Background/Objective: The purpose of this study was to discuss some risk factors which may increase risk of infectious morbidity after cesarean section despite of applying prophylactic measures including skin cleansing and prophylactic antibiotic.

Methods: This single randomized controlled study was conducted at the Obstetrics and Gynecology department, El Minya general hospital, El Minya, Egypt, from January 2017 to January 2018. Women included in the study were: women undergoing cesarean delivery, both elective and non-elective, women with rupture of membrane and labor contractions, all maternal ages and parities, both single and multiple pregnancies. Skin cleansing with povidone-iodine was applied and antibiotic was administered to all women just before cesarean section was done. Patients were discharged after 24 hours and were recommended to re-visit on day 7 after CS and that’s when our first clinical evaluation of surgical wound was performed. A second wound evaluation was scheduled on day 14. In order to assess whether individual pre-, peri- and post-operative variables affect the development of surgical site infection in women undergoing CS, a logistic regression model with forward selection was designed. The model included the following variables: age, parity, gestational age, BMI, pre-gestational or gestational diabetes mellitus, chronic or pregnancy-induced hypertension, previous CS, mode of CS, and duration of surgery. The primary outcome in this study was development of superficial or deep surgical site infection within the first 14 days after a CS.

Results: Among 1500 mothers included in the study, 250 (16.7 %) women developed SSI. The odds of SSI was increased by 9.441(95% CI: 5.872-15.180) among mothers who had prolonged rupture of membrane. Diabetic mothers were at higher risk for developing SSI with OR 7.384(95% CI: 4.591-11.874). Increasing BMI was associated with SSI with OR 1.478(95% CI: 1.388-1.573). Prolonged duration of surgery was associated with SSI with OR of 1.048 (95% CI: 1.018-1.079).

Conclusions: In view of these results, a list of factors including prolonged labor and prolonged rupture of membrane, long duration of surgery, increase in BMI and presence of DM were associated with SSI. Clinicians should consider earlier or more frequent postoperative follow-up in case of presence of one or more of these factors in patients to monitor for wound complications.

Background

Infectious complications following obstetric surgical procedures are considered a significant source of maternal morbidity and even potential mortality [1]. As the cesarean birth rate continues to rise in most developing countries, postpartum infectious morbidity will become an even more significant problem [2]. Cesarean section is considered the most important risk factor for postpartum infection. Women undergoing cesarean section have a 5 to 20-fold greater risk for infectious morbidity compared with a vaginal birth [3]. Incisional wound infection defined according to the Centers for Disease Control and Prevention (CDC) criteria as a superficial or deep surgical site infection occurs after a CS, being one of the most common complications that may lead to wound dehiscence or systemic infections in case of lack of sufficient prophylaxis or inappropriate treatment [4-9]. Increased morbidity, prolonged hospitalization time, increased rate of hospital readmissions and growing treatment costs are all consequences of the above [10].

Infectious complications following cesarean birth include fever, wound infection, endometritis, and urinary tract infection. Serious infectious complications including pelvic abscess, bacteremia, septic shock and septic pelvic vein thrombophlebitis; sometimes these complications can lead to maternal mortality [11]. Preventive measures have been suggested to avoid post cesarean infection including proper preparation of an incision site which will reduce the bacterial population to a minimal level [12].

Also, guidelines recommend the use of antibiotics for prophylaxis against post cesarean section infection in both high-risk women “e.g. women in labor, after rupture of membranes’’ and low-risk patients ‘‘women not in labor, with intact membranes” with decreasing rates of wound infection and endometritis [13]. Taking into account the continuously increasing number of CS and wide spread of factors responsible for wound healing disturbances in the population of women of reproductive age, such as obesity, diabetes and smoking, it is necessary to search for new, more effective methods to prevent infections of surgical wounds.

So this study aims to discuss some risk factors which may increase risk of infectious morbidity after cesarean section despite of applying prophylactic measures including skin cleansing and prophylactic antibiotic.

Material and Methods

Study setting

This study was carried out in the Obstetrics and Gynecology department, El Minya general hospital, El Minya, Egypt, from January 2017 to January 2018.

Study design

This study is a single randomized controlled study. (ClinicalTrials.gov ID: NCT03007706).

Ethical issues

Ethical permission was sought from a Local Research Ethics Committee (REC) .The potential benefit, the nature, the aim and inconveniences of all aspects of the study were clearly stated to the participants. So the study poses no harm regarding the safety issues to the mother or the fetus. In order to assure confidentiality, the data were extracted without any personal identifiers.

Study participants

All the following women were included in our study: women undergoing cesarean delivery, both elective and non-elective, women with rupture of membrane ad labor contractions, all maternal ages and parities, both single and multiple pregnancies were included.

However, women with unknown outcome, those who refused to participate in the study, women with fever > 38°C, and those who were having any visible infection or allergy to antibiotics were excluded.

Pursuant to the valid study protocol, skin cleansing with povidone-iodine was applied and antibiotic was administered to all women just before cesarean section was done. According to management strategy patients were discharged after 24 hours and were recommended to re-visit on day 7 after CS and that’s when our first clinical evaluation of surgical wound was performed.

On the discharge day all patients received detailed instructions regarding Surgical Site Infections (SSIs) and were informed about the need to report at hospital in case at least one of the following symptoms was observed: fever, suppurative secretion from the surgical site, redness, edema, warmth, pain or tenderness of the surgical site area. A second wound evaluation was scheduled on day 14. Patients who didn’t report for follow-up visits were excluded from the final analysis.

Statistical Analysis

The primary outcome in this study was development of superficial or deep SSI within the first 14 days after a CS.

In order to assess whether individual pre-, peri- and post-operative variables affect the development of surgical site infection in women undergoing CS, a logistic regression model with forward selection was designed. The model included the following variables: age, parity, gestational age, BMI, pre-gestational or gestational diabetes mellitus, chronic or pregnancy-induced hypertension, previous CS, mode of CS, and duration of surgery.

Data were collected, revised, verified, coded, then entered PC for statistical analysis done by using SPSS statistical package version 20.

The following had been done:

Descriptive statistics

• For quantitative data: mean (X~) and Standard Deviation (SD).

• For qualitative data: number (n) and percentage (%)

• Kolmogorov- Smirnov for normality test was used to differentiate between parametric data and non-parametric data.

Analytical statistics

• Independent sample t-test for analysis of quantitative data.

• Chi square (X2) test, Fisher Exact test for analysis of qualitative data.

• Binary logistic regression for risk factors of postoperative infection for all tests probability (p) was considered:

o Non-significant if ≥ 0.05

o Significant if < 0.05

o Highly significant if < 0.01

o Very highly significant if < 0.001

Results

Socio-demographic and medical characteristics

Among 1550 women, 1500 women were included in our study in the reference period; the mean age was 28 years ranging from 18 to 42 years. Regarding parity 250 (16.7%), 980 (65.3 %) and 110 (7.3%) were primigravida, 1-4 and more than 4 respectively. Regarding BMI 1000 (66.7%), 440 (29.3%) and 60 (4%) were of BMI < 25, 25-30 and > 30 respectively.

Prevalence of SSI

Among 1500 mothers included in the study 250 (16.7 %) women developed SSI.

Factors associated with SSIs after CS

Variables were considered for the analysis include: maternal age, parity, previous CS, gestational age, BMI, presence of chronic disease, duration of CS, rupture of the membrane, circumstance of the surgery (elective or emergency). Of these variables, six were significantly associated with SSI and hence considered for the multivariate analysis. In the multivariate model, four turned out to be significant (Table 2).

The odds of SSI was increased by 9.441(95% CI: 5.872-15.180) among mothers who had prolonged rupture of membrane. Diabetic mothers were at higher risk for developing SSI with OR 7.384(95% CI: 4.591-11.874).Increasing BMI was associated with SSI with OR 1.478(95% CI: 1.388-1.573). Prolonged duration of surgery was associated with SSI with OR of 1.048 (95% CI: 1.018-1.079).

Discussion

The study showed that surgical site infection after CS is common. It is also affected by various modifiable factors. The study found that 16.7% of the women who had CS developed wound infection. This study may be considered insufficient as the diagnosis of SSI was solely made on clinical basis so, localized infection, which may not be presented with the classical manifestations of inflammation, might have been missed [14].

It is worth mentioning that other studies as that had been conducted in Southern Ethiopia in 2017 at University Teaching and Referral Hospital by Samuel W. et al. reported prevalence of SSI 11%. A study conducted in Tikur Anbessa Hospital, Addis Ababa, found 14.8% wound infection rate among surgical patients operated for various conditions [15]. Studies from Nepal [16], Tanzania [17], Nigeria [18] and Cameroon [19] reported 9% -13% prevalence. However, a study from Kenya reported a relatively higher (19%).

From the analyzed data in this study, it was revealed that there were some important risk factors associated with the development of infectious morbidity:

In this study, rupture of membrane had substantially increased risk of SSI [p-value < 0.001]. Studies conducted in Ethiopia, Kenya [20], Tanzania [17], Nigeria [18], Qatar [21], Israel [22] and US [23] reported more or less similar findings. Prolonged labor and rupture of membranes contribute to amniotic fluid colonization from the normal flora of the lower genital tract and lead to surgical wound and peritoneal cavity contamination [24].

In this study, prolonged duration of surgery (more than 40 minutes) was associated with increased risk of SSI. Other studies also witnessed the same. A case-control study in Nigeria by Jido et al. in 2012 found that 55% of SSI cases, compared to 31.7% in controls, had prolonged duration of surgery [18]. In Tanzania, long duration of surgery was significantly associated with the outcome with hazard ratio of 2.3 [17]. A study in China came up with a parallel finding [25]. Prolonged duration of surgery may raise the risk of SSI by increasing the risk of exogenous contamination [26].

We observed in this study that overweight and obese patients with BMI > 25, have a considerable increase in risk for postoperative complications compared with non-obese patients. Most recently, Connor and colleagues [27] performed a retrospective cohort study that revealed a positive dose-response relationship between obesity severity and cesarean wound complication rate.

Regarding presence of chronic disease, it was obvious in our study that women with diabetes mellitus are more likely to develop postoperative SSI than non-diabetic women (with odds ratio 7.384 and P-value < 0.001) thus considering Diabetes mellitus as a long-recognized comorbidity associated with postoperative wound complication. This result is similar to other studies in the surgical literature [28] mentioning that poorly controlled diabetes results in advanced glycosylation end products, with impairment of the host immune response and decreased re-epithelialization of wounds [28].

An unintended side-effect of suppressing the immune system is a direct impairment of the inflammatory phase of wound closure. As a result, there is decreased fibro genesis, macrophage response, and angiogenesis [28]. This situation may lead to delayed closure, wound breakdown, and infection [28].

Other studies identified DM as an important risk factor associated with increased rate of wound infection [29-32].

Conclusion

In conclusion, a list of factors including prolonged labor and prolonged rupture of membrane, long duration of surgery, increase in BMI and presence of DM were associated with SSI. Surgical wound infection should be prevented by implementing infection prevention techniques. Pregnant patients with one or more of these factors are at increased risk for developing post cesarean infectious morbidity and other postoperative complications. These data can be used to counsel these patients on operative risks. Our findings suggest that clinicians should consider these factors in delivery mode decisions and may need to alter the threshold for using cesarean delivery in those patients compared.

Additionally, clinicians should consider earlier or more frequent postoperative follow-up in case of presence of one or more of these factors in patients to monitor for wound complications. Our results confirm an urgent need for clinical trials to research novel strategies to minimize unnecessary CD and to develop perioperative methods to reduce the risks of cesarean delivery in high risk patients.

Ethical Consideration

Institutional Review Board (IRB) approval: The protocol was discussed and approved by the ethical scientific committee of Minia University Maternity Hospital.

Subject Confidentiality

All reports, operative details and other records that leave the site would not comprise unique personal data to maintain subject confidentiality.

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