HUMAN MEDICAL BIOLOGY, ANATOMY, PHYSIOLOGY, AND PATHOLOGY - Ya.I. Fedonyuk 2010

BIOLOGY

CHAPTER 1. BIOLOGICAL FOUNDATIONS OF HUMAN VITAL ACTIVITY

1.4. ONTOGENETIC LEVEL OF LIFE ORGANIZATION

1.4.2. Basics of Human Genetics

Prenatal Diagnosis of Hereditary Pathology

Prenatal diagnosis makes it possible to detect congenital developmental defects or Hereditary diseases of the fetus at Cytology/cytology/16.html">Early stages of its development. Early diagnosis helps either to make a decision on Pregnancy termination or to prepare the family for the birth of a sick child. Prenatal diagnostic Methods can be divided into three groups: 1) screening; 2) non-invasive; and 3) invasive.

Screening methods. These methods help identify women who have an increased risk of giving birth to a child with hereditary or congenital pathologies. Such methods include laboratory assays for determining the levels of a (alpha)-fetoprotein, chorionic gonadotropin, and unconjugated estriol. Alpha-fetoprotein (a-FP) is a protein of fetal origin. It is initially produced by the yolk sac and, starting from the end of the first trimester, by the fetal Liver. Its concentration varies throughout pregnancy and also depends on environmental conditions. The level of a-FP is measured in the maternal serum and Amniotic Fluid between 16 and 18 weeks of gestation. An elevated a-FP level may indicate neural tube defects, abdominal wall defects, or malformations of other systems. A decreased a-FP level is observed in chromosomal abnormalities (Down syndrome, Edwards syndrome) and fetal demise. A highly effective method for diagnosing Down syndrome is measuring the level of chorionic gonadotropin in maternal serum. After the first trimester of pregnancy, it should normally decrease. When a mother carries a fetus with a chromosomal abnormality, the concentration of this hormone remains unchanged. In Down syndrome, the level of unconjugated estriol in the pregnant woman's Blood serum is significantly lower.

Non-Invasive Methods do not require surgical intervention. Ultrasound examination is the most frequently used method.

Ultrasound examination (ultrasound, echography, Ultrasonography). The method is based on transmitting ultrasonic waves through the Abdominal cavity, which are reflected from the surfaces of fetal Tissues, captured, and amplified to produce an image of the Placenta outlines and fetal Organs. A transducer serves as both the source and receiver of the ultrasonic waves. During an uncomplicated pregnancy, ultrasound is performed twice: at 20-24 weeks and 28-32 weeks. Ultrasound allows for the detection of fetal malformations and Central Nervous system pathologies such as hydrocephaly (Water on the Brain), microcephaly (abnormally small brain), and anencephaly (absence of the brain); gastrointestinal and Kidney disorders, such as agenesis (absence) or hypoplasia (underdevelopment), Hydronephrosis, and Polycystic Kidney Disease; respiratory and cardiovascular organ anomalies, skeletal abnormalities, and fetal tumors, among others. There are certain cautions regarding The Use of ultrasound in early pregnancy, as neither harmful nor completely harmless effects of ultrasound on the fetal Organism have been definitively proven.

Invasive methods. Invasive Methods for the prenatal diagnosis of hereditary diseases include chorionic villus sampling, amniocentesis, cordocentesis, fetal tissue biopsy, and fetoscopy.

Chorionic villus sampling and trophoblast testing are performed in the first trimester of pregnancy (9th-11th weeks) under ultrasound guidance. The Procedure is carried out via a transabdominal or transcervical approach. The retrieved chorionic Cells are analyzed to determine the chromosomal set, DNA, Enzymes, fetal sex, and the presence of hemoglobinopathies (Sickle Cell anemia, P-thalassemia).

Amniocentesis is the extraction of amniotic fluid using a fine needle to obtain and analyze the fetal cells suspended within it (Fig. 1.83). The transabdominal method (through the abdominal wall) is the most common. It is performed under ultrasound guidance between 12 and 18 weeks of gestation. Fetal cells are either examined immediately or cultured for 2-4 weeks for subsequent cytogenetic, molecular-genetic, and biochemical analyses. This method makes it possible to detect chromosomal abnormalities and Metabolic Disorders.

Class="center">

Fig. 1.83. Amniocentesis as a method of prenatal diagnosis for hereditary diseases.

Cordocentesis is the puncture of fetal umbilical cord vessels to obtain a blood sample. It is performed under ultrasound guidance. Blood samples are used for the same purposes as in amniocentesis. However, cordocentesis has the advantage that blood is a more convenient specimen for research than amniotic fluid cells. Blood Cells can be cultured faster (within 2-3 days) and more reliably than amniocytes.

Fetal tissue biopsy is performed in the 2nd trimester of pregnancy under ultrasound guidance without fetoscopy. For the diagnosis of hereditary Skin diseases (ichthyosis, epidermolysis bullosa), a skin biopsy is performed. The material is examined using a light or Electron microscope. For the diagnosis of Duchenne muscular dystrophy, a Muscle biopsy is carried out, followed by immunofluorescence analysis to detect the dystrophin protein. Affected individuals lack this protein because the normal Gene responsible for producing it is non-functional.

Fetoscopy is a visual examination of the fetus using an endoscope (fetoscope). Introduced into the amniotic cavity (via the anterior abdominal wall or the posterior vaginal fornix), the endoscope makes it possible to inspect PARTS OF THE fetus, perform blood sampling, and take skin biopsies for analysis. The method allows for the diagnosis of visible Congenital Malformations (polydactyly, Achondroplasia, etc.) and the detection of ichthyosis or epidermolysis bullosa through the analysis of skin biopsies. It can also be used to diagnose hereditary hemoglobinopathies, erythrocyte enzymopathies, and immunodeficiency states. It is performed only under specific indications at 18-23 weeks of gestation under ultrasound guidance. Miscarriages have been reported in 7-8% of cases following fetoscopy.

In recent years, the hypothesis of preconception Prevention has been developing. It begins a few months before conception and continues through the early stages of embryonic development. Preparing the mother's body (vitamin supplementation, antioxidant therapy, immune boosting, stress avoidance) prior to conception and maintaining these conditions during the early stages of embryonic development (up to 10 weeks) helps reduce the incidence of multifactorial congenital malformations. According to N.P. Bochkov (1997), in women who received additional vitamin supplementation, the recurrence rate of giving birth to a child with neural tube defects decreased from 4.6% to 0.7%.