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Prenatal diagnosis of congenital diseases
Last reviewed: 18.10.2021
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Prenatal diagnosis is the most effective method of preventing congenital diseases. It allows in many cases to unequivocally solve the problem of possible damage to the fetus and the subsequent termination of pregnancy.
The prenatal diagnosis in the first trimester of pregnancy includes the determination of the following biochemical markers: PAPP-A and the free β-subunit of CG (β-CG) from the 8th to the 13th week of pregnancy, and then the ultrasound examination of the collar fetal space with 11- th to the 13th week. This algorithm is the most effective screening system primarily for Down's syndrome, as well as other chromosomal abnormalities (Edwards, Kleinfelter, Turner syndromes, etc.), which allows to identify them in approximately 90% of cases with a false-positive rate of 5%.
In addition to the detection of chromosomal abnormalities, the combined determination of these biochemical markers makes it possible to assess the risk of having a number of morphological defects of the fetus and obstetric complications.
The limit of risk is considered to be a probability of 1: 540 (that is, no higher than the average in the population).
The study of biochemical markers during the second trimester of pregnancy (14-18 weeks) allows assessing the risk of the presence of the following disorders:
- chromosome abnormalities in the fetus (Down syndrome, Edwards syndrome, etc.);
- defects of the neural tube and abdominal wall of the fetus;
- obstetric complications in the III trimester of pregnancy.
The risk of having a child with Down's syndrome depends on the age of the pregnant woman and is 1: 380 for women over 35 years old, and 1: 100 for 40 years. Defects of the neural tube - the most common morphological disorders, detected in 0.3-3 out of 1000 newborns.
The possibility of prenatal detection of Down's syndrome and neural tube defects is based on the relationship between changes in the concentration of a number of biochemical markers present in the blood of pregnant women and the presence of congenital malformations.
Prenatal diagnosis in the second trimester of pregnancy is based on the use of a triple or quadro test.
The triple test includes the determination of the concentration of AFP in the blood, the free β subunit of the chorionic gonadotropin and free estriol. The optimal time for screening is 16-18 weeks. The effectiveness of the detection of Down's syndrome with the use of these markers is approximately 69% (the incidence of false positive results is 9.3%).
The quadro-test is the most common and generally accepted method of prenatal screening for Down's syndrome and trisomy 18. It includes the determination of the concentration in the blood of a pregnant AFP, free estriol, inhibin A, and chorionic gonadotropin. The test is conducted between 15 and 22 weeks of pregnancy. The effectiveness of the quad-test for Down's syndrome is 76% (the incidence of false positive results is 6.2%).
To identify congenital malformations of the fetus in the I-II trimesters of pregnancy, an integral test is used (two-stage prenatal screening for Down's syndrome and other chromosomal abnormalities, as well as neural tube defects). The first stage is optimally performed at the 12th week of pregnancy (between the 10th and 13th weeks), it involves determining the concentration of PAPP-A, β-chorionic gonadotropin in the pregnant woman's blood and ultrasound examination of the fetus. The second stage is carried out 3-4 weeks after the first, it includes a study of the concentration of AFP, free estriol and chorionic gonadotropin in the blood of a pregnant woman. With positive results of screening, the pregnant woman is offered additional ultrasound and, in some cases, amniocentesis.
The use of the integral test is based on the fact that the I trimester markers do not correlate with the markers of the II trimester, therefore it is possible to calculate the risk independently for two trimesters. The sensitivity of the integral test reaches 85%.
The reference level of markers (PAPP-A, AFP, β-CG, free estriol) can vary in different populations and ethnic populations and depends on the method of determination. In this regard, individual levels of markers in pregnant women are assessed using the indicator MOM (Multiple of Median). This indicator is the ratio of the individual value of the marker to the median of the corresponding reference series established for a certain population. The reference values of serum markers for any gestation period are MoM values from 0.5 to 2.
On a large statistical basis, it was found that, with Down's syndrome, the average AFP level is 0.7MoM, XG is 2MoM, estriol is 0.75MoM. In Edwards syndrome, the level of AFP, chorionic gonadotropin and estriol is 0.7 MoM. When considering the distribution curves of the values of the main markers, there is a large overlapping area of the norm and pathology, which does not allow using only one indicator for screening, so a complete complex of markers is needed.
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