Biochemical screening
(from the English “to screen” – sift, sort) – a set of diagnostic tests during pregnancy, aimed at identifying women at risk with an increased likelihood of having a child with serious diseases – chromosomal disorders and defects in the closure of the neural tube.
Biochemical screening is an important component of comprehensive prenatal screening. Studies conducted as part of prenatal screening are safe, do not have a negative impact on the course of pregnancy and fetal development, and therefore can be used on a mass scale for all pregnant women. Carrying out mass prenatal screening is regulated by Order of the Ministry of Health of the Russian Federation No. 457 of 2000 and is recommended for all pregnant women.
Currently, biochemical screening is carried out in two stages – screening in the first trimester (10-14 weeks) and screening in the second trimester (16-20 weeks).
Biochemical screening determines the levels of marker compounds in the mother’s blood. Marker compounds include alpha-fetoprotein (AFP), human chorionic gonadotropin (CG), free (unconjugated) estriol (NE) and some others. All these compounds are produced by cells of the fetus or placenta and enter the mother’s bloodstream. Their concentration in blood serum varies depending on the duration of pregnancy and the condition of the fetus.
AFP is a protein produced by the yolk sac and liver of the fetus. The protein enters the amniotic fluid with fetal urine, enters the mother’s blood through the placenta and is absorbed through the fetal membranes.
AFP is detected in the mother’s blood from the 5th to 2th week of pregnancy. Open neural tube defects (NTDs) lead to the effusion of fetal fluid into the amniotic cavity, resulting in a sharp increase in the concentration of AFP in the mother’s blood. Therefore, an increase in the level of AFP in maternal serum in the 15nd trimester of pregnancy highly likely indicates the presence of NTD in the fetus. Significant increases in the level of AFP in the mother’s blood are also observed in other pathological conditions of the fetus (gastroschisis, kidney anomalies), threatened miscarriage, etc. At the same time, in cases of chromosomal disorders in the fetus, the level of AFP at 20-XNUMX weeks of pregnancy is reduced.
Chorionic gonadotropin (CG) is secreted by trophoblast cells and appears in a woman’s blood 3-5 days after egg implantation. Its concentration increases rapidly and reaches a maximum by 8-10 weeks of pregnancy. The level of hCG in the fetus with Down syndrome (trisomy 21) usually increases, and with trisomy 18 (Edwards disease) it decreases.
Unconjugated estriol (NE) is produced by the fetoplacental complex. Estriol penetrates into the maternal bloodstream, where the concentration of its unconjugated form can be determined. It is this component that is of fetal nature, and its concentration in the blood serum of a pregnant woman can be used to judge the condition of the fetus. Normally, the level of NE increases from 4 nmol/l at 15 weeks of pregnancy to 40 nmol/l by childbirth.
In order to identify women at high risk of having children with congenital and hereditary (chromosomal) defects, screening programs for all pregnant women to study the level of these markers have been developed and used. The effectiveness of this examination method varies, reaching 98% for detecting abnormalities of the nervous system and 60-70% for fetuses with chromosomal diseases. To determine the exact level of risk of susceptibility to hereditary diseases, genetic counseling may be necessary.
Biochemical screening to detect NTD and Down’s disease (DD) is carried out at 12-20 weeks of pregnancy, and the effectiveness of detecting chromosomal aberrations is maximum at 15-18 weeks and decreases at 19-20 weeks.
Since the absolute values of protein content depend on differences in the test systems used, the generally accepted designation for the deviation of protein levels from the norm has become a multiple of the median (median is the average in a series of ordered in ascending values of the protein level during a normal pregnancy of a given period) – Mom (multiples of median) – for example, an AFP level = 2,5 Mohm means that the protein content in the serum of a given pregnant woman is 2,5 times higher than the median (norm) for this stage of pregnancy. Protein levels from 0,5 to 2 MΩ are considered normal values during diagnostic periods.
A common cause of false screening results is incorrect calculation of the gestational age, therefore, if the protein level does not correspond to the norm, it is necessary, first of all, to clarify the gestational age using ultrasound.
Currently, the results of biochemical screening and ultrasound parameters are entered into a program that, using statistical analysis methods, assesses the risk of chromosomal disorders in the fetus. An indication for the use of invasive diagnostics for the purpose of fetal karyotyping is usually considered to be a risk higher than 1:250 (from 1:190 to 1:400 in different countries) calculated at the time of birth of the child.
The result of biochemical screening is the selection of pregnant women at high risk of having children with NTDs and with chromosomal diseases of the fetus. Such pregnant women require invasive diagnostics. In case of a high risk of NTD in the fetus, ultrasound scanning is indicated, followed by amniocentesis and analysis of the amniotic fluid for the content of markers characteristic of fetuses with NTD. If marker proteins are abnormal, indicating the possibility of chromosomal diseases in the fetus, an invasive procedure is performed to karyotype the fetus.
When screening, the number of pregnant women for whom an invasive procedure is indicated is usually about 5% of the total number of those examined.
It is important to understand that positive results (extreme deviation of protein levels from the median) are only a signal for a more in-depth examination of this patient, because chromosomal pathology will be detected in approximately one out of fifty pregnant women in this group, and NTD – in one out of four hundred examined.
An important additional ultrasound marker is also the thickness of the nuchal space (TN) during pregnancy 10-14 weeks. If the cumulative risk is calculated by measuring TVP and biochemical markers, then the efficiency of detecting Down syndrome in the fetus can reach 80-90%.