Peripartum infection at cesarean delivery may be related to uterine rupture during a subsequent trial of labor

doi:10.21203/rs.3.rs-1639623/v1

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Peripartum infection at cesarean delivery may be related to uterine rupture during a subsequent trial of labor

https://doi.org/10.21203/rs.3.rs-1639623/v1

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Background: Uterine rupture or dehiscence during trial of labor after cesarean is a cause of great concern for both parturitions and physicians. Although the risk-factors for uterine rupture are well-established, surgical site infection in the first cesarian-section has not been investigated in depth.

Aim: To evaluate the relation between peripartum infection after caesarean delivery to uterine dehiscence or rupture at the subsequent delivery.

Methods: A retrospective case-control study. The study group included women with a prior caesarean delivery and proven dehiscence, or uterine rupture diagnosed during their subsequent delivery. The control group were women who had a successful vaginal birth after cesarean section without evidence of dehiscence or uterine rupture. We compared the rate of infection during the cesarean delivery between the two groups.

Findings: A total of 168 women were included, 71 with uterine rupture or dehiscence and 97 with successful vaginal birth after cesarean section. The rate of peripartum infection at the first caesarean delivery was significantly higher in the study group compared to the control group (22.2% vs. 8.2%,p=0.013). Endometritis had the highest correlation to uterine rupture (9.8% vs. 0%,p=0.02)

Discussion: Peripartum infection in the first caesarean delivery, may be an independent risk-factor for uterine rupture in a subsequent delivery. Compared to other infections, endometritis may pose the greatest risk for uterine rupture or dehiscence.

Conclusion: when consulting with a patient on repeat cesarean section vs. trial of labor after cesarian, endometritis after the previous surgery should be included among the considerations, along with other traditional risk-factors.

Cesarean section

endometritis

infection

postpartum fever

TOLAC

Infection following a cesarean section is not an established risk factor for uterine rupture. This study presents a correlation between endometritis and uterine rupture.

Problem/issue: When consulting with a patient on repeat cesarean section vs. trial of labor after cesarian, risk factors for uterine-rupture should take into consideration. . Although some risk-factors for uterine rupture are well-established, surgical site infection in the first cesarian-section has not been investigated in depth.

What is already known: It is well-established that surgical scar infection is a risk-factor for impaired healing. Although not commonly considered a risk-factor, a surgical scar with previous surgical sight infection may have a higher tendency to rupture during trial of labor after cesarian.

What this paper adds: Peripartum infection in the first caesarean delivery, may be an independent risk-factor for uterine rupture in a subsequent delivery. Compared to other infections, endometritis may pose the greatest risk for uterine rupture or dehiscence.

Cesarean section (CS) is one of the most common surgeries worldwide, performed on one in three women in the United States and up to four in five women in other regions of the world.(1) The rate of vaginal birth after Cesarean section (VBAC) is low; estimated at 13.3% in the United States.(2) In the UK, only 52.2% attempt VBAC for their second birth.(3) The implications of repeat CS on morbidity include higher rates of blood transfusions, surgical injuries and hysterectomies, with increased rates of complications as the number of CS increases.(4)^,(5) When consulting a woman regarding mode of delivery, the risks and benefits of trial of labor after Cesarean (TOLAC) should be discussed.(6) Each woman should be advised according to her own obstetric and demographic characteristics for uterine rupture.(7) Known risk-factors for uterine rupture are well-established but surgical site infection (SSI) in the first CS has not been investigated in depth. The few studies are small and most did not isolate the type of infection as an independent risk factor.(8) .

Peripartum infections may influence scar tissue healing and consequently affect uterine scar strength and ability to remain intact during subsequent pregnancies and deliveries.

It is well-established that surgical scar infection is a risk-factor for impaired healing.(9) Although not commonly considered a risk-factor, a surgical scar with previous SSI may have a higher tendency to rupture during TOLAC.

This study investigated whether peripartum infection in the first CS is an independent risk-factor for uterine rupture in a subsequent delivery.

This retrospective case-control study was performed in a single academic medical center from March 2014 to October 2020. During this time 49,455 deliveries occurred, out of which 8,801 CS were performed and 237 TOLAC. Women with uterine rupture or dehiscence were included in the study group and compared to women who had a successful TOLAC (the control group). Demographic and obstetrical data, as well as any record of infection during or within a month after a prior CS were investigated.

Rupture of the uterus was defined as complete disruption of the previous Cesarean scar with communication between the uterine and abdominal cavities. Dehiscence of the scar was defined as incomplete disruption that included ruptured uterine muscle with intact serosa as the only layer keeping the fetus in the uterus. All cases of rupture and dehiscence were identified during CS.

The electronic medical records (EMR), were reviewed for demographic characteristics (age, BMI, gravity, and parity) and for medical information (regarding phase of delivery at first CS, surgical technique, and inter-delivery interval), and neonatal birth weight. Infection was defined as either intrapartum with maternal temperature above 38^°C during or up to 24 hours after delivery. Postpartum fever was defined as maternal temperature above 38^°C, 24–48 hours after delivery, and SSI was defined according to the 2018 ACOG criteria and included endometritis, infected hematoma or infection of surgical wound up to 30 days from the previous CS.(10) The diagnosis of SSI was determined based on readmissions after CS with non-prophylactic antibiotic treatment and the diagnosis of either Endometritis, Hematoma, Scar infection or wound infection, as well as analysis of laboratory data of wound cultures and the clinical impression written by the medical team in the EMR.

Based on a uniform protocol, all women undergoing CS received standard infection-prevention measures, including preoperative intravenous (IV) antibiotic prophylaxis with one to two grams of cefamezine based on maternal weight, surgical length and blood loss. For women allergic to penicillin, clindamycin and gentamicin were administered.(11)

Intrapartum fever was treated with a combination of ampicillin and gentamicin, while women with intrapartum fever undergoing CS also received IV metronidazole. Postpartum fever and endometritis were treated with IV Augmentin up to 48 hours from the last fever, according to protocols suggested by ACOG.(12) Women with large infected abdominal hematomas or any other severe infection were treated with a triad of ampicillin, gentamicin and IV metronidazole until improvement was noted or positive cultures allowed more specific treatment, according to institutional guidelines.

We compared three groups and subgroups: 1) All women with rupture or dehiscence compared to controls (no rupture or dehiscence), 2) Rupture vs dehiscence, and 3) Rupture vs controls. We evaluated each group in terms of the type of infection as a risk-factor for rupture or dehiscence: intrapartum chorioamnionitis, postpartum endometritis, or SSI.

Ethics approval

The Medical Center Institutional Review Board (IRB) approved the study, which was performed in accordance with the Ethical Standards of the Declaration of Helsinki and its later amendments, on 22 October 2020. Informed consent was waived due to the retrospective study design (Meir Center IRB)

Data analysis

Statistical analysis was performed using SPSS, version 21.0 software (IBM Corp., Armonk, NY). Continuous variables were compared with Mann-Whitney U-test. Chi-square or Fisher’s exact test was used for categorical data, as appropriate. Demographics and medical data were compared between the study and control group using univariate analysis. Potential confounders and significant variables in the univariate analysis were entered into multivariable binary regression analysis to establish their effect on the risk for uterine rupture. A probability value < 0.05 was considered significant.

A total of 71 women were included in the study group, of whom 40 experienced complete thickness uterine rupture and 31 had uterine scar dehiscence. They were compared to 97 cases of successful VBAC matched by maternal age, BMI, gestational age, and neonatal birth weights of the first and second deliveries.

The basic characteristics of the study and the control groups are shown in Table 1. Maternal age, gravidity and parity were higher in the study group, as expected by the study design. The study group included women with dehiscence or asymptomatic rupture in a repeat CS, whereas the control group included women at their VBAC, which means they only had one prior CS. Although the study group was statistically older than the control group (30.2 ± 4.8 years vs. 27.8 ± 4.6 years, p=0), this difference is not clinically significant. There were no significant differences between the groups regarding neonatal birth weight at first delivery and a statistical, but not clinically meaningful difference in birth weight at the second delivery. These potential confounders were included in the logistic regression (Tables 2,3). Infection in the previous delivery remained statistically significant, with odds ratio of 3.41

Sixteen of 71 (22.5%) women with uterine rupture or dehiscence during the current birth, had an infection in proximity to their previous CS, compared to 8 of 97 (8.2%) in the control group (p=0.01).

We also compared the group with complete uterine rupture to the control group. Among 40 women with uterine rupture, 10 (25%) had an infection at their first CS, as compared to 8 of 97 (8.2%) of the controls (p=0.008). This result remained statistically significant in the logistic regression (Table 3). There was no difference regarding the infection rate between the uterine rupture group and the dehiscence group (25% vs. 16%, p= 0.27).

We divided the type of infection into three groups: intrapartum fever, postpartum fever and SSI. SSI and in particular endometritis, had the strongest correlation to uterine rupture at subsequent delivery. None of the control group women had endometritis, but 7 of 71 (9.8%) in the study group and 5 of 40 (12.8%) in the complete rupture group did. No significant difference was found between groups in terms of intrapartum fever (Table 4).

This study found that women who experienced an infection at their previous CS had a significantly higher chance of uterine rupture at their next delivery. SSI found to be most correlated with uterine rupture, with endometritis the most common type. The least correlated was chorioamnionitis (intrapartum fever), meaning that the timing of infection may have a decisive effect on the risk of rupture or dehiscence.

Lieberman et al.⁷ found a correlation between infection and rupture. The rate of postpartum fever was 38% (8/21) in the uterine rupture group compared to 15% (13/84) in the control group (p = 0.03).(8) Like our study, no statistical difference in the intrapartum fever group was found. They reviewed women from 1984 to 1996, with 70–75% receiving antibiotic prophylaxis. Our results are based on deliveries from 2014 to 2022, with 100% antibiotic prophylaxis according to ACOG guidelines and a very organized, prospective data collection system, based on ICD-9 codes and detailed review of the EMR.

Gabbay‑Benziv et al. found a correlation between complications at first CS (infection, post-partum hemorrhage) and uterine rupture during TOLAC.(13) They had 3 cases of infection, all of which were fever documented during postpartum admission (4 days). In our study, 24 cases of infections were documented, 13 of which were diagnosed after readmission due to symptoms of infection.

Vilchez et al. found that chorioamnionitis during the index delivery is a risk-factor for uterine rupture (odds ratio 5.7).(14) They concluded that this was probably due to the association with protracted labor. Our study explored the impact of the infection itself on the uterine scar, evaluated at the next delivery.

Limitations of this study are its retrospective nature and the small number of women. Including dehiscence cases caused the groups to be heterogeneous in terms of gravity, parity and maternal age. However, none of these variables were significant in the regression analysis, showing that infection is well-correlated with uterine rupture. The average gestational age, was younger in the study group compared to the controls and birth weights were smaller. We believe this may be due to symptoms of rupture that developed earlier and led to an emergent CS.

Since our data come from a single tertiary center, treatment and surgical protocols were relatively uniform. Only 1% of the study group and 3% of the controls received pitocin for augmentation during TOLAC. One patient in the control group was induced using an Atad catheter, as compared to none in the study group. Uterine closures of the first CS were done in two layers. The interval between the initial and subsequent CS was 38.7 ± 24.4 months in the study group and 28.6 ± 10.7 months in the control group (p = 0.00). However, there were large variations within groups. The experience of a traumatic labor (such as one accompanied by infection or re-hospitalization) may affect the time interval between deliveries but many other factors can affect this decision and this topic requires further research.

We analyzed women with dehiscence or uterine rupture (n = 71) and a subgroup of women with complete uterine rupture (n = 40),because we believe that uterine rupture and dehiscence are one sequence of the same entity, with the same etiology. Thus, it was important to include cases of dehiscence in the analysis. However, we understand that including them may pose a confounder because some women in the control group may have had subclinical dehiscence during their VBAC, and since we do not perform a routine scar test after successful VBAC, these cases could be underdiagnosed. Therefore, we chose to analyze the groups together and separately and show that in both, infection in the first delivery was a risk-factor for uterine rupture.

This study investigated a possible new risk-factor for a disastrous event. Further studies are needed to establish this finding but this is a manageable risk and its incidence can be reduced.

Knowing that infection in general and endometritis specifically may increase the risk for uterine rupture in the next delivery, should inform the treating staff on the following issues: when consulting with a patient on repeat CS vs TOLAC, endometritis after the previous CS should be included among the considerations, along with other traditional risk-factors. In addition, our results emphasize the importance of adhering to the guidelines for perioperative preventative treatment of infection, and finally, diagnosed infection in general and endometritis, in particular, should be treated quickly and properly.

Ethics approval and consent to participate: The Medical Center Institutional Review Board approved the study, which was performed in accordance with the Ethical Standards of the Declaration of Helsinki and its later amendments, on 22 October 2020. Informed consent was waived due to the retrospective study design.

Consent for publication: All Authors consented the manuscript publication.

Availability of data and materials: The datasets generated and/or analysed during the current study are not publicly available due to patients privacy but are available from the corresponding author on reasonable request.

Competing interest: The authors report no conflict of interests.

Funding: None.

Author Contributions:

• R. Tamir Yaniv - Conception and design of the study and manuscript, critical revision of the manuscript for important intellectual content.

• S. Farladansky-Gershnabel- Conception and design of the study and manuscript, critical revision of the manuscript for important intellectual content.

• H. Gluska - Acquisition of data, statistical analysis, Critical revision of the manuscript for important intellectual content

• Y. Daykan- Critical revision of the manuscript for important intellectual content

• G. Shechter Maor - Critical revision of the manuscript for important intellectual content

• R. Schonman - Critical revision of the manuscript for important intellectual content

• T. Biron-Shental – Critical revision of the manuscript for important intellectual content, Supervision.

Acknowledgments: Faye Schreiber, MS edited the manuscript. She is an employee of Meir Medical Center.

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Table 1: Characteristics of the groups

First cesarean delivery	Control group: Successful VBAC (n=97)	Study group: Rupture& dehiscence (n=71)	P-value	Study group: complete uterine rupture (n=40)	P-value
Maternal age, years ± SD	27.8 ± 4.6	30.2 ± 4.8	0.00	29.9± 4.54	0.03
Gravidity	3	3.69	0.01	3.4	0.16
Parity	1.5	1.96	0.03	1.8	0.22
Timing of the CD, n (%)
Elective	27 (28)	24 (35)	0.34	9 (24)	0.69
Emergent before labor	10 (10)	6 (9)	0.73	4 (11)	0.93
Emergent at 1^st stage of labor	42 (43)	33 (48)	0.57	21 (57)	0.17
Emergent at 2^nd stage of labor	18 (19)	6 (9)	0.06	3 (8)	0.09
Postpartum hemorrhage, n (%)	4 (4)	4 (6)	0.6	4 (11)	0.24
Neonatal birth weight, grams	3024.03± 652.2	2933± 737.8	0.42	2730±798	0.05
Second delivery
Maternal age, years ± SD	29.94±4.63	33.46± 4.9	0.00	33.1±4.43	0.00
BMI	29.07±4.37	29.12±5.07	0.97	28.35±5.44	0.62
Months since CD	28.67± 10.7	38.7±24.4	0.00	41.34±25.4	0.00
Induction, n (%)	2 (2)	0	0.16	0	0.37
Gestational age, weeks	38.95±1.39	36.97±3.41	0.00	36.6±3.7	0.00
Augmentation (Pitocin), n (%)	1 (1)	1 (1)	0.81	1 (3)	0.92
Neonatal birth weight, g ± SD	3196.4± 434	2993.3± 669	0.03	2916± 709	0.03

VBAC- Vaginal Birth After Cesarean Section

CD- Cesarean Delivery

BMI – Body Mass Index

Table 2. Table of multiple logistic regression including possible confounders to demonstrate the independent association between infection and uterine rupture and dehiscence

Variable	B	Sig.
Infection	1.438	0.018
Parity	0.986	0.475
Gravity	0.149	0.659
Maternal age	0.129	0.004
Neonatal birth weight	-0.001	0.161
1^st stage duration	0.618	0.183
Constant	-5.057	0.024

B=Beta

Table 3. Table of multiple logistic regression including possible confounders to demonstrate the independent association between infection and uterine rupture only.

Variable	B	Sig.
Infection	1.421	0.053
Parity	0.231	0.891
Gravity	0.838	0.059
Maternal age	0.134	0.024
Neonatal birth weight	-0.001	0.04
1^st stage length	-0.039	0.949
Constant	-3.325	0.238

B= Beta

Table 4: Infection type

Variable	Control group (n=97)	Study group (n=71)		Complete rupture (n=40)
Intrapartum fever	8 (8.2%)	3 (4.2%)	P= 0.63	1 (2.5%)	P=0.42
Postpartum fever	0	5 (10%)	P=0.02	2 (5%)	P=0.16
Endometritis	0	7 (9.8%)	P=0.002	5 (12.5%)	P=0.02

No competing interests reported.

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Peripartum infection at cesarean delivery may be related to uterine rupture during a subsequent trial of labor

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Abstract

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Introduction

Material And Methods

Ethics approval

Data analysis

Results

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