Alpha fetoprotein (AFP) in prenatal screening

General information.

The content of the article:

AFP is produced by the cells of the fertilized egg in the body of a pregnant woman, but can also be found in a child or man. It indicates the likelihood of developing a malignant process and allows you to diagnose cancer at an early stage. Also, a blood test for AFP helps assess the effectiveness of antitumor treatment, identifies early metastases and indicates the condition of the fetus during pregnancy. etc.

At the moment, medicine knows two hundred tumor markers. One of them, AFP, is a protein macromolecule to which a carbohydrate or fat component is attached. AFP is produced by malignant cells and then enters the blood, where its level can be determined using an enzyme-linked immunosorbent assay (ELISA).

Regular testing of a pregnant woman's blood for AFP allows us to monitor some of the immune reactions of the mother's body. Since alpha-fetoprotein is produced by the embryo during pregnancy, the expectant mother's immune system often identifies the fetus with a foreign agent and tries to attack it. That is why increased AFP in pregnant women should be considered normal, and its low values, on the contrary, may indicate fetal malformations.

The tumor marker AFP is also detected in the body of adults and children, since it begins to be produced in the liver before birth (during embryonic development) and throughout life. Therefore, this indicator is one of the main criteria in the diagnosis of oncological pathologies of the liver and gastrointestinal tract. The significance of AFP also lies in the fact that it has independent antitumor activity - it can bind and remove malignant cells of the liver, uterus, respiratory system, mammary glands, etc.

The half-life of AFP is about 5 days. Therefore, the study of tumor markers for several weeks after chemotherapy, radiation therapy or surgical procedures allows us to monitor the effectiveness of treatment. If alpha-fetoprotein levels continue to rise, the prognosis for the patient is poor. If the intensity of the decrease in AFP is low, then tumor particles may remain in the patient’s body or the process of metastasis has begun.

The biomaterial for AFP is blood serum. But other biological media can be used periodically: the secretion of the pleural cavity of the lungs, bile, urine, ascitic or amniotic fluid.

AFP: Use in oncology and perinatology (literature review).

The history of the discovery of a-fetoprotein (AFP) is as follows. In 1956, C. Bergstrand et al. [16], using paper electrophoresis, isolated a certain protein from fetal blood serum, which was called “embryo-specific protein.” Interested in this discovery, the authors continued their research and in 1960 discovered in mouse hepatoma cells an antigen that was also present in the liver, blood and other tissues of pregnant and non-pregnant mice [34]. In terms of its electrophoretic properties, this antigen was very similar to the previously isolated “embryo-specific protein,” but the complete identity of the “embryo-specific antigen” and the “embryo-specific protein” could not be established. Later, in 1962, at the VIII International Congress on Oncology, G.I. Abelev et al. [4, 7] reported the discovery of large amounts of “hepatoma-specific antigen” in the blood and liver extracts of mouse embryos, as well as in the blood of mice with hepatoma. In subsequent years (1963-1964) Yu.S. Tatarinov et al. [53] isolated embryo-specific a-globulin (called a-fetoprotein) from the blood serum of people with hepatocellular carcinoma. It was Yu.S. Tatarinov who was the first to characterize the chemical structure of this protein. In 1964-1968. AFP determination has been widely used in East Africa and other African regions to identify patients with hepatocellular carcinoma, since these regions of Africa are endemic areas for this disease [4, 39]. These studies revealed that AFP was also found in the blood of patients with testicular teratoblastoma and ovarian germinoma [35, 39].
The next five years were spent developing chemotherapy monitoring schemes for patients with hepatocellular carcinoma, teratoblastomas and, especially, ovarian germinomas. These studies were very actively carried out in France by Uriel et al. [39].

Methods for determining AFP have also improved - from paper electrophoresis in 1960 to enzyme-linked immunosorbent assay today.

In 1972, D. Brock and A. Boltan discovered a high content of AFP in the amniotic fluid in the presence of a neural tube defect in the fetus [19]. Thanks to this, it became possible to use AFP as a marker to form a group at increased risk for the presence of a defect in the development of the neural tube. In 1987, Crandall et al. [22, 46] proposed the determination of AFP as a screening test for fetal pathology. More recently, the possibility of prenatal diagnosis of Down syndrome using AFP determination has been demonstrated [9, 14, 27, 28].

Despite more than forty years of research on AFP, to date only the following has been established with certainty:

1) the structure of this protein has been characterized,

2) its high affinity for fatty acids is shown,

3) it has been established that the site of AFP synthesis is certain fetal structures and proliferating tissues.

Key questions such as:

1) regulation of AFP synthesis,

2) the function of this protein in the body,

3) mechanism of action of AFP.

The main problem is the detection and characterization of AFP receptors [3, 6].

So, let's look at what is known about AFP to date.

The structure of AFP and some information about its function

AFP is a glycoprotein with a molecular weight of 69,000 daltons. The carbohydrate component is one oligosaccharide (4% of the total molecular weight), the protein component is one polypeptide chain (590 amino acids), organized into a three-dimensional domain [40].

AFP, present in all mammals, has almost the same structure, so cross-reactions between AFPs from humans, primates, mice, rats, rabbits, etc. are immunologically detected. AFP-like protein is found in birds, reptiles, amphibians and sharks [6].

In terms of physicochemical properties, AFP has much in common with serum albumin, the molecule of which is also represented by one polypeptide chain, 70% identical to that of AFP. In addition, both proteins have identical molecular weights, isoelectric points, and electrophoretic mobility. Serum albumin, however, does not contain a carbohydrate component, as a result of which there are no cross-reactions when determining serum albumin and AFP, since monoclonal antibodies for determining AFP are produced to the native molecule, taking into account its carbohydrate component [36].

A distinctive property of the AFP molecule is its microheterogeneity, revealed by isoelectric focusing. Seven subcomponents of the AFP molecule have been identified. Microheterogeneity was detected in the carbohydrate component and the N-terminal part of the polypeptide chain [50].

It has been shown that AFP synthesized in the visceral endoderm has a slightly different carbohydrate component from that of AFP synthesized by the fetal liver or hepatocellular carcinoma cells. Differences in the N-terminal part of the polypeptide chain can be attributed to structural polymorphism of the gene responsible for the synthesis of AFP or explained by the features of the post-translational stage of polypeptide chain formation (32). Since the antibodies used to determine AFP are produced to the native molecule, the antigen-antibody reaction does not reveal the microheterogeneity of the AFP molecule [48].

Understanding the function of AFP is the most confusing part of AFP research.

It seems that all discussions about the function of AFP are quite speculative. At the moment, only two facts can be considered reliable:

1. AFP exhibits high affinity for polyunsaturated fatty acids (PUFAs) [49];

2. AFP is associated with some internal fetal structures and actively proliferating tissues [51].

It most likely follows from this that AFP adsorbs PUFAs from the maternal blood circulation in the placenta and transfers them to embryonic tissues that do not have the ability to endogenously synthesize PUFAs. This hypothesis assumes the presence of specific AFP receptors. One of the main problems in studying the function of AFP is the isolation and characterization of its receptors, since only then will it be possible to answer the questions of what is the mechanism of transport of fatty acids into the cells of embryonic tissue; which epitope of the AFP molecule is a specific binding site; whether only AFP has the ability to transport fatty acids and how AFP is associated with proliferating tissues.

The discovery of AFP receptors will probably make it possible to regulate the growth of tumor cells by introducing substances into the cell that prevent proliferation [58].

The high affinity of AFP for estrogens (in experiments on mice) suggests that AFP protects fetal tissues from the effects of maternal estrogens [7, 43].

It has also been shown that AFP is an immunosuppressant, but its immunosuppressive activity is indirect and manifests itself only through interaction with ligands such as PUFAs [43, 49].

Biosynthesis of AFP

AFP synthesis begins in the yolk sac simultaneously with the onset of embryonic hematopoiesis, and more precisely in the visceral endoderm of the yolk sac. All serum proteins of the period of early embryonic development are synthesized in the visceral endoderm: serum albumin, α-aminotrypsin, transferrin and AFP [16, 33]. Later, when embryonic hematopoiesis transforms into fetal hematopoiesis, when the liver takes on the function of a hematopoietic organ, the synthesis of AFP and other serum proteins begins to occur in the liver. AFP is also synthesized in small quantities in the intestinal tube, since the viceral endoderm, intestinal tube and liver have the same embryonic origin [33, 42, 52].

Although it is known that AFP is an obligatory component of embryonic and fetal hematopoiesis, the role of this protein is practically unknown.

The study of the regulation of AFP synthesis and the formation of ideas about its relationship with tissue malignancy is the most attractive area of ​​research. As already mentioned, the site of AFP synthesis is early embryonic structures, such as the visceral endoderm, as demonstrated in tissue culture experiments using cytochemical methods [38, 40]. It is important to emphasize that no mechanisms for regulating AFP synthesis could be identified.

AFP is detected very early in liver formation, where it is produced by hepatocytes. In mice and rats, progressive synthesis of AFP is observed until birth, and in humans - until the second half of pregnancy. A decrease in AFP production is associated with the maturation of liver structures, which in mice and rats is completed after birth [34]. It is interesting to note that in adult individuals it was not possible to detect cells capable of synthesizing AFP [55].

Inhibition of AFP synthesis in hepatocytes is most likely reversible, which was confirmed by experiments with CCl4 - after exposure of the liver to CCl4, AFP synthesis resumes in it. The ability to synthesize AFP was discovered in hepatocytes localized in the necrosis zone [33].

Based on these experiments, it was suggested that mature hepatocytes do not lose the ability to synthesize AFP, but in adult individuals, AFP synthesis is blocked by some internal factors. Resumption of AFP synthesis is possible in the absence of these factors and activation of specific genes [36]. What are the mechanisms of these processes is the subject of further research.

The AFP synthesis gene has been cloned and its active zones have been identified. The AFP gene belongs to the albumin gene family. The genes for the synthesis of serum albumin, a-albumin, and vitamin D-binding protein in humans are localized in the same region on chromosome 4 as the gene for the synthesis of AFP. The AFP gene consists of 15 exons combined with 14 introns [36].

However, despite numerous studies in this area, the mechanism of starting and stopping AFP synthesis is not well understood. It is assumed that the inhibitor of AFP synthesis in the early postnatal period may be hormone-receptor complexes that interact with the corresponding binding sites on the AFP gene promoter and inhibit the expression of this gene [32, 43]. On the other hand, glucocorticoids act as activators of AFP gene expression, and then the hormone-receptor mechanism cannot be considered as the main regulator of AFP synthesis [15, 35]. There appear to be multiple factors involved in the regulation of AFP synthesis.

AFP and tumors

AFP is a specific marker of embryonal carcinoma [1, 3, 5, 53]. This type of tumor includes hepatocellular adenocarcinoma, teratoblastoma, dysgerminoma and stromal cell tumors. The ability of these tumors to synthesize AFP is due to the presence in them of the same elements of the visceral endoderm as in normal embryos [17, 39].

The concentration of AFP produced by embryonal carcinomas is very high. Ovarian dysgerminoma cells also contain elements of syncytiotrophoblast, and therefore, along with AFP, they synthesize human chorionic gonadotropin [CG]. Both of these markers are used for the differential diagnosis of dysgerminomas [2, 39].

An AFP level above 500 ng/ml [400 IU/ml] can be regarded as pathological. It is this concentration of AFP that is characteristic of dysgerminoma, hepatocellular adenocarcinoma, hepatoblastoma [children's variant of hepatocellular carcinoma]. In liver metastases of tumors other than those listed, an increase in AFP levels is usually not observed [51]. AFP can be considered as an “absolute marker” for the diagnosis of embryonal carcinomas and yolk sac tumors, however, AFP levels above 400 IU/ml are observed only in 80-90% of children with these tumors. In adults with hepatocellular adenocarcinoma, 50% of cases have AFP levels above 800 IU/ml. The half-life of AFP is 5 days, this fact is successfully used in assessing the effectiveness of chemotherapy. Dynamic monitoring of AFP levels in patients at risk is of great importance. Populations of Southern and Eastern Africa and Southern and Central Asia are considered high-risk populations for hepatocellular adenocarcinoma. AFP screening can effectively detect this disease before clinical signs, thereby increasing the effectiveness of treatment. Thus, in a survey of 3,400,000 Chinese, 782 people with hepatocellular adenocarcinoma were identified, of which 301 were in the preclinical stage of the disease [5]. Patients with chronic hepatitis B and C also require dynamic monitoring of AFP levels [18, 25].

AFP and pregnancy

The onset of AFP synthesis in the human fetus coincides in time with the onset of embryonic hematopoiesis, which corresponds to the 3-4th week of intrauterine development. The site of synthesis is the visceral endoderm of the yolk sac. By the end of the first trimester of pregnancy (12-13 weeks), fetal liver hepatocytes become the main site of AFP synthesis. The maximum concentration of AFP in the blood of the fetus is observed at 12-14 weeks of pregnancy. The maximum concentration in the mother’s blood is at the 30-35th week of pregnancy [24, 29].

Part of the AFP synthesized by the fetus enters the amniotic fluid [AF], from where it passes through the membranes of the placenta and transcellularly enters the maternal bloodstream [37]. The dynamics of AFP exchange between fetal tissues and maternal blood serum have not been sufficiently studied; It has only been established that the content of AFP in fetal blood serum is approximately 1000 times higher than in AF. It has been shown that damage to the amniotic membranes or disruption of their permeability leads to a sharp increase in the content of AFP in the mother’s blood.

After the completion of the formation of the uteroplacental blood flow, AFP enters the maternal blood mainly from the fetal blood [57]. The presence of two pathways for the penetration of AFP from the fetal blood into the maternal blood explains the lack of correlation between the concentrations of AFP in the fetal blood, AF and maternal blood. Only their approximate ratio has been established:

maternal blood/AF = 1/100;

AF/fetal blood = 1/1000;

maternal blood/fetal blood = 1/100,000

During physiological pregnancy, modern methods for determining the concentration of AFP make it possible to register reliable changes in the level of AFP in the mother’s blood starting only from the 14-15th week of pregnancy, i.e. from the moment of completion of placentation. Data on the dynamics of AFP concentration in the blood of pregnant women are presented in the table.

Concentration of AFP in the blood of women during physiological pregnancy
Duration of pregnancy, weeks

Median, IU/ml	Tolerance limits, IU/ml
6–8		2–12
15	29	15–60
16	33	17–65
17	38	19–75
18	43	22–85
19	48	25–95
20	53	27–105
21	58	32–110
22	63	37–115
23	68	42–120
24	73	47–125
25	78	52–130
26	83	57–135
27	88	62–140
28	93	67–145
29	98	72–150
30	103	77–155
31–32	140	100–250

Data obtained using the Cobas Core AFP EIA test systems were kindly provided by , Switzerland.

Determination of AFP in the blood serum of pregnant women is currently considered as the basis of screening programs for detecting fetal malformations. If the fetus has such defects as a neural tube defect, gastroschisis, sacrococcygeal teratoma, or fetal hernia, there is a sharp increase in the concentration of AFP in the mother’s blood [8-12]. The concentration of AFP also increases when there is a threat of miscarriage and fetal death [20, 24]. The reasons for the increase in the concentration of AFP in the mother's blood may be increased synthesis of AFP in the fetus (sacrococcygeal teratoma, fetal hernia), features of the uteroplacental blood flow (increased blood pressure in the fetus with the threat of miscarriage), features of fetal hematopoiesis in open malformations of the fetus (neural tube defect and gastroschisis) [31].

The effectiveness of determining anencephaly up to 24 weeks of pregnancy is on average 85.7%, with open and closed spina bifida - 62.5%, with encephalocele - 100% [13, 19]. It is believed that with open neural tube defects, protein leaks from the fetal vascular bed into the AF through the resulting defects [32], as a result of which the level of AFP in it increases several times [10, 12]. If the level of AFP is elevated and there is a neural tube defect, then the risk of the same defect in the next pregnancy increases 5 times [31], however, it should be noted that 90% of cases of these defects in fetuses occur in mothers who have not previously had children with this defect. pathology.

Women who give birth to children with neural tube defects are at higher risk of developing this pathology. Even with a normally developing fetus, the level of AFP in the blood of these women in subsequent pregnancies, as a rule, exceeds normative values. If the AFP level is normal and anencephaly is excluded by ultrasound, the risk of spina bifida is low, so diagnostic amniocentesis is not appropriate. If the AFP level is elevated, an ultrasound scan should be performed; if the results are negative, a diagnostic amniocentesis should be performed [14].

In case of twins, the level of AFP is on average 2 times higher than in pregnancy with one fetus [20]. An increase in the concentration of AFP by more than three times, in addition to the conditions listed above, also occurs with defects of the anterior abdominal wall [10], atresia of the esophagus and/or duodenum and omphalocele [22], congenital nephrosis (Finnish type) [20], polycystic kidney disease , renal agenesis [24], with increased echogenicity of the fetal intestine [according to ultrasound] [15]. In epidermolysis bullosa simplex, when the gastrointestinal mucosa is affected, the level of AFP increases significantly in the AF [26].

An increase in the concentration of AFP in the blood serum of women in the second and third trimesters of pregnancy is determined by severe hemolytic disease and fetal death [57]. It is believed that an increase in AFP levels is associated with fetal cell lysis, in particular liver cytolysis [58].

An increase in AFP concentration is observed in Shereshevsky-Turner syndrome [54], as well as in some types of obstetric pathology.

It should be especially noted that in Down syndrome, the concentration of AFP in the mother’s blood is significantly reduced [9, 14, 26, 28, 45]. This fact forms the basis for prenatal diagnosis of this syndrome. The diagnostic efficiency for this indicator, however, does not exceed 60%, since a decrease in the concentration of AFP in the mother’s blood, characteristic of Down syndrome, may not be detected for a number of reasons. One of these reasons is toxicosis of pregnancy. In this case, the concentration of AFP in the mother's blood can be increased due to the synthesis of AFP by the liver; Another possible reason may be an unfavorable course of pregnancy - the threat of miscarriage, as mentioned earlier, is accompanied by an increase in blood pressure in the fetus and, as a result, an excessive entry of AFP into the mother’s bloodstream [57]. It has also been established that in Down syndrome, the concentration of AFP is reduced not only in the maternal blood, but also in the AF and in the blood of the fetus [28]. The reason for the decreased activity of AFP synthesis in fetuses with Down syndrome has not yet been clearly established [56].

A decrease in AFP levels is also observed in other chromosomal syndromes: deletion of chromosome 18 [21] and Klinefelter syndrome [30]. In Edwards syndrome and some trisomies, the AFP level remains unchanged [30]. Defects such as hydrocele, hypospadias and cryptorchidism are not determined by AFP testing [12].

When determining AFP in blood serum and AF, two main groups of errors can occur. False-negative results can occur if the fetus has a closed defect of the central nervous system, and false-positive results can occur if the AF is contaminated with fetal blood and in some types of obstetric pathology [57]. An increase or decrease in AFP concentration is sometimes temporary [37].

If an increase in the level of AFP in the blood serum of pregnant women is detected, the test is repeated after 1-2 weeks. If a similar result is obtained, then an ultrasound is performed, which can reveal multiple pregnancies, fetal death or obvious malformations. If ultrasound cannot determine the cause of the increase in AFP, then amniocentesis is performed. In such cases, an increased level of AFP in the AF is an indication for fetoscopy, after which the issue of continuing the pregnancy is decided [29].

Work has been carried out to identify the relationship between the content of AFP in the blood of pregnant women and the condition of newborns [11, 57]. It has been established that a higher concentration of AFP at 39-40 weeks of pregnancy is characteristic of the state of intrauterine malnutrition. The highest concentrations of AFP (up to 350 IU/ml) during pregnancy 39-40 weeks were determined in the blood of women with dead fetuses.

When comparing clinical data with indicators of AFP content in the blood, it was revealed that pregnant women with elevated AFP concentrations are more likely to have combined extragenital and obstetric pathology, such as threatened miscarriage, late gestosis, fetoplacental insufficiency [23, 24].

A significant increase in AFP levels was observed in women with placental hemangioma with a normally developing fetus [47]. It is noted that in women with low AFP levels, the risk of premature birth and severe late gestosis is lower than the general population. In women with developing Rh-conflict hemolytic disease of the fetus, an increase in AFP concentration is observed [24].

Diseases such as systemic lupus erythematosus [44], acute eczema, dermatitis [11] during pregnancy also lead to an increase in the level of AFP in the blood of women. In pregnant women with diabetes mellitus, the AFP concentration is usually at the lower limit of normal [41].

In conclusion, it seems appropriate to provide data on the concentration of AFP in the blood of patients under various physiological and pathological conditions.

1. newborns	80–100 IU/ml;
2. children 3–4 months of age	5–10 IU/ml;
3. patients with hepatocellular adenocarcinoma	more than 800 IU/ml;
4. patients with hepatoblastoma (children)	more than 400 IU/ml;
5. patients with testicular teratoblastoma	more than 500 IU/ml;
6. patients with ovarian dysgerminoma	more than 1000 IU/ml; (along with an increase in the concentration of hCG);
7. patients with liver metastases	less than 10 IU/ml;
8. patients with hepatitis B and C	10–50 IU/ml;
9. acute poisoning	up to 100 IU/ml;
10. Down syndrome (mother's blood)	more than 0.5 MOM
11. open fetal defects (maternal blood)	more than 2 PTO

M.L.
Alekseeva Scientific Center for Obstetrics, Gynecology and Perinatology, Russian Academy of Medical Sciences, Moscow
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Toftager-Larsen K, Benzie RI, Doran TA et al. Alpha-fetoprotein and ultrasound scanning in the prenatal diagnosis of Turner's syndrome. Prenat Diagn 1983; 3: I: 35-40. 55. Vacher J., Tildman SM Dominant negative regulation of the mouse alpha-fetoprotein gene in adult liver. Science 1990; 250: 1732-1735. 56. Wald NJ, Densem JW, Smith D., Klee GG Four-marker serum screening for Down's syndrome. Prenat Diagn 1994; 14: 8: 707-716. 57. Waller DK, Lustig LS, Cunningham GC et al. The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications. Obstet Gynecol 1996; 88:5:816-822. 58. Wen P. A novel hepatocytic transcription factor that binds the alpha-fetoprotein promotor-1 inked coupling element. Mol Cell Biol 1994; 14:10:6616-6626.

Indications

The tumor marker AFP in the blood is studied for the following reasons:

• Diagnosis of primary hepatocellular carcinoma (liver cancer);
• high risk of developing liver tumors (with liver cirrhosis, chronic hepatitis);
• suspicion of cancer (confirmation of the diagnosis of testicular teratoblastoma, low-grade tumors);
• predicting the likelihood of cancer metastasis to the liver;
• definition of antitumor therapy;
• screening for the quality of removal of malignant tissues after radical surgery;
• predicting the clinical picture of the disease, its progression, the likelihood of relapse or remission;
• diagnosis of diseases of the lungs, liver, uterus, mammary glands, etc.;
• monitoring the condition and development of the fetus in the second trimester of pregnancy.

An obstetrician-gynecologist, oncologist and other specialized specialists, as necessary, refer you for the study and interpret the results.

Interpretation of results

Important! Standards vary depending on the reagents and equipment used in each particular laboratory. Therefore, when interpreting the results, it is necessary to use the standards adopted in the laboratory where the analysis was carried out. You also need to pay attention to the units of measurement.

Floor	Age	Normal values, IU/ml
Man	Up to 1 month	0,5 — 13600
From 1 month to 1 year	0,5 — 23,5
Over 1 year old	0,9 — 6,67
Woman	Up to 1 month	0,5 — 15740
From 1 month to 1 year	0,5 — 64.3
Over 1 year old	0,9 — 6,67

Important! The interpretation of the results is always carried out comprehensively. It is impossible to make an accurate diagnosis based on only one analysis.

The standard units for measurement are IU/ml, however, some laboratories use ng/ml. In order to convert units of measurement, you must use the formula: 1 ng/ml * 0.83 = IU/ml.

How to convert ng/ml to IU/ml and vice versa for AFP:

• IU/ml=0.83 * ng/ml
• ng/ml=IU/ml / 0.83

Factors influencing the result

• In patients of the Negroid race, there is an increased content of alpha-fetoprotein, and in representatives of the Mongoloid race, on the contrary, it is decreased.
• Against the background of some endocrine pathologies, false-positive results of an AFP test can be determined.
• Taking monoclonal antibodies
• Insulin-dependent diabetes reduces AFP in the blood of pregnant women

Increasing values

Elevated levels of alpha-fetoprotein in non-pregnant women, children and men may indicate the following malignant processes:

• hepatocellular carcinoma, hepatoblastoma (malignant neoplasms of the liver);
• liver metastases;
• oncology of the pancreas, colon or sigmoid colon, lungs, uterus and appendages, breast, gallbladder and bile ducts, as well as squamous cell cancer of the esophagus;
• germ cell pathological formations in the testicles or ovaries;
• embryonal tumors (teratomas);
• acute or chronic liver pathologies (hepatitis, alcohol intoxication, failure, cirrhosis, jaundice);
• liver injuries, surgical operations;
• kidney stone disease;
• blockage of the bile ducts;
• tyrosinemia (congenital inability to break down the amino acid tyrosine);
• ataxia-telangiectasia (Louis-Bar syndrome) – non-inflammatory enlargement of small vessels and cerebellar ataxia.

Important! Malignant processes are indicated by an excess of the AFP norm by several tens of times. In primary cancer, a concentration of the substance of more than 10 IU is observed in 95% of patients, and in half of the cases, the release of a tumor marker is recorded a quarter before the first symptoms of the disease.

Early diagnosis of pregnancy

The first signs of pregnancy can be very diverse. The most reliable one is a delay in menstruation. However, if your cycle is irregular or you have suffered illness, stress, or travel, this sign may not be entirely reliable. Several other signs may indicate a possible pregnancy:

Increased basal temperature. If you regularly measured basal temperature (BT) in the rectum, then a persistent increase in temperature (37 - 37.2 C) within 18 days after ovulation may indicate pregnancy. But if you have never measured your BT, now is the time to do it - a temperature above 37 C against the background of a delay in menstruation indicates a possible pregnancy.

Enlarged and painful breasts. Many women always have pain in their breasts before their period, but when you are pregnant, the sensations in your breasts may be stronger or slightly different - tingling, heaviness, increased sensitivity, heat, or, on the contrary, your breasts “freeze” and get goosebumps.

Nausea. You may feel nauseous all day long or only feel nauseous in the morning. Nausea can be caused by strong odors (perfume, cigarettes, cafeteria smells), and it can get worse when you are very tired, for example, at the end of the day. If you feel sick to the point of vomiting several times a day, this may be an indication for hospitalization, as severe dehydration is possible.

Frequent urge to urinate. A slightly enlarged uterus begins to put pressure on the bladder, the pregnancy hormone (human chorionic gonadotropin) also has an effect, so you run to the toilet more often.

Weakness, drowsiness, dizziness. The hormone progesterone, the content of which increases during pregnancy: firstly, it dilates blood vessels, and accordingly there is a decrease in blood pressure, so feelings of weakness and fatigue may occur; secondly, it has an inhibitory effect on the nervous system, so you constantly want to sit down or lie down.

Mood swings. You suddenly become very irritable, whiny, and nervous. This is also due to strong hormonal changes in your body.

Changes in appetite. You may suddenly be drawn to completely unusual foods or combinations thereof, for example, herring with milk. You may be attacked by a “zhor”, and at the most inopportune time of day, for example, at night. The opposite situation also occurs - you don’t feel like eating at all. But this is more often associated with nausea.

In addition to all of the above signs of pregnancy, you may also experience: increased vaginal discharge, increased salivation, a strange taste in the mouth (usually metallic), constipation. Most of these changes are caused by hormonal changes - your body is preparing for the nine-month marathon of bearing a child.

If you feel the presence of one or more of the above symptoms, you need to conduct a home pregnancy test. The sensitivity of this test is low, but sufficient to detect pregnancy starting from the first day of the delay. If the test shows that you are not pregnant, but you feel signs of pregnancy, repeat the test after 3-4 days. In addition, sometimes it happens that with a slight delay, it makes sense to evaluate the test results not within 1-5 minutes, but after half an hour - an hour. Practice shows that in this case the second band appears weakly and after a much longer period than what is written on the packaging.

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For a more accurate diagnosis of pregnancy (starting from the 1st-2nd week), you can donate blood for the pregnancy hormone - human chorionic gonadotropin (hCG). Sometimes donate blood for hCG

During examination, the doctor may detect the following signs of pregnancy:

• swelling of the external genitalia;
• change in the uterus - it takes on a rounded shape and increases slightly;
• change in color of the mucous membrane of the vagina and cervix - it acquires a cyanotic (bluish) tint.

Well, if you are already two weeks late, then you can go for an ultrasound and make sure that the pregnancy is intrauterine, corresponds to the term and will develop in you for 9 months!

AFP in pregnant women

As a rule, the tumor marker AFP during pregnancy is rarely determined separately. Most often, the study is carried out as part of a triple screening together with free estriol and hCG. In pregnant women, this method makes it possible to diagnose oncopathologies of the uterus and appendages, mammary glands and liver, and developmental defects of the child. It also makes it possible to predict the development of preeclampsia: an excessively high level of AFP in the blood of women in the 2nd trimester of pregnancy is a risk factor for the development of preeclampsia. Starting from the 10th week, the expectant mother's AFP level gradually increases. By week, its norm is:

Gestational age:	Values, IU/ml	Values, ng/ml
up to 12 weeks	less than 15	less than 18.07
13 to 15 weeks	15-60	18,07-72,29
from 15 to 19 weeks	15-95	18,07-114,46
from 20 to 24 weeks	27 – 125	32,53-150,6
from 25 to 27 weeks	52 – 140	62,65-168,67
from 28 to 30 weeks	67 – 150	80,72-180,72
from 31 to 32 weeks	100 – 250	120,48-301,2

Important! The interpretation of the results is always carried out comprehensively. It is impossible to make an accurate diagnosis based on only one analysis.

Alpha-fetoprotein reaches its maximum concentration by week 34, after which its level begins to decline.

Leading specialists in the management of complex pregnancies in the Southern Federal District

Ermolaeva Elvira Kadirovna is a well-known and recognized specialist in the North Caucasus in the field of diagnosis and treatment of miscarriage, miscarriage, recurrent miscarriage, management of pregnant women with thrombophilia, antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), uterine fibroids, management of pregnancy in young and old pregnant women (after 38 years), management of capricious pregnant women, management of pregnant women with excess body weight. A good obstetrician-gynecologist, a specialist in rational nutrition during pregnancy, a physiotherapist-resortologist, an experienced ultrasound doctor to identify fetal malformations and placental insufficiency.K Women who want to maintain their figure and successfully carry out pregnancy come to her.

Ermolaev Oleg Yurievich Candidate of Medical Sciences, gynecologist-endocrinologist with 25 years of experience and successful experience in managing pregnancy in women with uterine prolapse, bicornuate uterus, saddle uterus and other malformations of the genital organs, managing pregnant women with livedo, thrombophilia and antiphospholipid syndrome (APS) , polycystic ovary syndrome. Management of multiple pregnancies, which require special attention and experience from doctors. Management of pregnancy after IVF, ICSI, after artificial insemination. Management of pregnant women with placental insufficiency. Management of pregnancy against the background of an IUD.

About the doctors of the Clinic in detail...

INTERNATIONAL RECOGNITION of the reputation and achievements of the Women's Health Resort Clinic in the development and implementation of effective and safe treatment methods and the quality of medical services provided is the AWARDING of the Women's Health Resort Clinic in Pyatigorsk with the SIQS International QUALITY CERTIFICATE in the field of medicine and healthcare. International Socratic Committee, Oxford, UK and Swiss Institute for Quality Standards, Zurich, SWITZERLAND. Read more…

We work seven days a week and on holidays:

Monday - Friday from 8.00 to 20.00, Saturday - Sunday from 8.00 to 17.00.

Screening during pregnancy, ultrasound of the fetus and consultation with an experienced obstetrician-gynecologist by appointment by multi-line phone 8 (800) 500-52-74 (toll-free within Russia), or +7 (for international calls).

ONLINE gynecologist in Pyatigorsk can be found at

BOOK ONLINE for an appointment with a gynecologist in Pyatigorsk here.

Doctors and midwives of the Women's Health Resort Clinic are ALWAYS READY for regular patients and those who have visited the Clinic at least once, if it is impossible to contact the Clinic in person, to comment remotely (by phone, Internet) on an existing or newly emerging situation and SUGGEST ways to solve it.

Obstetricians and gynecologists at the Women's Health Resort Clinic have accumulated extensive experience in successful and joyful pregnancy management. WE LOVE PREGNANT PEOPLE!

Low AFP during pregnancy

An indicator that is too low indicates the following deviations:

• malnutrition (malnutrition);
• hypoxia (oxygen starvation);
• Down syndrome;
• Edwards syndrome (trisomy 18 chromosome),
• Patau syndrome (trisomy 13 chromosome),
• frozen pregnancy;
• intrauterine death;
• diabetes mellitus or gestational diabetes in a pregnant woman;
• obesity of various types;
• low placenta previa;
• endocrine disorders.

High AFP in pregnant women

An increased level of AFP by more than 2-3 times is observed in the following diseases:

• anencephaly (severe pathology of the formation of cranial bones and cerebral hemispheres);
• hydrocephalus;
• spinal malformation (spina bifida);
• kidney and liver defects in the embryo;
• atresia of the esophagus or intestines;
• umbilical hernia, gastroschisis (defect of the anterior abdominal wall),
• teratocarcinoma (cancer) of the yolk sac;
• pathology of the placenta;
• encephalocele (cranial hernia);
• threat of miscarriage or premature delivery;
• large fruit;
• multiple pregnancy, etc.

Important: to diagnose pathology of fetal development, it is necessary to know the exact duration of pregnancy. The AFP level alone cannot serve as a diagnostic criterion.

Preparing for analysis

Biomaterial for research: blood serum.

Collection method: venipuncture of the ulnar vein.

Recommended time for collecting material: morning hours from 7.00 to 10.00.

Required conditions: strictly on an empty stomach.

The remaining requirements for preparation for analysis are standard:

• the night before dinner, do not eat heavy, spicy, fatty, sour or spicy foods;
• a day, exclude the intake of alcohol, tonic drinks (tinctures of Eleutherococcus or ginseng, energy drinks), medications;
• Limit physical activity and heavy lifting during the day, avoid psycho-emotional stress;
• stop smoking within 2-3 hours;
• within a few hours, switch to plain water, avoid drinking tea, coffee, juices, etc.

NORMAL ESTRIOL IN BLOOD SERUM

Week of pregnancy	Free estriol rate
6-7 week	0,6 — 2,5
8-9 week	0,8 — 3,5
10-12 week	2,3 — 8,5
13-14 week	5,7 — 15,0
15-16 week	5,4 — 21,0
17-18 week	6,6 — 25,0
19-20 week	7,5 — 28,0
21-22 weeks	12,0 — 41,0
23-24 week	18,2 — 51,0
25-26 week	20,0 — 60,0
27-28 week	21,0 — 63,5
29-30 week	20,0 — 68,0
31-32 weeks	19,5 — 70,0
33-34 weeks	23,0 — 81,0
35-36 week	25,0 — 101,0
37-38 week	30,0 — 112,0
39-40 week	35,0 — 111,0