RU2419385C2 - Method of confirming role of infectious process in uteroplacental region in genesis of combination of threat of abortion and development of fetus growth retardation syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to obstetrics. In order to confirm role of infectious process in uteroplacental region in genesis of combination of threat of abortion and development of fetus growth retardation syndrome in future in pregnant women with symptoms of abortion threat leukocyte intoxication index is determined by formula: LII=segmentonuclear + stab + immature + myelocytes/monocytes + lymphocytes + eosinophils. In case if LII is higher than 1.8, infectious nature of said complication is detected.

EFFECT: method makes it possible to diagnose endogenic intoxication in case of abortion threat and establish infectious cause of fetus development retardation syndrome.

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Description

 The invention relates to medicine, namely to obstetrics, and can be used to confirm the infectious cause of the combination of the development of the threat of abortion and fetal growth retardation syndrome.

The relevance of the proposed method is determined by the high frequency of the threat of abortion and the development of fetal growth retardation syndrome (FPS) in the future. Despite the fact that obstetricians and perinatologists have been dealing with the problem of SZRP all over the world for more than 40 years, until now the etiology has not been fully studied, and therefore there is no consensus on the issue of treatment. SZRP is diagnosed in every 5-6 women with a threat of termination of pregnancy, and if this complication is detected in the second trimester, in every 2nd trimester [Kerimova Z.M. Intrauterine growth retardation. Principles of pregnancy and childbirth. Abstract. diss. ... candidate of medical sciences, 2002, 25 p.]. A special place in the development of SZRP is occupied by acute and chronic infections transmitted by a pregnant woman, which affect the number of cells in the fetal organs and their mitotic activity. Perinatal infections account for at least 10% of all cases of SZRP [Beznoshchenko GB, Sharypova LV Features of the gestational period in associated opportunistic infections, 2000, p. 42-43].

However, most authors are of the opinion about the polyetiological nature of SZRP and many reasons are not associated with an infectious factor [B. Naumchik A differential approach to the diagnosis, treatment and obstetric tactics in pregnant women with fetal growth retardation syndrome. Nearest and long-term results: abstract. dis ... cand. honey. Sciences, 2001, - 21 s]. The proposed method allows to identify the risk group of pregnant women for the development of SZRP with an infectious cause and to carry out appropriate treatment during pregnancy.

Spiral arteries are a traditional object of study in the uteroplacental region, and most authors limited themselves to the study of their pathology in various diseases [A. Milovanov Intrauterine development of a person, 2006; Radzinsky V.E. Early pregnancy, 2005. - 384 p.]. Most publications have studied in detail the pathomorphology of these arteries in women with preeclampsia, hypertension, and with SZRP. However, the drawback of studying only spiral arteries is the inability to describe with their help the features of inflammation and sclerotic processes in the placental bed of the uterus, despite the significant spread of endomyometritis of various etiologies in non-pregnant women.

As a prototype, we used the value of the clinical analysis for C-reactive protein (CRP), an increase in the level of which is observed in response to infection [V. Velkov. The value of determining C-reactive protein for the diagnosis of chronic infections // Laboratory, No. 3, 2006, p.6-10]. However, the disadvantage of this method is:

- CRH appears in the blood serum shortly after the onset of inflammation and rapidly decreases, and in pregnant women it is not always possible to catch the moment of the onset of infection;

- during the threat of termination of pregnancy, the CRH, as a rule, does not increase;

- the level of CRH does not change with some viral infections;

- the methodology for determining the long and costly;

- the level of the central heartbeat can change during the day and it must be determined in dynamics;

- insufficient information content indicator in practice.

The objective of the invention is to eliminate the above disadvantages of the prototype.

Technical result:

1) determine the value of the leukocyte intoxication index (LII), which would make it possible to diagnose endogenous intoxication with the threat of abortion and establish the infectious cause of the fetal growth retardation syndrome;

2) establish new diagnostic morphological criteria for chronic endometritis, realized during pregnancy in the form of basal deciduitis.

The technical result is achieved by determining LII in pregnant women, the gestational period of which was complicated by the presence of SZRP, and studying the influence of inflammatory processes in the placental bed on the development of SZRP.

One of the indicators characterizing the severity of endogenous intoxication is considered to be the leukocyte intoxication index (LII), which is calculated by the Kalf-Kalif formula and, according to modern ideas, reflects the severity of inflammation in the body and the reaction to endogenous intoxication [Kalf-Kalif Y.Ya. About the leukocyte intoxication index and its practical significance. // Medical business. 1941. No. 1. S.31-35]. Several modifications of the method for calculating LII are described, including the modification of B. A. Reis, which we propose to use in pregnant women with the threat of abortion [Reis B. A., Poluektov L. V. Isolation of a toxic polypeptide of medium molecular weight with experimental diffuse peritonitis. Bull. Expert. Biol. Honey. 1983. No. 7. - S.53-55].

This method involves the use of the definition of leukocyte intoxication index in pregnant women with the threat of abortion at different times. A LII value of more than 1.8 indicates endogenous intoxication during pregnancy and requires antibiotic therapy.

We have established the diagnostic parameters of chronic endometritis, which occurs during pregnancy in the form of basal deciduitis, presented as morphometric objects: areas of decidual cells of the placental bed, necrosis, fibrosis and leukocyte infiltration. The diagnosis of chronic endometritis, which occurs during pregnancy in the form of basal deciduitis, can be made on the basis of leukocyte infiltration of more than +++, areas of fibrosis with an area of more than 1.0 and areas of necrosis of decidual cells with an area of more than 2.0.

After assessing LII in pregnant women with a physiological pregnancy and pregnancy, complicated by the threat of termination and the development of SZRP in the future, we came to the conclusion that the value of LII = 1.0-1.8 corresponds to the physiological course of pregnancy, and the value of LII more than 1.8 confirms the role the infectious process in the threat of abortion and the development of SZRP. In the table. 1 presents the data of patients with physiological pregnancy. In all cases presented, LII was less than 1.8. In the table. 2 presents the data of the examined patients with the threat of termination of pregnancy and the development of SZRP in the future, from which it can be seen that the LII ranged from 1.8-3.35. The average LII in the group with the physiological course of pregnancy was 1.52 ± 0.02, in the group with SZRP - 2.40 ± 0.04, the difference in the indicators was statistically significant (p <0.001).

In order to establish a connection between the increase in LII with the threat of termination of pregnancy with the development of SZRP and pathology of the uteroplacental region, we have proposed a description of the pathological components of the placental uterine bed. To describe the inflammatory process in the placental bed of the uterus, we established the following morphometric objects: areas of decidual cell necrosis, areas of fibrosis and leukocyte infiltration.

To prove the significance of the influence of inflammatory processes in the placental bed on the laying of extraembryonic structures, we examined 120 pregnant women whose gestational period was complicated by the presence of fetal growth retardation syndrome, and 100 pregnant women with physiological pregnancy. The characteristics of the fetoplacental complex in the studied groups are presented in table. 3, from which it follows that statistically significant differences were obtained in the mass and growth of the fetus and in the mass, volume and area of the placenta compared with the control group (p <0.05).

We propose to evaluate the intensity of the inflammatory process in the placental bed by the area of the detected changes, the measurement of which is carried out using the G.G. Avtandilov grid. The presented objects of morphometry of the placental bed are shown in table. 4. The diagnosis of chronic endometritis, which occurs during pregnancy in the form of basal deciduitis, was made on the basis of a leukocyte infiltration of more than +++, areas of fibrosis with an area of more than 1.0 and areas of necrosis of decidual cells with an area of more than 2.0. Semi-quantitative confirmation of differences in the detected pathological structural components, where each indicator was evaluated using a three-point system, is presented in table. 5.

In this way, 220 pregnant women were examined in the period of 20-32 weeks of pregnancy. An increase in LII over 1.8 was observed in 43 women whose gestational period was complicated by the presence of a threat of termination of pregnancy and the development of SZRP in the future. 52 women identified a threat of termination of pregnancy without an increase in LII (less than 1.8), while SZRP was not diagnosed in any case. 8 women showed an increase in LII without the development of SZRP in the future. 106 women did not show an increase in LII and were not diagnosed with the threat of termination of pregnancy and SZRP. Thus, the sensitivity of the method was 40.57%, and the specificity was 92.98%.

Table 3
Characterization of the fetoplacental complex, confirming the significance of differences in the studied groups Indicator main group (n = 120) control group (n = 100) The mass of the fetus, g 2610.5 ± 29.8 3582.1 ± 37.95 Fetal growth, cm 48.4 ± 0.23 53.68 ± 0.21 The mass of the placenta, g 354.8 ± 7.47 ** 470.2 ± 9.71 The volume of the placenta, ml 517.11 ± 18.18 ** 714.7 ± 21.39 The placenta area, cm ² 260.68 ± 4.69 ** 335.58 ± 6.53 Fetal-placental coefficient 0.13 ± 0.002 ** 0.15 ± 0.002 Note: ** - p <0.01, the difference between the indicators is statistically significant

Table 4
Features of pathological reactions in the placental bed of the uterus in women of the studied groups Indicator Exhaust gas KG (n = 120) (n = 100) abs. % abs. % Inflammatory infiltration (+) 28 23.33 ± 3.86 *** 68 68.0 ± 4.66 (++) 56 46.66 ± 4.55 ** 22 22.0 ± 4.14 (+++) 36 30.0 ± 4.18 ** 10 10.0 ± 3.0 Fibrosis sites (area) _^1/4 - ^_1/2 73 60.83 ± 4.46 ** 86 86.0 ± 3.47 1,0 12 10.0 ± 2.74 fourteen 14.0 ± 3.47 2.0 fourteen 11.67 ± 2.93 - - 3.0 21 17.5 ± 3.47 - - Necrosis sites (area) _^1/4 - ^_1/2 fourteen 11.67 ± 2.93 ** 44 44.0 ± 4.96 1,0 24 20.0 ± 3.65 * 32 32.0 ± 4.66 2.0 44 36.67 ± 4.40 ** 16 16.0 ± 3.67 3.0 38 31.67 ± 4.25 ** 8 8.0 ± 2.71 Note: * - p <0.05; ** - p <0.01; *** - p <0.001; the difference in indicators is statistically significant

Table 5
Semi-quantitative assessment of pathological structural components of the placental bed in the examined groups on a three-point scale Indicator Exhaust gas (n = 120)
M ± m KG (n = 120)
M ± m Inflammatory infiltration 2.08 ± 0.067 *** 1.42 ± 0.067 Decidual cell necrosis 2.0 ± 0.073 ** 1.32 ± 0.062 Perivascular fibrosis 1.46 ± 0.071 ** 1,0 ± 0,0 Note: ** - p <0.01; *** - p <0.001 the difference between the indicators is statistically significant

The advantages of the proposed method

- The method confirms the infectious cause of the threat of termination of pregnancy and allows you to justify the appointment of antibiotic therapy during pregnancy.

- The method has high accuracy, accessibility and information content.

- The definition of LII does not require additional material costs and proves the infectious cause of placental insufficiency and SZRP.

- The study is safe for the mother and the fetus.

- The duration of the calculation of LII takes no more than 5 minutes.

- The proposed method avoids unreasonable prescription of antibiotic therapy.

The essence of the proposed method is illustrated by the following examples.

Example 1. Pregnant Z., 22 years old. The primordial, primogenous woman. From extragenital pathology, mixed-type neurocirculatory dystonia was revealed. Gynecological diseases were not detected. Registered in the antenatal clinic is from 8 weeks of pregnancy, visits regularly. It was examined for 7 sexually transmitted infections: ureaplasmosis, mycoplasmosis, chlamydia, toxoplasmosis, herpes simplex virus, cytomegalovirus, human papillomavirus. No infections detected. At 24 weeks of pregnancy, she was hospitalized in maternity hospital No. 1 with a diagnosis of a threatening late miscarriage. When screening ultrasound revealed fetoplacental insufficiency, SZRP 2 degrees, chronic fetal hypoxia. When carrying out standard tocolytic therapy for 3 days, the threat of abortion remains. LII equal to 2.45. A presumptive diagnosis of chronic endometritis is made. Antibacterial therapy has been prescribed to treat the threat of abortion (rovamycin 3 million 3 times in 8 hours 14 days). 18 hours after the start of treatment, a significant improvement in the condition of the pregnant woman is noted. After 2 days, the threat of abortion is completely absent. During the third screening ultrasound examination at 32 weeks, the progression of placental insufficiency, SZRP 2-3 degrees, chronic fetal hypoxia were revealed. At 37 weeks of gestation, due to a decompensated form of placental insufficiency, a cesarean section was performed. A live boy was born with a mass of 1750.0 g and a height of 43 cm. During the operation, scraping of the placental bed was performed under vision control. Confirmation of the infectious nature of the threat of abortion and the development of SZRP was obtained by morphological examination: revealed leukocyte infiltration +++, decidual cell necrosis with an area of 3.0 and a portion of fibrosis with an area of 2.0. Based on these parameters, a diagnosis of chronic lymphocytic endometritis of the uteroplacental region is made. A morphological study of the placenta revealed a productive lymphocytic placentitis and funiculitis. Conclusion: LII detected the infectious nature of a threatening late miscarriage in the early stages of pregnancy, despite the lack of data for a possible infection of the pregnant woman. A morphological study of the placental bed of the uterus and placenta confirmed the infection of extraembryonic structures, which was the reason for the development of decompensated fetoplacental insufficiency and grade 3 SROP. The patient received a course of intensive antibacterial therapy after childbirth and a thorough examination and treatment is strongly recommended before the planned next pregnancy.

Example 2. Pregnant M., 27 years old. Re-pregnant, primiparous woman. A history of spontaneous miscarriage at 6 weeks of gestation. Extragenital pathology and gynecological diseases were not detected. Registered in the antenatal clinic consists of 10 weeks of pregnancy, visits regularly. It was examined for 7 sexually transmitted infections: ureaplasmosis, mycoplasmosis, chlamydia, toxoplasmosis, herpes simplex virus, cytomegalovirus, human papilloma virus. No infections detected. At 28 weeks of pregnancy, she was hospitalized in maternity hospital No. 1 with a diagnosis of threatening premature birth. Standard tocolytic therapy has begun. According to the claimed method calculated LII: equal to 1.5. It was decided to continue standard tocolysis for 5 days. After the treatment, the threat of abortion was removed. Discharged home with a progressive pregnancy. At 39 weeks, she was admitted to maternity hospital No. 1 for delivery by cesarean section in connection with mixed gluteal presentation of the fetus. She gave birth to a live boy weighing 3580.0 g and a height of 54 cm. During a caesarean section, scraping of the decidual tissue of the placental bed of the uterus was performed. Morphological study revealed leukocytic infiltration, + necrosis area decidual cells _^1/2, no fibrosis. Thus, a normal gestational restructuring of the placental bed was revealed. The placenta without inflammatory infiltration. Conclusion: the infectious nature of the threatening preterm birth according to the claimed method was not confirmed, the rejection of the choice of antibacterial therapy as a treatment for the threat of termination of pregnancy was correct.

Claims (1)

A way to confirm the role of the infectious process in the uteroplacental region in the genesis of the combination of the threat of abortion and the development of fetal growth retardation syndrome in the future, characterized in that in pregnant women with the threat of abortion, a leukocyte intoxication index is determined (LII = segmented + stab + young + myelocytes / monocytes + lymphocytes + eosinophils); and its value of more than 1.8 reveals the infectious nature of this complication.