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Multiple pregnancy: a modern view on the problem of managing pregnancy and childbirth (literature review) | Tsivtsivadze E.B., Novikova S.V.

The problem of the appearance of twins has been worrying the minds since the existence of mankind, has ethnic, cultural, social and economic implications. Traditions associated with the birth of twins have appeared in all ages. Hippocrates believed that twins were the result of the division of the seed into two parts, Democritus considered twins as the result of an excess of the seed, Aristotle explained the appearance of twins by the splitting of one germ into two. But even so far there is no unambiguous hypothesis explaining the formation of monozygotic twins. nine0003

The relevance of the problem of multiple pregnancy lies in a significant number of complications during pregnancy and childbirth, an increase in the proportion of cesarean section, postpartum complications, an increased level of antenatal losses at various gestational periods, and a high incidence of neurological disorders in surviving children [44].

Multiple pregnancies occur in 1.5–2.5% of cases, more often in families where the mother or father, or both spouses, were born as a result of a multiple pregnancy [1]. In this case, the genotype of the mother plays the most significant role. It is impossible not to recall the well-known formula, according to which multiple pregnancies occur with a frequency of geometric progression, which is formed when the number is raised to the power of 80: one twin occurs in 80 births, triplets - in 80 births in a square (6400), quadruple - in 80 births in a cube ( 512,000), five - for 80 births in the fourth degree (40 960,000).

The interest in multiple pregnancies that has existed since ancient times has increased in the last 15–20 years due to the avalanche-like increase in multiple pregnancies associated with the introduction of assisted reproductive technologies.

Patients with multiple pregnancies remain at a high risk of perinatal complications. Even with the modern development of medicine, perinatal mortality during twin pregnancy is 5 times higher than in singleton pregnancy, intrauterine fetal death is 4 times higher, neonatal - 6 times, perinatal - 10 times. The frequency of cerebral palsy in children from twins is 3-7 times higher, with triplets - 10 times. The level of ante- and intranatal complications on the part of the mother is 2-10 times higher than that in patients with singleton pregnancies [7, 14, 17, 19, 35, 40, 60].

Perinatal morbidity and mortality in twins depend on chorionicity. According to Sebire studies, the perinatal mortality rate, mainly due to severe prematurity at birth, is higher in monochorionic twins than in dichorionic twins (5 and 2%, respectively). The frequency of preterm birth up to 32 weeks. in monochorionic pregnancy is 10% compared to 5% in dichorionic twins. The frequency of spontaneous abortion in the period from the 11th to the 24th week. with dichorionic twins it is 2%, with monochorionic twins it is about 10% [1, 33, 50, 64, 65]. nine0003

Interesting data were obtained by a group of authors who studied sex-associated differences in perinatal complications in 16,045 pregnant women with twins. Women with female twins have been found to have an increased risk of preeclampsia, but after birth, these twins had lower rates of neonatal and infant mortality, as well as a lower risk of respiratory disease than male twins [66].

Determination of zygosity before delivery is possible only when examining DNA in fetuses obtained as a result of amniocentesis, chorionic biopsy or cordocentesis. However, on the basis of zygosity, one cannot judge the type of placentation. Monozygotic twins can be either monochorionic or bichorionic [56]. nine0003

Determination of the chorionicity of the fetuses is possible during an ultrasound scan, during which the number of placentas, the sex of the fetuses, and the presence of an amniotic septum are determined. The optimal time for the diagnosis of chorionicity is 6–9 weeks. pregnancy. In the presence of dichorionic twins, two fetal eggs are determined, separated by a thickened septum of 2 mm or more. The use of this criterion makes it possible to diagnose mono- and bichorionic twins with an accuracy of up to 85% and 92.3%, respectively [71]. nine0003

Multiple pregnancy may be complicated by growth retardation of one or both fetuses, feto-fetal transfusion syndrome (FFTS), intrauterine death of one or both fetuses.

FFTS, first described by Schatz in 1982, occurs in 1 out of 5 monochorionic twins [47, 48]. Its morphological substrate is the anastomosing vessels between the two fetal circulatory systems [28]. This is a specific complication for monozygotic twins with a monochorionic type of placentation. Of particular difficulty are monochorionic monoamniotic twins, when pregnancy is complicated not only by FTTS, but also by problems with the umbilical cords of the fetuses (Fig. 1). nine0003

The criteria for FFTS are an intra-pair difference in weight of more than 20% and different concentrations of hemoglobin in fetuses [23]. For many years, the diagnosis of TTTS was established retrospectively in the neonatal period. Based on the data of ultrasound diagnostics, FFTS criteria were developed, which are used in practice to determine the management of pregnancy [63].

The most common factor associated with ante- and neonatal mortality and morbidity in twin pregnancies is low birth weight. In the vast majority of cases, low body weight of children is due to preterm birth. Various hypotheses of threatened miscarriage in multiple pregnancies are discussed in the literature. According to one of them (premature birth is a natural consequence of twin pregnancy), the main cause of premature development of labor is the overstretching of the muscle fibers of the uterus, the release of prostaglandins and reduced uteroplacental blood flow. Another hypothesis is based on the data of the Joint Perinatology Project [4], indicating that infection of the amniotic membranes contributes to their premature rupture, which most often leads to preterm birth. nine0003

A systematic review of randomized controlled trials evaluating the efficacy of antenatal screening for lower genital tract infections and their treatment in reducing preterm birth and associated morbidity demonstrated the high efficacy of such screening programs. Thus, in the intervention group (2058 women) screening and treatment of bacterial vaginosis, trichomoniasis and candidiasis were performed, in the control group (2097 women) were not screened, they were examined only in the presence of complaints or clinical manifestations. Preterm birth before 37 weeks. were observed significantly less frequently in the intervention group (3% vs. 5% in the control group) with a relative risk (BP) of 0.55 (95% CI 0.41 to 0.75). The frequency of birth of children with low body weight (weighing 2500 g or less) was 52% lower in the intervention group (BP 0. 48, 95% CI 0.34 to 0.66), and very low birth weight children (weighing 1500 g or less) - 6% lower in the intervention group than in the control group (BP 0.34, 95% CI 0.15 to 0.75) [53].

Thus, there is high-certainty evidence that screening and treatment programs for vaginal infections in pregnant women reduce preterm and low birth weight preterm births.

The high-risk group for complications during pregnancy and perinatal outcomes should include women with congenital anomalies in the development of the uterus. The results of numerous studies have shown that the outcome of pregnancy is largely due to the nature and severity of the malformation of the uterus. Relatively favorable outcomes were observed with a saddle uterus, unfavorable - with a bicornuate uterus and intrauterine septum [2, 9, 11, 38]. So, in the literature available to us, only 7 cases of multiple pregnancy in a bicornuate uterus were found. A. Bongain et al. (1994) suggest that the possibility of fertilization of two eggs in a pregnant woman with a congenital anomaly of the uterus (bicornuate, complete doubling) is 1:1,000,000.

Based on the foregoing, our clinical case of multiple pregnancy with complete duplication of the uterus is of scientific and practical interest.

Pregnant S., 1988 years of age, was observed under the conditions of MONIIAG in 2010 due to the presence of an anomaly in the development of the genitourinary system - complete doubling of the uterus and pregnancy with twins. The pregnancy proceeded with the phenomena of the threat of termination, for which inpatient treatment was repeatedly carried out. On December 28, 2010, emergency delivery was performed at a gestational age of 35 weeks. due to premature rupture of amniotic fluid. A Pfannenstiel transection was performed, caesarean sections were performed in the lower uterine segments of both uterus with Derfler incisions (Fig. 2). The children were born weighing 2320 and 2000, are currently healthy. nine0003

Neurological complications are a significant problem in multiple pregnancies [6, 44]. The greatest number of neurological complications is observed in premature babies and in children with malnutrition, as well as in the presence of FTTS.

Stillbirth and neonatal mortality in multiple pregnancies are recorded 3 times more often than in singleton pregnancies, and are respectively 14.9 and 19.8 per 1000 live births. The financial costs of providing medical care to each child from twins with multiple pregnancies during the first 5 years of life are 2 times higher than those for children born with a single pregnancy. nine0003

Prematurity is considered as the main cause of neonatal mortality in multiple pregnancies. Preterm birth is the leading cause of neonatal death, as well as early and delayed disability. The rate of preterm birth varies from 6% to 12% in developed countries, and this figure is usually higher in developing countries. About 40% of all preterm births occur before 34 weeks. and 20% - up to 32 weeks. The contribution of these preterm births to the total perinatal morbidity and mortality is more than 50% [38, 46]. nine0003

Despite a significant arsenal of tocolytic agents, the frequency of preterm births in the world is not decreasing, and the decrease in perinatal mortality is mainly due to the success of neonatologists in nursing premature babies. In connection with the foregoing, the tactics of managing and treating the threat of preterm labor should take into account the possible causes of their development, and not consist only in the appointment of symptomatic agents aimed at reducing the contractile activity of the uterus. nine0003

At present, some progress has been made in the treatment of threatened preterm labor due to drugs that suppress the contractile activity of the uterus.

In practical obstetrics, magnesium sulfate is often used. The mechanism of action of Mg2+ ions on smooth muscles has not been finally established. An important aspect of the use of magnesium sulfate in obstetric practice is the presence of an anticonvulsant effect in the drug, which allows it to be used to treat preeclampsia and eclampsia. With the threat of preterm birth, the prophylactic use of magnesium sulfate as a monotherapy has a less pronounced effect. nine0003

There is evidence of a relationship between the use of magnesium sulfate in the prenatal period in preterm labor or preeclampsia and a subsequent decrease in the risk of developing cerebral palsy in premature newborns with low birth weight. It should be emphasized that a neuroprotective effect was demonstrated for low total doses of magnesium sulfate (4 and 12 g), while for high total doses (>30 g) a toxic effect was demonstrated, which was accompanied by an increase in infant mortality. Incidence statistics were assessed using electronic databases and journal publications [25]. nine0003

The Committee on Obstetrics of the American College of Obstetricians and Gynecologists (ACOG, March 2010), based on multicenter data on the neuroprotective effect of magnesium sulfate and the reduction in the incidence of cerebral palsy in preterm infants, recommends that the use of this drug be added to protocols for impending PR <30 weeks: bolus 4-6 g of magnesium sulfate, then infusion of 1-2 g/h for 12 hours [27, 32, 33].

In recent decades, both foreign and domestic researchers have accumulated considerable experience in the use of calcium channel blockers in obstetric practice, primarily in diseases accompanied by an increase in blood pressure. However, the use of calcium channel blockers as tocolytic agents in case of threatened miscarriage is often accompanied by undesirable effects. It should also be remembered that in Russia nifedipine is not registered as a tocolytic agent, therefore, before using it, it is necessary to obtain the written informed consent of the patient for its use [10, 22, 55]. nine0003

As you know, the decisive role in the regulation of the contractile function of the uterus during childbirth is assigned to biologically active substances of a lipid nature - prostaglandins (especially PGF2a). The tocolytic effect of prostaglandin synthesis inhibitors has been proven experimentally and as a result of clinical observations. However, without selective properties, prostaglandin synthesis inhibitors cause undesirable effects on the fetus and newborn. The most severe complications are manifested in premature closure of the arterial duct and a pronounced increase in pulmonary arterial pressure [59, 71].

Progesterone, although not a tocolytic in the true sense of the word, is increasingly being used in the protocols of tocolytic therapy for preterm birth. There is no effective way to prevent preterm birth during twin pregnancy. At the same time, three large randomized trials have demonstrated that progesterone is effective in preventing preterm birth in high-risk singleton pregnancies. In recent years, the main (primarily immune) mechanisms for the implementation by gestagens of their protective function in relation to the fetus have been revealed [19, 35, 40, 74].

In patients belonging to the high-risk group (history of preterm birth or shortening of the cervix), the use of progesterone in the prenatal period led to a decrease in the frequency of early termination of pregnancy by 35% [28, 30, 52, 53, 63, 68].

It is noteworthy that the reduction in the incidence of preterm birth with the use of progesterone is not accompanied by a significant improvement in neonatal outcomes and a decrease in perinatal mortality. However, antenatal use of progesterone in singleton pregnancies has been found to be associated with a reduced risk of neonatal sepsis. nine0003

British experts conducted a study to evaluate the value of progesterone in the prevention of preterm birth in twins (STOPPIT - STudy Of Progesterone for the Prevention of Preterm Birth In Twins). It was concluded that the use of progesterone in twins does not reduce the incidence of preterm birth or intrauterine fetal death up to 34 weeks. pregnancy [21]. Perhaps this is due to the insufficient dosage of progesterone preparations [3].

Differences in the biological effectiveness of progesterone in multiple and singleton pregnancies should be the subject of further research. According to the authors, such differences are associated with the predominance in the pathogenesis of preterm labor with twin overstretching of muscle fibers, while in singleton pregnancy, infectious and inflammatory processes play the main role [58]. nine0003

When prescribing progesterone preparations, the informed consent of the woman is required, since the manufacturing companies, when registering these medicines in the Russian Federation, in the indications for the use of progesterone do not indicate threatening preterm labor and the possibility of using the drugs in the second and third trimesters of pregnancy.

In recent years, in Russia, the most common and frequently used drug from the group of β-mimetic agents is hexoprenaline, a selective β2-sympathomimetic that relaxes the muscles of the uterus. However, according to the results of systematic reviews of randomized controlled trials, the effect of tocolytics alone on reducing the incidence of preterm birth has not been proven. The main goal of prescribing tocolysis is to delay delivery by 48 hours in order to transport the pregnant woman to the perinatal center and conduct a full course of antenatal steroids [31, 43, 56, 73]. nine0003

Risk of preterm birth: diagnostic criteria

Diagnosis of preterm labor is associated with certain difficulties, since there are no specific symptoms. The diagnosis of the onset of preterm labor can be clarified using transvaginal ultrasound with the measurement of the length of the cervix or the determination of fetal fibronectin in the cervico-vaginal secret [1, 70].

In 2010, Conde-Agudelo et al. summarized the available data on the accuracy of predicting spontaneous preterm birth in twins by measuring the length of the cervix. They conducted a systematic review and meta-analysis of 21 non-randomized studies (16 studies of pregnant women with clinical signs of possible preterm birth and 5 studies of pregnant women without symptoms of threatened miscarriage, a total of 3523 women). It was concluded that vaginal echocervicometry is a good diagnostic criterion for spontaneous preterm birth in the absence of clinical symptoms in pregnant women with twins at 20–24 weeks of gestation. [26]. nine0003

In twin pregnancy, suturing the shortened cervix increases the risk of preterm birth [17].

At the same time, a number of authors describe the positive experience of applying U-shaped and circular sutures, which contribute to the prolongation of pregnancy until the birth of viable children with twins, triplets and even quadruplets [42].

In order to determine the risk of preterm birth, available express test systems are used to determine phosphorylated protein-1 that binds insulin-like growth factor (PSIFR-1) in cervical secretion [12]. These methods increase diagnostic accuracy and reduce the risk of iatrogenic complications, as they prevent overdiagnosis of preterm labor. nine0003

Two indicators are important for the diagnosis of active preterm labor: regular contractions and dynamic changes in the cervix. The degree of cervical dilation is an indicator of the prognosis of the effectiveness of tocolysis. If the opening of the pharynx is more than 3 cm, tocolysis is likely to be ineffective. Changes in the cervix are a more objective indicator than the assessment of labor activity. With a cervical length of more than 3 cm, the probability of labor onset within the next week is about 1%, which does not require hospitalization of the patient [48]. nine0003

The algorithm of actions of a doctor in case of a threat of preterm birth depends on the clinical picture, gestational age, integrity of the membranes and consists of the following main areas: risk assessment of preterm birth, prevention of RDS of the newborn, prolongation of pregnancy to transfer the mother to the perinatal center, prevention and treatment of infectious complications, in including with premature rupture of the membranes.

At present, the most accurate marker of preterm labor should be considered the detection of fibronectin in the cervico-vaginal secretion at gestational age up to 35 weeks, which indicates an increased risk of preterm labor, especially within 2 weeks. since the test. It is very important for clinical practice that this test has a high predictive value of a negative result - in the absence of fibronectin in the vaginal secretion, the probability that a woman will give birth within 1 week is about 1% [37]. nine0003

Prescription of antenatal steroids significantly reduces morbidity and mortality in children from RDS, IVH, NEC, and patent ductus arteriosus.

Roberts et al. in a recent meta-analysis of 21 randomized trials, a single antenatal course of steroids (24 mg betamethasone or 24 mg dexamethasone over 48 hours) significantly reduced neonatal mortality by 31%, RDS by 34%, and early sepsis within the first 48 hours life - by 44% and the need for artificial lung ventilation - by 20%. A repeated antenatal course of corticosteroids may be useful in the case when more than 7 days have passed from the previous course and symptoms of threatened preterm labor continue or reappear. nine0003

Laswell et al. in 2010, conducted a meta-analysis of 41 publications that examined neonatal mortality among infants weighing <1500 g or <32 weeks gestation in perinatal centers compared with infants born in lower-level medical facilities. The results of the meta-analysis showed that timely transportation of a pregnant woman with a high risk of preterm birth to a perinatal center is an event that significantly increases the chances of survival of a premature baby. nine0003

Antibiotic therapy for premature rupture of membranes

The effect of prescribing antibiotics in reducing the incidence of chorioamnionitis and neonatal morbidity in cases of premature rupture of membranes has been confirmed in qualitative studies.

A systematic review of 22 randomized controlled trials showed that the use of antibiotics for preterm rupture of membranes and preterm pregnancy significantly reduces the incidence of chorioamnionitis and the number of children born within 48 hours after rupture of the membranes. In addition, the use of antibiotics in this clinical situation can reduce the incidence of neonatal infection, the need for surfactants, the use of oxygen therapy in the newborn, and the incidence of pathological symptoms in neurosonography. nine0003

All of the above suggests that those carrying multiple pregnancies are a special contingent that needs careful monitoring at all stages of pregnancy.

It is necessary to say a few words about childbirth. Undoubtedly, this group of pregnant women represents women whose caesarean section rate is much higher than in the population [13].

According to MONIIAG, in spontaneous multiple pregnancies, the percentage of spontaneous births and caesarean sections is 46.4 and 44.9, respectively.%. Delivery operations used at the birth of the second fetus account for 8.7%. Nevertheless, we do not deny the possibility of conducting childbirth through the natural birth canal. It should be noted that the course of the second stage of labor with twins is often unpredictable and uncontrollable, and much is determined by the skill of the obstetrician-gynecologist. If the doctor has the necessary skill, then both the application of a vacuum extractor to the head of the second fetus and the extraction of the second fetus by the pelvic end will be common obstetric operations that do not affect the child's condition at birth and during the period of neonatal adaptation. nine0003

As for multiple pregnancies that occurred as a result of IVF, in many obstetric institutions, planned abdominal delivery is carried out. Under the conditions of MORIAG, 30% of pregnant women with multiple pregnancies resulting from IVF were delivered through the natural birth canal.

It should be emphasized that in general there can be no standards in obstetrics, and clinical success is possible only with an individual, balanced and thoughtful medical approach. nine0003

Thus, patients with multiple pregnancies constitute a high-risk group for the development of maternal and perinatal complications. This is directly related to the fact that, evolutionarily, the body of a pregnant woman is adapted for bearing one fetus.

The key to the success of carrying multiple pregnancies and nursing newborns should be continuity in the activities of all obstetric and gynecological departments and departments of newborns. And, of course, further in-depth study of this problem should be aimed at reducing perinatal losses and maintaining the reproductive health of women. nine0003

Literature

Multiple pregnancy: modern aspects - Extempore

In recent years, the frequency of multiple pregnancies has increased, which is associated with the use of assisted reproductive technologies, and this entails the occurrence of many complications both on the part of the mother and newborns, requiring careful monitoring, timely treatment and delivery. One of the main tasks of the Perinatal Center is to provide assistance in case of premature birth, which often occurs in multiple pregnancies. nine0126