RU2729942C1 - Method for prediction of spontaneous early preterm delivery - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to obstetrics, and can be used for prediction of spontaneous early preterm delivery. If pregnant women with clinical signs of the threatening interruption in gestation from 22 weeks to 27 weeks of 6 days are examined peripheral venous blood by determining concentration of C-reactive protein. Simultaneously, the pregnant woman is exposed to ultrasonic transvaginal examination using a three-dimensional Doppler mode by determining a cervical vascularization index. Based on the obtained data – C-reactive protein level equal to 6 mg/l and more, and the cervical vascularization index equal to 20 % and more, an increased risk of spontaneous early preterm delivery is predicted.EFFECT: method enables preventing the early preterm delivery unfavorable outcomes by detecting the pregnant women belonging to the high risk group.1 cl, 2 dwg, 2 ex

Description

The invention relates to medicine, namely to obstetrics, and can be used to predict spontaneous very early premature birth.

Early preterm birth is an interruption of pregnancy in the gestational period from 22 to 27 weeks 6 days, they are officially registered in the Russian Federation since 2012 [1]. Early preterm labor deserves special attention due to the high incidence of adverse perinatal outcomes. Babies born very early tend to have extremely low or very low body weight, and they initially require intensive care. That is why ultra-early preterm labor should only occur in Level 3 facilities. To ensure timely transportation of the fetus in utero ("in the uterus"), as well as the prevention of respiratory distress syndrome, it is necessary to predict delivery in terms of 22 to 27 weeks 6 days. It should be noted that transportation of an already born child with a body weight of 500 to 1000 g is extremely undesirable, since it increases the mortality rate of newborns due to hemorrhages. Early labor can be induced and spontaneous. The onset of spontaneous early labor may be associated with the development of regular labor against the background of a whole fetal bladder, and with prenatal rupture of amniotic fluid. Induced labor is “iatrogenic,” meaning that the time of birth is determined by the doctor. Therefore, it is of practical importance to predict spontaneous early preterm labor. The essence of forecasting is to identify the preparatory processes in the mother's body. First of all, before childbirth, both premature and urgent, structural changes occur in the cervix: its length, consistency, and position relative to the wired axis of the pelvis change.

There is a method for assessing the degree of maturity of the cervix using the Bishop E.N. scale, modified by RCOG (2008):

Scoring interpretation:

0-5 points - "immature" cervix

6-7 points - "insufficiently mature" cervix

8-13 points - "mature" cervix

The specified method for assessing the preparation of the cervix for childbirth is simple to perform, does not require the use of equipment, but differs in the subjectivity of the result, in addition, it is applicable for full-term pregnancy.

In order to more objectively assess the state of the cervix, transvaginal cervicometry is used in practice [2, 3]. This method of ultrasound diagnostics allows us to assess the length of the cervix and the shape of the cervical canal, however, it does not provide information about its consistency. It is known that a "short" cervix can be congenital in nature, as a result of previous operations - excision, conization.

To judge the consistency of the cervix, ultrasound elastography was proposed [4]. But this method has not yet been sufficiently tested, in addition, it requires special expensive equipment.

According to domestic scientists G.A. Savitsky. and Savitsky AG, the change in the length and consistency of the cervix is associated with a change in its vascularization before childbirth [5]. Due to the beginning of the functioning of a special venous network in the uterus (sinusoidal venous lacunae) on the eve of childbirth, a "cavernous" transformation of the cervix occurs. Thus, an increase in the index of vascularization of the cervix, determined by transvaginal ultrasound examination with three-dimensional reconstruction, indicates the preparation of a pregnant woman's body for childbirth.

A well-known analogue of the claimed invention is a method for ultrasound diagnostics of the "maturity" of the cervix during pregnancy (RF patent No. 2370213, publ. 20.10.2009, IPC А61В 8/06) [6]. However, this method is intended to study the readiness of a pregnant woman's body for urgent labor - it is carried out in the period of 37-42 weeks. Another disadvantage is that when conducting only ultrasound examination, the possibility of starting labor with prenatal rupture of amniotic fluid with an "immature" cervix is not taken into account.

In the works of R. Romero, it was shown that in the amniotic fluid on the eve of preterm labor obtained with transabdominal amniocentesis, there are increased concentrations of the pro-inflammatory cytokine IL-6 [7].

This substance stimulates the synthesis of C-reactive protein. The concentration of C-reactive protein in the peripheral blood of the mother increases as early as 6 hours after stimulation and reaches a maximum in 24-72 hours [8].

The objective of the claimed invention is to expand the arsenal of methods for predicting spontaneous very early premature birth, which will reduce the risk of death and development of pathology of the newborn.

The technical result of the proposed method is to timely identify pregnant women belonging to the high-risk group for the development of spontaneous ultra-early premature birth for the timely transportation of patients to obstetric facilities of the third level and the full course of prevention of respiratory distress syndrome (RDS) of the fetus.

The task is achieved by the fact that when pregnant women with clinical signs of a threat of interruption in gestation periods from 22 weeks to 27 weeks of six days are treated, the peripheral venous blood is examined by determining the concentration of C-reactive protein. At the same time, pregnant women undergo transvaginal ultrasound examination using a three-dimensional Doppler mode, determining the index of vascularization of the cervix. Based on the obtained data - the level of C-reactive protein equal to 6 mg / l or more and the value of the vascularization index of the cervix equal to 20% or more, an increased risk of spontaneous early preterm birth is predicted.

The method is carried out as follows.

To determine the concentration of C-reactive protein, 5.0 ml of venous blood is taken from the peripheral vein when a pregnant woman is admitted to the hospital due to the threat of very early premature birth. The reaction is carried out with the patient's blood serum. The concentration of C-reactive protein is measured turbidimetrically. After blood sampling, an ultrasound examination is performed for pregnant women at a period from 22 to 27 weeks 6 days in a supine position in real time on a General Electric Voluson E8 ultrasound device equipped with a specialized three-dimensional transducer (RIC5-9-D). The vascularization index is calculated in the energy mapping mode with three-dimensional reconstruction. The vascularization index (VI) reflects the percentage of vascular elements in the volume of interest. The color window is set on the cervix, the minimum speed is set. The 3D imaging angle is 360 °. The VOCAL (Virtual Organ Computeraided AnaLysis) application program traces the contour of the cervix, which automatically determines the volume and vascularization index.

The study included 54 pregnant women hospitalized in the department of pregnancy pathology with a clinical picture of threatening very early preterm labor. The patients were divided into two groups depending on the outcome of hospitalization. The main group included 34 women who gave birth very early. The control group included 20 women who were discharged home with a preserved pregnancy. When comparing the groups by the concentration of C-reactive protein, statistically highly significant differences were revealed (p <0.001). In the main group (Fig. 1, group 2), in most cases, the level of C-reactive protein exceeded the reference value (6 mg / l). In the control group (Fig. 1, group 1), in most cases, the level of C-reactive protein was within the normal range - below 6 mg / l.

The differences between the control and the main groups in terms of the cervical vascularization index were also statistically highly significant (p <0.001). Using the logistic regression method, a curve was plotted for the probability of spontaneous very early preterm labor versus the cervical vascularization index (Fig. 2). It follows from the graph that the value of the vascularization index equal to 20% corresponds to 95% of the likelihood of developing spontaneous very early preterm labor. The forecast sensitivity was 89.6%, the specificity was 85.7%.

Example 1. Patient A., 28 years old, primiparous primiparous was admitted to a level 3 facility due to the threat of very early preterm birth at 25 weeks 3 days. On admission she complained of nagging pain in the lower abdomen. On objective examination, the assessment of the cervix by Bishop is 5 points ("immature"). According to cervicometry, the length of the cervix is 17 mm. The vascularization index is 26.3%. The concentration of C-reactive protein in peripheral blood is 6 mg / l. After 1 day, spontaneous ultra-early premature birth occurred, labor activity developed against the background of a whole fetal bladder. A live premature male newborn was born, weighing 650 g and 30 cm long, transferred to the intensive care unit for newborns (ICU).

Example 2. Patient V., 28 years old, re-pregnant (2) multiparous was hospitalized in the department of pathology of pregnancy in the period of 27 weeks 2 days with complaints of pulling and irregular cramping pains in the lower abdomen. Irregular uterine activity was recorded on the cardiotocogram. Anamnesis: anomalies in the development of the uterus - incomplete septum, twice resection of the ovaries for rupture of corpus luteum cysts. On objective examination, the cervix is "immature" (3 points). On ultrasound examination, the length of the cervix is 25 mm, the vascularization index is 2.5%. The concentration of C-reactive protein is less than 6 mg / l. The patient was discharged home with a preserved pregnancy at 28 weeks 2 days. This pregnancy ended in urgent labor.

Thus, the proposed method makes it possible to identify pregnant women belonging to the high-risk group for the development of spontaneous early preterm birth to prevent adverse outcomes of very early preterm birth.

List of used literature

1. Order of the Ministry of Health and Social Development of Russia dated December 27, 2011 No. 1687n "On medical criteria for birth, the form of a birth document and the procedure for its issuance." - M., 2011 .-- 2 p.

2. Grishaeva L.A., Chekhonatskaya M.L., Rogozhina I.E., Yannaeva N.E. Ultrasound assessment of the state of the cervix before childbirth // Saratov Journal of Medical Scientific Research. 2010.V.6. # 2. S. 288-292

3. Kaplan Yu.D., Zakharenkova T.N. Positional test in transvaginal ultrasound examination in women with physiological pregnancy // Problems of health and ecology. 2019. No. 1 (59). Pp. 14-20

4. Swiatkowska-Freund, M. Cervical elastography during pregnancy: clinical perspectives / M. Swiatkowska-Freund, K. Preis // Int. J. Womens Health. -2017. - Vol.21, N 9. - P. 245-254.

5. Savitsky A.G. Human labor contraction: clinical and biomechanical aspects / A.G. Savitsky, G.A. Savitsky. - SPb: Elbi-SPb, 2011 .-- 240 p.

6. Pat. 2370213 Russian Federation, IPC А61В 8/06. Method of ultrasound diagnostics of the "maturity" of the cervix during pregnancy / Yannaeva N.Ye., Chekhonatskaya ML; Applicant and patentee Yannaeva N.Ye. - No. 2008109395/14; declared 03/14/2008; 20.10.2009, Bul. No. 29. - 6 p.

7. Romero, R. Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical signiHcance / R. Romero, J. Miranda, P. Chaemsaithong [et al.] // J. Matem. Fetal. Neonatal Med. - 2015. - Vol.28, N 11. - P. 1343-1359.

8. Sarapultsev P.A. The role of c-reactive protein in acute phase response in myocardial infarction / P.A. Sarapultsev, A.P. Sarapultsev // Cytokines and inflammation. - 2013. - T. 12. No. 4. - S. 18-24.

Claims (1)

A method for predicting spontaneous very early preterm labor, characterized by the fact that when pregnant women with clinical signs of the threat of interruption in gestation periods from 22 weeks to 27 weeks 6 days are treated, peripheral venous blood is examined by determining the concentration of C-reactive protein and at the same time transvaginal ultrasound examination is performed with using three-dimensional Doppler mode, determining the index of vascularization of the cervix, on the basis of which, with the obtained level of C-reactive protein equal to 6 mg / l or more, and the value of the vascularization index equal to 20% or more, an increased risk of spontaneous early preterm birth is predicted.

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