Premature birth: treatment

In our country, threatening premature birth is recognized as an indication for hospitalization.

In the case of the possibility of prolonging pregnancy, treatment should be directed, on the one hand, to suppress the contractile activity of the uterus, and on the other hand, to the induction of ripening of the fetal lung tissue (in the period of 28-34 weeks of pregnancy). In addition, it is necessary to correct the pathological process, which caused premature birth.

To stop tonic and regular contractions of the uterus use complex treatment and individual selection of therapy, taking into account the obstetrical situation.

[1], [2]

Non-drug treatment of preterm labor

The preferential position on the left side, which helps restore blood flow, reduce uterine contractility and normalize the tone of the uterus in 50% of pregnant women with threatening premature birth. According to other studies, prolonged bed rest, used as the only method of treatment, does not give positive results.

There is no conclusive evidence of the benefits of hydration (enhanced drinking regimen, infusion therapy) used to normalize fetoplacental blood flow to prevent premature birth.

Drug treatment of preterm labor

In the presence of conditions, tocolytic therapy is preferred. Currently, β-adrenomimetics remain drugs of choice, and magnesium sulfate, the second-line preparation, that allows rapid and effective reduction of contractile activity of myometrium.

β-adrenomimetics can be used to delay delivery during the prophylaxis of respiratory distress syndrome with glucocorticoids or, if necessary, transfer of a woman in childbirth to the perinatal center, where it is possible to provide highly qualified care for premature newborns.

Among β-adrenomimetics, hexoprenaline, salbutamol, fenoterol are used.

Mechanism of action: stimulation of β2-adrenergic receptors of smooth muscle fibers of the uterus, which causes an increase in the content of cyclic adenosine monophosphate and, as a consequence, a decrease in the concentration of calcium ions in the cytoplasm of myometrium cells. The contractility of the smooth muscle of the uterus is reduced.

Indications and necessary conditions for the appointment of β-adrenomimetics

• Therapy of menacing and beginning premature births.
• Whole bladder (exception is the situation when leakage of amniotic fluid in the absence of chorioamnionitis, when it is necessary to delay labor for 48 hours to prevent the respiratory distress syndrome of the fetus using glucocorticoids).
• Opening of the uterine throat no more than 4 cm (otherwise the therapy is ineffective).
• Live fruit without developmental abnormalities.
• Absence of contraindications for the use of β-adrenomimetics.

Contraindications

Extragenital pathology of the mother:

• cardiovascular diseases (stenosis of the aortic estuary, myocarditis, tachyarrhythmias, congenital and acquired heart defects, cardiac rhythm disturbances);
• hyperthyroidism;
• angle-closure glaucoma;
• insulin dependent diabetes mellitus.

Obstetric contraindications:

• chorioamnionitis (risk of generalization of infection);
• abruption of normal or low-lying placenta (risk of development of the uterus of Kuveler);
• suspicion of incompetence of the uterine cicatrix (risk of a painless rupture of the uterus along the scar);
• state, when the prolongation of pregnancy is impractical (eclampsia, pre-eclampsia).

Contraindications from the fetus:

• developmental disparities incompatible with life;
• antenatal death;
• distress, not associated with hypertension of the uterus;
• pronounced fetal tachycardia, associated with the features of the conduction system of the heart.

Side effects

• On the part of the mother's body: hypotension, palpitation, sweating, tremor, anxiety, dizziness, headache, nausea, vota, hyperglycemia, arrhythmia, myocardial ischemia, pulmonary edema.
• From fetus / newborn: hyperglycemia, hyperinsulinemia after birth as a result of inefficient tocolysis and, as a consequence, hypoglycemia; hypokalemia, hypocalcemia, intestinal atony, acidosis. When using tablets in medium doses, side effects are not expressed. The drugs used.
• Hexoprenaline. In menacing and beginning premature births, it is advisable to start with an intravenous drip of the drug at a rate of 0.3 μg per minute, i.е. 1 ampoule (5 ml) is dissolved in 400 ml of 0.9% sodium chloride solution and injected / drip, starting from 8 drops per minute and gradually increasing the dose to reduce the contractile activity of the uterus. The average speed of administration is 15-20 drops per minute, the duration of administration is 6-12 hours. For 15-20 minutes before the end of intravenous administration, oral administration of the drug in a dose of 0.5 mg (1 tablet) 4-6 times a day for 14 days.
• Salbutamol. Intravenous tocolysis: the rate of intravenous administration of the drug is 10 μg / min, then gradually, under the control of tolerance, it is increased with a 10-minute interval. The maximum permissible speed is 45 mcg / min. Orally, the drug is taken 2-4 mg 4-6 times a day for 14 days.
• Fenoterol. For intravenous tocolysis, 2 ampoules of 0.5 mg of phenoterol are dissolved in 400 ml of a 0.9% solution of sodium chloride (1 ml - 2.5 μg of fenoterol), which is injected iv at a rate of 0.5 μg / min. Every 10-15 minutes the dose to be injected is increased until the effect is achieved. The average injection rate is 16-20 drops per minute, the duration of administration is 6-8 hours. For 20-30 minutes before the end of intravenous administration, the drug is taken inside at a dose of 5 mg (1 tablet) 4-6 times a day for 14 days.

There are data on the non-processability of prolonged oral use of beta-adrenomimetics in connection with receptor desensitization. Some foreign authors recommend using tocolithics within 2-3 days, i.e. During the period when the prevention of distress syndrome of the fetus is carried out.

Intravenous tocolysis is carried out in the position of the woman on the left side under the cardiomonitor control.

During the infusion of any beta-adrenomimetics it is necessary to control:

• the mother's heart rate every 15 minutes;
• arterial pressure of the mother every 15 minutes;
• blood glucose level every 4 hours;
• volume of injected fluid and diuresis;
• the number of electrolytes of blood once a day;
• BH and lung conditions every 4 h;
• condition of the fetus and contractile activity of the uterus.

The frequency of side effects as a manifestation of the selectivity of the action on the receptors depends on the dose of beta-adrenomimetics. When tachycardia, hypotension, the rate of administration of the drug should be reduced, with the appearance of chest pain, the drug should be discontinued.

The use of calcium antagonists (verapamil) for the prevention of side effects of beta-adrenomimetics in a daily dose of 160-240 mg in 4-6 receptions for 20-30 minutes prior to taking a tablet preparation of beta-adrenomimetic is substantiated.

Tocolytic therapy of magnesium sulfate is used in the presence of contraindications to the use of beta-adrenomimetics or when they are intolerant. Magnesium sulfate is an antagonist of calcium ions that participate in the contraction of the smooth muscle fibers of the uterus.

Contraindications:

• violation of intracardiac conduction;
• myasthenia gravis;
• severe heart failure;
• chronic renal failure. Intravenous tocolysis with magnesium preparations.

When premature birth begins, intravenous tocolysis with magnesium sulfate is carried out according to the scheme: 4-6 g of magnesium sulfate is dissolved in 100 ml of 5% glucose solution and injected / in 20-30 minutes. Then go to the maintenance dose of 2 g / h, if necessary, increasing it every hour by 1 g to a maximum dose of 4-5 g / h. The efficiency of tocolysis is 70-90%.

In case of threatening preterm delivery, add a solution of magnesium sulfate intravenously at a rate of 20 ml of 25% solution per 200 ml of 0.9% sodium chloride solution or 5% glucose solution at a rate of 20 drops per minute or 25% solution twice a day for 10 ml.

The tokolytic concentration of the drug in serum is 5.5-7.5 mg% (4-8 meq / l). In most cases this is achieved at a rate of administration of 3-4 g / h.

When carrying out the tocolysis of magnesium sulfate, it is necessary to control:

• arterial pressure;
• the amount of urine (not less than 30 ml / h);
• knee-jerk reflex;
• respiratory rate (not less than 12-14 per minute);
• condition of the fetus and contractile activity of the uterus.

When there are signs of an overdose (oppression of reflexes, reduction in the frequency of respiratory movements) it is necessary:

• stop intravenous administration of magnesium sulfate;
• within 5 minutes intravenously, 10 ml of a 10% solution of calcium gluconate.

Nonsteroidal anti-inflammatory drugs have anti-prostaglandin properties. They are preferred in cases where it is necessary to provide a quick effect for transporting the patient to the perinatal center.

Indomethacin is used in the form of rectal suppositories of 100 mg and then 50 mg every 8 hours for 48 hours. Orally, the drug is used (25 mg every 4-6 hours) with caution because of the ulcerogenic effect on the mucosa of the gastrointestinal tract. The drug has a cumulative effect. If necessary, you can resume taking the drug after a 5-day break.

To reduce the risk of arterial duct narrowing in the fetus and development of malnutrition, it is necessary to determine the volume of amniotic fluid before treatment, and then 48-72 hours after therapy. When detecting malic acid, indomethacin should be discontinued. The use limits the gestational age of less than 32 weeks in pregnant women with menacing or beginning premature births with a normal volume of amniotic fluid.

Contraindications from the fetus are delayed development of the fetus, kidney anomalies, hypochlorism, heart defects involving the pulmonary trunk, the transfusion syndrome with twins.

In our country, a scheme for the use of indomethacin, orally or rectally, has been developed and is being used. In this case, the course dose should not exceed 1000 mg. To remove tonic contractions of the uterus, indomethacin is used according to the scheme: 1st day - 200 mg (50 mg 4 times in tablets or 1 suppository 2 times a day), 2 and 3 days 50 mg 3 times a day , 4-6th day for 50 mg twice a day, 7th and 8th day for 50 mg per night. If it is necessary to reuse, the interval between administration of the drug should be at least 14 days.

Calcium channel blockers - nifedipine - are used to stop labor. Side effects are comparable with those when using magnesium sulfate and less pronounced than in beta-adrenomimetics.

Dosing regimen.

• Scheme 1. 10 mg every 20 minutes 4 times, then 20 mg every 4-8 hours for 24 hours.
• Scheme 2. Initial dose of 30 mg, then maintaining a dose of 20 mg for 90 minutes, then in the presence of the effect of 20 mg every 4-8 hours for 24 hours.
• A maintenance dose of 10 mg every 8 hours (can be used for up to 35 weeks gestation).

Possible complications: hypotension (nausea, headache, sweating, a feeling of heat), decreased uteroplacental and fetal blood flow. Contraindicated appointment with drugs magnesium because of the synergistic effect on the inhibition of muscle contractions, in particular the respiratory muscles (possible respiratory paralysis).

[3], [4], [5], [6],

Antibiotic therapy

The effectiveness of antibiotic therapy for the management of threatening premature birth in the absence of leakage of amniotic fluid and signs of infection has not been proven.

The effectiveness of antibiotic therapy has been proven to prevent premature births in the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, group B Streptococcus and asymptomatic bacteriuria (especially caused by group B Streptococcus) in all women regardless of anamnesis.

The implementation of antibacterial therapy in the detection of bacterial vaginosis, trichomonas vulvovaginitis in patients with risk factors for premature delivery is justified.

With gonococcal infection, cefixime is used at a dose of 400 mg once or twice with ceftriaxone at a dose of 125 mg. In case of allergic reactions to the above preparations, an alternative treatment with spectinomycin is used once at a dose of 2 g IM.

With chlamydial infection, drugs from the macrolide group are used. Assign josamycin 500 mg 3 times a day for 7 days. Another treatment option is erythromycin 500 mg 4 times a day for 7 days, spiramycin 3 million IU 3 times a day, course 7 days.

Bacterial vaginosis is considered as a risk factor for premature birth. Treatment of bacterial vaginosis in pregnant women should be carried out in the second and third trimesters with a high risk of premature birth (history of late termination of pregnancy and premature birth, signs of threat of premature birth).

Bacterial vaginosis is treated in patients with factors predisposing to premature birth, as it increases the risk of premature discharge of amniotic fluid, premature birth, postoperative and postpartum infectious complications.

Abroad, effective intake regimens are taken: metronidazole 500 mg 2 times a day for 7 days, clindamycin 300 mg 2 times a day for 7 days.

Patients with diagnosed bacterial vaginosis without local signs of threatening preterm labor are treated locally as vaginal suppositories with metronidazole (500 mg) for 6 days, vaginal forms of clindamycin (cream, balls) for 7 days. In women with threatening premature births or at risk of developing preterm labor in bacterial vaginosis, drugs are given orally.

Identification of asymptomatic bacteriuria should be a mandatory method of examination and when it is detected (more than 10 ⁵ cfu / ml), treatment is performed for all patients.

When detecting bacteriuria, treatment begins with a 3-day course of antibiotic therapy followed by a monthly culture of urine to monitor the possible recurrence of the disease.

Treatment of patients with group B streptococcus, as well as asymptomatic bacteriuria of streptococcal etiology, is performed taking into account the sensitivity of the isolated microflora, but the protected penicillins are the drugs of choice:

• amoxicillin + clavulanic acid 625 mg twice a day or 375 mg 3 times daily for 3 days;
• cefuroxime 250-500 mg 2-3 times daily for 3 days or ceftibutene 400 mg once a day for 3 days;
• phosphomycin + trometamol 3 g once.

In the absence of effect from 2 consecutive courses of etiotropic antibacterial treatment, suppressive therapy up to delivery and within 2 weeks after delivery is indicated. It is necessary to exclude complicated forms of infections of the urinary tract, especially obstructive uropathy.

Suppressive therapy:

• phosphomycin + trometamol 3 g every 10 days, or
• nitrofurantoin 50-100 mg once a day.

Women with trichomonas infection are treated with metronidazole at a dose of 2 g once orally in the II and III trimesters of pregnancy. The effectiveness of a single dose of 2 g of metronidazole for the elimination of trichomonads has been proven.

[7], [8], [9], [10], [11], [12], [13], [14],

The use of antibiotics in the premature release of amniotic fluid

Premature rupture of membranes occurs in 30-40% of all cases of premature birth.

When rupture of the membranes inevitably occurs infection of the uterine cavity, but the risk of infectious complications in the newborn is higher than that of the mother.

The probability of development of labor during the outflow of amniotic fluid is directly dependent on the gestational age: the shorter the period, the longer the period until the development of regular labor activity (latent period). Within the first day after a premature outflow of water, spontaneous labor begins: in 26% at a fetus weight of 500-1000 g, in 51% at a fetus weight of 1000-2500 g, in 81% at a fruit mass of more than 2500 g.

Extension of the anhydrous gap in the absence of clinical manifestations of infection contributes to the maturation of the fetal lungs. However, prolongation of pregnancy is possible only in the absence of clinical signs of chorioamnionitis, and therefore it is necessary to conduct a thorough examination of the pregnant woman, which includes:

• 3-hour thermometry;
• calculation of heart rate;
• monitoring of clinical blood analysis - leukocytosis, rod-nuclear shift;
• sowing from the cervical canal to Group B streptococci, gonococcus and chlamydia.

In addition, the fetus is monitored for fetal gestational age, assessment of fetometric parameters, detection of intrauterine growth retardation, CTG.

Evaluation of contractile activity of the uterus and the condition of its cervix is very important for determining the further tactics of patient management.

In the absence of signs of infection and labor, prolongation of pregnancy is possible, since active management tactics (induction) worsen perinatal outcomes.

The delivery is indicated for:

• anomalies of fetal development incompatible with life;
• term of pregnancy more than 34 weeks;
• violation of the fetus;
• Chorioamnionitis, when further prolongation of pregnancy is dangerous for the health of the mother.

Antibacterial therapy is indicated in the premature discharge of amniotic fluid and the presence of signs of infection (increased body temperature, leukocytosis, a stab-shift shift of the leukocyte formula). In this situation, a wide-spectrum antibiotic therapy is administered in combination with drugs with antianaerobic activity (metronidazole). Antibacterial therapy helps to reduce the incidence of chorioamnionitis and postpartum endometritis in mothers, and in children - the incidence of pneumonia, sepsis, intraventricular hemorrhage, bronchopulmonary dysplasia.

When sowing streptococcus group B recommend the introduction of an antibiotic in childbirth as a prophylaxis of sepsis of the newborn - ampicillin 1-2 g IV with repeated administration of 1 g in 4-6 hours.

According to I. Grable et al. (1996), with a premature outflow of water, this treatment can delay the development of labor for the prevention of fetal distress syndrome.

Mortality of newborns from sepsis is 5 times higher in postnatal treatment compared with intranatal treatment of the mother.

Schemes of antibacterial therapy for premature overflow of amniotic fluid

Several treatment regimens have been proposed for the premature discharge of amniotic fluid and the beginning of chorioamnionitis. Preference is mainly given to a combination of penicillin drugs (preparations of choice - protected penicillins) with macrolides (mainly erythromycin). As an alternative, third generation cephalosporins are used. In bacterial vaginosis, as well as planned delivery by caesarean section, treatment should be supplemented with drugs with antianaerobic activity (metronidazole). This therapy is especially justified in gestational terms from 28 to 34 weeks, when prolonging pregnancy increases the chances of a newborn's survival.

• Ampicillin 2 g IV every 6 hours for 48 hours, then amoxicillin inside for 250 mg every 8 hours in combination with erythromycin 250 mg every 6 hours for IV for 48 hours, followed by a transition to oral administration at a daily dose 1-2 g.
• Ampicillin + sulbactam 3 g every 6 h / w for 48 h, then amoxicillin + clavulanic acid inside every 8 h for 5 days, course 7 days.
• Ampicillin 2 g IV every 4-6 hours in combination with erythromycin 500 mg 4 times a day (daily dose of 2 g).
• Amoxicillin + clavulanic acid 325 mg 4 times a day inwards or ticarcillin + clavulanic acid in combination with erythromycin at a daily dose of 2 g.
• Cephalosporins: cefotaxime, cefoxitin, cefoperazone, ceftriaxone IV up to 4 g / day.
• With abdominal delivery, metronidazole is added to the therapy in / in the drop by 500 mg (100 ml) 2-3 times a day.

Prevention of respiratory distress syndrome of the fetus

According to the recommendations of American authors, all pregnant women between the 24th and 34th weeks of gestation in the presence of threatening and beginning premature birth should be considered as a patient who demonstrates antenatal prevention of fetal respiratory distress syndrome with glucocorticoids, which contributes to the maturation of the fetal lungs surfactant.

In our country, the prevention of distress syndrome of the fetus is carried out during the gestational period of 28-34 weeks.

The effect of antenatal prophylaxis of distress syndrome of the fetus is proved, its benefit for the newborn surpasses the potential risk and is expressed in the reduction of perinatal morbidity and mortality, the frequency of respiratory distress syndrome, the frequency of intraventricular and periventricular (hemicellular) hemorrhages, and the frequency of necrotic enterocolitis.

At the time of pregnancy more than 34 weeks, the prevention of respiratory distress syndrome is not indicated.

In case of premature rupture of amniotic fluid within a period of up to 32 weeks, glucocorticoids are used in the absence of signs of chorioamnionitis.

Signs of chorioamnionitis are recognized as a combination of body temperature of the mother 37.8 ° C and higher with two or more of the following symptoms:

• tachycardia of the mother (more than 100 beats per minute);
• Fetal tachycardia (more than 160 beats per minute);
• soreness of the uterus during palpation;
• amniotic fluid with an unpleasant (putrefactive) odor;
• leukocytosis (more than 15.0 × 10 ⁹ / l) with a shift of the leukocyte formula to the left.

In addition to chorioamnionitis, gastric and duodenal ulcer, severe forms of diabetes, nephropathies, active form of tuberculosis, endocarditis, nephritis, osteoporosis, circulatory insufficiency of the third stage are contraindications to glucocorticoid therapy.

Dosage regimens: 2 doses of 12 mg betamethasone IM in 24 hours; 4 doses of 6 mg dexamethasone IM in 12 hours; as an option - 3 intramuscular injections of dexamethasone per day for 4 mg for 2 days.

The optimal duration of prophylaxis is 48 hours. The preventive effect of glucocorticoids is realized 24 hours after the initiation of therapy and lasts 7 days.

The benefit of a second course of prevention has not been proven.

A single repeated (after 7 days) administration of glucocorticoids with a gestational age of less than 34 weeks and no signs of maturity of the fetus is permissible.

In our country, oral administration of glucocorticoids - dexamethasone 2 mg (4 tablets) is also used 4 times a day for 2 days.

Prognosis for premature birth

Survival of preterm neonates is determined by a number of factors:

• gestational age;
• birth weight;
• sex (girls have a greater ability to adapt);
• the nature of the presentation (mortality in pelvic presentation is 5-7 times higher than in the case of headache in the case of birth through natural birth canals);
• method of delivery;
• the nature of labor activity (risk factor - rapid labor);
• the presence of premature placental abruption;
• severity of intrauterine infection of the fetus;
• multiple pregnancy.