RU2469331C1 - Method for prediction of threatened miscarriage in 1 trimester - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is described is a method for prediction of threatened miscarriage in the 1^st trimester by examining a biological fluid wherein pregnant women in their 1^st trimester are examined for the values of lateral behavioural phenotype, and in case of observing oppositely directed sensomotor and motor phenotype values; additionally morning and evening urine is analysed for a melatonin level, and if a difference of the melatonin values is 30% and less, a high risk of threatened miscarriage in the 1st trimester is predicted.

EFFECT: method is noninvasive.

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Description

The invention relates to medicine, namely to obstetrics, and can be used to predict the threat of termination of pregnancy (UPB), starting from an early date.

UPB currently remains one of the most urgent and complex problems of modern obstetrics, despite numerous studies in this area (V.M.Sidelnikova, Z.S. Khodzhaeva, A.A. Agadzhanova and others. Actual problems of miscarriage: a clinical cycle lectures. - M .: Medicine, 2001. - 167 p.).

Currently, UPB is a polyetiological complex, in the development and implementation of which the most important systems of the woman’s body take part. In the genesis of reproductive losses at any stage of pregnancy, the role of persistent urogenital bacterial-viral infection (V.M.Sidelnikova, 2001), endocrine pathology (V.M.Sidelnikova, 1986) has been convincingly proven. Immune mechanisms play an important role in initiating premature termination of pregnancy (E.K. Aylamazyan, O.V. Pavlov, S. A. Selkov, 2004). Moreover, the interaction between the endocrine and immune systems in the body of pregnant women is carried out through neurotransmitters (Z.N. Nikitin, 2004).

However, despite the numerous efforts of many scientific teams, the development of expensive equipment, the final solution to the problem of miscarriage is still far: its titer has not tended to decrease for many decades. Therefore, the search for new pathogenetic mechanisms for the development of spontaneous abortion is of great practical interest, because will allow the development of new diagnostic criteria and, as a consequence, management tactics.

All of the above determines the need to develop prognostic criteria for UPB, which will reduce the percentage of fruit losses due to the timely formation of risk groups and a set of therapeutic and preventive measures.

To date, a significant amount of work has been devoted to forecasting and early diagnosis of UPB. At the same time, two main directions of the developed methods are viewed: biochemical, hormonal and immunological, on the one hand, and instrumental - on the other. Moreover, the instrumental techniques mainly include ultrasound and Dopplerometry methods.

From the first group of methods, a method is known for predicting UPB in the early stages by determining in peripheral blood the concentration of a factor inhibiting the migration of leukocytes before and after a single immunization with donor leukocytes (RF patent No. 20144598, 1994).

The disadvantages of the method are the technical complexity of the implementation, as well as the inability to dynamically monitor the state of pregnancy using this method.

There is a method of early diagnosis of miscarriage by determining in the peripheral blood the relative content of neutrophils having structures on their surface that react with trophoblastic X-glycoprotein (RF patent No. 2077729, 1997). The disadvantages of the method include its complexity and non-specificity.

A known method for preclinical prediction of miscarriage by determining the plasma content of fibrin-monomer complexes. By their size, termination of pregnancy in I, II or III trimesters is predicted (RF patent No. 2123698, 1998). The disadvantage of this method is its non-specificity.

A known method for predicting the threat of abortion by determining the concentration of estriol, placental lactogen and interleukin (IL) - 6 in the blood serum (RF patent No. 2285926, 2006).

A known method for predicting the threat of miscarriage by determining the content of peripheral T-lymphocytes before and after incubation with AMHF (RF patent No. 2077727, 1997).

The disadvantage of these methods is their complexity.

A known method for predicting miscarriage by ultrasound of the pelvic organs and determination of serum progesterone, chorionic gonadotropin and serum alpha-2-microglobulin level (RF patent No. 2004135161, 2006). The disadvantage of this method is its non-specificity.

There is a method for predicting miscarriage by determining the content of cytokines in the peripheral blood and mucus of the cervical canal in women with miscarriage of infectious origin by the level of IFN-γ and IL-8 in peripheral blood and mucus of the cervical canal, the increase of which serves as markers of distress in the early stages of pregnancy ( T.N.Sumedy, L.V. Gankovskaya, E.N.Dolgina, etc. The content of cytokines in the peripheral blood and mucus of the cervical canal in women with miscarriage of infectious origin / / Russian Journal of Immunology, 2005 - vol. 9. - N2. - pp. 93-102). The disadvantage of this method is the inability to diagnose UPB in the 2nd trimester.

A known method for determining the serum of pregnant women with sexually transmissible and opportunistic infections IL-12 and IL-10 (O.V. Shitova, E.Yu. Khagina, N.A. Osna and others. The level of IL-10 and IL -12 in pregnant women with sexually transmissible and opportunistic infections // Medical Immunology, 1999 - v. 1. - N2. - p. 94). The increase in the level of IL-12 is considered by the authors as a risk factor for pregnancy.

However, this work does not indicate specific values for predicting miscarriage. Another disadvantage of this method is that to improve the accuracy of forecasting, two markers are studied: IL-10 and IL-12, which complicates the study.

A method for predicting miscarriage during urogenital infection (RF patent No. 2341799, 20.12.2008) by determining the level of IL-12 in the biological fluid, characterized in that the level of IL-12 is determined in the mucus of the cervical canal, and with its values of 102.0 pg / ml and above, predict a high risk of miscarriage in the I and II trimester.

A method for predicting threatening preterm birth (RF patent No. 2344424, 01/20/2009) in women with a threat of miscarriage by examining peripheral venous blood, characterized in that at 6-12 weeks of gestation they determine the ratio of the relative content of CD25 + to IL-2 + lymphocytes and when the ratio is equal to or more than 1.0, the development of threatening preterm birth is predicted.

The disadvantage of these methods is their complexity.

A method for predicting miscarriage in the first trimester (RF patent No. 2341800, 20.12.2008) by examining blood serum, characterized in that the content of substance P (SP) and tumor necrosis factor- (FNO) are determined in blood serum by ELISA, the values of which are substituted in the formula and calculate the prognostic coefficient K:

K = (0.006 · FNO · SP-0.065 · FNO · SP2-0.00004 · FNO) / (0.005-0.031 · FNO),

where SP is the level of substance P in absolute terms;

FNO - level of tumor necrosis factor-in absolute terms. If the value of the prognostic coefficient K is more than 0.48, then in this pregnant woman predict UPB. The disadvantages of this method include the invasive nature of the study, its complexity and the high cost of diagnostic tests.

This method is accepted by us as a prototype.

The disadvantages of the prototype are eliminated in the present method.

From the foregoing, it is obvious that today the main disadvantages of methods for predicting miscarriage are nonspecificity and complexity.

The objective of the invention is the development of a specific method for predicting the threat of termination of pregnancy in the 1st trimester for the appointment of timely therapeutic measures.

The problem is solved by the fact that in pregnant women in the first trimester they examine the lateral behavioral phenotype and, if multidirectional sensory and motor indicators of the phenotype are detected, they additionally examine the level of melatonin in morning and evening urine and, if the difference between the melatonin levels is less than 30%, they predict a high risk UPB pregnancy in the 1st trimester.

We have proved that this method has high accuracy, sensitivity and specificity, and allows us to predict the threat of miscarriage at an earlier date for timely preventive and therapeutic measures.

We have not found in the available literature the use of the difference in melatonin levels in evening and morning urine as a screening marker for preclinical prediction of UPB.

The fundamental property of the mother-placenta-fetus functional system is the lateralization of central-peripheral integration mechanisms, the direction of which is determined by the displacement of the uteroplacental complex relative to the sagittal plane, and which is formed under the influence of the entire set of functional environmental systems (A.B. Poroshenko, 1985; .I. Orlov, A.B.Poroshenko, 1988; T.L. Botasheva, 2007). The manifestation of these asymmetries are indicators of the behavioral lateral phenotype (PSL) (A.B. Poroshenko, 1985). In turn, PSL is an accessible correlate of interhemispheric asymmetries (NN Bragina, T.A.Dobrokhotova, 1988), which, to a large extent, modulate the activity of the subcortical structures of the brain and affect the level of hormonal secretion of the epiphyseal-hypothalamic-pituitary link. The modified Annette test allows one to identify the nature of motor and sensorimotor asymmetries, various signs of which significantly correlate with various physiological and pathological conditions of the female reproductive system (A.B. Poroshenko, 1984; A.V. Chernositov, 1996; V.I. Orlov, T. L. Botasheva, 1999). Literature data indicate the existence of a reliable relationship between PSL, placental lateralization, and the nature of the course of pregnancy: the interaction of the response (right-sided, left-side contractile activity) with asymmetry of the nail beds of the little fingers of the hands was found (private connection criterion: X = 7.93137; df = 2; p = 0.01833; conditional connection criterion: X = 7.82332; p = 0.02006), which indicates that the lateralization of contractile activity is interconnected precisely with the morphological sign of hand inequality (T.L. Botasheva, 1992; R. BUT. Amayeva, 2010).

For example, inversion of motor asymmetries of the lower extremities significantly increases the likelihood of lateral ovarian lesions (V.V. Logachev, 1991), and the left phenotype “width of the nail bed of the little fingers of the hands” in pregnant women with the right phenotypic symptoms is accompanied by an increased likelihood of threatening premature birth (T.L. Botasheva; R.A. Gamaeva, 2010).

PSL indicators are markers of a right-handed, left-handed and combined programs of functional “behavior” at various levels of central regulation and allow the selection of pregnant women with a mixed phenotype in the testing process. It is in this group, according to the literature, that the phenomenon of “competition in the center” is most often realized, accompanied by the threat of abortion (N. A. Agadzhanyan, V. I. Orlov, T. L. Botasheva, 1999).

When studying the features of the course of pregnancy in the risk group, we found a reliable relationship between the probability of a threatening state of pregnancy, MPL and melatonin metabolism. The occurrence of a threatening state of pregnancy is most often observed in women with a contra-focus of sensory-motor visual and auditory signs. The same category of women showed a change in the amplitude of the daily biorhythm of melatonin secretion: a decrease in the difference between the levels of melatonin in morning and evening urine is recorded. According to the results of our studies, the sensorimotor asymmetries, in particular, the leading eye and leading ear phenotypes, as well as the motor asymmetries of the lower extremities (A. B. Poroshenko, 1992; T.L. Botasheva, 1989, 2011; R.A. Gamaeva, 2010).

When examining the sensorimotor group of signs of the lateral behavioral phenotype (“leading eye” and “leading ear”), the pregnant woman is asked to answer the following questions and demonstrate: “with which ear do you listen to the telephone receiver?”, “To which ear do you put a shell?”, “With which do you aim with your eye? ”and“ with what eye do you look into the keyhole? ” If there is one of the right signs of the “leading eye” and the left sign of the test of the “leading ear” (or vice versa), the pregnant woman is selected at risk and the next stage of the study is carried out - determining the level of melatonin in the evening and morning urine. The influence of motor asymmetries of the lower extremities (test “leading leg” and “push leg”) was also statistically significant, in connection with which these tests are also used as verification in the formation of risk groups for UPB.

One of the most studied biogenic amines of the DNIES / diffuse neuroimmunoendocrine system / significantly affecting the nature of the course of pregnancy, is melatonin. In the placenta, during its normal development, it is produced and deposited in the structural elements of the villous chorion: syncytiotrophoblast, syncytiocapillary membranes, syncytial nodes, single stromal cells and vascular endothelium (RH Li et al., 1991; A. Malassine, L. Cronier, 2002; EA Lapina, 2004).

The level of melatonin in the urine (especially the morning fraction), according to the literature, reliably reflects the intensity of the pineal gland activity and is an integral indicator of the antigonadotropic activity of the epiphysis-hypothalamus-pituitary gland system at all stages of a woman's reproductive life and outside it (V.N. Anisimov, I .A. Vinogradova, 2008). Determining the level of melatonin allows us to judge the adequacy of the central link in the regulation of reproductive processes, in particular uterine activity.

Pregnancy and childbirth are accompanied by very profound changes in the endocrine profile of the woman’s body, including the functioning of the pineal gland. With a physiologically ongoing pregnancy, an increase in the excretion of melatonin with urine is noted, which decreases before childbirth. Regarding the secretion of melatonin with UPB, there are very conflicting data in the literature. It was established that melatonin is formed in the pineal gland cells and then secreted into the blood. The secretion of melatonin occurs mainly in the dark, at night, and in the light, in the morning and afternoon, the production of the hormone is sharply suppressed.

The pineal gland of a healthy adult releases about 30 micrograms of melatonin into the blood per night; in constant darkness, the daily rhythm of ejection, supported by the periodic activity of SCN, is maintained. Therefore, its maximum level in the pineal gland and blood of humans and animals is observed at night, and the minimum - in the morning and afternoon.

Within the framework of daily biorhythms in pregnant women, two peaks of melatonin secretion (evening and morning) are recorded: nighttime hours account for 70% of the daily production of melatonin (N.A. Agadzhanyan et al., 2007; A.M. Ichmelyan, 2009). For each person, the melatonin curve is stable and has differences in different people.

Changes in the formation of melatonin during life coincide with the stages of development of the body, are associated with them and have a direct effect on physiological processes. Embryos and newborns of mammals themselves do not form melatonin, they use maternal, which passes through the placenta, and then - with mother's milk. The hormone secretion begins in the third month of the child's development and its concentration reaches a maximum in the first years of life (no later than 5 years). It is also known that the expression of melatonin in the placenta increases with chronic placental insufficiency, and a significant increase in the expression area is observed with subcompensated placental insufficiency and the presence of an IUGR in the child. In the presence of chronic placental insufficiency and intrauterine growth retardation syndrome, the content of melatonin in the blood of pregnant women is reduced (Y. Okatani et al., 1998; K. Watanabe et al., 2004; D.X. Xu et al., 2007). Numerous studies are devoted to the study of the threatening state of pregnancy that occurs against the background of chronic placental insufficiency (N.K. Askarova et al., 1997; V.N. Chernyshev et al., 1998; N.P. Shabalov et al., 1999; A. B. Palchik, 2000). It has been established that in chronic intrauterine hypoxia, the formation of a cyclical organization of sleep is disrupted, which determines the features of the formation of the mechanisms of regulation of cardiac activity, respiration and other functions of the child’s body during the early postnatal adaptation and, to a large extent, affects the subsequent development of the child (I.I.Evsyukova , 1985, 2004; O.T. Shevchenko, 1986; M.N. Kosov, 1999).

Of greatest interest are data on the existence of a close relationship between the state of the birth canal and the level of melatonin in a full-term pregnancy, which allowed the authors to establish the potentiating properties of melatonin during the initiation of labor, including premature (A.M. Ichmelyan, 2009). It was established that before birth, the amount of melatonin secreted drops sharply, this contributes to the release of products of the neurosecretory nuclei of the hypothalamus, especially oxytocin, which is one of the leading factors initiating uterine activity and, thus, determining fetal expulsion. Urinary excretion of melatonin in women with threatening abortion or threatening preterm birth is significantly reduced throughout pregnancy compared to healthy pregnant women (V.I. Gryshchenko, 1979). In this regard, the study of the level of melatonin in complicated pregnancy appears to be extremely important for determining new approaches to prevention and pathogenetic therapy in obstetric practice.

Our studies made it possible to establish very important quantitative values of the melatonin level in evening and morning urine, which, in combination with the detection of different directions of the localization side of the chorion and PSL, are crucial for selecting pregnant women at risk.

The method is as follows:

In a pregnant woman of the first trimester, the determination of PSL is carried out using tests: asymmetry of sensorimotor signs, comparing the width of the nail bed of the little finger of the leading leg. To determine the initial PSL, the modified Annette test is used, which allows one to determine sensorimotor asymmetries, which are a marker of behavioral skills associated with simple emotionally colored movements, which are fixed in early ontogenesis (M. Kinsbourn, 1978). Judging by the literature, they have a significant relationship with the functional state of the female reproductive system (A.B. Poroshenko, 1985). Researchers are offered the following questions:

- Test “interweaving of fingers”;

- Test "crossing arms on the chest";

- Test "applause";

- A test to determine the leading leg;

- Test to determine the jogging leg;

- Test "foot to foot";

- Test with a phone to identify the leading ear;

- Test with a sink to determine the leading ear;

- Test "keyhole" to determine the leading eye;

- Aiming test to determine the leading eye.

The detection of mismatch of the sides of the sensorimotor, visual and auditory signs / sensorimotor asymmetries / is recorded during the tests for the “leading eye” and “leading ear”. To this end, the woman is asked to answer the following questions and demonstrate: “with which ear do you listen to the telephone?”, “Which ear do you put the shell on?”, “With which eye do you aim?” And “with what eye do you look into the keyhole?”. In the presence of one of the right signs according to the "leading eye" and the left sign of the test according to the "leading ear" (or vice versa), a conclusion is made that the motor-sensory visual and auditory signs are counter-directed.

Morphological inequality of the hands is determined by measuring the width of the nail beds of the little fingers with a ruler. The test attribute is considered to be right or left on the side of prevailing width of the nail bed. Equality of indicators allows us to consider the sign of ambilateral.

The methods for determining the asymmetry of the legs are constructed so that their inequality is revealed:

1. To determine the leading leg: a woman should push with her foot an object lying on the floor / ball /. The leg she manipulates is the lead;

2. To determine the jogging leg: a woman must cross an imaginary barrier / pit, strip, object /. That leg with which a woman pushes off when overcoming an obstacle is the lead.

Pregnant women who have a multidirectional sensory-motor and motor phenotype indicators are additionally prescribed a study of melatonin levels in morning and evening urine.

To assess the secretion of melatonin, in urine in pregnant women, at 8.00 and at 18.00, 3 ml of urine was collected in epindorfs and by ELISA (ELISA) from BUHLMANN (Germany), the level of its main metabolite 6-sulfate-simelatonin was determined. For this, standards, controls and samples were bred 1:51. Then 10 μl of standards, controls and patient samples were pipetted into tubes, 500 μl of Buffer was added and mixed with a mixer.

Before analysis, the reagents are brought to room temperature. Unused reagents are stored at 2-8 ° C (Standards, Controls and samples are recommended to be tested in three analytical replicates).

Dispense 50 μl of the diluted standards, controls and samples into the appropriate wells and add 50 μl of the diluted enzyme conjugate (Preparation of reagents, # 2) and 50 μl of antiserum. Cover the plate with adhesive film and incubate for 120 minutes at room temperature with shaking (500 1 / min). Wash the wells four times with 250 μl wash buffer (Reagent Preparation # 1, use of a wash device is recommended). Carefully remove the wash buffer. Turn the plate over and tap the remaining drops of moisture onto absorbent paper and drop 200 μl of Substrate Solution (Reagent Preparation, # 3) into each well. Incubate at room temperature in a shaker for 30 minutes. Stop the reaction by adding 100 μl of Stop Solution to each well, then gently shake the plate to mix the contents. Optical density is considered at 450 nm for 60 minutes after stopping the reaction. Analysis of the results was carried out automatically using a computer program - “Viktor-Wallak” Finland.

If a difference in the levels of melatonin in evening and morning urine is found to be 30% or lower, UPB is predicted, which allows the obstetrician-gynecologist to prescribe adequate therapy in a timely manner.

Example 1

Pregnant E-va, 29 years old. A history of 1 normal term labor. At the next appointment in the antenatal clinic, she has no complaints. Diagnosis: pregnancy 6-7 weeks.

Ultrasound: in the uterus, one fetal egg is located on the left, corresponding to 6-7 weeks of pregnancy. Appendages without features. There are no signs of UPB.

When a vaginal examination: the cervix is rejected posteriorly, the vaginal part of the cervix is 2.5-3 cm long, dense, the external pharynx is closed. The uterus is enlarged according to the gestational age, out of tone. Appendages on both sides without features.

Thus, there were no clinical symptoms of a threatening miscarriage. The lateral behavioral phenotype was determined - the multidirectionality of the sensorimotor phenotype indicators (the left sign of the test “leading ear” and the right sign of the test “leading eye”), the right sign of the test characterizing morphological inequality of the hands (the prevalence of the width of the nail bed of the little finger of the right hand) were revealed. Leading foot is right.

In order to choose further tactics for pregnant management, a study of the level of melatonin was carried out: in the morning urine - 29.00 ng / ml, in the evening - 23.20 ng / ml. Thus, the difference in the level of melatonin is 20%, which allows the pregnant woman to be classified as at risk for UPB. Taking into account the absence of a burdened obstetric-gynecological history, well-being, the pregnant woman refused a course of preservation therapy. After a week, the patient enters the gynecological department with complaints of pain in the lower abdomen, spotting. Diagnosis: Pregnancy 7-8 weeks. Threatening self-abortion. Ultrasound: gestational 7 weeks. 4 days fetal egg - 31 mm corresponds to 8 weeks. 1 days, KTR-13 mm-7 weeks. 4 days. Rhythmic heartbeat.

Chorion on the left side of the uterus. In the lower pole of the fetal egg, a slit-like echo-negative formation of 12 ^* 3 mm is visualized - a detachment site. Conclusion: Pregnancy 7-8 weeks. KM: signs of threatened abortion. In the mirrors: the cervix is not changed. Vaginal examination of the uterus was not performed due to the threat of abortion. The patient underwent a course of preventive therapy in a hospital, aimed at prolonging pregnancy. Pregnancy saved.

Example 2

The first pregnant I-va, 27 years old, had another appointment at the antenatal clinic. There are no complaints. Diagnosis: Pregnancy 9 weeks. Ultrasound: gestation 10 weeks. Fetal egg 46 mm - 10 weeks, KTR-31 mm - 10 weeks. 3 days The heartbeat is rhythmic. Chorion on the right wall, thickness 11 mm. Conclusion: Pregnancy 10 weeks. When a vaginal examination: the cervix is rejected posteriorly, the vaginal part of the cervix is 2.5-3 cm long, dense, the external pharynx is closed. The uterus is enlarged according to the gestational age, out of tone. Appendages on both sides without features.

A lateral behavioral phenotype was determined - unidirectional in terms of leading sensorimotor signs (the right sign of the “leading eye” test and the right sign of “leading ear”), as well as the motor signs of the test corresponding to the right phenotype variant (right leading leg and left push leg). The right sign of the test, characterizing the morphological inequality of the hands (the prevalence of the width of the nail bed of the little finger of the right hand).

In order to choose further tactics for pregnant management, a study of the level of melatonin was carried out: in the morning urine - 65.20 ng / ml, in the evening - 44.34 ng / ml. Thus, the difference in the level of melatonin is 32%, which allows the patient to be attributed to the group of healthy pregnant women who do not require drug therapy. This pregnancy had a physiological course.

Example 3

Pregnant Fr., 22 years old. Pregnancy 2nd, a history of self-abortion in a period of 10 weeks. Registered in the antenatal clinic is from 6 weeks. On external examination, the uterus is enlarged up to 8 weeks of pregnancy, the cervix is softened on the periphery, endocervicitis. When PCR diagnosis revealed Herpes virus, Chlamidia trachomatis. Pregnant examined by the present method. The localization of the chorion is on the right. The multidirectionality of the sensorimotor signs of PSL (the right sign of the test “leading ear” and the left sign of the test “leading eye”), the inversion of motor asymmetries of the lower extremities (right push leg and left leading leg), as well as the left sign of the test “width of the nail bed of the little fingers of the hands”.

In order to choose further tactics for pregnant management, a study was conducted of the level of melatonin: in the morning urine - 56.80 ng / ml, in the evening - 39.76 ng / ml. Thus, the difference in the level of melatonin is 30%, which allows the pregnant woman to be classified as at risk for UPB. Despite the ongoing preservation and antibacterial therapy, the pulling pains in the lower abdomen intensified, turned into cramping. In the period of 15 weeks, an abortion occurred, which confirmed the forecast made.

The reliability of the method is confirmed by clinical and laboratory studies. According to the claimed method, 50 women were examined in the first trimester of pregnancy.

In 30 of them (group 1), the difference in the levels of melatonin in morning and evening urine was 30% or lower, which indicated a risk of abortion and was confirmed in the course of further clinical and laboratory observation. In 20 pregnant women (group 2), this indicator was above 30%, which suggested a favorable course of pregnancy. In the first group, the percentage of threatened interruption was 90%, compared with 15% in the 2nd group.

The results of statistical analysis in the environment of the STATISTIKA 6 application software package made it possible to develop a prognostic rule for the formation of risk groups among pregnant women with the threat of interruption using the method of logistic regression (O. Yu. Rebrov, “Statistical Analysis of Medical Data”, Moscow, Media Sphere, 2003). The resulting rule provides high accuracy, sensitivity and specificity of the method.

The advantage of the proposed method is that in pregnant women, on the basis of highly sensitive modern laboratory markers, prediction of UPB is performed with the aim of early prescribing adequate therapy. In clinical practice, this will reduce the risk of perinatal losses due to the timely identification of pregnant risk groups and the beginning of adequate therapeutic measures.

This method is non-invasive, has a fast execution using standard test systems, which allows it to be widely used in practical health care.

Claims (1)

A method for predicting the threat of termination of pregnancy in the first trimester by examining the biological fluid, characterized in that in pregnant women in the first trimester, the lateral behavioral phenotype is preliminarily determined and, if the sensorimotor and motor phenotypes are differently directed, the level of melatonin in morning and evening urine is additionally examined, and if the difference between melatonin 30% or less, predict a high risk of threatened abortion in the 1st trimester.