauterine infection.
Cordocentesis is also performed to:
- implementation of intrauterine (prenatal) drug therapy;
- determining the indicator of intrauterine developmental delay - the acid-base balance of the fetus;
- identifying the causes of the pathological condition of the fetus;
- conducting therapeutic blood transfusion - with alloimmune, autoimmune conditions.
Compared to other diagnostic methods, the analysis of cord blood eliminates erroneous results and provides the most complete information about the condition of the fetus in the mother's womb, about its development and the presence of hereditary and genetic pathologies.
However, to consider it a priority compared to, say, amniocentesis or chorionbiopsy does not allow the fact that the manipulation itself is quite difficult to carry out. This is due to the determination of the optimal puncture site, the mobility of the umbilical cord of the fetus and other objective factors.
Therefore, they resort to it only in certain cases: if accurate information about the condition of the baby is needed urgently or when it is necessary to conduct drug therapy for the fetus.
Video "Cordocentesis - fetal cord blood sampling"
What is the duration of
On early dates During pregnancy, the volume of blood circulating in the umbilical cord is not yet large enough. Therefore, taking the amount needed for analysis can adversely affect the condition of the fetus.
In this regard, it is not recommended to take cord blood for research until the 18th week of pregnancy, but it is better to wait until 21–24 weeks. It is by this time that its volume increases, and the diameter of the vessels reaches the sizes necessary for analysis. And this is also important in the implementation of manipulation.
Indications
Cordocentesis is not included in the list of mandatory tests. Expectant mothers are sent for an invasive examination for certain medical reasons.
What are the indications for puncture of the umbilical cord vessels?
- The age of the pregnant woman (over 35 years). There is such a thing - "age threshold of pregnancy." The older the expectant mother, the greater the risk of giving birth to a child with chromosomal abnormalities.
- Non-compliance with the norms of the results of a biochemical test in the first trimester.
- Poor second screening results.
- Hereditary diseases that cause abnormalities in physical and mental development, in the anamnesis of one of the parents.
- Previous pregnancies aggravated by fetal malformations.
In such situations, the karyotype of the fetus (the number and quality of its chromosomes) doctors prefer to determine as early as possible. In order to be able to adequately respond if the results of the analysis turn out to be unfavorable - to determine further tactics for managing pregnancy or, as a last resort, terminate it at an early stage.
If at the very beginning of pregnancy, if there were indications, for some reason, karyotyping of the spouses (blood test for a karyotype) was not performed, or it turned out to be insufficiently informative, cordocentesis is used to determine the karyotype of the fetus.
In addition, this analysis may be required when:
- some complications of the course of pregnancy;
- diagnosing in the mother during the bearing of the baby diseases that have the ability to cause malformations of the fetus;
- suspected intrauterine infection in the fetus;
- the need for fetotherapy (administration of blood products, drugs).
Contraindications
However, even if there are medical indications for prenatal diagnosis, some pregnancy pathologies can become an obstacle to its implementation. And only your doctor can assess the risks and decide on the advisability of invasive intervention.
- the threat of miscarriage;
- acute infectious diseases in the expectant mother;
- the presence of large myomatous nodes in a woman.
Study preparation
The first thing you should be prepared for when going for analysis is that in most medical institutions you will be asked to stay in the hospital after the procedure to monitor the condition of the fetus. This is necessary so that doctors have the opportunity to respond in a timely manner to possible complications.
Therefore, it will be useful to have a change of clothes and personal hygiene products with you. In some centers, on the eve of the diagnosis, expectant mothers are advised to conduct preliminary hygiene of the pubic area.
You must provide:
- results of blood and urine tests (limitation period no more than 2 weeks);
- vaginal smear (not more than 3 months old);
- results of examinations for hepatitis B, C, HIV, syphilis (limitation period no more than 3 months);
- direction of genetics for diagnosis;
- screening ultrasound protocols (on request).
Immediately before the manipulation, you will be asked to give your written consent to cordocentesis.
Before you get to the operating table for cord blood sampling, you will undergo a thorough examination using an ultrasound machine, which will help clarify the timing and status of pregnancy and determine the location of the placenta. And only after that, already in the process of the manipulation itself, with the help of an ultrasound sensor, the puncture site will be determined.
If the expectant mother is very worried before the puncture, she is given a sedative. The abdomen will be treated with an antiseptic without fail, and if necessary, a local anesthetic will be administered.
Algorithm of carrying out and methods of diagnostics
Technically, manipulation, like other invasive procedures, is carried out either through the method " free hand"(more often), or using a puncture adapter (less often).
The puncture can be single-needle and double-needle.
- Single puncture. After the fetal bladder is pierced, the umbilical cord vessel is punctured with the same needle, a syringe is attached to the needle and the amount of cord blood necessary for diagnosis (1–4 ml) is taken, and then the needle is removed.
- Double puncture. In this case, a double needle is used: a small one is located inside the large outer one. The amniotic membrane is punctured first with a large needle. They bring it to a pre-selected point on the umbilical cord, and then the umbilical cord vessel is pierced with a small one and cord blood is taken for analysis. After that, the needles are removed from the uterine cavity in the reverse order.
The operation is carried out under the continuous control of the ultrasound machine, and in the third trimester, CTG (cardiotocography) is also used to monitor the condition of the fetus.
This is how puncture needles for invasive interventions and for ultrasonic sensors look like
Sequencing
- The intervention site is determined using an ultrasound probe. The puncture should not affect the placenta. But there are situations when it is technically impossible to comply with this condition. Then they try to designate the thinnest section on it.
- To obtain the material of only the fetus (without maternal admixture), the puncture is carried out in the area of the free loop of the umbilical cord. He, of course, is more mobile, but the results of the analysis will be more reliable.
- If necessary, the fetus is immobilized medically.
- The duration of the manipulation is about 30 minutes.
- After the cordocentesis, the expectant mother stays in the hospital for 1-2 days under the supervision of doctors.
Cord blood sampling is considered a painless procedure.
When to expect results
Cord blood does not require cell culture in an incubator. This is material ready for research. That is why the waiting time for the results of the analysis is relatively short - only a few days (no more than ten).
The higher risk of complications after cordocentesis (against the background of other invasive methods of prenatal diagnosis) is justified by the possibility of obtaining quick results. And in some cases, it is the time frame that is vital.
Reliability of analysis
As for the results of cordocentesis, there is no doubt about their reliability. When cultivating cells obtained, for example, from the collection amniotic fluid(amniocentesis), their mutation is possible, which affects the accuracy of the results obtained.
When determining the fetal karyotype by cord blood cells, any mutations are excluded. Distortion of the results of the analysis due to placental mosaicism, possible with placentobiopsy, chorionic villus biopsy or amniocentesis, is also excluded here. Therefore, the analysis can be considered the most accurate of all prenatal invasive diagnostic methods.
The accuracy of the results can be affected by the fact that it is not always possible to obtain pure genetic material of the fetus on the first attempt - without impurities from the mother's cells. There are analyzers that determine the purity of the collected blood. They are used to eliminate errors in the results.
In many ways, the accuracy of diagnosis depends on the qualifications of the doctors performing the operation. With its technically correct performance, the reliability of the results of cordocentesis reaches 99.9%.
Complications and consequences
Invasive intervention, which is cord blood sampling, is a surgical operation, which, like any other, is associated with the risk of complications after it is performed. That is why doctors insist on hospitalizing the expectant mother and monitoring her condition and the condition of the fetus for several days after the cordocentesis.
- the fetal heart rate decreases to 100 bpm. And in 12% of cases, the puncture of the umbilical cord ends with cardiac arrest in the fetus. The likelihood of developing bradycardia depends on the gestational age and increases in proportion to it. But most often, the baby's heartbeat is restored without outside interference;
- may bleed from the puncture point. According to statistics, this happens in half of the cases. But only 19% of the puncture can bleed for more than 1 minute. To avoid this type of complications, blood sampling is done not from the arterial vessel of the umbilical cord, but from the venous one. And for manipulation, needles of the smallest diameter are selected. Special treatment is not required here. Yes, and a slight bleeding at the puncture site does not pose a danger to the course of pregnancy;
- the appearance of hematomas in the area of the puncture of the umbilical cord is a very rare phenomenon. But in 0.4% of cases it occurs. As practice shows, this complication does not negatively affect the condition of the fetus;
- in about 3% of cases, after cordocentesis, expectant mothers develop an inflammatory process - chorioamnionitis. For its prevention and treatment after an invasive intervention, a pregnant woman is prescribed a course of antibiotics;
- with a negative Rh-factor in the blood of a woman, she is given anti-Rhesus immunoglobulin within 48 hours after the operation. This helps to avoid the Rhesus conflict that may result from the manipulation;
- in 3% of cases, spontaneous abortion occurs after cordocentesis, the risk of miscarriage increases with twin pregnancy. Increasing the tone of the uterus is the most serious complication. You need to be wary of such a development of events for another 14 days after the procedure. During this period, it is better for the expectant mother to observe bed rest and be under the constant supervision of doctors. And to relieve uterine tone, take tocolytic drugs.
The development of complications after cordocentesis can be influenced by many factors: from the professional qualities of the physicians conducting the diagnosis to the characteristics of the state of pregnancy at the time of blood sampling.
Difference between cordocentesis and amniocentesis
If we talk about which of the methods of invasive diagnostics is the most common, then with confidence the primacy can be assigned to amniocentesis.
Amniocentesis involves puncture of the amniotic membrane and sampling of amniotic fluid for analysis
Amniocentesis is a puncture of the amniotic membrane, the purpose of which is to obtain amniotic fluid for analysis. This type of diagnosis is carried out at 14–20 weeks of gestation and is considered not so difficult, and also less associated with various kinds of risks.
Video "What is amniocentesis?"
When issuing a referral for diagnosis, the geneticist takes into account a number of factors that affect which method will be more preferable in each case. There are situations when it is cordocentesis for all indicators of pregnancy that becomes a priority. But there are not so many such circumstances.
Table "Cordocentesis or amniocentesis?"
For example, in order to confirm or refute the presence of fetal malformations that are incompatible with life, a pregnant woman will, of course, be sent for cordocentesis, since not only accuracy is important here, but also the speed of obtaining the result.
After all, if the diagnosis is confirmed, a decision will be made to terminate the pregnancy for medical reasons. And such an operation cannot be postponed in order to avoid complications in a woman.
If the fetal karyotype is determined according to other indications, then amniocentesis is more often preferred.
Where is it made, how much does it cost
To date, cordocentesis is performed in women's consultations where available necessary equipment and in private clinics. The procedure will be paid in both cases.
The price fluctuates between 18-23 thousand rubles. - for LCD and 27-28 thousand rubles. - for private clinics and medical centers. It all depends on the status of the chosen medical institution and the qualifications of the specialists performing the operation.
Be very responsible when choosing a clinic where you will have a cord blood puncture. When making a decision, carefully study the statistics of complications for a particular center, read the book of complaints and suggestions, seek information on the forums where expectant mothers share their impressions and reviews.
Prenatal (in other words, prenatal) diagnostics is one of the youngest and most rapidly developing areas of modern reproductive medicine. Representing the process of detecting or excluding various diseases in the fetus located in the uterus, prenatal diagnosis and genetic counseling based on its results answer vital questions for every future parent. Is the fetus sick or not? How can the detected disease affect the quality of life of the unborn child? Is it possible to effective treatment sickness after the baby is born? These answers allow the family to consciously and timely resolve the issue of the future fate of pregnancy - and thereby alleviate the mental trauma caused by the birth of a baby with an incurable, disabling pathology.
Modern prenatal diagnosis uses a variety of technologies. All of them have different capabilities and degrees of reliability. Some of these technologies - ultrasound screening (dynamic observation) of fetal development and screening of maternal serum factors are considered non-invasive
or minimally invasive
- i.e. do not provide for surgical intervention in the uterine cavity. Practically safe for the fetus, these diagnostic procedures are recommended for all expectant mothers without exception. Other technologies (chorionic biopsy or amniocentesis, for example) are invasive
- i.e. suggest a surgical invasion of the uterine cavity in order to take the fetal material for subsequent laboratory testing. It is clear that invasive procedures are not safe for the fetus and therefore are practiced only in special cases. Within the framework of one article, it is impossible to analyze in detail all the situations in which a family may need invasive diagnostic procedures - the manifestations of hereditary and congenital diseases known to modern medicine are too diverse. However, a general recommendation to all families planning the birth of a child can still be given: be sure to visit a medical genetic consultation (preferably even before pregnancy) and in no case ignore ultrasound and serum screening. This will make it possible to timely resolve the issue of the need (and justification) for an invasive study. With the main characteristics of various methods prenatal diagnosis can be found in the tables below.
The vast majority of the methods listed below prenatal diagnosis congenital and hereditary diseases today is widely practiced in Russia. Ultrasound screening of pregnant women is carried out in antenatal clinics or medical genetic services. In the same place (in a number of cities), screening of maternal serum factors (the so-called "triple test") can also be done. Invasive procedures are carried out mainly in large obstetric centers or interregional (regional) medical genetic consultations. Perhaps in the very near future all these types of diagnostic assistance in Russia will be concentrated in special centers prenatal diagnosis. At least, this is how the Ministry of Health of the Russian Federation sees the solution to the problem.
Well, as they say, wait and see. In the meantime, it would not hurt for all residents of cities and villages of the fatherland planning to replenish the family to ask in advance what opportunities in the region prenatal diagnosis has local medicine. And if these opportunities are insufficient, and the need for quality prenatal diagnosis objectively available, you should immediately focus on the examination of the expectant mother outside the native locality. Moreover, part of the financial costs in this case may well be borne by the very local health care, in the arsenal of which there is no type of diagnostic service necessary for the family.
| INVASIVE METHODS OF PRENATAL DIAGNOSIS | |||||||
| Method name | Terms of pregnancy | Indications for carrying out | Object of study | Methodology | Method capabilities | Advantages of the method | |
| 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 germinal membrane). | 1 way. A small amount of chorionic tissue is aspirated with a syringe through a catheter inserted into the cervical canal. 2 way. A tissue sample is aspirated into a syringe using a long needle inserted into the uterine cavity through the abdominal wall. Both options for chorion biopsy are performed on an outpatient basis or with a short-term hospitalization of a pregnant woman. Manipulation is performed under ultrasound control. Depending on the practice adopted in a particular medical institution, a biopsy is performed either under local or general anesthesia (anesthesia). Before the procedure, a woman must undergo laboratory examination(blood tests, smears, etc.). |
Determination of Down syndrome in the fetus, Edwards syndrome, Patau syndrome 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 single genetic syndromes to dozens of different disabling diseases). Determining the sex of the fetus. Establishment of biological relationship (paternity). |
Quick results (within 3-4 days after sampling). It is possible to diagnose a severe disabling disease in a fetus in the period up to the 12th week, when abortion occurs with fewer complications for a woman, and the stress load on family members also decreases. |
For a number of technical reasons, it is not always possible to conduct a qualitative analysis of tissue samples. There is a slight risk of false positive and false negative results due to the phenomenon of the so-called. "placental mosaicism" (non-identity of the genome of chorion and embryo cells). Risk of accidental damage to the amniotic sac. The risk of adverse effects on the course of pregnancy in Rh-conflict. 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 limbs in newborns who underwent chorionic biopsy have been described. In general, the risk of complications from chorionic biopsy is low (less than 2%). |
| Placentocentesis (late chorion biopsy) | II trimester of pregnancy. | Similar indications for a chorionic biopsy. | Cells of the placenta. | Similar to the method of the 2nd method of chorion biopsy described above. It 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 pregnant woman before placentocentesis are identical to those for a chorionic biopsy. |
Similar to the possibilities of chorion biopsy. | Cultivation of cells obtained during placentocentesis may be less effective than cultivation of chorion cells, so 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 gestational age (in case of detection of a serious pathology, termination of pregnancy during this period requires long-term hospitalization and is fraught with complications). |
|
| Amniocentesis | 15-16 weeks. |
Same as chorion 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, epitheliocytes from the urinary tract, etc.). | Amniotic fluid is drawn into the syringe with a needle inserted into the uterine cavity through the abdominal wall. Manipulation is performed under the control of an ultrasound machine, on an outpatient basis or with short-term hospitalization. Local anesthesia is most often used, 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. | Diagnosis 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. Determining the severity of the Rhesus conflict between mother and fetus. Diagnosis of some fetal malformations (for example, gross deformities of the brain and spinal cord anencephaly, exencephaly, spinal hernia, etc.). |
Wider (in comparison with chorionic biopsy and other invasive methods of prenatal diagnosis) range of detected pathologies. The risk of miscarriage is somewhat less than with a chorionic biopsy. This risk is only 0.5-1% higher than in pregnant women who did not undergo 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 artificial conditions. This requires special nutrient media, a certain temperature, reagents, 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 big amount complications than, for example, at week 12. 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. | Cord blood of the fetus. | A fetal blood sample is obtained from the umbilical cord vein, which is punctured under ultrasound control with a needle inserted into the uterine cavity through a puncture in the anterior abdominal wall of the woman. 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. | Similar to the possibilities of chorionic biopsy and placentocentesis, partially amniocentesis. Possibility of medical manipulations (administration of medicines, etc.). |
Minimal chance of complications. | Conducting a survey at a long gestational age (in case of detection of a serious pathology, termination of pregnancy during this period requires a long hospitalization and is fraught with complications). |
| NON-INVASIVE METHODS OF PRENATAL DIAGNOSIS | |||||||
| Method name | Terms of pregnancy | Indications for carrying out | Object of study | Methodology | Method capabilities | Advantages of the method | Disadvantages of the method, risk during the procedure |
| Screening for maternal serum factors | The gap between 15 and 20 weeks of pregnancy. 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 examined for the content of three substances: alpha-fetoprotein (AFP); human chorionic gonadotropin (hg); unconjugated estriol (NE). Sometimes the "triple test" is supplemented by a study of the level of neutrophilic alkaline phosphatase (NSHF). |
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. |
Sufficiently 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 NSHF detection of fetuses with Down syndrome reaches 80%. This makes it possible, when the family makes an appropriate decision, to terminate the pregnancy without any special complications for the woman's body. The risk of complications for the fetus is negligible. |
The results of the analyzes are influenced various factors- multiple pregnancy, features of the female body, obstetric problems, etc. The result of this can often be false-negative or false-positive results of the study. In all suspicious cases, a clarifying examination of ultrasound scanning, amniocentesis, placentocentesis or cordocentesis is prescribed. | |
| Ultrasound (US) screening of the fetus, membranes and placenta | Standard obstetric ultrasound screening for fetal malformations is carried out in two stages: at 11-13 weeks of gestation and 22-25 weeks of gestation. | Shown to all pregnant women. | fetus and placenta | 1 way. A sensor (transducer) is placed on the surface of the woman's abdomen, which emits high-frequency sound waves. Reflected from the tissues of the fetus, these waves are again captured by the sensor. Computer processing of the waves generates a sonogram - an image on the monitor screen, which is evaluated by a specialist. 2 way(used more often in the early stages). A specially designed transducer, protected by a latex condom, is inserted into the woman's vagina. |
Diagnosis of dozens of varieties of congenital malformations in the fetus (malformations of the brain and spinal cord, heart, kidneys, liver, intestines, limbs, facial structures, etc.). Early (before 12 weeks of pregnancy) detection of specific signs of Down syndrome in the fetus. Also, clarification: 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; sex of the fetus; location and condition of the placenta; state of amniotic fluid; violations of blood flow in the vessels of the placenta; 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 harmful effects x-ray radiation (a group of WHO experts has officially recognized the safety of quadruple ultrasound of the fetus during pregnancy). | Technical limitations and relative subjectivity in the interpretation of scan results. The diagnostic value of ultrasound screening can be significantly reduced with the weak technical capabilities of the device and the low qualification of the specialist. |
| Sorting of fetal cells | Between the 8th and 20th weeks of pregnancy. | Similar to those for chorion 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 laser sorting are used. The resulting fetal cells are subjected to molecular genetic studies. | Practically similar to the possibilities of chorionic biopsy, placentocentesis and cordocentesis | Negligibly low risk of complications for the fetus, due to the low invasiveness of the procedure in combination with diagnostic capabilities identical to those of highly invasive manipulations (chorionic biopsy, etc.) | The 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 predominantly experimental and is rarely used in routine practice. |
| 1
Both of the above disadvantages of amniocentesis are canceled if the procedure is carried out earlier (12 weeks) and the laboratories use modern methods of cytogenetic diagnostics. 2 AFP It is produced by the liver of the fetus, and then through the placenta enters the blood of the pregnant woman. Level AFP in the blood of the mother increases with some severe malformations leading to death or disability (defects in the closure of the neural tube, etc.); and, conversely, markedly reduced in Down syndrome. Level NSHF in the blood of the mother with Down syndrome in the fetus increases. Level CG And NE in Down syndrome, the fetus also deviates from the norm. |
Chorionic villus biopsy (CVB), amniocentesis, or cordocentesis can be used to obtain fetal cells for cytogenetic, biochemical, or molecular genetic analysis.
Preparation and analysis of chromosomes from amniotic fluid cell culture or chorionic villus mesenchymal tissue requires 7-10-14 days, although chorionic villi can also be used for karyotyping "direct preparations" without incubation and "semi-direct" preparations with short-term incubation.
Although short-term incubation provides faster results, it produces preparations of comparatively inferior quality, with color not always adequate for detailed analysis.
Fluorescent in situ hybridization (FISH) makes it possible to examine the interphase nuclei of fetal cells, and quantitative fluorescent PCR - DNA of fetal cells to exclude frequent aneuploidies of chromosomes 13, 18, 21, X, and Y immediately after cordocentesis, amniocentesis or CVS. These methods of prenatal prenatal diagnosis require 1 to 2 days and can be used when a rapid determination of aneuploidies is needed.
Chromosomal analysis after ultrasound examination
Since some birth defects found on ultrasound are associated with chromosomal abnormalities, karyotyping of amniotic fluid cells, chorionic villus cells, or fetal blood cells obtained by inserting a needle into the umbilical cord vessel (cordocentesis) may be indicated after ultrasound detection of such an anomaly.
Chromosomal abnormalities are more often detected after the identification of multiple rather than isolated malformations. Karyotypes more commonly found in fetuses with abnormalities on ultrasound are frequent autosomal trisomies (21, 18, and 13), 45,X (Turner syndrome), and unbalanced structural abnormalities.
The presence of cystic hygroma may indicate a 45,X karyotype, but also occurs in Down syndrome and trisomy 18, as well as in fetuses with a normal karyotype. Thus, in such cases, a complete chromosomal analysis is indicated.
Problems of prenatal chromosome analysis
mosaicism
Mosaicism is the presence of two or more cell lines in a patient or tissue sample. When mosaicism is found in fetal cell culture, it can be a challenge to decide if the fetus is a true mosaic and to determine the clinical significance of this mosaicism.
Cytogeneticists distinguish three levels of mosaicism in cultured amniotic fluid or CVS cells:
- True mosaicism is found in numerous colonies from several different primary fetal cell cultures. Postnatal studies confirm that true mosaicism in culture is associated with a high risk of its presence in the fetus. The probability of confirmation of mosaicism varies in different situations; for example, mosaicism in cell culture for structural rearrangements of chromosomes is almost never confirmed in the fetus.
- Pseudomosaicism in the form of an unusual karyotype found only in a single cell can usually be ignored. Mosaicism involving multiple cells or colonies of cells in a single primary culture is difficult to interpret but is generally thought to reflect pseudomosaicism resulting from in vitro culture.
Maternal cell contamination is a possible explanation for some cases of pseudomosaicism when both XX and XY cell lines are present. This is more common in cell cultures obtained from CVS than from amniocentesis, as a result of the close proximity of chorionic villi and maternal tissues (see Fig. 15-2). To minimize the risk of maternal contamination, all decidual villi present in a villus biopsy should be carefully removed, although even the most careful separation of the villi does not guarantee the removal of all cells of maternal origin. If maternal contamination is suspected and cannot be refuted (eg, by genotyping DNA polymorphisms), an amniocentesis for re-chromosomal analysis is recommended.
In the study of VC, discrepancies between karyotypes were found between the cytotrophoblast, the stroma of the villi and the fetus in approximately 2% of pregnancies examined at 10-11 weeks of gestation. Mosaicism is sometimes present in the placenta, but absent in the fetus, the so-called limited placental mosaicism (Fig. 15-7). Placental mosaicism has been described with normal and trisomic cell lines, with the neonate or fetus having non-mosaic trisomy 13 or 18, with a proportion of placental cells with a normal karyotype ranging from 12% to 100%. This fact suggests that if the zygote is trisomic, then normal placental cells appear due to the postzygotic loss of an additional chromosome in the cytotrophoblast progenitor cell, which may increase the likelihood of intrauterine survival of the trisomic fetus.
Limited placental mosaicism on any chromosome, but especially in trisomy 15, raises the additional concern that the diploid set in the fetus may indeed have arisen due to the restoration of trisomy. This term refers to the postzygotic loss of an extra chromosome, an event that may result in a viable fetus. However, if the fetus retains two copies of chromosome 15 from the same parent, the result is uniparental disomy. Since some genes on chromosome 15 are imprinted, uniparental disomy of this chromosome must be ruled out, since two maternal copies of chromosome 15 cause Prader-Willi syndrome, and two paternal copies cause Engelman syndrome.
Confirmation and interpretation of mosaicism is one of the most difficult problems in prenatal diagnosis in genetic counseling, as there is currently no adequate clinical information on the outcome of the many possible types and extent of mosaicism.
Some help can be provided additional research(amniocentesis after CVS, or cordocentesis after amniocentesis), as well as analysis of the medical literature, but sometimes interpretation remains difficult. Some confidence can be added by ultrasound scanning, if noted normal growth and no visible birth defects.
Parents should be advised in advance of the possibility of detecting mosaicism, and that it may not be possible to accurately interpret the result in mosaicism. After the birth of a child, efforts must be made to exclude all chromosomal abnormalities suspected on the basis of prenatal diagnosis. In case of termination of pregnancy, it is necessary to analyze the tissues of the fetus. Confirmation of the presence or absence of mosaicism may be useful for the treatment and genetic counseling of a particular couple and other family members.
Lack of culture growth
A married couple should be able to consider the decision to terminate the pregnancy in the event of a fetal pathology, so it is necessary to provide them with the necessary information as early as possible. Because prenatal diagnosis is always a race within a certain time limit, the lack of culture growth factor can be a concern; fortunately, the frequency of this event is low.
When it is not possible to grow a CVS culture, there is time to repeat the chromosomal analysis by amniocentesis. If amniotic fluid cell culture fails, depending on the age of the fetus, repeat amniocentesis may be considered, or cordocentesis may be offered.
Unexpected adverse information
Occasionally, prenatal chromosome analysis, originally performed to rule out aneuploidy, shows some other unusual chromosomal finding, such as a normal number of chromosomes but frequent polymorphism (eg, pericentric inversion of chromosome 9), a rare rearrangement, or a marker chromosome.
In such cases, since the significance of such a finding in the fetus cannot be assessed until the karyotypes of the parents are known, it is necessary to karyotype both parents to determine whether the detected change in the fetus is de novo or inherited.
Unbalanced or de novo structural changes can cause severe fetal abnormalities. If it turns out that one parent is the carrier of a structural change found in an unbalanced form in the fetus, the consequences for the fetus can be severe.
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What is amniocentesis?
Amniocentesis- this is a biochemical study of the amniotic fluid (the fluid that surrounds the fetus in the womb) to detect oxygen starvation of the fetus and determine its malformations. Amniotic fluid (from 3 to 30 ml) is obtained by puncturing the anterior abdominal wall, uterus and amnion (a protective bladder with a liquid in which the fetus is located). Together with the fluid during amniocentesis, desquamated fetal cells are also taken, by which experts judge the presence or absence of gene mutations.In recent years, another diagnostically valuable method has been used - cordocentesis. To do this, a vein of the umbilical cord (cords) is punctured and a small amount of blood is taken for analysis, and if necessary, medicinal substances are injected into the same vein. Typically, cordocentesis is used in cases where it is necessary to identify chromosomal or hereditary diseases, Rhesus conflict between the fetus and mother, hemolytic disease.
Both of these procedures became possible only thanks to the introduction of ultrasound into medical practice, which allows you to visually track the progress of the manipulation. It is difficult to overestimate the importance and necessity of these diagnostic methods, because with their help it is possible to judge the existing anomalies in individual genes or entire chromosomes, without affecting the integrity of the tissues of the fetus itself.
A simple biochemical study of the amniotic (amniotic) fluid allows you to determine the level of enzymes, hormones and amino acids, on which the growth and development of the fetus largely depends. Cord blood analysis makes it possible to detect such serious intrauterine infections as HIV, rubella, cytomegaly, parvovirus B19 (chronic anemia virus).
How is an amniocentesis performed?
Before amniocentesis, the pregnant woman is carefully examined by ultrasound, while paying special attention to the location of the placenta and the volume of amniotic fluid, the number of fetuses, their cardiac activity. After clarifying all the features of the attachment of the placenta in the uterus and the location of the fetus, they proceed directly to the procedure itself. Usually it is carried out without anesthesia, but with a low threshold of pain sensitivity, the introduction of anesthetics into the skin of the abdomen is allowed. The duration of manipulation is no more than 2-3 minutes. According to many women, the procedure is not painful, but causes discomfort, which shortly after the study independently pass.
The puncture is made with a special thin needle with a mandrel (a metal wire that prevents air from entering the amnion cavity). The length of the needle is selected individually, depending on the physique of the woman and the location of the amnion in the uterine cavity.
During the entire procedure, ultrasound monitoring is performed so as not to touch the fetus with a needle and not damage the umbilical cord. When the placenta is located on the anterior wall of the uterus, a puncture through it is allowed, however, for a puncture, they always try to choose the thinnest place.
There are no big differences between early and late amniocentesis, but carrying out this manipulation for periods up to 14 weeks requires the doctor to be more careful and move the needle more slowly, because. the fetal membranes are not yet firmly attached to the walls of the uterus.
At the end of the procedure, the amniotic fluid syringe is sent to the laboratory, and the patient is instructed about possible changes in well-being and behavior after amniocentesis. A woman must observe strict bed rest for several days. At the same time, attention should be paid to leakage of amniotic fluid or redness of the puncture site, and slight pain in the puncture area or pulling, not severe pain in abdominal cavity- the phenomenon is normal, these symptoms will soon pass on their own. The pregnant woman should be alerted by an increase in temperature or the appearance of heat in the puncture area. All changes must be immediately reported to the gynecologist in order to prevent the development of complications and save the life and health of the fetus.
At what gestational age is amniocentesis performed?
Amniocentesis can be performed at any stage of pregnancy, with the exception of the last trimester. The optimal period for this manipulation is the period from 16 to 18 weeks of gestation, when the fetus is still relatively small, and the amount of amniotic fluid is already sufficient.However, if indicated, amniocentesis may be given early in pregnancy (weeks 7 to 14). In this case, it is possible to puncture (puncture) the amniotic bladder not through the anterior abdominal wall, but along the posterior fornix of the vagina. Such access is sometimes even more preferable, especially when the ovum is located near the entrance to the vagina.
Despite the rather low success rate of early amniocentesis, it is recommended to be performed in cases where there is a very high probability of intrauterine fetal anomalies. In this case, it often becomes necessary to terminate the pregnancy, and the sooner it is carried out, the less psychological and physical trauma the woman will experience.
Indications for amniocentesis
In early pregnancy, amniocentesis is indicated if one or more of the following conditions are present:
1. The age of the pregnant woman is less than 20 or older than 40 years.
2. The presence of at least one of the spouses of a hereditary disease, which theoretically a child can inherit.
3. Birth in the past of a child with any hereditary disease.
4. The presence of explicit laboratory and instrumental indications of the need for a deeper diagnosis.
In addition, regardless of the duration of pregnancy, the doctor has the right to prescribe amniocentesis in the following cases:
- Suspicion of abnormal fetal development or fetal hypoxia.
- Assessment of the state of the fetus, the maturity of his lungs, the diagnosis of intrauterine infections.
- Taking pregnant drugs that have a toxic effect on the fetus.
- Polyhydramnios. In this case, the procedure is carried out repeatedly, its main goal is to remove excess amniotic fluid so that they do not impede the growth and development of the fetus / s.
- The need for intrauterine treatment of the fetus or for the purpose of terminating the pregnancy (according to strict indications).
- Surgical treatment of the fetus.
How and why amniocentesis is done - video
Contraindications for amniocentesis
There are very few contraindications for amniocentesis, all of them are dictated by safety considerations to preserve pregnancy or the health of the fetus.The main contraindications include:
- The threat of miscarriage and placental abruption;
- Fever in a pregnant woman;
- Acute infectious processes of any localization or exacerbation of a chronic infection;
- Myomatous nodes of large sizes.
Amniocentesis Test Results
The results of the amniocentesis are usually ready in 2-3 weeks. However, the timing of the results of the tests may vary depending on the type of study that is necessary to identify abnormalities in the fetus. So, in the study of desquamated fetal cells, they are first cultivated on nutrient media for 2-4 weeks, and only after that they proceed directly to the study of the material obtained. If molecular genetic diagnostics is carried out, cultivation (growing) is not required, so the results can be obtained within a week.The reliability of amniocentesis results is very high, approximately 99.5%. The remaining percentage of failures is usually due to the entry of the mother's blood into the puncture material or an insufficient amount of fluid received.
Every woman who decides to conduct this test should be prepared for bad news, because. this analysis is prescribed only in case of serious suspicions from the doctor about possible abnormalities in the development of the fetus. If the results of the study show violations in the development of the fetus, a woman has to make a choice - to keep the pregnancy or to terminate it. The doctor in this situation can and should inform about the possible consequences of this or that decision, but in any case, the woman herself has to make the final decision.
Should I do an amniocentesis or not?
Whether or not to do an amniocentesis is up to the woman to decide on her own. The doctor may recommend this test (in some cases, he may very strongly recommend it), but amniocentesis is not included in the list of mandatory studies. If in the past a woman had cases of giving birth to a child with abnormalities, or in the early stages of pregnancy she took teratogenic and toxic drugs, amniocentesis is especially important. This will avoid the birth of a handicapped child or mentally prepare for the fact that the baby will have malformations.
You should not be afraid of the consequences of this procedure, because. the risks are very minimal, both for the pregnant woman and for the fetus.
Possible consequences of amniocentesis
Most often, the consequences of amniocentesis occur in those women whose pregnancy proceeded with any complicating moments, or there were various chronic diseases. In healthy pregnant women, complications of amniocentesis almost never occur or they are easily corrected.Possible side effects of an amniocentesis include:
- early discharge of amniotic fluid (most often occurs during transvaginal puncture);
- injury to the vessels of the umbilical cord or the fetus itself;
- violation of the integrity of the bladder or intestinal loops of the mother;
- detachment of membranes and the threat of miscarriage;
- premature birth.
Amniocentesis or cordocentesis?
Which study is more appropriate to conduct - cordocentesis or amniocentesis - will, no doubt, be decided by the doctor. The informativeness and reliability of both methods is very high and amounts to more than 95%. The choice is usually influenced by the timing of pregnancy.In the second trimester (up to 20 weeks), amniocentesis remains possible, and conditions for cordocentesis appear. On later dates cordocentesis is a more informative method of pregnancy, due to the fact that in most cases it is easier to get into the blood from the umbilical cord, the obtained material is cultivated much faster (only 2-3 days), and the probability of false results is much lower.
The possible consequences of both manipulations are the same and do not exceed 1-1.5%.
Can an amniocentesis determine the sex of a baby?
Amniocentesis allows you to determine the sex of the child, because. The material for research is genes and chromosomes. As you know, the sex of a person depends on the combination of only two chromosomes - X and Y. If only X chromosomes are present, a girl is born, the presence of X and Y chromosomes determines the male sex of the child.Determining the sex of the child during amniocentesis is an important part of the study when there is a suspicion of a hereditary disease that is transmitted exclusively through the male line.
To satisfy the mother's personal interest regarding the sex of the unborn child, neither amniocentesis nor cordocentesis is performed.
Where to do amniocentesis?
Amniocentesis is a procedure that requires considerable knowledge and experience from the doctor. The higher the qualification of the doctor, the less chance of any complications, both from the health of the pregnant woman and from the condition of the fetus. That is why this manipulation is carried out only in specialized clinics and medical genetic centers.In Russia and Ukraine, in almost every major city there are medical genetic centers that perform this procedure. In addition, in these cities you can find private institutions that are equipped with everything necessary for amniocentesis and other research methods for the early detection of pathologies in the fetus. The multidisciplinary medical center "Mother and Child" can be attributed to the long-standing and well-established medical centers. In it, a woman can receive qualified medical assistance, consult on all issues of concern, and also pass the necessary laboratory tests.
Amniocentesis cost
The average price for an amniocentesis varies between 5000-7000 rubles or 1300-1800 hryvnias (in Ukraine), depending on the location of the medical institution.Amniocentesis Reviews
Olga, Kazan:“My pregnancy was smooth and smooth throughout the first trimester. The uzist told me that a girl should be expected, and my husband and I even began to choose a name for our baby. All laboratory tests were perfect, the child developed according to the timing, and then how out of the blue - screening tests revealed that I have trisomy on chromosome 21, for those who don’t know what it is, I’ll say that Down syndrome is called in medical language! Naturally, I was offered to do an amniocentesis. To say that I was shocked - do not say anything! I cried for days on end and refused to take this test. My husband supported me as much as he could. Once, when my doubts and torments reached the limit, I could not stand it and told about my trouble best friend. She took my hand and without further ado led me to her obstetrician-gynecologist. The doctor was able to calm me down and convince me to undergo an amniocentesis without delay. I won’t bore you with the details for a long time, but I’ll say that I still did an amniocentesis - it turned out not to hurt, but rather unpleasant. After 3 weeks, they called me from the medical genetic center and said that the girl was healthy, without deviations. My happiness knew no bounds, I cried and laughed at the same time. Now we have a pretty daughter Sashenka, she was born absolutely healthy!"
Irina, Minsk:
"I decided to write my own review, perhaps it will help someone to accept correct solution. At the 20th week of pregnancy, I wanted to find out the sex of the unborn child, I had no other reasons for going to the doctor - I felt great, no toxicosis, no deviations in the tests. I came to ask about one thing, and they told me about something completely different. On ultrasound, the doctor saw anomalies in the structure of the heart and umbilical cord of the fetus. It turns out that these are two indicators that indicate Down's syndrome. With a frightened look, I went to see my gynecologist. She immediately sent me to a day hospital for the prevention of fetoplacental insufficiency and hypoxia in the fetus. At 21 weeks, after a repeated bleak ultrasound, I was prescribed cordocentesis (amniocentesis was no longer suitable in terms of timing). After the doctor took blood from the umbilical cord of the fetus, she said that the tests would be ready in 5 days, and then there were the holidays, in general, I had to wait as long as 2 weeks! I omit here all my experiences, they were unbearable, I thought I would go crazy. When the geneticists called, I thought my heart would jump out of my chest, the pressure rose from excitement. I went to the doctor for a consultation in a semi-conscious state, if it were not for my husband, I would not have arrived. At the meeting, the doctor said that the chromosome set of the fetus is 46 XY, I did not understand anything and started crying. She began to calm down and say that this means that a HEALTHY boy is growing and developing in my stomach! My husband cried with me. Both of us were then soldered with valerian. The last months of pregnancy, I just enjoyed my condition and constantly talked with my boy, told him stories, sang songs. It is terrible to imagine how I would feel and act if the result was different. Although, over time, I came to the conclusion that cordocentesis, as well as other similar procedures, are very important and necessary. It is better to know what awaits you and your baby than to be in complete ignorance. Such analyzes are needed at least so that a woman can make a decision - is she ready to take on such a responsibility and live with her all her life? Forgive me women who have a different opinion on this matter, but I believe that if the baby is deviant in ALL tests, then you should not doom him (and yourself, probably) to long, lifelong torment. I understand that the question is controversial, and philosophical, so to speak, but I decided for myself that way. I wish all future mothers healthy and happy kids!