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Clinical guidelines. Untimely discharge of amniotic fluid. Normally at the time of delivery under the influence of hormones. Comparison of active and expectant tactics

Almost the entire period of bearing the baby, the expectant mother is worried about the condition of the baby. Of course, many of the experiences are contrived, but there are also real ones. A woman suffers from toxicosis, constantly puts her hand to her tummy to find out if the baby is moving or not, anxiously awaits the test results, controls the tone of the uterus, anxiously awaits an ultrasound scan to look at the future baby and hear the cherished words that the baby is developing fine.

Among the possible reasons for concern, there is a rather significant one, however, alas, few women know about it. Based on the statistics of the Obstetrics Center, about 20% of all cases of loss of a baby are due to premature rupture of the fetal bladder.

However, there is still a chance to diagnose and prevent this threat at an early stage. The rupture of the fetal bladder is not a sentence, and the baby can develop normally in the future.

What is the fetal membrane?

During the entire waiting period for the baby, it is a safe place that protects the baby from discomfort. You can even call the fetal membrane a small world, where a future baby is gradually formed from a tiny embryo. And so that for nine months nothing could disturb the peace of the baby, nature "invented" such a rather reliable protection for him.

The membranes are an excellent barrier that can keep your baby safe from infections and bacteria. Many, having seen the transparency of the shells on ultrasound, are not sure that they are capable of something significant, but in fact they are dense and have high strength.

The fetal membranes save the baby from the influence of external environmental factors thanks to 3 layers:

  • the outer layer, which is formed from tissue that covers the inner cavity of the uterus. It is considered the most durable, since it must guarantee special rigidity to the shells so that under the influence of negative conditions the developing fetus cannot deform;
  • the middle layer includes the cells of the embryo;
  • the inner layer is elastic and delicate. By its structure, it resembles a barely perceptible veil that carefully envelops the fruit.

The safety and integrity of the fetal bladder is the key to the purity and normal growth and development of the baby... And if at least one layer is violated, the likelihood of infection and the occurrence of all kinds of complications during pregnancy increases.

Which women are at risk?

Among women in a position, experts single out expectant mothers who must monitor the emerging symptoms of rupture of membranes during pregnancy. This group includes:

  • women with multiple pregnancies;
  • expectant mothers who have any infectious disease that can thin the membranes of the bladder;
  • women with;
  • expectant mothers who do not feel well during pregnancy, feel pain in the lower back, aching abdominal pain and sensations that are similar to labor pains;

  • women who had a rupture of the membranes during the first birth;
  • pregnant women who smoke cigarettes;
  • women with low weight or the presence of vitamin deficiency;
  • Pregnant women who are injured or concussed during a fall. In this case, the woman may feel good, but the shells may have tears or small cracks.

Treatment of ruptured membranes

Alas, rupture of the membranes can occur even in women whose pregnancy proceeds without any complications. According to statistics, it occurs in 1 in 10 women in a position. At the same time, doctors cannot understand why this is happening.

Even one small crack can be enough for bacteria to easily penetrate into the uterine cavity. At the same time, the future baby has no protection, so the fetus becomes infected, and with it the uterine cavity, as a result of which the baby may die, and the mother receives dangerous purulent complications.

Early rupture of the membranes during premature pregnancy requires immediate medical attention. The method of treatment in this case is influenced by the duration of pregnancy and the infection itself.

If the gap was detected early and the probability of infection is close to zero, then the doctor will prescribe antibiotics, steroids and tocolytics to the woman, which will help to prolong the bearing of the baby. In this case, it is imperative to adhere to all the doctor's recommendations and not miss an ultrasound scan, which allows you to observe the unborn baby.

If a gap was detected in the last months of pregnancy, but there is no risk of infection of the baby, experts prescribe a treatment that is focused on normalizing the course of pregnancy. The woman is left in a hospital, where conditions of sterility are created, since her condition requires special control. Thermometry and warning are carried out, blood tests are taken, the contents of the vagina are examined for bacteria, the well-being of the fetus is monitored to prevent the development of hypoxia and circulatory disorders between the uterus and the placenta.

If an infection occurs during the rupture, doctors resort to stimulating premature birth. A woman is prescribed antibiotics, then a certain hormonal background is formed and labor arousal is carried out.

Rupture of the membranes (membranes) before labor is called spontaneous rupture of the membranes before regular contractions of the uterus begin. This condition is often referred to as "premature rupture of membranes", but this definition can lead to some confusion, as the term "premature" is more associated with the definition of preterm birth and low birth weight. The term "before labor" is more accurate and more reflective of the obstetric situation.

In case of rupture of membranes before the onset of labor at gestational age up to the 37th week, the term “rupture of membranes before the onset of preterm labor” is used, and starting from the 37th week of pregnancy - “rupture of the membranes before the onset of urgent labor”. Despite a certain convention, separate consideration and assessment of these conditions is important from the point of view of both the prognosis and the management of pregnancy.

It is important to be sure whether the membranes of the membranes have actually ruptured. The diagnosis of rupture of the membranes is often not in doubt with the spontaneous discharge of a significant amount of light amniotic fluid and their subsequent leakage from the vagina. In some cases, it is difficult to distinguish amniotic fluid from other liquid secretions, such as vaginal discharge or urine. If the membranes have ruptured recently, you can collect some fluid in an appropriate container by asking the woman to take a certain position, or get amniotic fluid from the posterior fornix of the vagina when examining in the mirrors.

The nitrazine test appears to be the most widely used for differential diagnosis of amniotic fluid from other fluid, but false positives are almost 15% for this test. In this regard, additional tests are of certain importance; as a rule, this is a microscopic examination of the cells of the amniotic fluid. Compared to nitrazine, a cytological test is much less likely to be accompanied by false-positive results, although a higher rate of false-negative results appears.

If the rupture of the membranes occurred several hours ago and most of the fluid has already flowed out of the vagina, then it can be difficult or even impossible to establish or confirm the diagnosis with any degree of reliability. In these circumstances, much depends on the thoroughness of the history taking. It is necessary to obtain information as to when and under what circumstances the liquid was discharged, whether something like this happened before, approximately how much liquid was released, what color, odor this liquid had, and whether there were any other peculiarities. The last question can be clarified by explaining that we are talking, for example, about the presence of an admixture of white or gray flakes in the liquid. Ultrasound examination confirming the presence of oligohydramnios is a reliable criterion for the diagnosis of rupture of membranes of the membranes before labor, if there is an indication of a sudden outflow of fluid from the vagina.

It is still unclear whether a high rupture of the membranes of the fetal bladder (discharge of posterior waters) should be considered from a clinical point of view separately from the rupture of the membranes in the lower pole of the fetal bladder. There is little information about how these two types of rupture of the membranes differ from each other and whether this is the basis for using different methods of pregnancy management. In the absence of such data, a case-based approach may be the only viable option.

Vaginal examination

It is likely that vaginal examination can cause or increase the risk of intrauterine infection, although no controlled comparisons have been made to confirm or reject this opinion. The only justification for conducting a manual vaginal examination would be the urgent need to obtain information that would be useful to determine the tactics of further management of pregnancy or childbirth, which could not be obtained in a less invasive way. There appears to be little benefit either from manual vaginal examination or from speculum examination. An examination in the mirrors allows you to identify the accumulation of amniotic fluid in the posterior fornix of the vagina, to take a fluid sample for a nitrazine test, microscopic examination or to determine phosphatidylglycerol; in addition, it allows you to take crops for culture microbiological research, in particular in order to identify group B streptococci. The value of these data is undoubtedly greater than those that can be obtained only with manual vaginal examination. However, examination in mirrors, obviously, causes more inconvenience for a pregnant woman in comparison with manual examination and hardly makes it possible to obtain the necessary amount of useful information if a considerable time has passed after the rupture of the membranes of the membranes. Unfortunately, no controlled clinical trials have been conducted to determine the comparative efficacy of manual vaginal examinations and speculum examinations.

Infection risk assessment

If the membranes of the fetal bladder rupture before the onset of labor, it is necessary to conduct an examination aimed at the timely identification of signs of the development of an intrauterine infection. Symptoms of infection may include maternal fever and fetal tachycardia. If any of these symptoms is accompanied by an increase in the tone of the uterus and discharge from the genital tract with a putrid odor, the diagnosis becomes certain. Meanwhile, uterine tension and odorless discharge are late signs of infection.

The earliest signs of intra-amniotic infection include fetal tachycardia and a slight increase in the mother's body temperature, but both of these symptoms are not pathoa-gomonic. A few years ago, there was a hope that the determination of C-reactive protein in the mother's blood might provide more precise criteria for the diagnosis of intrauterine infection, but these hopes did not materialize, and the value of C-reactive protein determination has never been studied in controlled clinical trials. ...

Despite the fact that intrauterine infection in a patient may precede rupture of the membranes, the main danger is the development of an ascending infection from the vagina. In this regard, data on the presence of pathogenic microorganisms in the vagina, in particular those responsible for the occurrence of most infectious complications in the fetus, such as group B streptococcus, Escherichia coli, bacterioids, may be useful. Antibiotics prescribed during childbirth in a patient who is a carrier of group B streptococcus reduce the incidence of sepsis and neonatal death from infectious complications.

Among populations with a high prevalence of carriage of group B streptococcus, either screening of all pregnant women for this infection is indicated, or a course of antibiotic therapy for all pregnant women. Immediate collection of cultures for culture bacteriological research in case of rupture of membranes of the membranes before labor should be an obligatory part of the tactics of managing pregnant women in this obstetric situation.

In order to determine the degree of risk of developing an intrauterine infection, some have recommended amniocentesis, especially in premature pregnancy. However, as the main danger is ascending infection, amniocentesis to obtain culture data directly from the amniotic cavity appears to be ineffective. In addition, amniocentesis has a number of limitations and complications, such as a high failure rate of amnional fluid extraction in low water, invasiveness and risk of the procedure itself, and, most importantly, a weak correlation between the results of amniotic fluid examination and the development of infection in the fetus. Microorganisms can not be detected in all patients who had clinical signs of the development of intrauterine infection, and in some cases they can be detected in the absence of any signs of this infection. On the basis of some studies, it was believed that the detection of leukocytes in the amniotic fluid is more prognostically significant for the diagnosis of an infectious lesion than the detection of the microorganisms themselves, but these data have not been further confirmed.

Rupture of membranes of the membranes in premature pregnancy

Complications

The most serious and most frequent consequence of rupture of membranes of the membranes during premature pregnancy is the development of premature birth. Moreover, the risk of complications is directly related to the duration of pregnancy and the degree of maturity of the fetus. With severe fetal immaturity, perinatal outcomes entirely depend on the duration of pregnancy after opening the fetal bladder. With sufficient maturity of the fetus, the management tactics remain practically the same as that applied after rupture of the membranes of the membranes during full-term pregnancy. The rupture of membranes of the membranes during gestation between these two boundaries (approximately between the 26th and 34th weeks of gestation) is a major problem in obstetric practice.

The second most dangerous complication is the development of an infectious lesion of the fetus due to an ascending intrauterine infection. At the same time, the risk of this lesion is the higher, the lower the gestational age of the fetus, probably due to the relative immaturity of the mechanisms of antibacterial protection of the fetus, as well as due to the underdevelopment of the bacteriostatic properties of the amniotic fluid during premature pregnancy.

In addition to these two main complications of rupture of membranes of the fetal bladder during premature pregnancy, there are others, which include: prolapse of the umbilical cord, compression of the umbilical cord due to the lack of a sufficient amount of amniotic fluid, the development of lung hypoplasia and various deformities of the fetal skeleton associated with its prolonged development against the background of oligohydramnios as well as placental abruption. In this case, it is necessary to remember about possible biomechanical problems in childbirth due to underdevelopment of the lower segment of the uterus with low water, which often leads to the need for surgical delivery,

Obstetric care before labor begins

Premature birth is the most significant complication of rupture of membranes of the membranes during premature pregnancy. In this regard, in the absence of a specialized department of intensive perinatal and neonatal care in this hospital, the patient should be transferred to medical centers, where such assistance can be provided in full.

In case of premature pregnancy, most patients enter childbirth within a few hours or (less often) days after the moment of rupture of the membranes of the membranes. However, for some, childbirth develops much later. Among the latter, the diagnosis of rupture of the membranes of the fetal bladder may be erroneous; in addition, there is a possibility of spontaneous stopping of the outflow of fluid and its subsequent accumulation in the amniotic cavity in full, however, this is rather an exception to the rule than a regularity. Amniotic fluid replacement allows a patient to be released for outpatient follow-up with some degree of safety, but this has never been studied in controlled clinical trials.

As soon as certain data are obtained about the well-being of the fetus and the mother, the main efforts in the first days after rupture of the membranes of the membranes should be directed to the timely diagnosis of the initial signs of infection or the development of contractile activity of the uterus. For this purpose, it is necessary to constantly measure the body temperature and pulse of the mother, assess the fetal heart rate and the contractile activity of the uterus. It is still unclear whether white blood cell count and C-reactive protein level in a blood test are additional valuable indicators. Variations in leukocyte counts and C-reactive protein levels can be significant, especially with labor advancing or corticosteroid administration.

Antibiotics

Controlled clinical trials have never addressed the question of whether antibiotics should be prescribed immediately in these circumstances. Both clinical prudence and evidence from studies comparing the efficacy of antibiotics for the treatment of intrauterine infection during childbirth and their administration immediately after delivery provide more support for initiating antibiotic treatment as soon as possible after the clinical diagnosis of intrauterine infection is established.

Tocolytics

Several small, controlled clinical trials have evaluated the effectiveness of tocolytic administration in the development of preterm labor after rupture of the membranes of the membranes. No statistically significant differences in the studied criteria could be obtained in comparison with the control group, in which tocolytics were not used. These criteria included the length of time to delivery, the incidence of re-development of labor, the incidence of preterm birth, newborn body weight, the amount of perinatal mortality, and the incidence of respiratory diseases in newborns.

There is no evidence that the use of tocolytics improves perinatal performance, and furthermore, they are not harmless. They should be used only in cases where delaying the moment of delivery allows you to use other methods that reliably improve the outcome of pregnancy in the presence of a premature fetus, such as prescribing corticosteroids or transferring a woman in labor to a perinatal center equipped with everything necessary for the management of premature birth and the provision of specialized care for the premature baby. newborn.

The development of decelerations of heart contractions during preterm labor is observed much more often if the rupture of the membranes of the membranes occurs before the onset of labor. Most fetal heart rhythm disturbances are due to compression of the umbilical cord, which, in turn, occurs due to the lack of protective effect of amniotic fluid during uterine contractions. The relative benefits and harms of using amnioinfusion in labor with rupture of membranes before the onset of preterm labor has not yet been adequately studied. Available publications suggest that amnioinfusion in the first stage of labor leads to a statistically significant decrease in the number of weak, moderate and strong decelerations and an increase in the pH value of blood from the umbilical artery after delivery. Assessing the ratio of positive and negative effects, comparing the benefits and potential complications of this method justifies further research in this direction.

Rupture of membranes of the membranes during full-term pregnancy

The rupture of membranes of the fetal bladder before the onset of labor is observed in 6-19% of all urgent deliveries. In most women, labor develops soon after rupture of the membranes and the outflow of amniotic fluid. In almost 70% of women in a similar situation, delivery occurs within 24 hours, and in almost 90% - within 48 hours, while with striking consistency in 2-5% of pregnant women labor does not begin even after 72 hours, and in almost the same the proportion of pregnant women does not come into childbirth even after 7 days. Perhaps the reason for this is the insufficient production of prostaglandins or the failure of the process of biosynthesis of prostanoids, as a result of which not only a reduced possibility of the development of spontaneous labor is observed, but also a slowdown in the rate of cervical dilatation against the background of labor induction by oxytocin is also often noted.

Infectious lesions of the mother and newborn are the main complications. Publications of the fifties showed that rupture of membranes of the membranes before the onset of term labor is accompanied by a high level of maternal and perinatal mortality. Unsurprisingly, immediate induction of labor is recommended to reduce this risk.

The prognosis for the mother and fetus with such a complication of full-term pregnancy as rupture of membranes of the membranes before the onset of labor has changed significantly in the second half of the last century. Long-term data, some of which include birth outcomes over twenty-five years ago, can hardly be used to analyze modern obstetric tactics. The death of mothers at that time was mainly associated with a long and severe course of intrauterine infection, which, from the modern point of view, was often accompanied by inadequate antibiotic therapy. In clinical studies of recent years, when the membranes of the fetal bladder rupture before the onset of term delivery, maternal mortality is almost never found, perinatal mortality due to prenatal infection is also becoming a rarity. Along with the change in the prognosis for the mother and the child, it is becoming increasingly important to discuss the complications of surgical delivery after induction of labor in the light of the greater safety of expectant tactics.

One of the main issues in the tactics of managing a full-term pregnancy in case of rupture of membranes is: it is necessary to immediately start induction of labor or to allow labor to develop independently. Another question: what drug, oxytocin or prostaglandins, is it more effective to induce labor, if the decision on its use is made. The patient must be fully informed about the effectiveness of the possible methods of managing her pregnancy in order to be able to choose the one that she most desires.

Oxytocin induction of labor

Induction of labor by prescribing oxytocin, compared with expectant management in the period close to the term of labor (when the risk of insufficient maturity of the fetal lungs is left behind), reduces the risk of developing infectious complications in the mother (chorioamnionitis and endometritis) and is accompanied by a tendency to reduce the risk of developing infectious complications in newborn. Most of the controlled clinical trials that examined the incidence of morbidity due to the development of neonatal infection, nevertheless, had methodological errors. In this regard, it is possible that the beneficial effect of induction of labor by oxytocin on the incidence of neonatal infections is somewhat exaggerated. However, it was found that the induction of labor with oxytocin reduces the frequency of transfer of newborns to the intensive care unit.

The induction of labor by oxytocin is accompanied by a small, although statistically unreliable, but still higher, level of operative deliveries or caesarean sections. In this case, epidural analgesia and internal monitoring of the fetal heart rate are more commonly used.

Labor induction by prostaglandins

Induction of labor by prostaglandins in combination with or without oxytocin in case of rupture of membranes of the fetal bladder against the background of full-term pregnancy indicates the same effectiveness of these methods in comparison with the action of oxytocin alone. When compared with expectant tactics, induction by prostaglandins is accompanied by a lower risk of infection in the mother and a tendency towards a decrease in the incidence of infectious neonates, which was combined with a decrease in the frequency of transfers of newborns to intensive care units. There were no significant differences in the frequency of surgical interventions during vaginal delivery or in the frequency of cesarean sections. The use of analgesia or anesthesia, as well as side complications of drug use in the mother (diarrhea), are more common in women after induction of labor with prostaglandins compared with expectant management.

Comparison of the effectiveness of using oxytocin and prostaglandins

Clinical studies on the direct comparison of the outcomes of induced labor using oxytocin and prostaglandins (in combination with or without oxytocin) suggest that there are no significant differences in the effectiveness of these drugs in terms of the frequency of surgical interventions for vaginal delivery or frequency. cesarean sections. The use of prostaglandins decreases the frequency of use of epidural analgesia, but there were no differences in the overall frequency of use of analgesia or anesthesia during labor.

With the use of prostaglandins, the incidence of infectious complications in the mother increased, which may be due to the higher relative frequency of vaginal examinations. There is also evidence of an increase in the incidence of infection in the neonatal period, especially if it is known that a woman is inoculated with group B streptococcus (although the study of neonatal infection was carried out only in one of 18 controlled blind studies according to the criteria of the treatment used and the duration of the anhydrous gap, the negative effect in regarding this complication with this method of induction of labor, perhaps, is not so great). Transfer of newborns to intensive care units is generally more common with prostaglandins.

Scientific evidence, therefore, gives reason to believe that if induction is considered necessary in full-term pregnancy immediately after rupture of the membranes of the membranes, then it is better to carry out it using oxytocin. Compared with the use of prostaglandins, this method is accompanied by greater advantages and fewer complications.

Antibiotic prophylaxis

The appointment of appropriate antibiotics for rupture of membranes of the fetal bladder against the background of full-term pregnancy, of course, is indicated in cases where there are clinical signs of infection. Moreover, the place of antibiotics in the absence of symptoms of inflammation is not so obvious. In the 1960s, two controlled clinical trials were conducted on the effect of prophylactic antibiotic prescriptions, but these studies used antibiotic regimens that were not subsequently used. Although at that time it was not possible to show any effect of prophylactic antibiotics on the incidence of infectious diseases of the fetus or newborn, a statistically significant decrease in the incidence of infectious diseases of mothers in the postpartum period was revealed. In some health centers, this has led to the introduction of a routine postpartum antibiotic for all women with prolonged anhydrous spacing. Since this tactic has not been studied in randomized clinical trials, it would be important to consider which women without obvious signs of infection actually need antibiotic prophylaxis in the postpartum period.

One small clinical randomized trial investigated the question of whether antibiotics should be prophylactically given to newborns with prolonged dry labor. While some evidence has been obtained to support the idea that prophylactic antibiotics reduce the risk of infectious diseases in newborns, the results of this study need to be confirmed using a larger sample and a blinded method of evaluating the results.

Premature rupture is called the rupture of the amniotic membranes before the onset of labor, regardless of the gestational age, clinically manifested by the rupture of amniotic fluid. The population frequency of premature rupture of membranes (PRPM) is about 12%, however, in the structure of causes of premature birth, this pathology reaches 35-60%.

Etiology

Epidemiological research data indicate a variety of etiological factors of PRPO. There was revealed a relationship between PRPO with high parity, as well as preterm birth, recurrent miscarriage and a history of PRPO. The reason for the rupture of the membranes can be acquired or congenital forms of collagen deficiency (Ehlers-Danlos syndrome), imbalance of trace elements, including copper deficiency, which is a cofactor of matrix metalloproteinases (MMPs) and their inhibitors that affect the properties of the components of the connective tissue matrix of the fetal membranes. One of the factors contributing to damage to the membranes is oxidative stress associated with the production of reactive oxygen radicals by neutrophils and macrophages when they are involved in the process of microbial elimination, which cause local collagen degeneration, thinning and rupture of the membranes by activating MMP, and hypochlorous acid directly destroys collagen Type I, which is the structural basis of the membranes.

The role of placental abruption both in the induction of preterm labor and PRPO associated with the release of a large amount of prostaglandins, high uterotonic activity of thrombin and the presence of a nutrient medium for the growth of bacterial microflora was confirmed.

Over the past years, a well-grounded opinion has been established that the leading cause of PRPO is ascending infection of the amniotic membranes and microbial invasion of the amniotic cavity, the frequency of which during the first days after PRPO ranges from 37.9% to 58.5%. Numerous studies confirm the ascending route of transmission of infection, indicating the identity of the strains of microorganisms isolated from fetuses and in the urogenital tract of pregnant women. Among the infectious agents that are the direct cause of the ascending inflammatory process, prevail Escherichia coli, Staphilococcus aureus, Streptococcus faecalis, Streptococcus group B, Bacteroides fragilis, Corinobacter, Campylobacter, Clebsiella pneumoniae... A number of authors emphasize the role of anaerobic bacteria in the etiology of ascending infection, in particular Fusobacterium. Common representatives of microbial associations include Ureaplasma urealiticum, Mycoplasma hominis and Gardnerella vaginalis... However, the widespread occurrence of urogenital mycoplasmas, the erased clinical picture and diagnostic difficulties make it difficult to determine the role of these microorganisms in the etiology and pathogenesis of preterm labor and PRPO. The risk of PRPO increases significantly in the presence of isthmico-cervical insufficiency and prolapse of the fetal bladder due to impaired barrier function of the cervical canal, as well as shortening of the cervix less than 2.5 cm.

The degree of damage to the amniotic membranes is associated with the type of pathogen and its ability to activate MMP. The close relationship between an increase in the concentration of most MMPs (MMP-1, 7, 8, and 9) and a decrease in tissue specific inhibitor of metalloproteinases (TIMMP-1) in amniotic fluid with intraamnial bacterial invasion and placental abruption is not questioned. The mechanism of bacterial action on the membranes is mediated, on the one hand, by the stimulating effect of microbial proteinases and endotoxins on the expression of MMPs and the production of proinflammatory cytokines (IL-2, IL-6, IL-12, tumor necrosis factor), followed by local degradation of the collagen of the membranes, and on the other hand, an increase in bacterial phospholipases of prostaglandin synthesis with the development of myometrial hypertonicity and an increase in intrauterine pressure.

Thus, the leading role in the etiology and pathogenesis of PRPO in premature pregnancy is played by factors that stimulate apoptosis, destruction of phospholipids and collagen degradation of the connective tissue matrix of the amniotic membranes, mainly associated with the action of infection.

Perinatal and postnatal outcomes

More than 30% of peri- and neonatal morbidity and mortality in preterm birth are associated with pregnancies complicated by PROM. In the structure of morbidity and mortality, the main place is occupied by the syndrome of respiratory disorders (SDR) (up to 54%), intrauterine infection and hypoxic brain damage, in the form of periventricular leukomalacia (PVL) of the brain (up to 30.2%) and intraventricular hemorrhage (IVH) ...

Respiratory Disorders Syndrome

SDR of newborns is a set of pathological processes that form in the prenatal and early neonatal periods and are manifested by an increase in symptoms of respiratory failure against the background of suppression of vital body functions. The main reason for the development of SDD is surfactant deficiency or inactivation. Predisposing factors include intrauterine infections (IUI) and perinatal hypoxia. The severity and frequency of SDR implementation progressively decreases with increasing gestational age and maturity of the fetus and is about 65% before 30 weeks of gestation, 35% at 31-32 weeks, 20% at 33-34 weeks, 5% at 35-36 weeks and less than 1% - at 37 weeks or more.

It is believed that intra-amnial infection associated with a long anhydrous gap promotes fetal lung maturation and reduces the incidence of respiratory disorders. In an experiment on sheep, it was shown that intra-amnial administration of endotoxin E. coli significantly increases the concentration of lipids and proteins of the surfactant, when using betamethasone, and increases the air volume of the lungs 2-3 times. However, clinical studies have not confirmed the hypothesis about the stimulating effect of PRPO on the maturity of the lung tissue, and it requires further study.

Congenital fetal infection

The most significant risk factor for an unfavorable peri- and postnatal outcome, aggravating the course of pneumopathies and pathology of the central nervous system, is IUI. This concept unites infectious processes (pneumonia, sepsis, etc.), which are caused by various pathogens that have penetrated the fetus from an infected mother. For premature babies undergoing long-term inpatient treatment, nosocomial infections are also of great danger. Stillbirth and early neonatal mortality in IUI is associated with the severity of the inflammatory process, depending on the gestational age of the fetus, the type and virulence of the pathogen, protective factors of amniotic fluid and nonspecific immunity, and according to the literature, it is 14.9-16.8% and 5.3 -27.4%, respectively.

The predominant clinical form of neonatal infection in PRPO, ranging from 42% to 80%, is pneumonia, usually associated with aspiration of infected waters, often combined with signs of necrotizing enterocolitis. The progression of foci of primary inflammation in the lungs or intestines of the fetus makes it possible to develop metastatic purulent meningitis, peritonitis, as well as intrauterine sepsis, the frequency of which with PRPO up to 32 weeks ranges from 3% to 28%. The main risk factors for neonatal sepsis are gestational age and the development of chorioamnionitis (CA).

The influence of IUI on the long-term outcome is not unambiguous. There is evidence indicating the risk of developing cerebral palsy associated with intra-amnial infection and gestational age of the fetus. At the same time, a number of studies have not confirmed a reliable connection between IUI and impaired mental and psychomotor development in children.

Posthypoxic brain damage

The main hypoxic brain injuries in premature infants include PVL and IVH.

PVL is a coagulative necrosis of white matter, followed by degeneration of astrocytes with proliferation of microglia, due to hypoxemia and cerebral ischemia. With extremely low and very low birth weight, the pathological frequency of PVL varies from 25% to 75%, and in vivo- from 5% to 15%. Complications of PVL in the form of destruction of afferent fibers of the thalamocortical and corticocortical pathways negatively affect the formation of interneuronal associative connections, white matter myelination processes and can cause the development of cognitive impairments. A prognostic criterion for the development of PVL and distant neurological disorders is a significant increase in the concentration of pro-inflammatory cytokines in the amniotic fluid and umbilical cord blood of newborns, including IL-6, which confirms the hypothesis of cytokine-mediated brain damage and indirectly indicates the role of IUI in the development of PVL.

IVH in the structure of perinatal mortality in premature newborns is from 8.5% to 25%. The main risk factors for their development include acute fetal hypoxia and CA. The incidence of severe IVH decreases with increasing gestational age and with delivery by caesarean section. Several studies support the role of glucocorticoid therapy in reducing the risk of IVH and PVL. At the same time, the development of reliably effective methods for the prevention of IVH is still in the field of attention of scientific research.

Infectious complications of pregnant women, parturient women and parturient women in premature pregnancy complicated by PRPO

Prolongation of preterm pregnancy with PRPO poses a significant risk for the mother, primarily due to the addition of an infectious process and the development of purulent-septic complications (GSO), in most cases of CA, postpartum endomyometritis and, less often, sepsis. Risk factors for the implementation of GSO include surgical intrauterine interventions, chronic urogenital infection, rupture of the membranes against the background of prolapse of the fetal bladder, as well as antenatal fetal death.

The risk of purulent septic infections (PSI) of the mother has a significant relationship with the duration of the anhydrous interval and the gestational age. The total frequency of realized CA in premature pregnancy complicated by PRPO is 13-74%, and in case of rupture of membranes up to 28 weeks 28.8-33%. However, according to our data, based on the analysis of the course of 912 pregnancies complicated by PROM at 22-34 weeks, the frequency of CA up to 31 weeks of gestation and the duration of the latency period of more than 2 days - the time required for effective exposure of glucocorticoids in order to prevent SDR - is reliably does not change. At the same time, with prolongation of pregnancy after the 31st week, the risk of CA realization increases. Thus, in our opinion, the optimal approach for the management of pregnancies complicated by PRPO should be considered the maximum prolongation of pregnancy until the 31st week of pregnancy, and in case of rupture of the membranes at a later date, only for the period of glucocorticoid prophylaxis of SDR. At the same time, it should be remembered that the issue of the possibility of prolonged prolongation of pregnancy in PRPO should be resolved individually, taking into account the possibilities of obstetric and, to a greater extent, neonatal services, as well as risk factors for HSI in a pregnant woman.

Predictive criteria for infectious complications and CA include oligohydramnios and indirect signs of placental inflammation. According to our data, with a normal volume of amniotic fluid with an amniotic fluid index of more than 8 cm, the frequency of CA realization is 4.9%. At the same time, with a decrease in the amniotic fluid index less than 5 cm, the risk of CA development doubles.

Postpartum morbidity in puerperas is manifested by endometritis in 3.5-11.1% of cases. The incidence of sepsis according to different authors reaches 1.7%, and the maternal mortality associated with the management of premature pregnancy complicated by PRPO is 0.85%.

Clinical and laboratory diagnostics and prognostic criteria for chorioamnionitis and systemic inflammatory response

Early detection of CA signs presents certain difficulties due to changes in the body's reactivity during pregnancy and the tendency to form latent forms of inflammatory diseases. Typical symptoms of CA are fever, maternal and fetal tachycardia, a specific smell of amniotic fluid, or abnormal vaginal discharge. Unfortunately, hyperthermia up to 38 ° C and above is often the only indicator of CA development, and the values ​​of traditional markers of the inflammatory process - the number of leukocytes and segmented neutrophils - during pregnancy have wide variability, are dependent on medications, including steroids and antibiotics, and, according to data some studies have low diagnostic value. Of the routine clinical and laboratory criteria for CA, hyperthermia more than 37.5 ° C, leukocytosis more than 17 × 10 9 / l and a stab shift of the leukocyte formula up to 10% or more have a high diagnostic value. The development of these symptoms should be used as indications for delivery on the part of the mother when prolonging a premature pregnancy complicated by PRPO.

The greatest difficulties are presented by early diagnosis of septic conditions. In recent years, great progress has been made in the study and use of blood plasma proteins involved in the so-called acute phase response - a set of systemic and local reactions of the body to tissue damage caused by various reasons (trauma, infection, inflammation, malignant neoplasm, etc.). Determination of the concentration of C-reactive protein (CRP) is widely used as a prognostic criterion of infection in PRPO, an increase in which in the blood serum of more than 800 ng / ml is an indicator of intra-amnial infection and closely correlates with funisitis, histologically and clinically pronounced CA with a sensitivity of 92% and specificity. 96%. In addition, the concentration of CRP in the amniotic fluid may indirectly reflect the condition of the fetus, since it is produced by hepatocytes and does not cross the placenta. At the same time, a number of authors consider CRP to be of low specificity, and an increase in its concentration is possible during the physiological course of pregnancy.

Among the biomarkers of sepsis, procalcitonin (PCT), a precursor of the hormone calcitonin, produced by several types of cells in various organs under the influence of bacterial endotoxins and proinflammatory cytokines, has the highest diagnostic accuracy. In case of systemic infection, its level increases within 6-12 hours and can serve as an early diagnostic criterion for sepsis and systemic inflammatory response. Viral infections, local infections, allergic conditions, autoimmune diseases and transplant rejection reactions usually do not lead to an increase in PCT concentration, and its high levels indicate a bacterial infection with a systemic inflammatory reaction. According to our data, the average PCT levels in the normal course of pregnancy and realized CA are 0.29 and 0.72 ng / ml (p< 0,05) соответственно. При септическом шоке концентрация ПКТ достигает 4,7-11,32 нг/мл.

The course of pregnancy against the background of a long anhydrous period is not limited only to the GSO. It has been proven that pregnancy against the background of intra-amnial infection increases the incidence of placental abruption to 4.0-6.3%, which exceeds the general population risk by 3-4 times. The probability of detachment with oligohydramnios increases by 7 times, with the implementation of CA - 9 times, and during labor arousal with oxytocin against the background of an infectious process, its frequency increases to 58.3%.

Obstetric tactics of management of premature pregnancy complicated by PRPO

Of the factors affecting the outcome of pregnancy, the method of delivery is important, the choice of which is difficult due to the deep prematurity of the fetus and, in some cases, questionable viability. The most difficult issue is the ratio of the risk of infection in the case of prolonged pregnancy, with the risk of prematurity due to active management of labor.

Independent prognostic factors that determine the duration of the latency period are the gestational age at the time of the outflow of water, intra-amnial infection and the severity of the inflammatory reaction, the volume of amniotic fluid and the clinical and histological variant of rupture of the amniotic membranes. However, the minimum gestational age of the fetus, at which it is advisable to prolong pregnancy, and the optimal duration of the latency period depending on the duration of pregnancy in PRPO have not been determined to date. So, with PRPO up to 22 weeks, termination of pregnancy is recommended due to the nonviability of the fetus and the extremely high risk of intrauterine infection. Outpouring of water at 22-25 weeks is also associated with an unfavorable prognosis for the fetus and a high frequency of mother's GSO, which suggests a wait-and-see approach with bacteriological monitoring of infection and dynamic control of the volume of amniotic fluid without tocolytic therapy. With PRPO after 25 weeks, according to most clinicians, tactics should be aimed at prolonging pregnancy with the prevention of SDR with glucocorticoids and antibiotic therapy. A number of authors concluded that prolongation of pregnancy is advisable until 28 weeks of gestation, since delivery at a later date does not improve the perinatal outcome and increases the number of infectious complications, including CA, up to 77%. This assumption is confirmed by the data on the absence of a significant decrease in the incidence of SDR, IVH, necrotizing colitis in newborns and neonatal mortality with prolongation of pregnancy after 30 weeks. According to other researchers, prolongation to 34 weeks helps to reduce both perinatal mortality and the severity of neonatal pathology. With PRPO at a later date, expectant management does not reduce neonatal morbidity and mortality, but significantly increases the risk of neonatal sepsis.

Indications for early termination of a premature pregnancy complicated by PRPO, regardless of gestational age, are deterioration of the functional state of a viable fetus, the development of CA and other complications that threaten the mother's life. For a long time, obstetrics has been dominated by the tactics of delivering a preterm pregnancy complicated by PRPO through the vaginal birth canal with labor activation by intravenous administration of oxytocin and / or oxytocin in combination with prostaglandins. Alternative approaches may be induction with prostaglandin gels E2 or misoprostol. Currently, with the introduction of effective antibacterial drugs, detoxification methods of treatment and hypoallergenic suture material, the possibilities for operative delivery have expanded. When deciding on a caesarean section, much attention is paid to the gestational age, presentation of the fetus and its functional state. In newborns weighing less than 1500 g during natural childbirth, the frequency of PVK and IVH of the 3rd degree, PVL, is significantly higher than in case of caesarean section performed before the onset of labor, which is probably associated with mechanical pressure on the fetal head during contractions. However, the overall incidence of IVH during vaginal delivery and delivery by caesarean section in the first stage of labor is the same. At the same time, in children after cesarean section, pathology of the respiratory system, including SDR and bronchopulmonary dysplasia, develops significantly more often. In the II trimester of pregnancy, with cephalic presentation of the fetus, vaginal delivery is preferable, since the population survival rate up to 28 weeks does not depend on the method of delivery. From 28 weeks of gestation, the role of caesarean section in reducing neonatal survival and mortality progressively increases.

Special attention should be paid to the operation against the background of CA and generalized inflammatory reaction. With the development of CA during pregnancy and the onset of labor, delivery by caesarean section is indicated, followed by a complex of therapeutic and prophylactic measures. In some cases, including the detection of thrombosed veins and myometrial abscesses. the traditional approach is hysterectomy. However, the question of the volume of surgical intervention in CA has not yet been determined.

Summarizing the above data, it should be emphasized that at present, conservative management of labor is carried out in two directions: 1) non-intervention in PRPO up to 24-25 weeks, in which a spontaneous onset of labor is expected; 2) conservative tactics for PRPO at 25 weeks or more against the background of antibacterial, glucocorticoid and tocolytic therapy to stop the premature rupture and provide sufficient exposure time to corticosteroids in order to stimulate fetal lung maturation.

After confirming the diagnosis of premature rupture of amniotic fluid, the pregnancy management plan is finally adopted taking into account the gestational age and the degree of risk of complications for the mother and fetus after a consultative discussion of obstetricians and neonatologists with the pregnant woman and her relatives. When deciding to prolong pregnancy, dynamic monitoring of the state of the fetus, bacteriological cultures of urine and detachable genital tract is carried out with determination of the sensitivity of the pathogen to antibiotics, careful monitoring of the possible development of complications, including placental abruption and thromboembolic complications. With cervical cerclage, the infected suture material is a source of additional intra-amnial seeding, and removal of the sutures is advisable. In order to avoid infectious complications and reduce the latency period, one should refrain from vaginal examination. Drug therapy includes the mandatory prevention of SDS with glucocorticoids, antibiotic therapy and a short course of tocolytic therapy in order to stop labor and transport the pregnant woman to a specialized hospital.

Thus, the presented literature data show that the course of a premature pregnancy complicated by PROM is associated with a high risk of infectious complications of the mother and fetus and a number of concomitant pathologies. Obstetric tactics of pregnancy management primarily depend on the gestational age, the condition of the fetus, the severity of the infectious process and the presence of concomitant extragenital pathology and complications of pregnancy. Optimization of management algorithms for pregnant women with PRPO, development of methods for the prevention of perinatal losses and neonatal morbidity remain one of the priority tasks of perinatology.

Literature

  1. V. I. Kulakov, L. E. Murashko Premature birth. Moscow: Medicine, 2002.
  2. Makarov O.V., Kozlov P.V., Nikolaev N.N. Modern perinatal approaches in the management of premature pregnancy complicated by premature rupture of the membranes // Bulletin of the Russian State Medical University. 2006. No. 4. S. 64-67.
  3. Makarov O.V., Kozlov P.V., Dulenkov A.B., Taktashova R.N., Vorontsova Yu. N. Ways of preventing perinatal morbidity and mortality in premature pregnancy // Bulletin of the Russian State Medical University. 2009. No. 4, p. 70-75.
  4. Makarov O.V., Kozlov P.V. Septic shock in preterm labor // Midwife. and gyno. 2009. No. 3, p. 20-26.
  5. Sidelnikova V.M. Habitual pregnancy loss. Moscow: Medicine, 2002.304 p.
  6. Practice bulletins No. 139: premature rupture of membranes // Obstet Gynecol. 2013. Vol. 122, No. 4. P. 918-930.
  7. Al-Kadri H. M., Bamuhair S. S., Johani S. M., Al-Buriki N. A. et al. Maternal and neonatal risk factors for early-onset group B streptococcal disease: a case control study // Int J Womens Health. 2013. Vol. 29, No. 5. P. 729-735.
  8. Ananth C. V., Oyelese Y., Srinivas N. Preterm premature rupture of membranes, intrauterine infection, and oligohydramnios: risk factors for placental abruption // Obstet. Gynecol. 2004. Vol. 104, No. 1. P. 71-77.
  9. Azizia M. M., Irvine L. M., Coker M. The role of C-reactive protein in modern obstetric and gynecological practice // Acta. Obstet. Gynecol. Scand. 2006. Vol. 85, No. 4. P. 394-401.
  10. Baud O., Fontaine R. H., Olivier P., Maury L. Premature rupture of membranes: pathophysiology of neurological impact // Arch Pediatr. 2007. Vol. 14, Suppl 1. S. 49-53.
  11. Biggio J. R. Jr., Ramsey P. S., Cliver S. P., Lyon M. D. Midtrimester amniotic matrix fluid metalloproteinase-8 levels above the 90 th percentile are a marker for subsequent preterm premature rupture of membranes // Amer. J. Obstet. Gynecol. 2005. Vol. 192, No. 1. P. 109-113.
  12. Chan G. J., Lee A. C., Baqui A. H., Tan J. et al. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis // PLoS Med. 2013. Vol. 10, No. 8. P. 1001502.
  13. Frenette P., Dodds L., Armson B. A., Jangaard K. Preterm prelabour rupture of membranes: effect of latency on neonatal and maternal outcomes // J Obstet Gynaecol Can. 2013. Vol. 35, No. 8. P. 710-717.
  14. Hong J. S., Park K. H., Noh J. H., Suh Y. H. Cervical length and the risk of microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes // J Korean Med Sci. 2007. Vol. 22, No. 4. P. 713-717.
  15. Jobe A. H., Newnham J. P., Willet K. E., Sly P. Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs // Amer. J. Obstet. Gynecol. 2000. Vol. 182. P. 401-408.
  16. Ismail A. Q, Lahiri S. Management of prelabour rupture of membranes // J Perinat Med. 2013. Vol. 1, no. 41 (6). P. 647-649.
  17. Kent A., Lomas F., Hurrion E., Dahlstrom J. E. Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants // J. Pediatr. Child Health. 2005. Vol. 41, No. 4. P. 186-190.
  18. Kenyon S., Boulvain M., Neilson J. P. Antibiotics for preterm rupture of membranes // Cochrane Database Syst Rev. 2013. Vol. 2, No. 12. CD001058.
  19. Li W., Unlugedik E., Bocking A. D. The role of prostaglandins in the mechanism of lipopolysaccharide-induced proMMP 9 secretion from human placenta and fetal membrane cells // Biol Reprod. 2007. Vol. 76, No. 4. P. 654-659.
  20. Medina T. M., Hill D. A. Preterm premature rupture of membranes: diagnosis and management // Amer. Fam. Physician. 2006. Vol. 73, No. 4. P. 659-664.
  21. Menon R., Fortunato S. J. Infection and the role of inflammation in preterm premature rupture of the membranes // Best. Pract. Res. Clin. Obstet. Gynaecol. 2007. Vol. 21, No. 3. P. 467-478.
  22. Morales W. J., Schorr S., Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: A placebo-controlled, double-blind study // Amer. J. Obstet. Gynecol. 1994. Vol. 171. P. 345-349.
  23. Moretti S., Volante E., Gramellini D., Kaihura C., Bevilacqua G. Alteration of the amniotic fluid and neonatal outcome // Acta Biomed. Ateneo. Parmense. 2004. Vol. 75, No. 1. P. 71-75.
  24. Munz W., Seufert R., Stopfkuchen H. Perinatal outcome of premature infants weighing less than 1500 g // Z. Geburtsh. Neonatol. 2005. Vol. 209, No. 1. P. 29-33.
  25. Oludag T., Gode F., Caglayan E., Saatli B. et al. Value of maternal procalcitonin levels for predicting subclinical intra-amniotic infection in preterm premature rupture of membranes // J Obstet Gynaecol. 2013. Vol. ten.
  26. Polam S., Koons A., Anwar M. Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants // Arch. Pediatr. Adolesc. Med. 2005. Vol. 159, No. 11. P. 1032-1035.
  27. Puthiyachirakkal M., Lemerand K., Kumar D., Moore R. et al. Thrombin weakens the amnion extracellular matrix directly rather than through protease activated receptors // Placenta. 2013. Vol. 34, no. 10. P. 924-931.
  28. Richardson B. S., Wakim E., Dasilva O. Preterm histologic chorioamnionitis: Impact on cord gas and pH values ​​and neonatal outcome // Amer. J. Obstet. Gynecol. 2006. Vol. 2.P. 212-214.
  29. Salem S. Y., Sheiner E., Zmora E. Risk factors for early neonatal sepsis // Arch. Gynecol. Obstet. 2006. Vol. 21. P. 78-81.
  30. Sereepapong W., Limpongsanurak S., Triratanachat S. The role of maternal serum C-reactive protein and white blood cell count in the prediction of chorioamnionitis in women with premature rupture of membranes // J. Med. Assoc. Thai. 2001. Vol. 84, Suppl. 1. S. 360-366.
  31. Storme L., Rakza T., Houfflin-Debarge V. Consequences of premature rupture of the membranes in the perinatal lung // Arch Pediatr. 2007. Vol. 14, No. Suppl 1. S. 42-48.
  32. Van der Ham D. P., Nijhuis J. G., Mol B. W. Induction of labor versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks // BMC Pregnancy Childbirth. 2007. Vol. 6, No. 7. P. 11.
  33. Vermillion S., Soper D., Newman R. B. Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy // Amer. J. Obstet. Gynecol. 2007. Vol. 27. P. 589-593.

V. N. Kuzmin, Doctor of Medical Sciences, Professor

GBOU VO MGMSU them. A. I. Evdokimova, Moscow

Perinatal outcomes with premature rupture of membranes / V. N. Kuzmin

For citation: Attending physician No. 3/2018; Issue page numbers: 34-38

Tags: premature pregnancy, complications, obstetric tactics

Premature rupture of the membranes is especially dangerous in the early stages. But even with a full-term pregnancy, it can become disastrous for the child, if the mother hesitates with hospitalization, the onset of labor is delayed. Let's talk about what causes the premature rupture of the membranes and what to do if water begins to drain.

Most often, the causes of this pathology remain unclear. However, it is believed that ischemic-cervical insufficiency (ICI) and various infections of the genital tract can become provocateurs. With the first problem, the cervix begins to shorten and open much earlier than delivery, which leads to a gradual movement of the presenting part of the child's body downward, as a result of which the fetal bladder is under pressure and breaks. The rupture can also be facilitated by pathogenic bacteria, viruses, which, figuratively speaking, corrode the membrane of the bladder, provoking premature rupture of amniotic fluid in a pregnant woman.

How can you avoid this? The answer immediately suggests itself - it is necessary to prevent infectious diseases, as well as any injuries of the cervix - the most common cause of isthmic-cervical insufficiency. However, sometimes this does not help when the causes of cervical weakness lie in hormonal imbalance.

But the development of ICI can be prevented if you visit a gynecologist on time. It is also mandatory to measure the length of the cervix using a vaginal probe for ultrasound. This is the only way to find out its exact length. If it is less than 3 cm, then the woman can be offered 2 options: installing a pessary ring on the cervix or suturing on the cervix - this reduces the risk that a premature rupture of the amniotic fluid will occur, childbirth will begin prematurely, and the baby will die. Gynecologists pay special attention to those women who have already been diagnosed with ICI in the past, or who have lost amniotic fluid at an early stage.

What to do if amniotic fluid starts to leak? First you need to make sure that this is it. This is best done in your doctor's office using a test that takes a swab from your vagina. If the leak is confirmed, further tactics are largely determined by the gestational age. With a period of less than 22-24 weeks, unfortunately, it is most often recommended to induce premature birth, since bearing a child even up to 30-32 weeks will be accompanied by a huge risk of infection of the membranes - and this is detrimental to the fetus and threatens blood poisoning for the mother.

If the gestation period is more than 28-30 weeks, doctors prescribe a course of antibiotic therapy to prevent infection, and they carry out treatment like the prevention of premature birth (reduce the tone of the uterus, etc.). All this is carried out in a hospital under the close supervision of a doctor. Pregnancy is carried out to the maximum possible term to give the child and his lungs to mature.

If the fetal bladder has ruptured a month or less before childbirth, then doctors often decide on urgent delivery. If the contractions do not start on their own, the cervix is ​​long and closed, special drug preparation is carried out, after which the onset of labor is stimulated.