Method of predicting preterm effusion of amniotic fluid in pregnant women

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.

1 tbl, 4 ex

 

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

The relevance of the proposed method is determined by the fact that untimely rupture of amniotic fluid is a frequent complication of pregnancy, including observed in 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 high frequency of complications from the mother: anomalies of labor (the weakness of patrimonial activity, discoordinated labor activity), Hypo - and atonic bleeding, injuries of soft tissues of generic ways, infections; fruit - infectious complications, neurological disorders (V. M. Sidelnikov Premature birth. Premature baby. - M.: GEOTAR-Media, 2006. - S).

Prediction of late using amniotic fluid is an important issue, which will reduce the frequency of the above complications.

There is a method of forecasting untimely using amniotic fluid, comprising gastrografin registration contractile activity of the uterus, characterized in that conduct resistive is ometry, and hysterography carried out before and after the introduction of 0,09-1,1 ME of oxytocin and when the resistance value of the cervix more than 240 Ohms and the increase in contractile activity of the uterus in the lower segment of the uterus in relation to the bottom more than 0.52 times predict premature rupture of amniotic fluid (Patent No. 2018261. A method for predicting premature using amniotic fluid / Gromov A.M., hasin AS // Invention. - 1994. No. 16. - P.14).

The method has drawbacks:

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

- do not specify the duration of the pregnancy when predicting premature using amniotic fluid;

- conducted research due to the manipulation in the area of the vagina and cervix, which could cause untimely rupture of amniotic fluid;

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

A known method for predicting premature rupture of fetal membranes by examining the contents of the vagina, characterized in that to increase the accuracy of prediction is to determine the activity of neuraminidase and when the value, equal to 2.5 mmol/l and above, predict premature raritetnyh membranes (Patent No. 2014601. A method for predicting premature rupture of fetal membranes. / Pogorelov T.N., Drucker N.A., V.I. Orlov, Bruckner I.I. // Invention. - 1994. No. 11. - P.132).

This method was chosen as a prototype. However, it has several drawbacks:

method of sampling of vaginal contents are not standardized;

- requires vaginal access, which could cause untimely rupture of amniotic fluid;

is not specified in what period of gestation it is necessary to carry out the sampling of the contents of the vagina and with any pregnancy predicted premature rupture of amniotic fluid;

- in the vaginal secretion may be pathogenic or opportunistic microflora, which may affect the results of the method of prediction.

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

The novelty of the proposed method lies in the fact that for the first time proposed to predict premature rupture of amniotic fluid to determine the content of IL-8 in peripheral venous blood of pregnant women at term gestational age 32-36 weeks.

In R is the bot Shavrina A.P. et al. it was shown that with the development and progression of atherosclerosis was increased in the peripheral blood level of IL-8, which may serve as a marker of developing atherosclerotic process (Shavrin A.P., Ganovska BV, Hawai IAB Indicators of the inflammatory process at different stages of development of atherosclerosis. // Medical immunology. - 2007. - V.9, No. 2-3. - S-335).

A large number of works devoted to studying the role of cytokines, there are attempts to use the levels of cytokines in the amniotic fluid as prognostic markers for premature using amniotic fluid. Holsi R. et al. believe that the increase in the content of IL-8 in amniotic fluid indicates a possible premature rupture of amniotic membranes (Holsi R., 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 representative of the family of chemokines, small polypeptides. It stimulates chemotaxis of neutrophils, the change of the cell shape, actin polymerization and degranulation, increases the production of reactive oxygen species in response to various inducers (Sukhikh G.T., Vanko L.V. Immunology of pregnancy. - M.: Izdatelstvo, 2003. - 400 C.). In the work of Juan A. Garsia-Velasco et al. (1999) have shown that levels of IL-8 in the cervix in pregnant 6 times higher than in non-pregnant women, 11 times higher among patients who were vodorazdelny through the birth canal. This indicates the involvement of IL-8 in the remodulation of the connective tissue of the cervix before labor. IL-8 induces the migration of neutrophils to the cervix and stimulates them to produce neutrophil collagenase (MMP-8), which can also disrupt the matrix of the cervix (Juan A. Garsia-Velasco, M.D. and Aydin Arici, M.D.Chemokines and human reproduction. // Fertility and sterility. - 1999. - Vol.71, No. 6. - P.989-990).

Reduced levels of IL-8 in peripheral blood of patients with premature rupture of amniotic fluid, likely reflects the switching production of IL-8 from the system level to the local level, which leads to the process of starting this pathology.

The method is as follows.

1. Produce blood from the cubital vein into a sterile tube in a volume of 1 ml After the formation of a clot the blood is centrifuged with a speed of 1500 rpm for 10 minutes and selected for the given reaction 100 ál of serum.

2. To determine serum concentration of IL-8 (ng/ml) by the method of enzyme-linked immunosorbent assay (ELISA) using commercial test systems (Bender Medsystems, Austria; LLC "Cytokine", Russia) in accordance with rekomendaciyami developer test systems. Analysis carried out on a spectrophotometer using a wavelength of measurement, specified by the company-Builder.

Distinctive features of the claimed method are:

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

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

Example 1. Patient Z., 18 years old, first pregnancy, desirable, in a registered marriage. History of appendectomy, laparoscopic removal of a cyst of the right ovary. In the period of 19 weeks suffered gestational pyelonephritis, treatment in hospital at the place of residence, was held antibacterial therapy. At discharge, the symptoms of pyelonephritis were cropped.

At 32 weeks of pregnancy hospitalized in OPB FDI Foreign Ministry with complaints of swelling of the lower extremities. At external examination: the uterus is painless to palpation, in a normal tone. The position of the fetus longitudinal head. The fetal heart beat is clear, rhythmic to 142 beats per 1 minute. Swelling of the lower legs.

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

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

Conclusion: predicted premature rupture of amniotic fluid.

Were treated dropsy, with effect. At the time of discharge, edema of the lower extremities were absent.

In the period of 34 weeks enrolled in the research Institute of the Ministry of Foreign Affairs with complaints about the discharge of amniotic fluid in the last days. Diagnosis: Pregnancy 34 weeks. Head presentation of the fetus. Prenatal rupture of amniotic fluid. Prolonged rupture of membranes.

2 hours after admission he developed an independent labor activity. Delivery was complicated by discoordinating generic activities were conducted epidural anesthesia. Born alive premature boy, weight 2300 g, a height of 46 cm, as assessed by the Apgar scale 7-8 points on the scale of the downs - 1 point. The duration of labour was 9 hours and 30 minutes, anhydrous period was 35 hours and 40 minutes.

The child underwent follow-up care after discharge from the maternity hospital in conditions 5 children's hospital, Ivanovo.

Forecast premature using amniotic fluid was confirmed.

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

History: chronic pyelonephritis, diffuse enlargement of the thyroid gland 1 degree. The pregnancy was complicated by the threat of termination in the period 18-19 weeks, about which were conducted in-patient treatment at the research Institute of the ID. Complained of the increase in uterine tone. Conducted preserving therapy with the effect.

In the period of 34 weeks again hospitalized in the Department of pathology of pregnant women with threatened preterm birth. Complained of the increase in uterine tone. According to the U.S.: fetometry corresponds to the period of pregnancy, hypertonicity of the lower segment.

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

Conclusion: predicted premature rupture of amniotic fluid.

Conducted preserving therapy effect. At the time of discharge symptoms of threatened abortion was absent.

At 36 weeks enrolled in rogovy unit of the research Institute of the Ministry of Foreign Affairs with complaints of rupture of membranes. Diagnosis: Pregnancy 36 weeks. Head presentation of the fetus. Prenatal rupture of amniotic fluid. Chronic pyelonephritis without exacerbation.

After the external examination: the uterus on palpation in a normal tone, painless on palpation. Labor activity no. The position of the fetus longitudinal previa head. The fetal heart beat is clear, rhythmic, to 142 in 1 minute.

At vaginal examination: external genitals are developed correctly, the vagina is narrow. The cervix is shortened to 1.5 cm, softened. The cervical canal pass for 1 issleduyuschego the finger, fold transition is poorly expressed. Membranes no. Slated to be actually the fetus's head, pressed against the entrance to the pelvis. The contours of the pelvis are not changed. Selection - bright amniotic fluid.

Considering prenatal rupture of amniotic fluid, the absence of an independent labor activity within 4 hours it was decided to hold labor induction. After 30 minutes has developed a generic activity. Delivery was complicated by discoordinating generic activities were conducted medical-obstetric anesthesia.

Born alive prematurely girl weighing 2500 g, a height of 46 cm, as assessed by the Apgar scale 7-8 points on the scale of the downs - 2 points. The duration of labour 11 hours and 30 minutes, anhydrous period amounted to 15 hours and 30 minutes. From maternity newborn was transferred to the second stage of premature children.

Forecast premature using amniotic fluid was confirmed.

Example 3. Patient N., 24 years. Pregnancy the second, desired. History 1 medical abortion, without complication, mild myopia. The pregnancy was complicated by dropsy 1 degree 27 weeks of pregnancy, was conducted outpatient treatment with a positive effect. In the period of 33 weeks entered the OPB research Institute of the Ministry of Foreign Affairs with the threat of premature birth. Complained of the increase in uterine tone. According to the U.S.: fetometry corresponds to the period of gestation, hypertonicity in front the wall.

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

Conclusion: it is Predicted during pregnancy without premature using amniotic fluid.

Was carried out keeping therapy effect. At discharge symptoms threats of termination was not.

In the period 39-40 weeks enrolled in the research Institute of the Ministry of Foreign Affairs with a diagnosis of Pregnancy 39-40 weeks. Head presentation of the fetus. 1 the period of confinement. Myopia of a weak degree. At vaginal examination: external genitals are developed correctly. The vagina is narrow. The cervix is smooth, edges thin, the disclosure of uterine OS 7 see the Fetal bladder is intact, the fetus's head is pressed to the entrance to the pelvis. The contours of the pelvis are not changed. Selection mucous.

The pregnancy ended in a timely first childbirth in the head previa. Born live, full-term girl, weight 3350 g, the height of 51 cm, as assessed by the Apgar scale 8-9.

The duration of labour 10 hours and 30 minutes, anhydrous period was 2 hours and 30 minutes.

The forecast for the claimed method was confirmed.

Example 4. Patient K., 21 years. Pregnancy the second, desirable, in a civil marriage. The first ended in a medical abortion, without complication. History: chronic tonsillitis, anemia 1 degree. The pregnancy was complicated by the threat of termination ber is mennoti in week 36, underwent inpatient treatment in OPB research Institute of the Ministry of Foreign Affairs. Upon receipt complained of nagging pain in the lower abdomen, was conducted preserving therapy.

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

Conclusion: predicted premature rupture of amniotic fluid.

The pregnancy ended in the first preterm birth in term of 37 weeks in the main presentation of the fetus. Delivery was complicated by antepartum rupture of amniotic fluid, were perineotomy, perineorrhaphy. Born alive prematurely girl with the weight of 2950 g, a height of 46 cm, as assessed by the Apgar scale 7-8 points.

The forecast for the claimed method was confirmed.

The research results are summarized in table 1.

Table 1.
IndexThe number of the examined
Total female50
True-positive result26
False positive result4
True-negative result17
False-negative result3
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 of 86%, sensitivity 90% and specificity of 81%.

2. Good reproducibility of the method.

3. The simplicity of execution methods.

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

5. Ease of interpretation of the survey results.

6. The method allows a certain period of gestation (32-36 weeks) to predict premature rupture of amniotic fluid, which enables prevent this complication of pregnancy and to prevent as complications of labor and perinatal pathology.

A method for predicting premature using amniotic fluid in pregnant women by examining biological material, characterized in that women in gestation 32-36 weeks in serum to determine the level of IL-8 and when it is equal to or less than the 15.4 ng/ml, predict premature rupture of amniotic fluid.



 

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5 cl, 4 tbl, 5 ex

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

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