RU2407015C1 - Method of abortion threat prediction - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: in blood serum of women in II term of pregnancy content of epidermal growth factor (EGF) is determined. If EGF value is equal 463 pg/ml and higher in women with male fetus threat of abortion is predicted. ^ EFFECT: method application allows to increase accuracy of abortion threat prediction and form high risk groups in proper time. ^ 4 ex

Description

The invention relates to medicine, namely to the obstetrics section, and will find wide application for objective forecasting of the threat of interruption.

Over the past decades, one of the obstetric causes leading to childhood morbidity and mortality has been attributed to such a complication of pregnancy as the threat of its termination (V.I. Orlov, 2006).

For the timely prevention of this gestational pathology, the prediction of this pregnancy complication is of utmost importance.

The main problem in solving the issue of a particular pregnancy complication and, in particular, the threat of its termination is the lack of specific, original approaches in assessing certain etiological factors underlying the pathogenesis of this complication of the gestation period.

Of the generally accepted indicators characterizing the formation of pregnancy complications or their prediction, there are two main directions of the developed methods: biochemical and immunological, on the one hand, and instrumental - on the other.

In the patent of the Russian Federation No. 20144598, 06/15/1994 a method for predicting the threat of termination of pregnancy is proposed, for which purpose the production of factor LIF that inhibits the migration of leukocytes in peripheral blood is determined in the blood.

The disadvantage of this method is its non-specificity, since the LIF level can vary with various infectious diseases, and in pregnant women, it must be assumed, with the threat of interruption due to the infectious factor.

A known method for diagnosing the threat of termination of pregnancy (RF patent 2120636, 12.10.1998) in terms of the coefficient, KIA = (SBAG + TBH): TBG, where SBAG is associated alpha2-globulin, TBH is trophoblastic beta-globulin. When the value of KIA <1,5 amid a decrease in SBAG diagnosed with the threat of interruption.

A significant disadvantage of this method can be considered that this method is intended only for the diagnosis of this pathology, along with the complexity and duration of this test.

A method is proposed for predicting the threat of termination of pregnancy (RF patent No. 2255339, June 27, 2005) by the ratios of the ratio of the content of lactobacilli to the conditionally pathogenic flora in smears taken after removal of mucus from the surface of the posterior fornix of the vagina and cervical canal, and when they decrease not less than 2 times in relation to the norm, they predict the threat of abortion.

The disadvantage of this method is the ability to predict the threat of interruption only in those cases where an impeccable sampling of material for research will be carried out. It is also known that significant variability of opportunistic flora always occurs both in the posterior vaginal fornix and in the cervical canal. And most importantly, the threat of termination of pregnancy in 80% of cases is combined with pathogenic microorganisms, which in themselves are a factor in terminating pregnancy.

The known methods for predicting the threat of termination of pregnancy also include the determination of serum concentrations of estriol, placental lactogen and interleukin-6 with the calculation of a diagnostic indicator (RF patent No. 2285926, 10.20.2006). D = 0.05x1 + 0.7x2-0.18x3-0.37, where x1 is the concentration of estriol in ng / ml; x2 - the level of interleukin-6 in PG / ml; x3 - the amount of placental lactogen in mg / ml, with D less than 0, make a conclusion about the absence of signs of the development of the threat of termination of pregnancy, and with D more than 0 - diagnose the development of the threat of termination.

The use of this method is possible only to confirm the threat of abortion. The use of a fairly significant set of indicators (three), determined by expensive sets and on equipment that requires highly qualified specialists, limits the replication of this method.

In addition, the use of biochemical compounds indicated in the patent that are not metabolically metabolically related is determined in various units (estriol - ng / ml; interleukin-6 - pg / ml; placental lactogen - mg / l) and also reduces the specificity of the method.

RF patent No. 2317554, 02.20.2008. "A method for predicting the threat of termination of pregnancy in the first trimester." The essence of the method for predicting the threat of abortion in the first trimester is to determine the blood content of the receptor antagonist interleukin-1 (IL-1-Ra) in 6-12 weeks and, with an increase of more than 700 pg / ml, the threat of termination is predicted throughout the gestation period. The disadvantages of the method include, first of all, its nonspecificity, since an increase in the interleukin-1 receptor antagonist can occur not only with the threat of abortion, but also in cases where any inflammatory process with the formation of compensatory reactions is observed. The use of this method in obstetric practice is difficult due to the high cost of the initial kits for determining IL-1-Ra, the presence of nano-equipment and highly qualified specialists.

Another well-known method for predicting miscarriage (RF patent 2340899, 12/10/2008) is to determine the level of TGF-β in blood serum in the second trimester of gestation. However, when its value is more than 1806.8 pg / ml, the content of substance P (SP) is additionally examined and, if it exceeds the level of 0.274 ng / ml, then only in this case the threat of termination of pregnancy is predicted. The disadvantages of the method include the need for re-analysis of blood serum for the content of SP, which will require unreasonably high costs.

A known method for predicting miscarriage (RF patent 2341800, 12/20/2008) in the first trimester of pregnancy by determining the content of substance P (SP) and tumor necrosis factor (FNO-α) in blood serum by enzyme-linked immunosorbent assay (ELISA), after which the coefficient is calculated, allowing to predict the threat of abortion.

The disadvantages of this method include, first of all, the difficulty of determining SP and FNO-α, the values of which are used to calculate the coefficient, the probability of termination of pregnancy is predicted by its value. The use of FNO-α values in this formula can be attributed to specific indicators of the threat of termination of gestation, but SP cannot be attributed to those, in connection with which, the specificity of the method decreases.

The prototype of this invention selected the method described in the patent of the Russian Federation No. 2340899, 12/10/2008. "Method for the diagnosis of obstetric pathology."

The essence of the prototype method is that in the second trimester of pregnancy in the blood serum determine the content of TGF-β. However, when its value is more than 1806.8 ng / ml, the level of substance P is additionally examined and, if it exceeds the value of 0.274 ng / ml, the threat of termination of pregnancy is also predicted.

This method has several disadvantages:

1. There is a need to determine an additional indicator.

2. The method is not specific, since the features of the feto-placental complex are not taken into account, taking into account the sex of the fetus.

3. The ability to reproduce the method is reduced, as a result of which the use of the method is limited to large obstetric institutions.

These disadvantages are eliminated in the claimed invention.

The objective of the invention is the development of an exact specific method that allows at the preclinical stage to predict the threat of termination of pregnancy.

The problem is solved as follows: first, by any known method, the sex of the pregnant woman’s fetus is determined, then in the second trimester of pregnancy the serum of epidermal growth factor (EGF) is examined and, with its value equal to 463 pg / ml and higher, in women with a male fetus and with an EGF of 594 mg / ml and higher in women with a female fetus, a threat of abortion is predicted.

The technical result obtained during the use of the invention consists in increasing the accuracy of predicting the threat of termination of pregnancy as a result of a differentiated approach to evaluating EGF indicators depending on the sex of the fetus and the timely formation of high-risk groups.

The most common complication of pregnancy, especially in the second trimester, is the threat of her termination, which ultimately often ends in a late abortion or premature birth (V. M. Sidelnikova. Materials of the 8th All-Russian Scientific Forum “Mother and Child.” - Moscow. - 2006. - P.241).

There is evidence that during pregnancy with a male fetus, early discharge of water during childbirth is more often observed, an increase in the risk of premature birth by 70%, and a caesarean section - by 10% (Burton V.K. // Amer. J. Obstet. Gynec . - 1986. - 155, N 5. - P. 984-985). Differences in the 2nd and 3rd trimesters of pregnancy in the content in the amniotic fluid of biologically active substances (an antagonist of the receptor for interleukin-1), depending on the sex of the fetus, indicates C. vgu et al. (1995). During pregnancy with a female fetus, this indicator is significantly higher than during pregnancy with a male sex (Bry K., Teramo K. // Acta Paediatrica. - 1995. - 84, N 3. - P.233-236).

Among the factors determining the state of the fetoplacental system, the dysfunction of which plays a major role in the etiology of the threat of termination of pregnancy, include changes in the biological system of the mother-placenta-male fetus or in the system of mother-placenta-female fetus. Since in the antenatal period there are differences in the formation of a male or female fetus, determined by the action of growth factors and, in particular, epidermal growth factor (EGF). EGF performs a regulatory signaling function.

This EGF function provides the reduction of wolf channels, as a result of which a female is developing (Erik Odeblad Planing Council of Victoria. 21: 3-34. Sept. - 1994. Vol.21; N.3). In this connection, the level of EGF in the blood serum may reflect the condition of the intrauterine fetus, male or female. If the regulatory features of cellular metabolism involving EGF in the antenatal period of human ontogenesis are differentiated by sex, then in the fetoplacental system, undoubtedly, changes due to sexual dimorphism are formed.

A change in EGF production during pregnancy leads to a disorganization of the main functions in the placenta, which in turn is realized in placental insufficiency, manifested by clinical signs of the threat of termination of pregnancy.

The pregnant woman from the risk group is previously determined by any known method, for example, by ultrasound or isosensitization by AB 0, the sex of the pregnant woman. After that, in the second trimester of pregnancy, the content of epidermal growth factor (EGF) is examined in blood serum.

Determination of EGF content in 0.05 ml of blood serum is carried out by enzyme immunoassay using kits (Cytimmune system, USA) in accordance with the manufacturer's protocol. The optical density of the color solution obtained after the end of the reaction is carried out on a Victor multilabe counter - 1420 photocolorimeter (Finland). Each set contains control samples for assessing variability, which when determining EGF does not exceed 10%. With an EGF of 463 pg / ml and higher, women with a male fetus and an EGF of 594 mg / ml and higher in women with a female fetus, a threat of termination of pregnancy is predicted.

The performance of the proposed method is confirmed by the following clinical examples.

Example 1

S-va, 26 years old. Case history No. 1114. It was examined in the framework of obstetric monitoring 03.03.09. A history of miscarriage of 27-28 weeks of pregnancy. Directed by a female consultation for observation in the framework of obstetric monitoring. Diagnosis: pregnancy 22 weeks. Burdened by AHA, FPN. Gestational diabetes is under compensation. SGA of the adrenal genesis in the stage of compensation. Secondary cardiopathy Mild myopia in both eyes. An ultrasound scan performed during this gestation period indicated the development of a female fetus.

After informed consent, blood was drawn from a vein to determine EGF. The EGF concentration was 595 pg / ml. The obtained EGF value for this pregnant woman allows predicting the threat of abortion.

03.24.09, the patient at 24-25 weeks of pregnancy had complaints of pain in the lower abdomen and in the lumbar region. Examination revealed signs of a threat of abortion. Ultrasound showed the beginning of detachment of a normally attached placenta.

This clinical example confirms the possibility of predicting the threat of termination of pregnancy for a given EGF in the case of the development of a female fetus.

Example 2

Sick B-va, 33 years old. Outpatient card number 1111. It was observed in the outpatient department of FGU "RNIIAP". It is included in the program of obstetric monitoring on 12.12.08, in which pregnant women are observed from an early gestation period due to the presence of complications in previous pregnancies.

Diagnosis: pregnancy 22 weeks. APS, subcompensation. Connective tissue dysplasia syndrome, Secondary cardiopathy. FPN. Male fetus according to ultrasound. Determination of EGF content in blood serum after obtaining informed consent. The EGF level corresponded to 463 pg / ml.

12.21.08. A pregnant woman at 25-26 weeks turned to the outpatient department of the Federal State Institution "RNIIAP" with complaints of poor health and the appearance of pulling pains in the lower abdomen and sacral discharge from the genital tract. Diagnosed with pregnancy 25-26 weeks, the threat of interruption. The patient was hospitalized in the department of pathology of pregnant women.

This clinical example confirms the possibility of predicting the threat of abortion in the presence of a male fetus by a previously determined value of EGF content.

Example 3

Patient B-va, 31 years old. History No. 1201. It was observed in the outpatient department of FGU "RNIIAP" as part of obstetric monitoring. With ultrasound, the gender of the fetus is established - male.

01.16.08. Diagnosis: pregnancy 21-22 weeks. OASA. Pregnant Anemia. Dysbiosis. Signs of fetal hypoxia. FPN. Violation of uteroplacental and fetoplacental hemodynamics. After obtaining informed consent, the EFR content in the blood serum was determined, the level of which was 462 pg / ml. According to our method, because the obtained EGF value is below 463 pg / ml in the blood serum of a woman with a male fetus, this allows us to predict the normal course of pregnancy.

05/30/08, the pregnant woman gave birth on time and without complications.

Example 4

Pregnant B-na, 27 years old. History No. 1131. It was observed in the outpatient department of FGU "RNIIAP" as part of obstetric monitoring. Isosensitization by AB 0, female fetus.

06/17/08, the Diagnosis: pregnancy of 19-20 weeks, with m-hyperandrogenism of the adrenal genesis. After obtaining informed consent, blood was taken for EGF. The value of EGF in serum was 593 pg / ml. According to our methodology, this made it possible to predict a favorable course of pregnancy. Monitoring prenatal pregnancy showed no signs of interruption.

06/17/08, there was a birth on time, a live full-term girl.

This clinical example confirms the ability to predict the absence of a threat of termination of pregnancy in a woman with a female fetus with a serum EGF below 594 pg / ml.

According to the claimed method, we examined 91 women, among whom, in the second trimester, 39 women were diagnosed with pregnancy by a male fetus and 52 by a female fetus. In the latter, the value of EGF in the second trimester in the blood serum of 594 pg / ml and higher was observed in 31 patients who had a threat of termination of pregnancy. At the same time, in 21 women, the level in the blood serum of EGF in the second trimester was lower than 594 pg / ml and they had no signs of a threat of termination of pregnancy. Of 39 patients with a male fetus, 21 had a serum EGF level of 463 pg / ml or higher, which was combined with a threat of termination of pregnancy. At the same time, in 18 women, EGF values did not reach 463 pg / ml. These patients showed no signs of threatened abortion.

The above confirms the prognostic value of the proposed method.

Thus, the claimed method is specific and accurate in comparison with the known.

1. The method is specific, as it allows predicting the threat of termination of pregnancy by the presence of different levels of EGF in the blood serum of a woman with a male or female fetus.

2. It has high accuracy. False negative indicators - 0.

3. Clinical application of the method will allow differentiated and timely implementation of obstetric tactics.

The inventive method is tested in the clinic and can be recommended for use.

Claims (1)

A method for predicting the threat of termination of pregnancy by examining a woman, characterized in that in the blood serum of a woman in the second trimester of gestation, the content of epidermal growth factor (EGF) is determined and when it is equal to 463 pg / ml and higher in women with a male fetus, a threat is predicted abortion.