RU2405453C1 - Method of predicting preterm effusion of amniotic fluid in pregnant women - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to obstetrics, and can be used for prediction of preterm effusion of amniotic fluid in pregnant women with gestation term 32-36 weeks. Essence of invention lies in the following: in blood serum of pregnant women with gestation term 32-36 weeks IL-8 level is determined, and if its value equals or is lower than 15.4 ng/ml, preterm effusion of amniotic fluid is predicted.

EFFECT: method is simple in implementation and allows to predict development of preterm effusion of amniotic fluid with high accuracy, sensitivity and specificity, which makes it possible to select correct tactics of monitoring women with risk of said obstetrics pathology development, to avoid complications of labour activity and perinatal pathology.

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Description

The invention relates to medicine, namely to obstetrics, and can be used to predict premature outflow of amniotic fluid in pregnant women at a gestational age of 32-36 weeks.

The relevance of the proposed method is determined by the fact that untimely discharge of amniotic fluid is a common complication of pregnancy, including 18-51% of cases of preterm birth (Goldenberg R. et al. The Alabama preterm birth Prevention project // Obstet. Gynecol. - 1990. - Vol. 75. - P.933-939; Carrol S. et al. Preterm Prelabour Amniorrhexis. - Brussels: The Partenon Publishining Group, 1995). The development of this pathology leads to a high frequency of complications from the mother: anomalies of labor (weak labor, discoordination of labor), hypo- and atonic bleeding, soft tissue injuries of the birth canal, infections; on the part of the fetus - infectious complications, neurological disorders (Sidelnikova V.M. Preterm birth. Premature baby. - M .: GEOTAR-Media, 2006. - P.207).

Prediction of untimely discharge of amniotic fluid is an important problem, which will reduce the frequency of the above complications.

A known method for predicting untimely discharge of amniotic fluid, including hysterographic registration of contractile activity of the uterus, characterized in that they perform resistive cervicometry, and hysterography is performed before and after the introduction of 0.09-1.1 ME Oxytocin and with a cervical resistance of more than 240 Ohms and an increase in contractile activity of the uterus in the region of the lower segment of the uterus with respect to the bottom more than 0.52 times predict premature amniotic fluid outflow (Patent No. 2018261. Method for predicting previous of the non-temporal outflow of amniotic fluid / Gromova A.M., Khasin A.Z. // Inventions. - 1994. - No. 16. - P.14).

The method has disadvantages:

- the method is extremely time-consuming, since it requires the use of several methods of instrumental diagnostics;

- the gestational age is not indicated when predicting premature amniotic fluid outflow;

- the study is associated with manipulations in the vagina and cervix, which can provoke untimely discharge of amniotic fluid;

- requires the introduction of a solution of oxytocin, which can induce an increase in contractile activity of the uterus and provoke untimely discharge of amniotic fluid.

A known method for predicting premature rupture of the membranes by examining the contents of the vagina, characterized in that in order to increase the accuracy of the prognosis, the activity of neurominidase is determined and when it is equal to 2.5 mmol / l or higher, premature rupture of the membranes is predicted (Patent No. 20144601. for predicting premature rupture of the membranes. / Pogorelova T.N., Drucker N.A., Orlov V.I., Krukner I.I. // Inventions. - 1994. - No. 11. - P.132).

This method was chosen by us as a prototype. However, it has several disadvantages:

- the method of sampling vaginal contents is not standardized;

- vaginal access is required, which can provoke untimely discharge of amniotic fluid;

- it is not indicated at what gestational age it is necessary to take the vaginal contents and from what gestational age a premature discharge of amniotic fluid is predicted;

- in the vaginal secretion, pathogenic or conditionally pathogenic microflora may be present, which may affect the results of the forecasting method.

The claimed technical result is achieved by the fact that in pregnant women at a gestational age of 32-36 weeks, the level of IL-8 in the blood serum is determined and with its value equal to or less than 15.4 ng / ml, premature amniotic fluid is predicted with an accuracy of 86%, sensitivity of 90% and specificity of 81%.

The novelty of the proposed method lies in the fact that for the first time it is proposed to predict premature amniotic fluid outflow by determining the content of IL-8 in the peripheral venous blood of pregnant women at a gestational age of 32-36 weeks.

In the work of Shavrin A.P. et al. it was shown that with the development and progression of atherosclerosis there was an increase in the level of IL-8 in the peripheral blood, which can serve as a marker of the developing atherosclerotic process (Shavrin A.P., Gonovskaya B.V., Khavaev Ya.B. Indicators of the inflammatory process at different stages the development of vascular atherosclerosis. // Medical immunology. - 2007. - T.9, No. 2-3. - S.334-335).

A large number of works are devoted to the study of the role of cytokines; attempts are being made to use indicators of the content of cytokines in amniotic fluid as prognostic markers of premature amniotic fluid effusion. Holsi R.M. et al. consider that an increase in IL-8 in amniotic fluid indicates a possible premature rupture of the amniotic membranes (Holsi RM, Mattshy-Baltzer I., Wennerholm U. Interleukin-6 and Interleukin-8 in cervical fluid of Swedish women in preterm labor relationship to microbial invasion of amniotic fluid, intraamniotic inflammation, and preterm delivery. // Acta Obstetr.Gynecol.Scand. - 2005. - Vol 84, No. 6. - P.516). However, many aspects of this problem need to be clarified.

IL-8 is a member of the chemokine family of small polypeptides. It stimulates neutrophil chemotaxis, cell shape change, actin polymerization and degranulation, increases the production of reactive oxygen species in response to various inductors (Sukhikh G.T., Vanko L.V. Pregnancy Immunology. - M.: RAMS Publishing House, 2003. - 400 from.). Juan A. Garsia-Velasco et al. (1999) showed that the content of IL-8 in the cervix in pregnant women is 6 times higher than in non-pregnant women, 11 times higher in patients who were delivered through the natural birth canal. This indicates the involvement of IL-8 in the remodeling of connective tissue of the cervix before delivery. IL-8 causes the migration of neutrophils to the cervix and stimulates them to produce neutrophil collagenase (MMP-8), which can also destroy the cervical matrix (Juan A. Garsia-Velasco, MD and Aydin Arici, MDChemokines and human reproduction. // Fertility and sterility. - 1999. - Vol. 71, No. 6. - P.989-990).

The decrease in the content of IL-8 in the peripheral blood in patients with premature amniotic fluid flow probably reflects the switch of IL-8 production from the systemic level to the local level, which leads to the process that triggers this pathology.

The method is as follows.

1. A blood sample is taken from the ulnar vein into a sterile tube in a volume of 1 ml. After the formation of a clot, the blood is centrifuged at a speed of 1,500 rpm for 10 minutes and 100 μl of serum are taken for the reaction.

2. The serum concentration of IL-8 (ng / ml) is determined by enzyme-linked immunosorbent assay (ELISA) using commercial test systems (Bender Medsystems, Austria; LLC "Tsitokin", Russia) in accordance with the recommendations of the developer test -systems. The results are taken into account on a photometer using the measurement wavelength specified by the developer.

Distinctive features of the claimed method are:

- a new prognostic indicator of the level of IL-8 in blood serum has been proposed, at a value of which equal to or less than 15.4 ng / ml, premature amniotic fluid is predicted in pregnant women at a gestational age of 32-36 weeks.

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

Example 1. Patient Z., 18 years old, first pregnancy, desired, in a registered marriage. In the history of appendectomy, laparoscopic removal of a cyst of the right ovary. In the period of 19 weeks she underwent gestational pyelonephritis, treatment in a hospital setting at the place of residence, antibiotic therapy was carried out. At discharge, the symptoms of pyelonephritis were stopped.

At 32 weeks of gestation, she was hospitalized at the Department of Health and Safety at FDI MiD with complaints of swelling of the lower extremities. On external examination: the uterus is painless on palpation, in a normal tone. The position of the fetus is longitudinal, head. The fetal heartbeat is clear, rhythmic up to 142 beats per 1 minute. Swelling of the legs.

Diagnosis: Pregnancy 32 weeks. Head presentation of the fetus. Dropsy 1 tbsp. Gestational pyelonephritis, remission.

A survey was conducted according to the claimed method: the content of IL-8 was 15.4 ng / ml, which is equal to the claimed level. (= 15.4 ng / ml).

Conclusion: premature discharge of amniotic fluid is predicted.

Dropsy treatment was carried out, with effect. At the time of discharge, swelling of the lower extremities was absent.

In a period of 34 weeks, she was admitted to the MII Research Institute with complaints of amniotic fluid overflow during the last 24 hours. Diagnosis: Pregnancy 34 weeks. Head presentation of the fetus. Prenatal discharge of amniotic fluid. Long dry span.

2 hours after admission, independent labor activity developed. Childbirth was complicated by discoordination of labor, and epidural anesthesia was performed. A lively premature boy was born, weighing 2300 g, height 46 cm, grading on the Apgar scale 7-8 points, on the Downs scale - 1 point. The duration of labor was 9 hours 30 minutes, the anhydrous period was 35 hours 40 minutes.

The child underwent aftercare after discharge from the maternity hospital in conditions of 5 children's hospital in Ivanovo.

The prognosis of premature amniotic fluid outflow was confirmed.

Example 2. Patient A., 18 years old, first pregnancy, desired.

History: chronic pyelonephritis, diffuse enlargement of the thyroid gland of 1 degree. The course of pregnancy was complicated by the threat of interruption in the period of 18-19 weeks, about which inpatient treatment was carried out at the Research Institute of MiD. Complained of increased uterine tone. Conservation therapy was carried out with effect.

In a period of 34 weeks, she was again hospitalized in the department of pathology of pregnant women with the threat of premature birth. Complained of increased uterine tone. According to ultrasound: fetometry corresponds to the gestational age, hypertonicity of the lower segment.

A survey was conducted according to the claimed method: the content of IL-8 was 3.64 ng / ml, which is less than the declared level (<15.4 ng / ml).

Conclusion: premature discharge of amniotic fluid is predicted.

Conservation therapy was carried out with effect. At the time of discharge, there were no symptoms of threatened abortion.

At 36 weeks, she was admitted to the birth block of the Research Institute of MiD with complaints of amniotic discharge. Diagnosis: Pregnancy 36 weeks. Head presentation of the fetus. Prenatal discharge of amniotic fluid. Chronic pyelonephritis without exacerbation.

With an external examination: the uterus on palpation is in a normal tone, painless on palpation. There is no clan activity. The position of the fetus is longitudinal, the presentation of the head. The fetal heartbeat is clear, rhythmic, up to 142 in 1 minute.

With vaginal examination: the external genitalia are developed correctly, the vagina is narrow. The cervix is shortened to 1.5 cm, softened. The cervical canal is passed for 1 examining finger, the fold of the transition is weakly expressed. There is no fetal bladder. Slated to be the head of the fetus, pressed to the entrance to the small pelvis. The contours of the pelvis are not changed. Allocations are light amniotic fluid.

Given the prenatal discharge of amniotic fluid, the absence of an independent labor activity within 4 hours, it was decided to carry out labor delivery. After 30 minutes, labor began to develop. Childbirth was complicated by discoordination of labor, obstetric anesthesia was carried out.

A live premature girl was born weighing 2500 g, height 46 cm, grading on the Apgar scale 7-8 points, on the Downs scale - 2 points. The duration of labor was 11 hours 30 minutes, the anhydrous interval was 15 hours 30 minutes. From the maternity hospital, the newborn was transferred to the second stage of nursing of premature babies.

The prognosis of premature amniotic fluid outflow was confirmed.

Example 3. Patient N., 24 years old. Second pregnancy, desired. History 1 medical abortion, without complications, mild myopia. The course of pregnancy was complicated by dropsy of the 1st degree from 27 weeks of pregnancy, outpatient treatment was carried out with a positive effect. In a period of 33 weeks, she was admitted to the OPB Research Institute of M&D with the threat of premature birth. Complained of increased uterine tone. According to ultrasound: fetometry corresponds to gestational age, hypertonicity on the front wall.

A survey was conducted according to the claimed method: the content of IL-8 was 385 ng / ml, which is higher than the claimed level (> 15.4 ng / ml).

Conclusion: Pregnancy is predicted without premature discharge of amniotic fluid.

Conservation therapy was carried out, with effect. When discharging symptoms, there was no threat of interruption.

In the period of 39-40 weeks was admitted to the Research Institute of MiD with a diagnosis of Pregnancy 39-40 weeks. Head presentation of the fetus. 1 period of childbirth. Mild myopia. With vaginal examination: the external genitalia are developed correctly. The vagina is narrow. The cervix is smoothed, the edges are thin, the opening of the uterine pharynx is 7 cm. The fetal bladder is intact, the fetal head is pressed to the entrance to the small pelvis. The contours of the pelvis are not changed. Discharge mucous.

Pregnancy ended with the first timely birth in the head presentation. A live full-term girl was born, weighing 3350 g, height 51 cm, rating on the Apgar scale of 8-9 points.

The duration of labor was 10 hours 30 minutes, the anhydrous interval was 2 hours 30 minutes.

The forecast for the claimed method was confirmed.

Example 4. Patient K., 21 years old. Pregnancy second, coveted, in a civil marriage. The first ended in medical abortion without complications. History: chronic tonsillitis, anemia of 1 degree. The course of pregnancy was complicated by the threat of termination of pregnancy in the period of 36 weeks, underwent inpatient treatment in OPB Research Institute of MiD. Upon admission, she complained of pulling pains in the lower abdomen, preserving therapy was carried out.

A survey was conducted according to the claimed method: the content of IL-8 was 8.2 ng / ml, which is higher than the claimed level (<15.4 ng / ml).

Conclusion: premature discharge of amniotic fluid is predicted.

Pregnancy ended with the first preterm birth at 37 weeks in the fetal presentation. The birth was complicated by the prenatal outflow of amniotic fluid, perineotomy, perineoraphy was performed. A live premature girl was born, weighing 2950 g, height 46 cm, rating on the Apgar scale of 7-8 points.

The forecast for the claimed method was confirmed.

The research results are summarized in table 1.

Table 1. Indicator The number of examined Total women fifty True positive result 26 Falsely positive result four True negative result 17 False negative result 3 Total: the accuracy of the proposed method is 86%
the sensitivity of the proposed method is 90%
the specificity of the proposed method is 81%.

The advantages of the proposed method.

1. High accuracy - 86%, sensitivity - 90% and specificity - 81%.

2. Good reproducibility of the method.

3. The simplicity and accessibility of the methodology.

4. The duration of the methodology for determining the level of IL-8 does not exceed 2 hours.

5. Simplicity in interpretation of survey results.

6. The method allows, at certain gestational periods (32-36 weeks), to predict premature discharge of amniotic fluid, which makes it possible to prevent this complication of pregnancy and to prevent the occurrence of both complications of labor and perinatal pathology.

Claims (1)

A method for predicting premature amniotic fluid outflow in pregnant women by examining biological material, characterized in that in women at a gestational age of 32-36 weeks, the level of IL-8 in the blood serum is determined and when its value is equal to or less than 15.4 ng / ml, they are predicted premature discharge of amniotic fluid.