The problem of preterm rupture of membranes (PROM) still does not lose its relevance in modern obstetrics. Despite the amount of accumulated knowledge about the causes of PROM, the question of the etiology and risk groups of this pregnancy complication remains open to date. Preterm rupture of membranes (PROM) is a spontaneous rupture of the fetal bladder before the start of regular contractions. Childbirth complicated by premature discharge of amniotic fluid during full-term pregnancy, according to various data, ranges from 8.2% to 19.6%, with premature birth (up to 37 weeks of gestation) – from 5 to 35%, without a tendency to decrease. It should also be noted that PROM tends to re-develop in subsequent births with a frequency of up to 20-32% [1][2].

In most cases, PROM occurs on the eve of childbirth, however, when the rupture of membranes occurs before the 37th week of pregnancy, it is called preterm prelabor rupture of membranes (PPROM). PPROM is one of the clinical forms of preterm labor, which occurs in ~ 3% of pregnancies, leading to one-third of preterm labor. It remains the main cause of premature birth, neonatal mortality and morbidity [3]. Premature birth can be subdivided according to gestational age: about 5% of premature births occur at less than 28 weeks (very early premature birth), ~ 15% – at 28-34 weeks (early premature birth), ~ 20% – at 34-36.6 weeks (premature birth).

Factors associated with PPROM include lower socio-economic status, previous preterm labor, previous PROM, sexually transmitted diseases, vaginal bleeding, connective tissue disorders, smoking, and uterine overgrowth. However, there are cases when the causes of PROM are unclear. The clinical significance and treatment of PPROM are still controversial. Despite the fact that PROM is associated with a lower rate of complications, PROM can lead to significant neonatal and maternal morbidity [4][5].

The first general blood test (GBT) and the level of C-reactive protein (CRP) were recorded when pregnant women were admitted to the maternity hospital. The diagnosis of PROM and PPROM was based on anamnesis, objective examination and laboratory studies of pregnant women. Gestational age was determined from the date of the last menstruation or ultrasound in the period up to 12 weeks of pregnancy. Pregnant women complained of the sudden appearance of copious watery discharge from the genital tract with continued leakage. The examination included a vaginal examination in mirrors for fluid accumulation in the vagina, a positive Amniotest (AmnioTest). The reliability of the results obtained was achieved due to statistical data processing by standard parametric and nonparametric procedures of STATISTICA packages (version 10, StatSoft, Persons. BXXR310F964808FA-V) and Excel, the threshold significance level was assumed to be 0.05.

The characteristics of pregnant women in the PROM and PPROM groups were comparable in age, number of births, time since the last birth, blood pressure and body mass index (p >0.05) (Tables 1, 2).

There were significant differences between the two groups in the terms of pregnancy when the rupture of the fetal bladder occurred (39 ± 1.5 weeks vs. 34.3 ± 2.0 weeks, p <0.05), the number of pregnancies (1.92 ± 1.16 vs. 2.18 ± 1.34, p <0.05), CRP (6.43 ± 5.63 vs. 7.76 ± 6.59 mg/l, p <0.05) and body temperature at admission (36.67 ± 0.31 vs. 36.76 ± 0.34, p <0.05). As for concomitant diseases in women in labor, there were no significant differences between patients with hypertensive disorders, gestational diabetes mellitus, placenta previa, fetal growth restriction, placental insufficiency (p >0.05). The frequency of patients with a history of cesarean section and patients with breech presentation was significantly higher in the PPROM group compared to the PROM group (14.6% vs. 4.7% and 9.5% vs. 1.9%, p <0.05).

The analysis of the PPROM group (Table 2) did not reveal a significant difference in maternal characteristics between the two subgroups, except for the difference in the gestation period when PROM occurred (30.80 ± 1.10 vs. 35.0 ± 1.40, p <0.05). Regarding concomitant pathology in the mother, the study showed that the percentage of patients with previous cesarean section was significantly higher in the group of earlier gestational age (28.6% vs. 12.1%, p <0.05).

As for obstetric outcomes for the mother (Table 3), there were no significant differences between the PROM and PPROM groups in terms of the method of childbirth and postpartum bleeding (p >0.05), but the PPROM group had a significantly longer latency period before childbirth (43.29 ± 50.33 hours versus 18.94 ± 17.11 hours, p <0.05). From the point of view of neonatal outcomes (Table 3), newborns in the PROM group had a significantly higher birth weight (3389.17 ± 453.88 vs. 2468.25 ± 551.63, p <0.05), the degree of meconium staining (10.6% vs. 3.6%, p <0.05), data on the APGAR score after 1 minute (7.94 ± 0.41 9 vs. 7.44 ± 1.21, p <0.05) and data on the APGAR score after 5 minutes (8.28 ± 0.22 vs. 7.71 ± 0.91, p <0.05). The rate of hospitalization in the NICU was significantly higher in the PPROM group than in the PROM group (65.7% vs. 11.8%, p <0.05).

The analysis of the PPROM subgroup (Table 4) also revealed no significant differences between the two subgroups in terms of the method of delivery and postpartum bleeding (p >0.05), but the latency period was significantly longer at an earlier gestational age (91.52 ± 56.94 h versus 34.56 ± 43.94 h, p <0.05). Newborns at 32-36.6 weeks gestation had a significantly higher APGAR score after 1 minute (8.58 ± 1.02 vs. 7.67 ± 1.82, p <0.05), and the frequency of hospitalization in the NICU was significantly higher at the gestational age of 28-31.6 weeks (100% vs. 57.6%, p <0.05).

According to this study, women in the PPROM group had significantly higher levels of CRP and body temperature compared to the PROM group (p <0.05). It is well known that CRP is released by the body in response to acute injury, infection or other inflammatory stimuli and is a leading marker in the blood of systemic inflammation. Its value is a general indicator. A high or increasing amount of CRP in the blood suggests the presence of inflammation, but does not allow to determine its location or the condition causing it. It is assumed that the proinflammatory cytokine interleukin-6 plays a crucial role in the induction of fever and in the synthesis of CRP by hepatocytes. The data obtained are consistent with the information provided in published reliable sources [6][7].

The study showed that PPROM is associated with a significantly lower gestational age, patients of this group demonstrated a higher level of C-reactive protein and body temperature upon admission to the maternity hospital (p <0.05). Breech presentation and previous cesarean section in the anamnesis were associated with the occurrence of PPROM in comparison with the PROM group (p <0.05). The PPROM group showed a significantly longer latency period compared with the PROM group, in which the latency period increased with a lower gestational age (28-31.6 weeks). A significantly higher rate of admission to the neonatal intensive care unit (NICU) was observed in the PPROM group in comparison with the PROM group, and also at the gestational age of 28-31.6 weeks, a more significant rate of admission to the NICU was shown in comparison with the gestational age of 32-36.6 weeks (p <0.05). Higher levels of C-reactive protein and body temperature in the PPROM group suggest an asymptomatic infection that requires careful monitoring to prevent any adverse effect on the outcome of pregnancy. A longer latency period in the PPROM group is predictable to minimize perinatal morbidity and mortality from prematurity itself [8].

This particular study showed that patients in the PPROM group were more likely to have breech presentation compared to the PROM group (9.5% vs. 1.9%, p <0.05). These results are consistent with the literature sources [9][10]. After the division into subgroups, there were no differences in the presentation of the fetus with a predominance in the PPROM group. The authors of this study assumed that the shorter the gestation period, the higher the probability of breech presentation. The natural correlation between breech presentation and earlier gestation combined with PPROM explains why we found a significant correlation between PPROM and breech presentation.

It was revealed that the previous cesarean section in the anamnesis significantly correlated with PPROM, and not with PROM (14.6% vs. 4.7%, p <0.05). After the distribution into subgroups, the earlier gestational age had a significantly higher level of previous cesarean section in the anamnesis (28.6% vs. 12.1%, p <0.05). Unfortunately, the authors of this study were unable to explain the correlation between the previous caesarean section and the PPROM. Perhaps these results were influenced by our study sample, which was not large enough.

As for maternal outcomes, the PPROM group had a significantly longer latency period than the PROM group. After the division into subgroups, the duration of the latency period was significantly longer at the gestational age of 28-31.6 weeks than at 32-36.6 weeks. The main problem of PPROM is prematurity, therefore, the latency period affects the outcomes for the mother and fetus. A study of 1,596 patients with PDR conducted by Drassinower et al. [11], showed that a long latency period in the conditions of PPROM was associated with a reduced risk of neonatal sepsis and that infants born shortly after PPROM were at the highest risk. Periventricular leukomalacia is damage to the white matter of the brain of premature newborns, which often leads to cerebral palsy. The prevalence of cerebral palsy at the age of 3 years is 21 per 1000 among those born at the age of 28 to 30 weeks and 0.6 per 1000 among those born at term. Therefore, when appropriate, wait-and-see tactics are usually recommended in the absence of labor or complications associated with childbirth in order to minimize perinatal morbidity and mortality [12].

During hospitalization in the absence of indications for delivery, all pregnant women were observed conservatively and expectantly: treatment was carried out in accordance with a standardized protocol. This included careful monitoring of the mother's condition, regular monitoring of the fetal heart rate and a blood test. Tocolysis and antenatal administration of steroids are common practice in the conditions of PPROM (four doses of dexamethasone 6 mg were administered intramuscularly at intervals of 12 hours for 2 days). In addition, prophylaxis with antibiotics was carried out. Tocolytic therapy suppresses uterine contractions and allows the administration of steroids and antibiotics. The decision to terminate the pregnancy by Caesarean section or normal delivery was based on the status of the mother and fetus. Cesarean section was mainly indicated for complications of pregnancy, for example, with maternal fever, the presence of clinical chorioamnionitis, unfavorable fetal status and death, as well as placental abruption.

As for neonatal outcomes, as expected, infants in the PROM group had a significantly higher birth weight and an APGAR score 1 minute and 5 minutes after delivery (p <0.05). The indicator of amniotic fluid staining with meconium was also significantly higher in the PROM group than in the PPROM group (p <0.05). Meconium is often found in amniotic fluid and placental samples, especially in full-term or post-term pregnancy. The physiological tendency of the fetus to secrete meconium increases with gestation. The results of this study corresponded to the literature data [13][14]. The rate of hospitalization in the ICU was significantly higher in the PPROM group than in the PROM group (p <0.05). After the division into subgroups, there were no differences in birth weight, meconium staining frequency and APGAR scores after 5 minutes (p >0.05), but APGAR scores after 1 minute were higher at a later stage of pregnancy. The authors of this study found a significantly higher frequency of hospitalizations in the NICU at the gestational age of 28-31.6 weeks compared with 32-36.6 weeks (100% vs. 57.6%, p <0.05). This showed that even if both subgroups did not reach the due date, an increase in the duration of pregnancy plays an important role that can influence the decision to transfer to the intensive care unit.

A higher C-reactive protein index and body temperature in the PPROM group suggest an asymptomatic infection that requires careful monitoring to prevent any adverse effect on the outcome of pregnancy. Patients with a previous cesarean section and a history of breech presentation strongly correlate with the occurrence of PPROM compared with PROM, in whom the history of the previous cesarean section remains correlated with a lower gestational age (28-31. 6 weeks). A longer latency period in the PPROM group compared to the PROM group is important for minimizing perinatal morbidity and mortality due to prematurity itself. Thus, an increase in gestational age plays an important role, and can also influence the doctor's decision regarding the placement of a newborn in the NICU.

A higher C-reactive protein index and body temperature in the PPROM group suggest an asymptomatic infection that requires careful monitoring to prevent any adverse effect on the outcome of pregnancy. Patients with a previous cesarean section and a history of breech presentation are a high-risk group for the occurrence of PPROM compared with PROM, in whom the history of the previous cesarean section remains correlated with a lower gestational age (28-31.6 weeks). A longer anhydrous period in the PPROM group compared to the PROM group is important for minimizing perinatal morbidity and mortality due to prematurity itself. Thus, an increase in gestational age plays an important role, and can also influence the doctor's decision regarding the placement of a newborn in the NICU.