Regional clinical and anamnestic characteristics of the course of the postpartum period in women according to the data in Krasnoyarsk and the Krasnoyarsk region

Currently there is no trend toward reduction in postpartum purulent-inflammatory diseases (PPID), and they account for 5–26% of all postpartum complications [1–3]. In recent years, prevalence of septic complications ranked third and reached 12% in the overall structure of the causes of maternal mortality [4–8].  Sepsis is a very serious delayed complication of PPID that requires timely diagnosis and immediate treatment [9–12].

Postpartum endometritis (PE) takes leading position in the structure of PPID, and is diagnosed in more than 40% of all cases of postpartum complications [13–18].  In Europe and the USA, the incidence rate of PE after vaginal delivery is 1–3%, in Russia 2–5%. The rate of PE after elective cesarean delivery in the countries of Europe and in the United States is 5–15%, in Russia 10–15% [13–15, 19–21].

Attention should be paid to the evolution of the clinical picture and the course of PPPID in the temporal aspect. Thus, in 1996, 3 288 562 birth histories were analyzed. The incidence rate of PPID was 21.7%, whereas in the period 1984–1988 the rate was only 10%. However, against the background of the total number of all PPID cases, the rate of PE increased from 33.2% to 39.5%. At the same time, in 92.4% of cases, there was a classical clinical picture of PE [11, 12, 22, 23].

The course of PPID is influenced by a number of features of the microbiological spectrum. The polyetiological nature of pathogens (especially enterobacteria and associations of enterobacteria) coexisting in the form of biofilms that have high resistance to the most important types of antimicrobial medicines was reported [24]. Moreover, according to a number of authors, opportunistic microorganisms can also be causative agents of postpartum infectious diseases against the background of blood loss, especially during abdominal delivery and in local immunosuppression [10, 24–28]. The widespread use of a wide range of antiseptics and antibacterials in obstetric practice, the rising antibiotic resistance and virulence of microorganisms lead to increasing percentage of obscure and abortive forms of postpartum diseases, that are often difficult to diagnose [29, 30].

It should also be noted that in recent years the activity in surgical delivery tends to increase. Thus, in level one obstetric care facilities, the percentage  of surgical methods of delivery is 19.0–24.2%, in level 2 – 30–37%, in level 3 – 35–40%, and in specialized research centers – up to  70% [12]. Despite the use of modern suture material and antibiotic prophylaxis, cesarean section (CS) remains a serious risk factor for the incidence of PPID [20, 21]. Thus, according to a number of authors, the incidence rate of endometritis after cesarean delivery is 2.5–20%; at the same time, 10–20% in pathological delivery, and 13.3–54.3% in women at high risk of infections [16, 22, 27, 31].

According to domestic authors, the rate of postpartum endometritis (PE) in general population of puerperant women after spontaneous vaginal delivery (SVD) is 3–8%, and 10–20% after CS [16, 22], and the rate of obstetric peritonitis after CS in maternity hospitals ranges from 0.1% to 1.5%. Most often, this pathology develops after operative delivery (98%). At the same time, postpartum endometritis is one of the major causes of generalized infection and formation of uterine scar defects [16, 21, 23].

Thus, due to the perinatal focus of modern obstetrics and worsening of general health status of women of reproductive age, the frequency of abdominal delivery significantly increased, that creates additional risk for intraoperative and postoperative complications [22]. So, according to foreign and domestic authors, the general rate of all complications in abdominal delivery is 16.3–21.4% [16, 22].

The level of socio-economic development of the region and the organization of medical care have a significant impact on the frequency of postpartum infectious complications [22, 27]. At the same time, systematic organization of medical care for patients with postpartum complications is an acute issue. Thus, postpartum women undergo treatment in gynecology hospitals, and there are no conditions for adequate postpartum care and keeping mothers and newborn babies together. There are also no standardized approaches to perform surgical interventions for treatment of postpartum complications. At the same time, radical interventions predominate with underlying insufficient use of endoscopic technologies [19, 32].

The studies by Oboskalova T.A. and Glukhova E.Yu. aimed at investigation of regional characteristics of PPID, reported the data on the system for prevention of PPID in maternity hospitals in Ekaterinburg and the program for providing medical care to women with complications of puerperium [33]. Since 2006, when financing of maternity hospitals in Ekaterinburg has been improved, there was increased delivery of medications and consumables; and improved technique for abdominal delivery was used; the frequency of severe purulent-septic complications, which previously ended with a surgical organ transplant, reduced by almost half. However, due to the increased frequency of abdominal delivery (from 14.8% to 31.2% in the period from 1998 to 2013), there was a trend toward the increase in the incidence of complications, such as postoperative wound suppuration in the anterior abdominal wall and uterine scar failure (by 2 times) [33].

The authors showed that to prevent PPID, a certain organizational structure of maternity hospitals is important, that provides maximum separation between parturient and puerperant women, but at the same time ensures keeping mothers and babies together. It is also relevant that there should be interchangeable, cyclically functioning units with high infectious risk in maternity hospitals – resuscitation and intensive care units, operating and birth rooms [33].

Based on the new regional data on the characteristics of PPID, future development of organizational measures in the obstetric and gynecological service of the city and region are possible, that will reduce the incidence of severe forms of postpartum complications.

The purpose of the study was to explore the clinical and anamnestic characteristics in women with postpartum purulent-inflammatory diseases (PPID according to the data obtained in Krasnoyarsk and the Krasnoyarsk region.

Materials and methods

A retrospective descriptive epidemiological study of clinical and anamnestic data of 387 birth histories of patients with various late postpartum complications and 446 histories of puerperant women with PE from 2017 to 2022 was conducted in the clinical hospitals of Krasnoyarsk State Medical University named after Professor V. F. Voino-Yasenetsky.

Group 1 in the study was arranged to determine the structure of postpartum complications, evaluation of the somatic status and clinical and anamnestic data of the general cohort of parturient and puerperant women obtained from data repository in maternity hospitals in Krasnoyarsk. According to the data of group 2, evaluation of clinical picture and anamnesis, specific features of the cause of PE depending on the type of delivery was performed. At the same time, group 2 was divided into two subgroups: 205 birth histories of puerperant women after spontaneous vaginal delivery (SVD) and 241 after CS. The archival data were collected from data repositories in Krasnoyarsk inter-district clinical hospital of emergency care named after N.S. Karpovich Regional Clinical Hospital, Maternity Hospital No.1, Krasnoyarsk Inter-District Clinical Hospital No. 4 (Fig. 1).

Inclusion criteria were reproductive age of women, postpartum period (up to 42 days inclusively), purulent-inflammatory diseases of the pelvic organs associated with pregnancy and delivery, SVD or CS.

Exclusion criteria were: endometritis after abortion, peritonitis after obstetric surgery, obstetric sepsis, vaginitis, inflammatory disease of the uterine appendages, diagnosed sexually transmitted infections, including in the postpartum period.

The research process included assessment of clinical and anamnestic data (time frames for occurrence of complaints, lower abdominal pain, vaginal discharge (purulent/bloody), temperature at admission to hospital), laboratory and instrumental data (complete blood count, C-reactive protein values, pelvic ultrasound), as well as the analysis of treatment and its effectiveness in comparison groups (Fig. 1).

Geographic distribution of the patient’ places of residence is shown in Figure 2. It should be noted, that most of puerperant women with postpartum complications (42.3% (164/387)) were in Krasnoyarsk.

Statistical analysis

Statisitical analysis was performed using IBM SPSS Statistics. Table sampling method was used to determine the required sample size. The normality of distribution was assessed by using the Lilliefors-corrected Kolmogorov–Smirnov test with critical value at the level of significance р>0.05. In this case, it was considered that the parameters follow normal distribution. The descriptive statistics is presented as qualitative data in percentage (%).

The quantitative data with normal distribution were described as M (SD) – the arithmetic mean (M) and standard deviation (SD. When distribution differed from normal, the data were presented as median (Me) and interquartile range Me (Q1; Q3).           

Results

The analysis of clinical and anamnestic data of patients in group 1 showed, that the mean age of puerperant women with PPID was 27.9 (27.4; 28.5) years.  The women gave birth on average at 39.5 weeks (38.3; 40.5) of pregnancy. At the same time 38.8% of women (150/387) gave birth via cesarean section, and 61.2% of women (237/387) had spontaneous vaginal delivery. It should be noted that only in 33.9% of cases (131/387) the patients with PPID were transferred from maternity hospitals to gynecology hospitals, in all other cases (66.1%), the puerperant women were transferred from home to hospital by the ambulance crew or they were admitted to hospital as self-referred patients (256/387).

In the structure of indications for cesarean delivery in group 1 in the study, weak labor contractions ranked first and were in 16% of women (24/150), C-section scar in history was in 14.7% (22/150), and acute fetal hypoxia was in 8% (12/150) of women. At the same time, premature rupture of membranes was in 33.3% of women (50/150)

Based on the results of histological findings of placentas in 15% of cases (58/387) of clinically diagnosed chorioamnionitis, the diagnosis was confirmed in 3.5% of puerperant women after СS, and in 4.6% of women after abdominal delivery.

The analysis of the frequency of concomitant somatic diseases in women of the study groups showed that pyelonephritis was most common disease in 30.8% of women (119/387), and acute respiratory infections (ARIs) were in 51.3% of women (199/387), while COVID-19 was only in 2.6% of women (10/387) (Fig.4).

Late postpartum complications in the group of puerperant women with PPID were in 25.9% of patients (100/387). In the structure of late postpartum complications, the rate of endometritis was the highest – 36.7% (142/387). The rate of perineal wound suppuration, as well as hematometra was 33.6% (130/387), which may be considered as a risk factor for endometritis; at the same time, with underlying residual placental tissue, it was diagnosed in 23.6% (31/130) of cases.

Most common complications in group 1 in women after SVD were hematometra in 27.3% (66/237) of women and residual placental tissue in 24% (57/237), while postoperative wound complications in the anterior abdominal wall were diagnosed most often in patients who underwent CS, and their rate reached 64.2% (96/150). Among them, infiltration was in 21.8% (21/96), seroma was in 19.8% (19/96), and hematoma was in 22.9% (22/96) of women (Fig. 5, 6).

All patients with the above complications were transferred from maternity hospitals to gynecological departments of multidisciplinary hospitals.

The mean age of patients with PE (group 2), who were admitted to gynecological departments of hospitals in Krasnoyarsk was 28.1 (27.2; 29.2) years. Among them, first delivery was in 17.7% (79/446) of women, second delivery was in 7.2% (32/446), and third delivery was in 2.5% (11/446) of women, and only one patient became mother for sixth time. The complaints with which the patients were admitted to hospital were manifested on average on day 10.8 (9.9; 11.9) of the postpartum period. It should be noted that paucisymptomatic PE prevailed, and only in one third of cases, uterine pain was diagnosed by palpation in 34.1% of women (70/205) after SVD, and in 34% of women (82/241) after CS, bloody vaginal discharge in 35.1% of women (72/205) after SVD and in 27.8% of women (67/241) after CS.  At the same time, purulent vaginal discharge, that was more specific for the classical manifestation of endometritis, was only in 18.5% of patients (38/205) with PE after SVD (Table 1), and more often after abdominal delivery – in 21.2% of women (51/241).

In group 2, only 38,1% of women (170/446) were admitted to hospital in satisfactory condition, moderate condition was in 57.4% of women (256/446), severe condition was diagnosed in 1.1% (5/446), sepsis was in 3,4% of women (15/446). At the same time, in the group of patients with PE after CS, moderate condition was significantly more often – in 63.5% (153/241) of women versus the women after SVD – 36% (88/241).

According to evaluation of indicators of coagulation hemostasis, fibrinogen level was slightly high – 4.7 g/l, and prothrombin time was slightly high 15.7 sec. It should be noted, that the differences between the groups of women after CS and SVD in the levels of hemoglobin (116.9 (112.9; 120.9) g/l in group with SVD and 104 (99.3; 108.6) g/l in the group after CS) and the values of C-reactive protein (39.5 (25.5; 56.1) mg/l in the group with SVD, and 90.9 (70.1; 113.1) mg/l in the group after CS) at hospital admission were statistically significant. At the same time, the group of patients after CS, in whom late postpartum complication was endometritis, had lower levels of hemoglobin, that can be explained by the volume of blood loss, and higher values of C-reactive protein (p<0.0001).

Pelvic ultrasound was performed when the patients were admitted to hospital. Ultrasound assessment showed subinvolutive dimensions of the uterus, the parameters which were: the mean length 77.2 (61.8; 93.4) mm, thickness 57.2 (48.4; 66.0) mm, width 76.7 (64; 88.4) mm.

 According to a number of authors, the clinical symptoms of PE after operative delivery occur on day 6±2 of the postpartum period, which after spontaneous vaginal delivery on day 4±2 [17, 23, 34]. The results of our study showed that PE was diagnosed on day 10.8 (9.9; 11.9). At the same time the clinical picture after CS occurred a bit earlier – on day 10.5 (9.1; 12.1) than after SVD – on day 11.3 (9.7; 13.1). Therefore, the debut of the clinical picture of PE usually occurs when the puerperant women is already discharged from maternity hospital, that may lead to untimely referral for medical care, delayed diagnosis and development of severe types of PPID.

Currently, the specific feature of postpartum infectious diseases is their polyetiological nature. According to the published data, the leading role in the etiological structure belongs to opportunistic microorganisms – non-fermenting gram-negative rods (predominantly Escherichia coli, Klebsiella pneumonia), enterococci, (predominantly Enterococcus faecalis), staphylococci (predominantly Staphylococcus aureus, Staphylococcus haemoliticus), massive colonization of which in the form of aerobic and anaerobic associations is present in the uterus in most cases [18, 21, 28, 29].

The results of our analysis of the microbial spectrum at the site of inflammation showed that most common, causative agents of PE are Escherichia coli (32.5% (145/446), Staphylococcus epidermidis (30.3% (135/446)), Enterococcus faecalis (18.6% (83/446)), Staphylococcus aureus (11.7% (52/446)). Monoculture of gram-positive bacteria was observed in 38.1% of cases (170/446), and gram-negative bacteria was in 44.2% of cases (197/446), and a mixture of gram-positive and gram-negative bacteria was diagnosed in 17.7% of cases (79/446) (Fig. 7, 8). 

The investigation of antibiotic resistance of most common bacteria to antimicrobial agents showed that resistance of Escherichia coli to ampicillin was in every third case (35.8% (52/145)), to doxycycline in 21.4% of cases (31/145). Moreover, in 21.4% (31/145) of Escherichia coli strains, the production of extended spectrum β-lactamases (ESBLs), the enzymes that confer resistance to first–fifth-generation of cephalosporins, were detected.

Gentamicin and amikacin resistant Escherichia coli were in 31.7% (46/145) и 33% (48/145) of cases, respectively.

Erythromycin resistant Staphylococcus epidermidis was in 45.9% (62/135) of cases, and in almost equal proportions ciprofloxacin and levofloxacin resistant S. epidermidis was in 16.3% (22/135) and 14.8% (20/135) of cases, respectively. Resistance of Methicillin-Resistant Staphylococcus epidermidis (MRSE) to cefoxitin in 15.6% (21/135) of cases indicates resistance to all β-lactam antibiotics except ceftaroline and ceftobiprole.

It should be noted that in 1992, the results of antibiogram of bacterial isolates of uterine discharge in puerperant women women with PE were the following: gram-negative bacteria were most sensitive to gentamicin (72.8%), carbenicillin (70.9%), monomycin (64.1%), kanamycin (62.7%), levomycitin (57.8%). Staphylococci were most sensitive to gentamicin (83.5%), carbenicillin (79.7%), tetracycline (75.8%), oxacillin (75.1%), methicillin (67.6%). Moreover, sensitivity of the groups of streptococcal bacteria proved to be most sensitive to monomycin (36%) and to ampicillin (96.3%) [30, 35–38].

However, the results of our analysis of the microbial spectrum from the uterine cavity proved the resistance of Escherichia coli to ampicillin in every third patient; and extended-spectrum β-lactamases (ESBL+) producing Escherichia coli, were resistant to extended-spectrum penicillins and first–fourth generation   cephalosporins. At the same time, β-lactamase inhibitors combined with penicillin group antibiotics were indicated in almost every second clinical case (in 53.4% of cases).

The retrospective analysis showed that the average duration of antimicrobial therapy for patients with PPID, including PE was 7.9 (7.4; 8.4) days. Moreover, β-lactamase inhibitors combined with penicillin group antibiotics were indicated in 53.4% (238/446) of cases, monotherapy was indicated in 11.2% of cases, and therapy with ciprofloxacin was in other cases. 

Since the species were collected from the uterine cavity before starting antimicrobial therapy, the subsequent antimicrobial therapy adjustment strategy was based on the results of bacterial culture and antibiogram. At the same time, treatment regimens changed in 30% (134/446) of cases – ceftriaxone in 6.3% (28/446), doxycycline in 5.6% (25/446)) and metronidazole in 14.8% (66/446) of cases (Table 2). However, in 11.7% (52/446) of cases, the results of bacterial culture showed no bacterial growth.    

Concomitant therapy with uterotonics (oxytocin) was indicated for 8.6 days in 58.9% (263/446) of cases, nadroparin calcium (fraxiparin) for 7.9 days in 46.4% (207/446), and iron preparations (sorbifer) for 9.6 days in 43.1% (192/446) of cases. Due to this, there was statistically significant increase in the level of hemoglobin from 111.2 to 118.3 g/l.

The analysis of surgical activity with regard to postpartum women with PPID in group 1 showed that 45.5% (176/387) of women underwent hysteroscopy in late postpartum period, and almost one third of patients (31.7% (123/387) 387)) underwent uterine aspiration for hematometra and residual placental tissue. On average, hysteroscopy was performed on day 14.5 (12.3; 16.5) of the postpartum period. Moreover, in 1.7% (3/176) of cases, hysteroscopy was combined with laparoscopy for suspected suture dehiscence after abdominal delivery according to ultrasound data. It should be noted that in the group of women with PE after abdominal delivery, hysteroscopy was performed significantly more often – in 84.6% (204/241) of cases versus the group of patients with PE after SVD –in 65.4% (134/205) of cases.

The average number of hospital bed-days for patients with PPID was 9.9 (9.4; 10.4). At the same time, treatment duration in hospital for the patients with PE after CS was significantly longer – 10.3 (9,8;11,5) bed-days versus the women after SVD – 9.3 (8,7;10,1) bed-days. On average, the puerperant women were discharged from hospital after conservative therapy on day 18 (15; 21) of the postpartum period, and on day 20 (19.3; 21.9) after operative treatment. According to ultrasound assessment, uterine size has decreased by 54.6%, the total number of white blood cells measured by WBC count was 6.2 (5.5; 6.8)×10⁹/l, and the C-reactive protein value was 17.7 (5.9; 33.2) mg/l.

All patients with PPID were discharged from hospital in satisfactory condition for subsequent outpatient follow-up by obstetrician-gynecologist.

Therefore, cesarean section takes leading position in the general structure of all risk factors for development of PE, despite the use of modern suture material and legitimate practices of antibiotic prophylaxis and treatment regimens. The results of our study showed that most cases of PPID were diagnosed in women who underwent cesarean delivery. At the same time, PE takes the leading position in the structure of PPID and reaches 36.7% among all cases of postpartum complications, while complications of postoperative wound in the anterior abdominal wall take the leading position in the group of puerperant women after abdominal delivery (64.2%).

It should be noted that the symptoms of PE appear on average on day 11 of the postpartum period, when the puerperant women are already discharged from maternity hospitals. The clinical symptoms of PE after CS appear on day 10, that is one day earlier than in patients with SVD. Due to obscure clinical forms, diagnostic delay of PPID occurs rather often leading to moderate severity of the disease in 57.4% of cases, and development of sepsis in 3.4% of cases.    

It is important to note operative activity in the group of patients with PE after abdominal delivery: virtually in every second case (45.4%), the women underwent hysteroscopy. At the same time, the frequency of surgical treatment reaches 84.6%, and is significantly higher versus the group of women with PE after SVD (65.4%).

In the spectrum of pathogens isolated from the uterine cavity, gram-negative bacteria take leading position (in 44.2% of cases), and among most often identified bacteria, Escherichia coli (32,5%) is diagnosed, (among them extended-spectrum beta-lactamases (ESBLs)+Escherichia coli are found in 21.4% of cases, Enterococcus faecalis in 18.6%, Staphylococcus epidermidis in 30%.

Also it is noteworthy that Escherichia coli isolates express resistance to ampicillin (35.8%). At the same time, it should be noted that ESBL+ Escherichia coli cultured in 21.4% of cases has extended spectrum of resistance, that may result in ineffective therapy with penicillins and first–fourth generation cephalosporins. However, according to the data in our study, most common antibiotic regimens for treatment  included indication of the group of drugs co-administered with β-lactamase inhibitors combined with penicillins (in 53.4% of cases).

Conclusion

Thus, the cause of PE in women after abdominal deliveer is more severe in comparison to puerperant women after SVD: the clinical picture occurs one day earlier, there are no inflammatory markers in patients at admission to hospital, and comorbidity of anemia is more often (especially in cases of emergency C-section), antibacterial therapy lasts longer versus women with PE after SVD, and operative activity with regard to these patients is 84.6% versus 65.4% in puerperant women after SVD.

Given a gradual increase in the number of resistant microorganisms, the issue of antibiotic resistance is becoming more acute every day. At the same time, optimization of using antimicrobial agents is a key issue in the global strategy to stop spread of superbugs.

In this regard, further researches are required to study the regional characteristics of the microbial landscape in the focus of inflammation and determine antimicrobial   sensitivity and resistance of isolated microorganisms to modern antibacterial drugs, as well as asses the immunological resistance of macroorganisms on the local and systemic levels.  These researches will help in future to develop rational regimens of antimicrobial therapy and immunocorrection in patients with PPID, reduce the frequency of severe destructive forms, preserve fertility, as well as achieve a significant socio-economic effect by reducing duration of therapy and hospital stay for this category of patients.