New biochemical markers of chromosomal pathology of a fetus.

New biochemical markers of chromosomal pathology of a fetus.

Pregnancy associated plasma protein A (PSPP A) is a glycoprotein, having a large molecular mass, produced by syncytiotrophoblasts and appear in maternal blood from 5 weeks of pregnancy. A small amount of PAPP –A is found in granulosa cells and can be determined in blood, follicular fluid, mucus of Fallopian tubes, in the contents of the cervical canal and the endometrium of non-pregnant women. In the 2nd trimester of pregnancy the main sources SPSS-f are the placenta and decidual tissue. During normal pregnancy, the concentration of PAPP – A in norm is constantly increases. In various pathological conditions (mIssed abortion, chromosomal abnormalities, including Down's syndrome) content of PAPP-A in maternal blood is significantly reduces. Changes in the levels of this marker both in norm and pathology more common in the Ist trimester of pregnancy than in later terms. The most optimal time to measure PAPP-A is from 10 to 12 weeks of pregnancy, when its concentration in maternal serum in case of trisomy 21 decreases more than 2 folds. The degree of detection of a fetus’ chromosomal abnormalities when using only one marker is 42 %. The combined use of the 2 markers (HCG and PAPP-A) increases the detection rate of affected fetus to 60%, and if the calculations take into account maternal age, the detection increases to 75%. Now-a-days PAPP-A is one of the most frequently studied biochemical markers, which are of great importance in the organization of prenatal screening in early pregnancy.

Inhibin A - is a glycoprotein, characterized by the ability to suppress FSH secretion. Inhibin A produced by the gonads, pituitary gland, adrenal glands and placenta. The concentration of inhibin a is increased to a maximum of 8-10 week, then decreases (from 14 to 20 weeks), and then again gradually increases to 40 weeks. Dynamics of the content of inhibin in suggests that the first peak reflects the function of the corpus luteum, the further increase reflects the rapidly growing function of the placenta. Usually, inhibin A disappears from the serum of the mother’ blood during the first 24 hours after childbirth.

When down syndrome in the fetus, the concentration of inhibin A is higher than in normal pregnancy.

One of the advantages of the use of inhibin A as a biochemical marker of prenatal fetal chromosomal pathology is its fairly stable level in the IInd trimester of pregnancy. Therefore, the error in determining of gestational age does not affect the accuracy of risk measurement.

Pregnancy-specific beta-1-glycoprotein (PSBG) aka Trophoblast-Specific Beta₁-Glycoprotein (TSG) – it is pregnancy-specific glycoprotein, which is produced by syncytiotrophoblast and its derivatives. In the mother's blood, it starts to be determined

7 days after ovulation. In physiological pregnancy PSBG concentration increases up to 35 weeks, and then remains constant or decreases slightly before delivery. Its concentration decreases with early spontaneous abortion, ectopic pregnancy, IUFGR, preeclampsia, trophoblastic diseases, as well as in fetal chromosomal pathology. Down's syndrome is characterized with marked reduction of PSBG concentration in the mother's blood in the 1^st trimester, while in the 2nd trimester the level exceeds the standard value. The difference in the medians for healthy fetuses and fetuses with down syndrome statistically significant, but insufficient for the use of PSBG in the 1st trimester.

Superoxide dismutase ( SOD) -  refers to metalloproteins, which play an important role in the protection of cells from toxic effect of oxygen derivatives. SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. Currently, publications on SOD potential use as a marker for Down Syndrome, very little, even though this feature has long been known in the presence of the substance to rise fetal Down Syndrome. Method for determining YSCHV in the mother's blood is simple and does not require expensive reagents, however, to use this method as the sole test for Doug syndrome is inappropriate. because the sensitivity of the test as a whole is low.

Hyperglycosylated HCG – it is one of the fractions of human chorionic gonadotropin, which accounts for about 3% of all molecules of HCG. Hyperglycolysis HCG is a product of cells of cytotrophoblast and can be determined in blood and urine of a pregnant. The popularity of this substance as a biochemical marker of blood is low, however, some authors propose to use the serum as a screening test for Down syndrome. Definition of hyperglycosylated HCG in the mother's blood allows us to identify 60% of cases with Down syndrome, which is comparable with the efficiency of standard triple test.

MARKERS OF A FETUS’ CHROMOSOMAL PATHOLOGY

1. Nuchal skin fold thickness (NFT) - is the maximum value echo negative section between fetal skin and the soft tissue surrounding the cervical spine. Nuchal thickness is measured on an axial section through the head and the level of the thalami, cavum septi pellucidum, and cerebellar hemispheres (i. e. in the same plane that is used to assess posterior fossa structures). Its increase to 3 mm or more is associated with a sharp increase in the frequency of chromosomal abnormalities in the fetus. According to the multicenter study, which involved 17 centers of prenatal diagnostics USA, Italy, Spain, and other countries, the calculation of risk by the age of the patient and the thickness of the NFT zone has allowed to diagnose Down syndrome in 81. 8% of cases. NFT expansion zone can be marked for various defects, many of which are usually diagnosed only in the late stages of pregnancy. However, this echographic marker cannot be fully identified with the concept of " unpromising pregnancy", and recommend termination of pregnancy, as NFT expansion zone does not exclude the birth of healthy children. Its expansion is observed in 5% of fetuses with normal karyotype. Molecular genetic studies have shown that the basis of pathological disorders in the formation and development of the heart, major blood vessels and the lymphatic system leading to the expansion of NFT zone in fetuses with chromosomal abnormalities are genetic disorders. In most cases of congenital heart diseases expansion of NFT zone disappears by 16-18 week of gestation. Temporality of this marker is associated with a differentiated growth of the diameter of large blood vessels: diameter of the aortic isthmus increases more rapidly than the aortic valve.