Obstetrics and Gynecology - A. M. Gromova 2000

Medical and Genetic Counseling in Obstetrics
Methods of Medical and Genetic Diagnosis

Determination of Genetic Risk Value

Genetic risk is determined as a percentage, which establishes the probability that a child with a congenital disorder will be born to a given couple. A baseline genetic risk of 5% is relevant to any family in the absence of additional compounding factors. Subsequent Clinical and Genealogical analysis allows for the Assessment of the additional genetic risk of inheriting a disorder identified within the family.

The genetic risk resulting from parental exposure to mutagenic and teratogenic agents is added to the first two values. Additional genetic risk from Mutagenic Factors can reach up to 2%, while teratogenic factors can account for up to several dozen percent, depending on the situation. The total genetic risk is calculated as the sum of all three components. It is standard practice to classify genetic risk values as follows: within 5%, low; up to 10%, slightly increased; up to 20%, moderate; above 20%, high.

Prenatal Diagnosis of Congenital Malformations

Prenatal diagnosis allows for the intrauterine detection of Congenital malformations and hereditary fetal diseases. If these conditions are associated with severe disability, early mortality, or are incompatible with life, the Pregnancy may be terminated prior to 28 weeks. Indications for prenatal diagnosis are determined by obstetriciangynecologists and geneticists during Genetic Counseling.

In accordance with Order No. 77 of the Ministry of Health of Ukraine dated April 14, 1993, indications for Medical-Genetic Counseling include:

- habitual Miscarriage;

- delivery of a child with congenital malformations in the family;

- presence of hereditary pathology in relatives or the couple themselves;

- presence of children with delayed mental and somatic development in the family;

- stillbirths unrelated to obstetric pathology;

- pregnant women over the age of 35;

- pregnant women who, prior to or during pregnancy, were exposed to mutagenic or teratogenic factors (or such exposure occurred in the father prior to conception);

- all pregnant women at 14–16 weeks who belong to high-risk groups.

Methods of Prenatal Diagnosis:

1. Non-Invasive Methods:

- Ultrasound examination;

- assessment of alpha-fetoprotein levels in maternal Blood;

2. Invasive methods:

- fetoscopy (cordocentesis, cardiocentesis, placentocentesis);

- feto- and amniography;

- amniocentesis;

- chorionic villus sampling and aspiration;

- placental biopsy.

Ultrasound examination makes it possible to detect congenital fetal malformations starting from 12–14 weeks of gestation. However, ultrasound screening is most informative at 16–18 and 22–24 weeks; detecting malformations during these periods leaves sufficient time for elective pregnancy termination (prior to 28 weeks). Given current advancements in modern equipment and the high qualifications of geneticists skilled in syndromic analysis, prenatal Diagnostics can identify not only major developmental defects (anencephaly, hydrocephaly, Polycystic Kidney Disease, hernias, atresias, etc.) but also diagnose various fetal syndromes (Patau, Down, Turner, Edwards, etc.). In addition, analyzing the Structure and size of the Placenta, the condition of the umbilical cord, and the volume of Amniotic Fluid provides immense clinical value for diagnosing Fetoplacental insufficiency, fetal Hypoxia, and intrauterine growth restriction, thereby enabling timely and appropriate Treatment.

Maternal serum alpha-fetoprotein screening for neural tube defects is based on the fact that during Embryogenesis, alpha-fetoprotein is synthesized in the fetal Liver and serves as the major serum protein, as well as playing an essential role in The Development of Nervous Tissue, Muscles, Skin, Lungs, and Kidneys.

In open Spina bifida and anencephaly, alpha-fetoprotein enters the amniotic fluid and subsequently crosses the fetal membranes and placenta into the maternal Circulation, where it accumulates in remarkably high concentrations. However, it should be kept in mind that elevated alpha-fetoprotein levels may result from a multifetal gestation or an underestimation of the gestational age.

Following the widespread adoption of ultrasound, fetoscopy has lost its primary diagnostic value for detecting fetal congenital malformations, yet it remains useful when fetal blood or tissue sampling is required. An endoscopic instrument equipped with a fiber-optic light source is introduced into the amniotic cavity under ultrasound guidance. Fetoscopic guidance allows for cordocentesis (umbilical vein puncture), cardiocentesis (cardiac puncture), and placentocentesis (puncture of placental vessels). Indications for these Procedures include the need to obtain blood samples for diagnosing fetal blood disorders, autosomal recessive immune system disorders, and more than 100 hereditary enzymopathies.

Blood sampling can also be performed to analyze the fetal karyotype in the diagnosis of chromosomal abnormalities and syndromes. Moreover, in cases of hemolytic disease, intrauterine exchange transfusion can even be performed. Fetoscopy is most commonly carried out between 15 and 22 weeks of gestation, as the volume of circulating fetal blood increases during this period and amniotic fluid clarity is optimal.

Invasive methods of prenatal diagnosis (chorionic villus biopsy and aspiration, placental biopsy, amniocentesis) are indicated in the following clinical scenarios:

- pregnancy complicated by persistently low or elevated maternal serum alpha-fetoprotein levels;

- pregnancies in carriers of balanced Chromosomal aberrations;

- presence of monogenic Autosomal Recessive Disorders in both parents or in two or more of their children;

- pregnant women who are carriers of X-linked diseases;

- pregnant women with a history of delivering children with Chromosomal Disorders;

- when it is necessary to determine bilirubin levels in fetal hemolytic disease.

Chorionic villus biopsy and aspiration. Indications for this Procedure include The Need for fetal karyotyping, diagnosis of various inherited Metabolic Disorders, and fetal DNA analysis. The particular value of these methods lies in The ability to perform such testing in early pregnancy—at 8–12 weeks. If a pathology is detected, this allows for the option of pregnancy termination prior to 12 weeks. The procedure can even be performed on an outpatient basis under aseptic and antiseptic conditions, guided by ultrasound. A transcervical approach is typically used. The obtained specimen is subject to immediate analysis. Another advantage of this method is the elimination of Cell culture, which is mandatory when obtaining material via amniocentesis. The mass of the chorionic biopsy sample should be at least 5 mg.

Placental biopsy is performed for the same indications as chorionic villus sampling, but after 16 weeks of gestation, when a transabdominal approach to the placenta becomes feasible. This procedure is also performed under ultrasound guidance.

Amniocentesis (puncture of the amniotic cavity to obtain amniotic fluid) is performed between 16 and 22 weeks of gestation for the indications mentioned above, under ultrasound guidance. Both transvaginal and transabdominal approaches may be used. Approximately 20 mL of amniotic fluid is collected; In addition to diagnosing chromosomal disorders and enzymopathies, the amniotic fluid can be analyzed to determine bilirubin levels in hemolytic disease and the lecithin-sphingomyelin ratio to assess fetal pulmonary maturity and surfactant system development.

Due to the risk of complications (such as spontaneous miscarriage or infection) associated with invasive diagnostic procedures, an informed consent form must be signed by both the pregnant woman and her partner prior to the intervention. Furthermore, the risk of procedure-related complications must be outweighed by the risk of giving birth to a child with a congenital or hereditary disorder.