Prevention and treatment of threatened abortion

The degree of threat of termination of pregnancy can be judged by:

• subjective complaints of women;
• colpocytological hormonal changes;
• changes in the contractile activity of the myometrium, recorded by palpation and external hysterography;
• data from external and internal examination;
• changes in the condition of the cervix;
• bloody discharge;
• socio-economic factors;
• laboratory methods (determination of the level of collagenase in the blood serum of a pregnant woman: determination of granulocyte elastase in cervicovaginal secretions, as well as oncofetal fibronectin.

The threat of interruption must be diagnosed by the following signs:

• pain in the lower abdomen and lower back of a pulling, aching or cramping nature, provided that the contractions occur less than every 10-15 minutes and last less than 20 seconds;
• increased excitability and tone of the uterus;
• bloody and serous discharge from the genital tract;
• changes in the cervix (shortening and softening, patency of the cervical canal for the examining finger);
• low position of the presenting part of the fetus in relation to the entrance to the small pelvis.

The onset of labor is diagnosed by cramping pains in the lower abdomen, provided that the contractions occur more often than every 10 minutes and last more than 30 seconds. The cervix is sharply shortened or smoothed, the opening of the cervix is 1 cm or more. The presenting part is located low or pressed to the entrance to the small pelvis, there is often bloody discharge from the genital tract.

To quantitatively determine the degree of threat of termination of pregnancy, it is recommended to use the modified Tsan-Troschinsky index.

Pregnant women should be instructed by their physician regarding the early signs of a threatened miscarriage: the presence of uterine contractions during self-palpation in the morning and evening, mild pain in the lower abdomen, sometimes tension in the uterus, reminiscent of menstruation, leading to a feeling of discomfort, mild pain in the pubic area and the appearance of minor discharge from the genital tract.

For the prevention and timely diagnosis of premature birth in pregnant women at high risk for miscarriage, it is also recommended to perform an ultrasound examination of the cervix and the area of the internal os and the presence of uterine contractions or myometrial tension of both the anterior and posterior walls of the uterus once a week, or an internal examination also every week during pregnancy between 26-30 weeks of pregnancy and up to 34 weeks of pregnancy, i.e., in the early stages of the third trimester of pregnancy.

Most pregnant women experience premature birth when they have 3 signs:

• opening of the internal os by 1 cm;
• the length of the cervical canal is less than 1 cm;
• the presence of painful uterine contractions.

Luminescent colpocytological classification of preterm labor

It is recommended that examination of native vaginal smears taken from the lateral vaginal fornix and air-dried be performed using a microscope at 100x magnification using acridine orange fluorochrome.

It is advisable to evaluate the smear at terms up to 36 weeks of pregnancy according to the Schmitt classification, according to which reaction 1 indicates a sharp estrogenic deficiency, reaction 2 - a moderate estrogenic deficiency, reaction 3 - a moderate estrogenic effect, reaction 4 - a sharp estrogenic effect. A study of vaginal smears conducted in 300 healthy women at a pregnancy term of 28-36 weeks revealed reaction 2, which is recommended to be taken as the norm at this term of pregnancy. The criterion of well-being in this group is the absence of signs of a threat of termination of pregnancy.

In cases of threatened premature birth, a fluorescent colpocytological study was performed in 9,500 women. In 85% of pregnant women, the 3rd and 4th reactions of the vaginal smear were established, indicating an increased level of estrogens. In 15% of pregnant women, symptoms of degeneration of squamous epithelium were detected, indicating a decrease in the level of estrogens. The following morphological changes are characteristic of degeneration of squamous epithelium in a fluorescent colpocytological study - blurring of cell contours, the exit of nuclei beyond the cytoplasm, the formation of homogeneous cellular complexes, leukocyte infiltration inside them, the absence of inflammatory cellular changes.

Taking into account the results of colpocytological studies, depending on the degree of severity of hormonal disorders, the following classification of the threat of termination of pregnancy according to colpocytological data is recommended.

In the hyperestrogenic form:

• low threat level (62%);
• moderate » » (27%);
• sharp » » (11%). In the hypoestrogenic form:
• low threat level (78%);
• moderate » » (16%);
• sharp » » (6%).

Thus, 15% of pregnant women with a threat of miscarriage show degenerative signs and changes in the squamous epithelium as a sign of hypostrogenia, reflecting fetoplacental insufficiency. Studying colpocytograms by the luminescent method in premature births allows using an important diagnostic test - degeneration of the squamous epithelium, indicating a decrease in the endocrine function of the placenta and the development of fetoplacental insufficiency.

Cardiotocography. It should be remembered that in the early signs of threatening premature labor, fetal tachycardia up to 180 beats/min should be regarded as a sign of immaturity of its organs and systems, and not as hypoxia (26-32 weeks of pregnancy). According to our data, symptoms of fetal dysfunction correlate with oxytocinase determination data.

Abroad, home monitoring of myometrial contractility in pregnant women at risk for miscarriage is becoming increasingly widespread.

Serum oxytocinase activity. Serum oxytocinase activity was determined using the method of Turri et al. as modified by Babun et al. In 120 pregnant women with threatened miscarriage from the 16th to 36th week of pregnancy, the oxytocinase activity level was significantly lower compared to physiologically progressing pregnancy at the same time (16-32 weeks of pregnancy). At later stages, i.e., at the 33rd to 36th week of pregnancy, this difference was less pronounced and unreliable. With a combination of threatened miscarriage and fetal malnutrition, oxytocinase activity levels were the lowest.

It is also necessary to take into account that, along with a decrease in oxytocinase activity, an increase in oxytocinase activity may also be observed in threatening labor. In these cases, children were born prematurely, at 35-36 weeks of pregnancy with signs of severe fetal hypoxia.

Thus, the level of oxytocinase activity in the blood serum is associated with the functional state of the placenta and therefore the determination of oxytocinase activity can be used as an additional functional test for the diagnosis and prognosis of disorders that may occur with functional insufficiency of the placenta during premature birth.

In addition, the level of oxytocinase in the blood serum can be used as an indicator of placental function and the condition of the fetus in premature birth, since it is known that the placenta is the site of formation of specific serum oxytocinase during pregnancy. It has been proven that this enzyme is localized in the syncytial cells of the placenta and secretes into the intravillous space.

A linear increase in oxytocinase activity is characteristic of a physiologically proceeding pregnancy. Deviation from the normal course of the curve, both downward and upward, characterizes functional insufficiency of the placenta.

Thus, it is recommended to use the identification of the dynamics of the activity of this enzyme as the most informative test for assessing the functional state of the placenta in cases of threatened premature birth.

Ultrasound determination of fetal respiratory movements. As is known, in full-term pregnancy, 24-36 hours before birth, a decrease or even complete disappearance of respiratory movements is observed.

To predict premature birth, it is recommended to take into account the respiratory movements of the fetus: if there are no respiratory movements, labor will occur in the next 48 hours. If there are respiratory movements of the fetus during premature birth, even without treatment, labor will occur in a week or more.

Contractile activity of the uterus. It is advisable to record the contractile activity of the uterus in outpatient settings of antenatal clinics for pregnant women at risk of miscarriage. At home, especially in the evening, it is determined by self-palpation of the uterus, and in some cases by using a special tocodynamometer, which is mainly done abroad. This is explained by the fact that both with self-palpation of the uterus, even with careful instructions to the pregnant woman, and with the use of a tocodynamometer, the latter detects the initial stages of the threat of termination of pregnancy earlier than the subjective sensations of the pregnant woman.

If there are 4 or more uterine contractions lasting 40-45 seconds or more in 1 hour, hospitalization is necessary. This allows 85% of premature births to be prevented by timely initiation of treatment.

There are four stages of threatened premature birth according to multichannel external hysterography:

• / stage - presence of small uterine contractions - less than 8 in 15 minutes;
• // stage - the appearance of large uterine contractions lasting up to 150 sec and a decrease in the frequency of small uterine contractions (like Alvarez and Braxton Hicks uterine contractions);
• Stage III - increase in uterine contractile activity from 150 to 250 sec, intensity - from 10 to 25 mm;
• Stage IV of threatened termination of pregnancy is characterized by an increase in uterine contractile activity over 250 sec in duration and over 25 mm in intensity; large contractions are coordinated; the phenomenon of fundus dominance and triple descending gradient is noted, and small contractions are rarely recorded (1-2 in 15 min).

Measuring vaginal pH. As is known, with normal acidity of the vaginal environment, the vital activity of pathogenic pathogens is hindered. At pH in the vagina < 4.2, the environment is too acidic. Therefore, a simple and effective method of preventive control of the threat of interruption is measuring pH, which is carried out either with a pH electrode or indicator paper. At pH 4.2, in the case of detection of a facultative pathogen, treatment with broad-spectrum antibiotics is necessary.

Serum relaxin is a potential marker of premature labor. When determining the concentration of relaxin in the blood serum at 30 weeks of pregnancy, its high levels indicate a threat of labor - 455 ± 169 pg / ml or 75 ± 7 mmol / l. Normally, the relaxin level is 327 ± 139 pg / ml or 54 ± 4 mmol / l.

Accurate diagnostics of rupture of fetal membranes is of great practical importance, since the tactics of management and prognosis of the outcome of premature birth depend on it. When testing amniotic fluid samples with nitrazine paper, an alkaline reaction is detected, and on dried slides - a fern pattern . In doubtful cases, the volume of amniotic fluid is assessed using echography data.

Amniocentesis is widely used in the management of premature births, allowing the detection of intrauterine infection, which is found in 10-20% of cases, and simultaneously assessing the degree of maturity of the fetal lungs.

The evaporation test is used to determine the rupture of membranes, first described by Iannetta in 1994. It is based on evaporation of material taken from the cervical canal on a glass slide. If there is amniotic fluid , a white precipitate remains after evaporation, and if there is no amniotic fluid, abrown precipitate. The test results were positive in 89.5% of cases, and false negative in 10.5%. There were no false positives, and true negatives were confirmed in 100% of cases.

Luminescent-colpocytological studies for the diagnosis of amniotic fluid discharge according to vaginal smear. A large number of studies devoted to the issue of diagnosing the discharge of amniotic fluid indicate the absence of an accurate and easily performed diagnostic test that reliably indicates the discharge of amniotic fluid.

To detect elements of amniotic fluid in vaginal contents, smears from the posterior vaginal fornix are used, applied in a thin layer to a glass slide with a wooden spatula or a thick glass pipette with a bulb at the end. In addition, a thick drop of vaginal contents is applied to the same glass slide to detect crystallization figures. The smears are dried in air for 3-4 minutes, after which they are examined under a fluorescent device with a microscope at 100x magnification. To form fluorescence, acridine orange fluorochrome is used in a dilution of 1:30,000. The study on a fluorescent microscope to detect crystallization figures of amniotic fluid was carried out without a blue-violet filter (FS-1) with the microscope condenser lowered. It is not advisable to use a fluorochrome to detect crystallization figures, since these crystallization figures are clearly visible on a yellow background, but are not contrasted by a fluorochrome.

To determine the diagnostic value of the proposed methods for detecting elements of amniotic fluid, we simultaneously conducted the Zeyvang test, a crystallization test with eosin staining, and amnioscopy.

When examining a vaginal smear against the background of the mother's squamous epithelium, leukocytes, mucus and vaginal flora, anuclear fetal cells-squamous cells are found, which are an undoubted sign of the presence of amniotic fluid in the vaginal contents. In the smear, fetal cells-squamous cells are located both singly and in groups among the mother's squamous epithelium. Fetal scales are 1% - 2 times smaller than the size of the mother's squamous epithelium, they glow with a soft green or slightly pink color. The intensity of the glow is less than that of other elements of the vaginal smear. Their shape is oval or polygonal. If there is a small number of cells-squamous cells in the vaginal contents, they are mainly located along the periphery of the smear.

The amniotic fluid crystallization test, which largely depends on the amount of water and the duration of the anhydrous interval, seems to us less reliable than the detection of fetal cells-scales. With a long anhydrous interval (more than 6-8 hours), the diagnostic value of detecting crystallization figures drops sharply. Unlike crystallization of cervical mucus, crystallization of waters forms figures of snowflakes and stars, which, located next to each other, create the impression of fine openwork embroidery. Crystallization of cervical mucus forms figures of fern leaves.

Thus, the most reliable test for water rupture is the luminescent colpocytology method with the detection of fetal cells-scales, which gives correct results in 98% of cases. The reliability of this method does not depend on the amount of water rupture and the duration of the anhydrous interval, it is applicable at a pregnancy term of over 33-34 weeks, since at earlier stages of pregnancy the rejection of the fetal epidermis is expressed extremely insignificantly.

Fetal fibronectin as a marker of preterm labor. In recent years, a biochemical marker of preterm labor has been widely discussed - fetal fibronectin, determined in cervical-vaginal contents.

To determine the concentration of fetal fibronectin in the secretion of the cervical canal and vagina, as well as in the amniotic fluid and in the blood plasma of the mother, the authors used a sensitive method with the determination of monoclonal antibodies. Immunohistochemical studies were also carried out to determine the distribution of fetal fibronectin in the placenta and in the amnion and chorion. The most thorough studies belong to Lockwood et al. It was established that during the physiological course of pregnancy and term labor, fetal fibronectin is very rarely determined in the cervicovaginal secretion in a concentration of no more than 0.05 μg / ml between 21-27 weeks of pregnancy from the cervical canal (4%) and in 3% in the vaginal secretion. High levels of fetal fibronectin are determined in the amniotic fluid, as well as in the cervicovaginal secretion in pregnant women with rupture of the fetal membranes (93.8%).

Cervical-vaginal fetal fibronectin was also detected in 50.4% of pregnant women with threatened premature labor against the background of increased contractile activity of the uterus and an intact fetal bladder. Fibronectin was determined in pregnant women who delivered prematurely with a sensitivity of 81.7% and a specificity of 82.5 %. Fetal fibronectin was also detected in the placenta and fetal membrane at the points of contact with the uterine wall.

Thus, the presence of fetal fibronectin in the second and third trimesters identifies a subgroup of pregnant women at high risk of preterm birth. This phenomenon can be explained by a reflexive separation of the chorion from the decidua layer of the uterus with the release of intact or decaying components of the chorion of the extracellular matrix into the cervical canal and vagina.

It should be noted that neither 17-beta-estradiol, nor plasma progesterone, nor C-reactive protein are markers of preterm labor. Fibronectin is found in blood plasma, extracellular matrix, amniotic fluid, placenta, malignant cells, is designated in the literature as "oncofetal domain" and is detected using monoclonal antibodies FDS-6. There are suggestions that fetal fibronectin can be released into the cervix and vagina in the presence of inflammation in the area of the fetal membrane, which is damaged.

In the dynamics of pregnancy it has been established that in uncomplicated pregnancy up to 22 weeks, fetal fibronectin is found in the cervical canal in 24% and in the vaginal secretion in 17% of pregnant women. After 37 weeks of pregnancy, in 32% and 17% of cases, respectively.

Between 21 and 37 weeks of pregnancy, fetal fibronectin was detected in only 4% of cervical secretions and only 3% of vaginal secretions. The average concentration of fetal fibronectin in cervical secretions was 0.26 ± 0.22 μg/ml and in the vagina - 0.27 ± 0.23 μg/ml. The average concentrations of fibronectin in maternal plasma in the first, second and third trimesters of pregnancy, respectively, were 1.3 ± 0.7 μg/ml; 2.0 ± 2.3 μg/ml and 3.5 μg/ml ± 2.2 μg/ml. The level of fibronectin in maternal plasma correlated with the duration of pregnancy.

In case of prenatal rupture of membranes, fibronectin is determined in 93.8% of cervicovaginal secretions and the average concentration is 5.5 ± 11.4 μg/ml and 6.9 ± 11.1 μg/ml, respectively; in case of full-term pregnancy, the fibronectin level in amniotic fluid is 27.1 ± 17.3 μg/ml. It is important to note that when fetal fibronectin is found in cervicovaginal secretions and prenatal rupture of membranes, the average time interval between rupture of the membranes and premature birth was 2.1 days, and in its absence - 21 days. With increased uterine activity and an intact membrane, 51.3% of pregnant women gave birth before the 37th week of pregnancy in the presence of fibronectin, and in 83.1% without it (p < 0.01).

In premature births, the average concentration of fetal fibronectin in cervicovaginal secretions was 2.2 ± 5.7 and 2.3 ± 5.7 μg/ml, respectively, compared to full-term pregnancy - 1.5 ± 3.4 μg/ml and 0.4 ± 1.0 μg/ml. The threshold of fetal fibronectin is 0.025-0.075 μg/ml.

Since in premature births in the lower uterine segment there is separation of the chorion from the decidual layer or there is inflammation in this area, fibronectin is released from the extracellular matrix of the chorion with the activation of neutrophils. Therefore, the appearance of fetal fibronectin in full-term pregnancy is a marker of the onset of labor, since both term and premature births have common changes - separation of the chorion from the decidual layer. At the same time, the presence of fetal fibronectin in the cervicovaginal secretion in the second and third trimesters of pregnancy is a marker of premature birth. Immunohistochemically, it has been shown that fetal fibronectin is determined in the extracellular matrix of the basal decidua and intervillous space.

At the same time, a number of researchers have shown that fibronectin increases in preeclampsia and damage to the vascular endothelium.

Until now, the source of "fetal" fibronectin has not been completely clarified. Thus, Feinberg, Kliman (1992) found that fetal fibronectin is actively synthesized, secreted and located in the extracellular matrix of the trophoblast. This gives grounds to believe that the chorion trophoblast in the extracellular matrix is an important source of fibronectin in the cervicovaginal secretion. In premature birth, proteolytic breakdown of fibronectin in the chorion can occur. By the way, fibronectin isoenzymes are found in both non-pregnant and pregnant women. The authors believe that the determination of fibronectin is an early and more specific marker of premature birth in the presence of an inflammatory process in the chorion of the fetal membrane.

The onset of labor is diagnosed by the following signs:

• cramping pains in the lower abdomen, provided that the contractions occur more often than every 10 minutes and last more than 30 seconds;
• the cervix is sharply shortened or smoothed, the opening of the cervix is 1 cm or more;
• the presenting part is located low or pressed against the entrance to the small pelvis;
• There is often bloody discharge from the genital tract.

It should be considered that even in the presence of regular contractions and a smoothed cervix, tocolytic therapy in the absence of an effect is advisable to maintain pregnancy, since it allows for the regulation of labor and the prevention of birth trauma in the mother and fetus. In addition, it is known that 15 hours are needed to develop adaptive mechanisms in a premature fetus. It should also be noted that the use of beta-adrenergic agonists, in addition to regulating labor, promotes the production of surfactant in the lung tissue of an immature fetus.

The presence of uterine contractions at least every 10-15 minutes, progressive shortening and smoothing of the cervix and descent of the presenting part of the fetus in a premature pregnancy are the basis for diagnosing premature labor.

Preterm birth is characterized by frequent obstetric complications:

• premature rupture of membranes;
• incorrect position of the fetus;
• breech presentation of the fetus;
• placenta previa and low attachment;
• premature detachment of a normally located placenta;
• multiple pregnancy;
• subsequent and early postpartum hemorrhage.

During labor, uncoordinated labor activity, rapid or impetuous labor are observed, which aggravates the severity of the fetus's condition. Thus, rapid and impetuous labor is observed in every third woman in labor, and every fourth woman has weak labor activity. This is probably due to the fact that premature labor occurs with a pronounced disruption of the hormonal function of the placenta: increased content of placental lactogen, a sharp drop in the levels of chorionic gonadotropin, estrogens, and pregnanediol.

In the complex of measures for treatment and prevention of threatened miscarriage, the most important place is given to the prescription of agents that inhibit the contractile activity of the myometrium: magnesium sulfate, metacin, prostaglandin inhibitors, progesterone, beta-adrenergic agonists, especially for subcutaneous administration with a special perfusor/device, GABA-positive substances (for example, phenibut) and their combination with phenazepam, oxytocin antagonists and some others. Given the frequent development of weakness of labor, we recommend the following option for labor stimulation in women with premature labor. The woman in labor is prescribed 30 g of castor oil, a cleansing enema. After cleansing the intestines, quinine is prescribed at 0.05 g every 15 minutes 4 times, then oxytocin intramuscularly at 0.2 ml every 30 minutes 5 times. At the same time, cardiac monitoring is carried out to monitor the dynamics of labor and the condition of the fetus. In case of a sharp increase in labor activity, labor stimulation at any stage can be cancelled or the intervals between the use of medications can be increased.

In premature births, threatening and incipient fetal hypoxia is observed in every fifth woman in labor, in connection with which special attention must be paid to intranatal protection of the fetus during labor, since approximately 90% of women deliver through the natural birth canal. The frequency of cesarean section in premature pregnancy is on average about 10%. The main indication for abdominal delivery in this case is premature detachment of a normally located placenta, as well as placenta previa, prolapse of the umbilical cord loops, and insolvency of the uterine scar. Surgical delivery should be resorted to mainly for vital indications on the part of the mother, less often - for indications on the part of the fetus.

Analyzing the features of the course of premature birth, we can come to the conclusion that in order to preserve pregnancy, it is necessary, first of all, to use more effective medications, especially beta-adrenergic agonists. Eden, Sokol, Sorokin et al., suggesting a test with stimulation of the nipples of the mammary glands of pregnant women in order to predict the possibility of premature birth, simultaneously indicate that this test reduces by 50% the need for outpatient monitoring of the nature of uterine contractile activity in pregnant women at high risk of miscarriage. Laros, Kitterman, Heilbron et al., when studying the outcomes of pregnancy and childbirth in pregnant women who received beta-adrenergic agonists and delivered fetuses with very low birth weight (< 1500 g), showed different effects on a newborn with low birth weight of isoxsuprine, ritodrine, terbutaline and their combinations. It was established that the lowest birth trauma was observed with the use of ritodrine compared to terbutaline.

Many domestic and foreign obstetricians provide data on the high effectiveness of these drugs.

Currently, there are mainly three groups of drugs used to maintain pregnancy: magnesium sulfate solution, prostaglandin synthetase inhibitors and beta-adrenergic drugs.

The following medications are recommended. Magnesium sulfate in the form of a 25% solution, 10 ml intramuscularly 2-3 times a day; metacin, in case of a pronounced threat, was initially prescribed intravenously - 2 ml of a 0.1% solution in 500 ml of a 5% glucose solution or isotonic sodium chloride solution at an administration rate of 20 drops/min. Subsequently, metacin is prescribed intramuscularly at 1 ml of a 0.1% solution 2-3 times a day. In case of a less pronounced threat, metacin is immediately prescribed intramuscularly or in the form of tablets of 0.002 g 2-3 times a day.

Partusisten is used intravenously by drip at a dose of 0.5 mg in 500 ml of 5% glucose solution or isotonic sodium chloride solution. The rate of administration is 10-20 drops/min. Intravenous administration of the drug is continued for 6-8 hours. Upon achieving a stable tocolytic effect, partusisten tablets are then prescribed at 5 mg 6 times a day. If necessary, intravenous tocolysis is repeated. Partusisten should not be used in women in the early stages of pregnancy. If the drug is poorly tolerated, we do not cancel it, but administer it intravaginally or subcutaneously, and in this case a more pronounced tocolytic effect is noted, probably due to the delay in the onset of beta-adrenergic receptor desensitization. In order to prevent premature birth, it is proposed to use a special device for subcutaneous administration of tocolytics. A tendency to return to the use of magnesium sulfate in small doses has been noted. It has been shown that magnesium sulfate does not have a negative effect on the condition and development of the fetus and is an effective remedy in the treatment of fetoplacental insufficiency.

Alupent should initially be administered intravenously by drip - 1 ml of 0.05% solution in 500 ml of 5% glucose solution or isotonic sodium chloride solution at an injection rate of 10-20 drops/min. After achieving a stable tocolytic effect (after 6-8 hours), Alupent is administered intramuscularly 1 ml 4 times a day.

The N-anticholinergic spasmolytin is prescribed in the form of a powder of 0.1 g 3-4 times a day; isadrine - in tablets of 0.0025 - 0.005 g 3-6 times a day.

Given the widespread use in the treatment of threatened and incipient premature labor, special attention should be paid to the indications and contraindications for the use of beta-adrenergic agonists.

Indications for the use of beta-adrenergic agonists are:

• the need to inhibit the contractile activity of the myometrium for the prevention and treatment of late miscarriages and premature births;
• regulation of labor activity during pathological labor - excessive labor activity, threatening rupture of the uterus;
• prevention of complications after surgery for isthmic-cervical insufficiency, myomecumina and similar surgical interventions during pregnancy;
• treatment of placental insufficiency.

Some authors suggest including treatment of late toxicosis of pregnancy in the indications.

A prerequisite for the use of beta-adrenergic agonists is the absence of contraindications (hypertension in pregnancy, hypertension with blood pressure of 20/12 kPa or 150/90 mm Hg, heart defects - congenital and rheumatic, insulin-dependent diabetes mellitus, hyperthyroidism, placental abruption or uterine bleeding, dilation of the cervix by more than 4 cm, high temperature during labor, fetal malformations and stillbirth, chorioamnionitis). Important are the integrity of the amniotic sac, the opening of the cervix of no more than 4 cm in primiparous women and no more than 3 cm in multiparous women. The duration of contractions is no more than 30 sec. The frequency of contractions is no more than every 10 minutes. The duration of regular contractions is no more than 2-3 hours.

When using beta-adrenomimetics, it is necessary to take into account possible minor side effects that are characteristic of the pharmacodynamics of these drugs. The appearance of tachycardia up to 120-130 beats/min upon administration of the drug and further increase in heart rate require discontinuation of the drug; to prevent this side effect, it is advisable to use isoptin (finoptin, verapamil) simultaneously with the beta-adrenomimetic, 1 tablet 1-2 times orally.

The increase in maternal blood pressure should not exceed 20 mm Hg from the initial level, and diastolic pressure should not decrease by less than 20 mm Hg. Therefore, the administration of the drug, especially intravenously, to a pregnant woman must be carried out on her side, at approximately 15°.

Sometimes the mother has hyperglycemia. In addition, when the drug is administered intravenously, it is necessary to measure blood pressure, pulse rate and breathing pattern every 10-20 minutes. If blood pressure, in particular diastolic, drops by 20 mm Hg or less, and systolic - decreases by 30 mm or more, appropriate drug correction is required.

A study of various pharmacological agents showed that the absolute and relative effectiveness of treatment with the indicated agents when using magnesium sulfate and metacin was noted in 54.4%. It should be noted that the treatment is considered absolutely effective if the pregnancy was prolonged to 36 weeks, and relatively - if the pregnancy was not maintained to 36 weeks, but prolonged by 10 days or more. Partusisten was effective in 95.5%, alupent - in 83.5% with intravenous and 72% with intramuscular administration; alupent in combination with spasmolitin - in 78%, metacin in 78 %, isadrin - in 86% and isadrin in combination with spasmolitin - in 91.3%.

The modified Baumgarten and Tsan-Troschinsky indices that we use are convenient criteria for assessing the degree of threat of termination of pregnancy, which allows for a more objective comparison of the results of preservation therapy with different treatment methods.

It is important to note that the combination of the beta-adrenergic agonist alupent with spasmolytin in recommended dosages in the treatment of threatened and incipient premature labor increases the effectiveness of tocolytic therapy by 20% compared to the use of a single beta-adrenergic agonist and by 30% compared to the use of magnesium sulfate and metacin.

These substances improve the condition of the fetus by changing the hormonal function of the placenta and fetus, i.e. the entire fetoplacental complex; after their use, the excretion of estrogens increases - estrone, estradiol and estriol, which simultaneously causes an increase in the tocolytic effect. It follows that beta-adrenergic agonists are the most effective tocolytic agents that can be used in the second half of pregnancy without the risk of their harmful effect on the fetus. Preparations of this group have a beneficial effect on the uteroplacental circulation, promoting the formation of pulmonary surfactant and faster maturation of the fetal lungs, which is an effective method of preventing hyaline membranes if the child is born prematurely, and, in addition, these substances contribute to an increase in fetal weight. Their use in the first half of pregnancy is contraindicated due to the possibility of embryotoxic effects.

The use of thyroxine for the growth of the fetus, placenta and newborn in the early neonatal period should be considered promising. At present, experiments on rats have shown that when the mother has a reduced level of thyroxine, the brain cells of the fetus are damaged and therefore thyroid hormones are necessary for the normal development of the mammalian brain. At the same time, the placenta is impassable for these substances. In humans, these processes have not been sufficiently studied, but it is known that thyroid hormones are already determined in a 7-week embryo, and in the 9-10th week of pregnancy - in the brain of the fetus and these hormones are well synthesized by the fetus. Thyroxine is determined in the fetus and in later stages of pregnancy. Extensive experimental studies have shown that the introduction of thyroxine (T4) in a dose of 10 mcg by injection to pregnant rats _resulted in a 10-fold increase in the concentration of thyroxine in the mother's blood, which remained elevated for 12 hours and returned to the basal level after 24 hours. At the same time, no increase in the T4 level was noted in the fetus _. The introduction of T4 _in doses of 10, 20 and 50 mcg/day resulted in an increase in the weight of the fetus by 20% and the weight of the placenta by 14.6%. In addition, in the postnatal period, faster growth of the newborn was noted. The half-life of T4 _in the mother's blood plasma is about 6 hours, i.e. less than in non-pregnant animals. Hypothyroidism leads to fetal hypotrophy with impaired maturation of the nervous system and, accordingly, to a delay in brain development. It has been established that thyroid hormones do not pass through the placenta from mother to fetus. However, modern studies indicate some passage of these hormones to the fetus in hypothyroidism. Most likely, secondary changes in metabolism in a mother with hypothyroidism (even without passage of hormones through the placenta to the fetus) can affect fetal development. In the neonatal period, hyperthyroidism was not detected even in cases where large doses of thyroxine were given. An increase in the mass of the fetus and placenta can occur indirectly through an increase in the amount of nutrients that pass to the fetus under these conditions or through an increase in the formation of placental hormones, as was shown with the introduction of estrogens. This increase in fetal mass is not associated with fluid retention or various forms of fetal tissue hyperplasia in the uterus. T ₄ stimulates postnatal growth of newborns, as has been shown with treatment with antiestrogens. Therefore, in pregnant women with a high risk of premature birth, prophylactic use of thyroxine in small doses and other substances that increase the weight of the fetus and placenta may be a promising direction for further reducing perinatal morbidity and mortality.

Treatment of threatened labor with progesterone

According to the literature, progesterone is considered the most common and proven treatment for threatened miscarriage. The experiment studied the effect of progesterone on labor, activation of hypothalamic large-cell neurons, and expression of oxytocin mRNA in the uterus of rats at the end of pregnancy. It was found that intramuscular administration of progesterone on the 20th day of pregnancy delayed the onset of labor by 28.2 hours compared to control animals, which, however, occurred despite the low content of oxytocin mRNA in the uterus and decreased activation of large-cell neurons in the hypothalamus during labor. Modern studies by a number of clinicians show that the use of progesterone in doses from 250 mg per week to 500 and even 1000 mg per week can prevent premature labor.

In clinical practice, in case of threatened miscarriage, progesterone was and is still prescribed intramuscularly daily at 0.01 g (1 ml of 1% solution) for 10-15 days per course of treatment. However, its effect does not manifest itself immediately, but after 7-15 days, and therefore it is difficult to determine what caused the result: the use of progesterone, long-term treatment in a hospital setting, or the use of other drugs. Treatment of threatened miscarriage with progesterone at 0.01 g once a day intramuscularly for 10-15 days leads to a decrease in the increased contractile activity of the uterus, but only in isolated cases allows it to be normalized. It is ineffective for normalizing the increased contractile function of the uterus. The low efficiency of progesterone treatment in the indicated dosage of a pronounced threat of miscarriage shows that the treatment of this pathology should be differentiated taking into account the stage of the pregnancy pathology.

In cases of severe threat of miscarriage, especially in combination with functional isthmic-cervical insufficiency, progesterone treatment was administered in doses significantly exceeding the usual ones. This was based on studies showing that the daily requirement of a pregnant woman's body for progesterone is at least 0.05 g, and given that progesterone introduced from outside is quickly excreted from the body, this dose should be increased even more. The drug successfully used in the treatment of threatened premature labor was oxyprogesterone capronate, containing 0.125 g of the substance in 1 ml. Doses of the corpus luteum hormone in its various preparations prescribed for a course of treatment range from 2 to 12 g and higher with a drug dosage per injection from 0.125 g to 0.25 g every 5-7 days. Treatment is continued until the 36th week of pregnancy with different intervals between repeated administrations of the drug. The effectiveness of treatment fluctuates between 80 and 93%. Literature data show that until recently, firm guidelines have not been defined on a number of issues related to treatment with high doses of progesterone. This concerns the selection of a contingent of pregnant women for treatment, the choice of optimal doses of drugs, etc.

In case of threat of termination against the background of habitual miscarriage with phenomena of functional isthmic-cervical insufficiency in the early stages of pregnancy, along with the use of progesterone in the above dosages, human chorionic gonadotropin (pregnyl) is prescribed simultaneously in the early stages of pregnancy at an initial dose of 10,000 IU and then 5,000 IU twice a week up to 12 weeks of pregnancy and then up to 16 weeks of pregnancy 5,000 IU once a week.

The results of the study of remote results did not reveal any adverse effects of this treatment on organogenesis in the fetus. As is known, there were indications in the literature about the virilizing effect of gestagens on the female fetus, however, there are drugs such as allylestrenol (gestanone), which do not have such an effect. Modern literature data did not reveal any negative effects of progesterone on fetal development.

Treatment should be started with intramuscular injection of 1 ml of 12.5% oxyprogesterone capronate solution (0.125 g) 2 times a week, and if external hysterography establishes increased uterine activity, this dose is doubled (up to 500 mg per week). It is important to emphasize one of the essential signs of the effectiveness of oxyprogesterone capronate treatment - after 3-4 injections of the drug, a more or less pronounced narrowing of the internal os, which was previously sometimes freely passable for the examining finger, is noted. Along with this, an increase in turgor of the cervical tissues is noted. Inpatient treatment should be carried out, especially in combination with functional isthmic-cervical insufficiency for up to 3 weeks, and then - outpatient with the appointment of the drug at a dose of 250 mg (2 ml of a 12.5% solution) 1 time per week until 36 weeks of pregnancy.

It was not possible to establish a relationship between the effectiveness of treatment and the gestational age at the start of treatment.

The labor proceeded without any special features, the birth of children and their subsequent development with the use of oxyprogesterone capronate - without deviations from the norm.

Treatment of threatened labor with metacin

Clinical and experimental studies have shown that at 25-34 weeks of pregnancy it is advisable to use metacin at 0.002 g 2 to 4 times a day. Hysterography has shown that complete normalization of increased uterine contractility is noted at the initial stages of threatened miscarriage and a positive effect, unlike hormonal drugs, is observed already in the first 15 minutes after taking metacin powder. It should be noted that in pregnant women with pronounced signs of threatened miscarriage, metacin in the specified doses (0.002 g) should be used more often - up to 6 times a day or supplemented with subcutaneous or intramuscular injections of 1 ml of a 0.1% solution in the morning and evening. The use of metacin allows to reduce the duration of treatment of patients with threatened miscarriage compared to the results of hormonal treatment.

Treatment of threatened and ongoing labor with prostaglandin synthesis inhibitors

Prostaglandin synthesis inhibitors can directly regulate the frequency and amplitude of uterine contractions. It is advisable to use one of the most effective prostaglandin synthesis inhibitors - indomethacin, which is most often indicated for increased concentrations of endogenous prostaglandins in the body, which is clinically most often manifested by high amplitude and frequency of uterine contractions. Indomethacin completely suppresses uterine contractions for 1-8 hours.

Method of application of indomethacinin case of threatened and started premature labor the following: the therapeutic dose of indomethacin should not exceed 0.125 g, with 1 tablet (pill or better capsule 0.025 g) of indomethacin administered orally at first, and the second dose is administered in the form of two rectal suppositories of 0.05 g. If there is no effect after 1-2 hours, it is again recommended to prescribe 0.1 g of indomethacin in the form of two suppositories of 0.05 g, and after 2-4 hours - 0.1 g rectally and 0.025 g orally. At the beginning of treatment, the dose of indomethacin should be 0.2-0.25 g / day and not exceed 0.3 g. Indomethacin after oral administration is quickly and almost completely absorbed from the intestine, 90% of it binds to plasma proteins.

Indomethacin is available in a prolonged-release dosage form of 75 mg (indomethacin retard, metindol retard).

The drug is an effective means for treating the threat of termination of pregnancy, is well tolerated by pregnant women, side effects are minimal, does not have a negative effect on the subsequent course of labor, the condition of the fetus and newborn. Remote results of child development are good.

Indomethacin is not recommended for use in gastrointestinal, renal and CNS diseases, as well as in infections. Dyspeptic symptoms of the drug can be reduced if indomethacin is used during meals or in the form of suppositories containing 10 mg of the drug. It has been established that phenibut at a dose of 50 mg / kg and phenazepam at a dose of 2.5 mg / kg intravenously have a depressing effect on uterine contractility in non-pregnant and pregnant rabbits. In addition, it has been shown that phenibut (150 mg / kg) and phenazepam (3 mg / kg) do not cause a negative effect on fetal development in rats. Clinical studies of phenibut and phenazepam as gravidoprotectors in the case of threatened miscarriage are recommended. When phenibut is administered at a dose of 100 mg / kg, contractions cease. Phenibut is recommended to be taken in the first 2 days at 0.75 mg/kg every 8 hours, on the 3rd day at 0.5 mg/kg every 8 hours for 3-5 days. After the course of treatment, a break of 5-7 days is taken. A more effective effect of phenibut is manifested when combined with phenepam as a result of mutual enhancement of the uterolytic and fetoprotective effect. Thus, in case of pronounced threat and psychomotor agitation, it is recommended to use phenibut at 0.5 mg/kg together with phenepam at 0.001 (1 mg) 3 times a day for 5-7 days, followed by a break of 3-5 days. In case of emergency tocolysis, phenibut is used intramuscularly at 1-2 ml of 0.1% ampoule solution.

Phenibut and phenazepam have a physiological GABA-ergic mechanism of inhibition of uterine contractility. GABA-positive substances: phenibut - a drug with nootropic and antihypoxic action and phenazepam - a tranquilizer with a GABA-ergic mechanism of action are effective protectors of pregnancy.

Other drugs that have recently been introduced into use (magnesium sulfate, calcium antagonists, oxytocin antagonists, diazoxide) have not yet been the subject of randomized controlled trials.

Surgical treatment of isthmic-cervical insufficiency in pregnant women suffering from preterm pregnancy

The main method of treating isthmic-cervical insufficiency of traumatic origin is surgical. In 1954, V. Shirodkar first proposed to strengthen the internal sphincter of the cervix with a circular suture of nylon thread. In subsequent years, a number of modifications of this operation were proposed.

The most favorable time for this operation is considered to be the period of pregnancy from 12 to 20 weeks, since the effectiveness of the surgical intervention at these times will be higher, since the opening of the cervix will not yet reach a significant degree. In addition, the advisability of surgical treatment at these stages of pregnancy is confirmed by data on the increase in the sensitivity of the uterus to irritation of the cervix with an increase in the period of pregnancy. In the case of a smooth course of pregnancy, it is recommended to remove the suture at 36-38 weeks, and in the event of contractions and bloody discharge - to resort to this immediately. However, the Shirodkar operation and its modifications eliminate isthmic-cervical insufficiency only temporarily. In subsequent pregnancies, repeated surgical treatment is usually required.

Preparation for surgery. In the evening, on the eve of the surgery, the pregnant woman is given a cleansing enema. At night, luminal (0.1 g) and goscholfen (0.025 g) are prescribed orally. The surgery is performed under viadril or thiopental anesthesia with the pregnant woman in a position with her pelvis elevated.

Technique of the operation. Both lips of the cervix exposed with spoon-shaped mirrors are grasped with Muso forceps and pulled downwards. At the border of the transition of the mucous membrane of the anterior vaginal fornix to the cervix, a median longitudinal incision of 0.5 cm in the vaginal fornix is made with a scalpel. Then the cervix is moved upward and forward. At the border of the transition of the mucous membrane of the posterior vaginal fornix to the cervix, a second longitudinal incision of 0.5 cm in the vaginal fornix is made, parallel to the first one. A blunt-ended needle is used to pass a 0.5 cm wide Letilan tape under the vaginal wall sequentially through the anterior and posterior incisions.

The free ends of the tape, brought out through the anterior incision, are tightened along the catheter inserted behind the internal os with a diameter of 0.5 cm. The ends of the tape are tied with two knots. To facilitate the removal of the suture, the ends of the tape are 3 cm long. This method of surgery does not cause complications during the latter - rupture of the membranes, bleeding, cutting of the tape. Pregnant women in the postoperative period must observe strict bed rest for the first 3 days, being in a position with an elevated pelvis; an antibiotic is administered intramuscularly for 2 days and simultaneously therapy (progesterone, metacin, beta-adrenergic agonists, magnesium sulfate) is carried out for 10 days, aimed at reducing uterine excitability. In the postoperative period, pregnant women are allowed to get out of bed on the 4th day, discharge from the hospital - on the 10th day.

In all pregnant women, such modification of the operation in the postoperative period does not give fever, bedsores, tissue compaction, as well as ischemia and edema of the cervix. Removal of the tape occurs without any difficulties.

Thus, treatment of premature pregnancy due to isthmic-cervical insufficiency by means of the modified Shirodkar operation contributes to the birth of live children in 85% of women. Unfavorable outcome of the operation is more often observed in pregnant women with prolapse of the amniotic sac. In such cases, Scheeier, Lam, Bartolucci, Katz developed a new technique of operation to reduce the frequency of failure in case of prolapse of the amniotic sac - they perform maximum filling of the urinary bladder and, under fluorothane anesthesia, 250 ml of isotonic sodium chloride solution is administered using a Foley catheter, after which the Shirodkar operation is performed with subsequent administration of magnesium sulfate and ritodrine in the postoperative period. Success was noted in all pregnant women.

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