Incidence of postpartum infection, outcomes and associated risk factors at Mbarara regional referral hospital in Uganda

Postpartum infection is a leading cause of maternal mortality worldwide. Approximately five million cases of pregnancy-related infection occur every year globally, and approximately 75,000 result in death [1, 2]. Infection incidence is higher in low-resource settings, and many infection-related maternal deaths are preventable [1, 2]. Postpartum infections are a subset of maternal infections occurring between delivery and the 42nd day postpartum [3]. The most common postpartum infections include endometritis (puerperal sepsis), urinary tract infections, surgical site infections, blood stream infection and wound infections [3, 4]. In a retrospective study from Mbarara Uganda, puerperal sepsis accounted for 31% of maternal deaths, making it the most common cause of maternal mortality at that facility [5].

Most research on postpartum infections has occurred in high resource countries, where risk factors include poor intrapartum hygiene, low socioeconomic status, primiparity, prolonged rupture of membranes, prolonged labor, and having more than five vaginal exams intrapartum [6]. In these settings, cesarean delivery appears to be the single most important risk factor for postpartum infection [3, 6]. In low-resource settings, risk factors for postpartum infection are poorly defined and may differ from high-resource settings due to patient, environmental and healthcare system factors [1]. In addition, most published studies from low-resource settings do not include microbiological confirmation of infection or infectious outcomes [3].

We performed a prospective cohort study to determine the incidence of postpartum infection among women with postpartum fever or hypothermia presenting for delivery or postpartum care at Mbarara Hospital. In addition, the study compared clinical outcomes between the fever/hypothermic group and the normothermic group, and examined risk factors associated with incident fever/hypothermia and a composite postpartum infection outcome.

In this prospective cohort of women presenting to a Ugandan regional referral hospital, among those who developed postpartum fever/hypothermia, cesarean delivery was the strongest independent risk factor for developing endometritis or a composite postpartum infection outcome. Other risk factors independently associated with postpartum infection included longer hospital stays and attending antenatal clinic fewer than the four visits recommended by 2015 Ugandan national guidelines. Therefore, efforts should be made to reduce the high proportion of cesarean deliveries, increase antenatal care attendance, reduce the number of days of admission and reduce the number of days of indwelling urethral catheters.

The incidence of postpartum fever or hypothermia in our cohort was 5%, and a source of infection was confirmed in 48% of those with documented fever or hypothermia, for a 2% overall incidence of confirmed in-hospital postpartum infection. The overall fever and infection incidence we report here is low. However, the most common infection among our participants was postpartum endometritis, and among cesarean deliveries we report an incidence of (7%), over 3-fold greater than estimates from high-resource settings (1.8–2.0%) [11‐13]. Though infection incidence in Mbarara appears higher than European and North American estimates, comparing our findings to other low-resource settings is difficult. The reported incidence of postpartum endometritis in sub-Saharan Africa varies widely, likely due to differences in infection definition, surveillance, diagnosis, patient population and healthcare practices. One study at Uganda’s largest referral hospital, where HIV prevalence is 21%, reported 73/478 (15%) patients undergoing emergency cesarean delivery developed postpartum endometritis [14], more than double the 7% incidence reported here. The lower incidence of postpartum endometritis we report may reflect differences in practice, antibiotic use, and infection control procedures within Uganda. Also, the other Ugandan study was published in 2011, at a time when fewer HIV-infected women were on antiretroviral therapy, which could have led to higher infection rates. Historically, HIV has been associated with increased risks of postpartum sepsis, including postpartum endometritis [15]. Other studies from sub-Saharan Africa report postpartum endometritis in 1–17% after cesarean delivery [16‐20], and our report of 7% incidence falls within this wide range. Though the incidence we report here is relatively low, postpartum infection may become more common in sub-Saharan Africa as a result of increasing cesarean delivery rates coupled with rising incidence of nosocomial infections [7].

We found UTIs in 14% and bloodstream infections in 3% of febrile/hypothermic participants. Comparisons of the incidence of UTI and bloodstream infections to other studies are difficult, as these infections are defined and reported inconsistently in the few other studies from sub-Saharan Africa [13, 14]. However, postpartum UTI incidence in some European studies is as low as 3% after cesarean delivery and 2% after vaginal delivery [21]. The difference in UTI incidence between our study and the other studies may be attributable to the fact that laboratory diagnosis of UTIs in our study was performed only for febrile and hypothermic participants, a group with a high likelihood of infection. It is also possible that cesarean delivery preparation and urinary catheter days may differ in other settings.

Report of sexually transmitted infection diagnosis during pregnancy, cesarean delivery, increasing number of hospital days, lack of formal employment and primiparity were independently associated with fever/hypothermia in our cohort. Predictors of postpartum fever in low-resource settings are not very well described in the literature, except that prolonged second stage of labor is a risk factor for postpartum fever [2]. Our report of postpartum fever associations with STIs and primiparity is not reported elsewhere in the literature, and merits further investigation.

Of note, birth and perinatal outcomes were overall worse in the fever/hypothermic group compared to the normothermic group. It is possible these differences reflect a pathological process present before delivery which could have contributed to poor fetal and neonatal outcomes. This is an area of investigation that should be explored to better understand maternal inflammatory and infectious contributors to stillbirth and early neonatal death and how to prevent postpartum infection.

Cesarean delivery was associated with the composite in-hospital postpartum infection outcome (including confirmed diagnosis of UTI, endometritis or bloodstream infection). In fact, in multivariable logistic regression models for each of the three outcomes (fever/hypothermia, endometritis, postpartum infection composite outcome), cesarean delivery was independently associated with each outcome with adjusted odds ratios of 2.7–3.9. This finding is consistent with other reports that postpartum infection is three times more likely to occur after cesarean section than after vaginal delivery [22]. In addition, the population attributable fraction of postpartum fever and postpartum infections due to cesarean delivery in our study was 44%. Our findings support previous research indicating that cesarean delivery is the most important risk factor for developing postpartum infection [3, 6, 23]. Our results should reinforce efforts to reduce cesarean delivery rates to appropriate levels to avoid preventable, cesarean-associated infections. In addition, antibiotic prophylaxis, hygienic delivery, and postpartum care conditions should continue to be emphasized as important factors mitigating infection risk. We also found that attending the recommended number of antenatal care visits (≥4 times during pregnancy at the time this study was conducted) was associated with reduced odds postpartum infection. Antenatal clinic interventions may help prevent postpartum infection through earlier detection and treatment of disease conditions, including sexually transmitted infections and UTI. Lastly, long hospital stays are a known risk factor for developing postpartum UTIs [23], and likely contribute to incident postpartum endometritis. Though prolonged hospitalization can result from fever or infection, it can also contribute to development of infection through increasing nosocomial transmission risk, prolonged exposure to invasive catheters and devices, and unhygienic conditions.

Strengths of our study include the prospective study design, large sample size, near-complete enrollment of eligible women seeking care at MRRH during the study period, and an in-depth clinical and microbiological evaluation of participants with suspected infection. Of note, at MRRH cesarean deliveries are performed under spinal anesthesia, and no cesarean or vaginal delivery participants had epidural anesthesia for labor analgesia. Epidural placement is one of the commonest causes of fever in labor and immediate postpartum period [24, 25], but does not confound the findings in our study.

Limitations of our study include reliance on chart diagnosis of surgical site wound infection, which was inconsistently documented. Though the initial study design did not include wound infection as part of the composite postpartum infection outcome, cesarean surgical site infection is a known cause of postpartum fever [26] and may account for a high proportion of fevers and hypothermia in participants with no other confirmed infectious source after our evaluation. We abstracted chart diagnosis of cesarean section surgical site infections but did not perform clinical or microbiologic evaluation of these infections. Lack of confirmation of cesarean wound infections is a limitation of our study since these are likely under-reported inpatient charts. In addition, due to resource constraints, we were unable to perform clinical or microbiological testing of normothermic participants and thus unable to determine the incidence of infection in the normothermic group. However, we expect that clinically significant in-hospital postpartum infections would include fever or hypothermia and therefore we believe we were unlikely to have missed significant infections in normothermic women. Prolonged rupture of membranes is a known risk factor for postpartum infection but was not directly measured in this study. We collected participant-reported duration of labor as one measurement of prolonged labor but we did not measure duration of membrane rupture directly. Lastly, at this regional referral hospital cesarean deliveries are common, accounting for 50% of all deliveries in this study. Though the cesarean delivery rate is high at MRRH, 50% may overestimate the true cesarean delivery rate due to early discharge and non-enrollment of some women delivering vaginally. We documented whether a woman was prescribed antibiotics on the same day as her cesarean section procedure, but we were unable to confirm whether these were given, nor determine the timing of the prescription relative to the procedure. Future research should address infections occurring after hospital discharge, incident in-hospital and post-discharge surgical site infection, and the impact of prophylactic antibiotics on incident infection and development of antimicrobial resistance.

In our low-resource setting, cesarean delivery is independently associated with risk of incident in-hospital postpartum fever/hypothermia, endometritis and a composite postpartum infection outcome. Other independent risk factors for postpartum infection include longer hospital stays and attending antenatal clinic fewer than the recommended four visits. Efforts at reducing the high proportion cesarean deliveries, increasing antenatal care attendance, and reducing the number of days admitted and days of urethral indwelling catheter need to be optimized. With the high proportion of women with no identifiable source of infection, there is need for better bedside diagnostic means and antimicrobial evidence-based prescription.