Fetal genetic material examination
Within the concept of complete monitoring of both normal and pathological pregnancies, „Jevremova” in cooperation with consultants having experienced thousands of invasive diagnostic procedures, provides to its patients the possibility of invasive prenatal diagnostic and early detection of fetal genetic material abnormalities.
WHAT IS GENETIC MATERIAL?
The whole process of growth and development of organisms is determined and controlled by the genetic material. Each cell carries the whole genetic mass (genome) which is, in cell division, completely transferred to the next generation of cells. The genetic material reflects itself in the cell function. There is a nucleus, inside each cell, which carries the genetic material in the form of chromosomes. Chromosomes comprise information, in biology known as genes, which directly control all cell functions and thereby the functions of the organism, as well. Human somatic cells comprise 46 chromosomes: 44 autosomes and 2 sex chromosomes. The sum of all the chromosomes in one cell is called karyotype. Along with 44 autosomes, men also carry XY sex chromosomes (karyotype 46XY), while the women carry XX sex chromosomes (karyotype46XX).
WHY TO EXAMINE FETAL GENETIC MATERIAL?
It is known that physical chemical and biological agents from our environment can cause changes in the genetic material and thus inevitably induce permanent damage to the fetus.
Prevention and timely detection of congenital diseases and congenital anomalies make one of the main tasks of the modern medicine in the struggle for healthy offspring.
However, a certain number of congenital diseases and congenital anomalies are not manifested as structural changes detectable by ultrasound.
For that reason, the invasive diagnostic methods are applied and with a minimum risk for mother, her fetus and the advance of the pregnancy, enable taking samples of fetal tissues.
Samples taken in prenatal diagnostics are: chorionic villi, amniotic fluid and fetal blood, although for appropriate reasons other fetal tissues and excretions (fetal skin, a part of a muscle, a part of a tumor, a part of the liver, etc.) can be sampled. The taken samples, besides examination of genetic material, can also be used for examination of metabolic anomalies, fetal infections, DNA analysis, gene loci, etc.
WHEN IS FETAL GENETIC MATERIAL EXAMINATION NECESSARY?
Anomalies related to number and structures of chromosomes are the base for abnormal development of the fetus. As certain conditions carry higher risk for anomalies in the number and structure of chromosomes, planning the examination of fetal genetic material (determination of fetal karyotype) is necessary.
Mother’s age is the primary reason for prenatal examination of fetal genetic material. It is known that abnormality in the genetic material exists with one of 200 newborn babies. This risk increases severely with the age of the mother.
With women up to 35 it is 1:204
With women at 40 it is 1: 65
With women at 45 it is 1: 20
Therefore, all around the world, fetal genetic material examination is considered medically justified and necessary for all women older than 35.
- A previous child with chromosomal abnormalities is also one of the reasons for prenatal karyotyping in the pregnancy.
- Balanced translocations with the parents are another indication for examination of fetal genetic material. Rarely ever, parents carry genetic material abnormalities, that they are unaware of and that have not been previously manifested (heterozygote). In certain circumstances, regarding that the „error” in the structure of chromosomes may be transferred to the offspring, the abnormality manifests only with children.
- Diseases related to „X” chromosome, i.e. congenital diseases that are specifically transferred only by X chromosome. Provided that there is a risk that these may be inherited, examination of genetic material and gender of the fetus is necessary.
- Double or triple: Experience proved that majority of children with genetic material disorder was born by women under 35. This controversy is due to the fact that even with women of this age there exists a certain risk (1:204) to give birth to a child with abnormality in genetic material, and that, different from women older than 35, where fetal karyotype examination is required, the first ones do not undergo such examination at all. Therefore, noninvasive screening of fetal chromosomopathies, by examination of certain hormones in the mother’s blood, being of fetal origin (alfa-fetoprotein and beta HCG) is being used. Due to the hormone levels, this method has enabled identification and selection of women under 35, which carry higher risk for fetal genetic material abnormality and which should undergo invasive prenatal diagnostics and fetal karyotype determination.
Anxiety, due to the fear of mothers-to-be about whether they will give birth to a healthy child, is the increasingly frequent reason why mothers insist on carrying out prenatal examination of genetic material.
WHAT METHODS ARE USED FOR FETAL GENETIC MATERIAL EXAMINATION?
As samples for prenatal diagnostics, for the purpose of fetal genetic material examination, nowadays most frequently used are chorionic villi samples (aspiration chorionic villi biopsy), amniotic fluid (amniocentesis-RAC) and fetal blood (cordocentesis CC).
Chorion biopsy - chorionic villi sampling (CVS)
In early prenatal diagnostic of congenital disorders, chorionic villi sampling (CVS) has become very popular recently. In the essence of the idea that chorionic villi may be used in prenatal diagnostic is the fact that their chromosomal and genetic characteristics are identical to the fetal ones.
The main advantage of this method is in the fact that the fetal genetic material abnormality is detected as early as the first 12 weeks of the gestation, in a quick (up to 48 hours upon the intervention), and simple way, with practically equal risk for mother and fetus as with other methods. When identification of the genetic material abnormality is confirmed, the process of abortion is carried out in a simple way prior to 10th week of pregnancy. As determination of fetal karyotype identifies also the sex of the fetus, this intervention is recommended to the patients carrying the risk of transmitting the diseases related to sex chromosomes.
Transabdominal approach is by far the most accepted method of chorionic villi sampling. The process is carried out with local anesthesia and is certainly most comfortable for the patients. The pregnant lies in a bed and the intervention is preceded by ultrasound examination for the purpose of estimation of vitality of the pregnancy and gestation age. By determination of the chorion frondosome position, the shortest way for insertion of aspirated needle is planned. Then, a needle (guiding needle with mandrel), is passed through the abdominal wall and uterine wall all up to the chorionic frondosome (amnion), and not disturbing the space of the embryo therewith, and then a certain quantity of chorionic villi for cytogenetic analysis is aspirated. The whole procedure is carried out in the specialized hospital / polyclinic and immediately upon the intervention the patient may go back to usual activities. Within 48 hours upon intervention, at latest, the patient is informed about the results of the intervention.
Amniocentesis – amniotix fluid sampling(AC)
This method consists basically of sampling amniotic fluid wherefrom numerous elements may be analyzed. In the examination of the fetal genetic material, the intervention is, as a rule, planned in the pregnancy from 12 to 24 weeks. Although modern sonographic devices enable safe amniotic fluid sampling even in early pregnancy, the ideal time for intervention is the pregnancy period between 15 and 18 weeks. 
During this period number of fetal cells in the fluid of the fetus is satisfying and the ratio between vital and non-vital cells is optimum. In view of the pregnancy period during which the intervention is carried out in the literature it is known also as an early amniocentesis. Amniotic fluid may be sampled even after 24th week of pregnancy. This intervention is called a late amniocentesis and it is carried out for estimation the condition of the fetus (with Rh-aloimmunization for example), or for determination of the level of maturation (maturity) of fetal lungs and planning the date of delivery.
Ultrasound examination determines vitality of the fetus, estimates the gestation age, quantity of the fetal fluid and the position of amnion, and finally planned is the optimum path for passing the needle up to ‘pocket’ of the amniotic fluid wherefrom the sample is taken. Amniotic fluid is aspired by a syringe 15-20 ml, and forwarded for further testing (cytogenetic analysis).
Fetus blood sampling - cordocentesis (CC)
Cordocentesis (CC) includes transabdominal puncturing of umbilical cord of the fetus and fetus blood sampling. Due to its invasiveness and somehow higher risk involved therein, this intervention is as a rule carried out mainly in hospitals in patients with strong indications, and the pregnancy must be 20 weeks or higher. The patient is informed about the results of the intervention. a week after the intervention
WHAT RISK DO INVASIVE PRENATAL DIAGNOSTIC METHODS INVOLVE?
Prenatal invasive diagnostic methods are very safe. Complications in the form of poor bleeding and uterine contractions upon the intervention are seldom, short and most often harmless. Infections and ruptures of fetal membranes occur very rarely. Likelihood for miscarriage is between 0, 5 and 2% depending on the method applied and the experience of the operator. Diagnostic security of prenatal invasive procedures exceeds 95 %.
In certain cases, accurate determination of the karyotype of the fetus is not possible, and most frequently those are:
- Insufficient quantity of material, i.e. impossibility to obtain sufficient number of cells in the cellular division to carry out appropriate analyses. When these occur, the intervention or some other diagnostic method is recommended.
- Twin pregnancies carry difficulty for identification of the position of the amnion belonging to each of the embryos in the uterus.
- Placental mosaicism. The obtained sample in 1 % of the patients comprises a mixture of normal and abnormal cells. In that case, results of the cytogenetic testing do not have to correspond to the karyotype of the fetus.
There is no 100 % safe prenatal diagnostic method. About 2-3 % of all the pregnancies are associated with genetic damage of the fetus, and they cannot be identified by determination of the genetic material of the fetus (karyotype).