Adapting the preterm birth phenotyping framework to a low-resource, rural setting and applying it to births from Migori County in western Kenya.

BACKGROUND: Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both maternal and fetal factors. To better understand preterm birth trends, the Global Alliance to Prevent Prematurity and Stillbirth published the preterm birth phenotyping framework in 2012 followed by an application of the model to a global dataset in 2015 by Barros, et al. Our objective was to adapt the preterm birth phenotyping framework to retrospective data from a low-resource, rural setting and then apply the adapted framework to a cohort of women from Migori, Kenya. METHODS: This was a single centre, observational, retrospective chart review of eligible births from November 2015 - March 2017 at Migori County Referral Hospital. Adaptations were made to accommodate limited diagnostic capabilities and data accuracy concerns. Prevalence of the phenotyping conditions were calculated as well as odds of adverse outcomes. RESULTS: Three hundred eighty-seven eligible births were included in our study. The largest phenotype group was none (no phenotype could be identified; 41.1%), followed by extrauterine infection (25.1%), and antepartum stillbirth (16.7%). Extrauterine infections included HIV (75.3%), urinary tract infections (24.7%), malaria (4.1%), syphilis (3.1%), and general infection (3.1%). Severe maternal condition was ranked fourth (15.6%) and included anaemia (69.5%), chronic respiratory distress (22.0%), chronic hypertension prior to pregnancy (5.1%), diabetes (3.4%), epilepsy (3.4%), and sickle cell disease (1.7%). Fetal anaemia cases were the most likely to transfer to the newborn unit (OR 5.1, 95% CI 0.8, 30.9) and fetal anomaly cases were the most likely to result in a pre-discharge mortality (OR 3.9, 95% CI 0.8, 19.2). CONCLUSIONS: Using routine data sources allowed for a retrospective analysis of an existing dataset, requiring less time and fewer resources than a prospective study and demonstrating a feasible approach to preterm phenotyping for use in low-resource settings to inform local prevention strategies.

Preterm birth is a complex syndrome, yet it is the leading cause of death in children worldwide. To help unravel the clinical complexities, preterm birth phenotyping is a framework that considers multiple diagnoses in the mother, helping to evaluate trends in causes of preterm birth in a given region. In our study, we adapted this international phenotyping framework to accommodate a rural, low-resource setting where obstetrical and neonatal technologies were limited, but preterm birth rates were high. We evaluated data from the patient records of a large hospital in Migori, Kenya, in the southwestern region of the country. By lowering the threshold of diagnostic criteria, we were able to apply this framework to our dataset and see that maternal infection and maternal chronic illness appear to be a significant driving forces of preterm birth. Given high rates of HIV and malaria in the region, this is not a surprising finding, but one that can inform antenatal care practices, mainly the need to test and treat for common infections (HIV, malaria, as well as urinary and reproductive tract infections), and to increase the frequency of antenatal care interactions per the World Health Organization recommendations.

Association of differential symptoms of stress to hair cortisol and cortisone concentrations among pregnant women in Kenya.

Objectives: The purpose of this study was to characterize the stress experienced by pregnant women in Kenya and assess the relationship between perceived stress and stress-related biomarkers of cortisol and cortisone.Background: Kenyan women are exposed to multiple stressors that may result in chronic stress. However, antenatal stress has not been examined and characterized in Kenya; nor has the relationship between pregnant women's self-reported stress and stress biomarkers been established.Methods: One hundred and fifty women were recruited between 22 and 28 weeks gestation. Participants completed the Perceived Stress Scale (PSS) and a sociodemographic questionnaire. Hair samples were obtained for analysis of cortisol and cortisone. Factor analysis was used to extract unique clusters of stress symptoms from items in the PSS. Regression models were computed to examine relationships of stress to cortisone and cortisol, controlling for obstetric risk.Results: Mean age of the women was 25 years (SD = 5, ±16-41). Their degree of perceived stress and cortisol/cortisone concentrations both indicated moderate levels of stress. There was no association between general perceived stress and either hair cortisol or cortisone. However, factor analysis of the PSS identified three clusters of stress symptoms and one cluster - a woman's negative frame of mind regarding life and inefficacy in handling its problems - was associated with higher levels of cortisone (ß= -.231, p = 0.011).Conclusions: Specific stress symptoms may have unique relationships to specific biomarkers and be more useful in assessment than general perceived stress. Assays of both hair cortisol and cortisone might enable a more comprehensive assessment of glucocorticoid activity and better prediction of health risks from stress.Lay summaryUnderstanding stress among rural pregnant Kenyan women may help in addressing risks during pregnancy that lead to adverse birth outcomes. Findings suggest that a woman's tendency to think negatively about life and to doubt her ability to handle life's problems are symptoms of stress that may contribute to higher levels of stress hormones. Assessing women's specific symptoms of stress and different stress hormones during pregnancy may more effectively identify women who need intervention to reduce their health risk.

International Image Concordance Study to Compare a Point-of-Care Tampon Colposcope With a Standard-of-Care Colposcope.

OBJECTIVE: Barriers to cervical cancer screening in low-resource settings include lack of accessible, high-quality services, high cost, and the need for multiple visits. To address these challenges, we developed a low-cost, intravaginal, optical cervical imaging device, the point-of-care tampon (POCkeT) colposcope and evaluated whether its performance is comparable with a standard-of-care colposcope. MATERIALS AND METHODS: There were 2 protocols, which included 44 and 18 patients. For the first protocol, white-light cervical images were collected in vivo, blinded by device, and sent electronically to 8 physicians from high-, middle-, and low-income countries. For the second protocol, green-light images were also collected and sent electronically to the highest performing physician from the first protocol who has experience in both a high- and low-income country. For each image, physicians completed a survey assessing cervix characteristics and severity of precancerous lesions. Corresponding pathology was obtained for all image pairs. RESULTS: For the first protocol, average percent agreement between devices was 70% across all physicians. The POCkeT and standard-of-care colposcope images had 37% and 51% agreement with pathology for high-grade squamous intraepithelial lesions (HSILs), respectively. Investigation of HSIL POCkeT images revealed decreased visibility of vascularization and lack of contrast in lesion margins. After changes were made for the second protocol, the 2 devices achieved similar agreement to pathology for HSIL lesions (55%). CONCLUSIONS: Based on the exploratory study, physician interpretation of cervix images acquired using a portable, low-cost POCkeT colposcope was comparable to a standard-of-care colposcope.

Coronavirus disease 2019 and the placenta: A literature review.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.

Stillbirth, neonatal and maternal mortality among caesarean births in Kenya and Uganda: a register-based prospective cohort study.

OBJECTIVE: To investigate the interaction of risks for adverse maternal and perinatal outcomes (stillbirth, predischarge neonatal and maternal mortality) among caesarean section (CS) compared with vaginal deliveries (VD). DESIGN: Prospective cohort study. SETTING: 10 CS-capable facilities in Busoga Region, East-Central Uganda and Migori County, Kenya. PARTICIPANTS: Individual birth data were extracted from maternity registers between October 2016 and April 2019. There were a total of 77 242 livebirths and 3734 stillbirths. Overall, 24% of deliveries were by CS with a range of 9%-49% across facilities. PRIMARY OUTCOME MEASURES: Stillbirth, predischarge neonatal mortality and maternal mortality. RESULTS: The adjusted ORs for stillbirth, predischarge neonatal mortality and maternal mortality after a CS were 1.3 (95% CI 1.1 to 1.6), 1.9 (95% CI 1.6 to 2.2) and 3.3 (95% CI 2.2 to 4.9), respectively, compared with a VD. The association between maternal mortality and CS was 3.9 (95% CI 2.8 to 5.5) when the delivery was a live birth and 1.7 (95% CI 1.0 to 3.0) when it was a stillbirth. Post hoc analyses showed that mothers who received a CS had a lower risk of stillbirth if they were documented as a referral. CONCLUSION: In this context, CS births were at higher risk for worse outcomes compared with VD. Better understanding of CS use and associated adverse outcomes within the mother-baby dyad is necessary to identify opportunities to improve quality of intrapartum care. TRIAL REGISTRATION NUMBER: NCT03112018.

Using clinical cascades to measure health facilities' obstetric emergency readiness: testing the cascade model using cross-sectional facility data in East Africa.

OBJECTIVES: Globally, hundreds of women die daily from preventable pregnancy-related causes, with the greatest burden in sub-Saharan Africa. Five key emergencies-bleeding, infections, high blood pressure, delivery complications and unsafe abortions-account for nearly 75% of these obstetric deaths. Skilled clinicians with strategic supplies could prevent most deaths. In this study, we (1) measured facility readiness to manage common obstetric emergencies using the clinical cascades and signal function tracers; (2) compared these readiness estimates by facility characteristics; and (3) measured cascading drop-offs in resources. DESIGN: A facility-based cross-sectional analysis of resources for common obstetric emergencies. SETTING: Data were collected in 2016 from 23 hospitals (10 designated comprehensive emergency obstetric care (CEmOC) facilities) in Migori County, western Kenya, and Busoga Region, eastern Uganda, in the Preterm Birth Initiative study in East Africa. Baseline data were used to estimate a facility's readiness to manage common obstetric emergencies using signal function tracers and the clinical cascade model. We compared emergency readiness using the proportion of facilities with tracers (signal functions) and the proportion with resources for identifying and treating the emergency (cascade stages 1 and 2). RESULTS: The signal functions overestimated practical emergency readiness by 23 percentage points across five emergencies. Only 42% of CEmOC-designated facilities could perform basic emergency obstetric care. Across the three stages of care (identify, treat and monitor-modify) for five emergencies, there was a 28% pooled mean drop-off in readiness. Across emergencies, the largest drop-off occurred in the treatment stage. Patterns of drop-off remained largely consistent across facility characteristics. CONCLUSIONS: Accurate measurement of obstetric emergency readiness is a prerequisite for strengthening facilities' capacity to manage common emergencies. The cascades offer stepwise, emergency-specific readiness estimates designed to guide targeted maternal survival policies and programmes. TRIAL REGISTRATION NUMBER: NCT03112018.

Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length.

Background: Maternal psychological stress has been linked to preterm birth. However, the differential contribution of psychological stress versus stress hormones is not clear. Studies focus primarily on perceived stress and cortisol, with few assessing its inter-convertible hormone cortisone. Furthermore, little is known about the potential moderating roles of obstetric risk and fetal sex in the relationship between maternal stress and gestational length. This gap in knowledge is particularly evident for rural women who typically experience chronic multiple stressors during pregnancy. We explored the relationship of hormonal and psychological stress to gestational length and the effects of obstetric risks and fetal sex on this relationship among Kenyan pregnant women. Methods: The sample included 130 women recruited between 22 to 28 weeks gestation. They completed a clinical and sociodemographic questionnaire together with the Perceived Stress Scale and provided a hair sample for cortisol and cortisone assay. Women underwent an ultrasound to assess weeks of gestation. At delivery, their pregnancy-related health problems were identified using information extracted from medical records to compile each woman's number of pregnancy risks on the Obstetric Medical Risk Index (OMRI). Results: Perceived stress and hair cortisol were not significant predictors of gestational length. However, a greater number of obstetric risks on the OMRI was associated with shorter gestational length. This effect was further explained by the interaction between obstetric risk and hair cortisone (B = 0.709, p = 0.02). Hair cortisone levels of mothers who had a shorter gestation were significantly higher in mothers with 2 or more risks on the OMRI but not among mothers with only one or no risks (t = 2.39, p = 0.02). Fetal sex had no relationship to gestational length and also had no moderating effect on the relationship between any stress-related metric and gestational length. Conclusion: Cortisone levels may increase in anticipation of shorter gestation as a compensatory response to increased obstetric risk. Elevated cortisone may be a more sensitive marker of risk for early delivery than cortisol or psychological stress, with salience for both the male and female fetus.

Prospective Cohort Study on Timing of Antimicrobial Prophylaxis for Post-Cesarean Surgical Site Infections.

Background: Sepsis is the leading cause of maternal death in sub-Saharan Africa (SSA), a region that sees some of the highest rates of maternal death and morbidity in the world. As one of the most commonly performed surgical procedures in SSA and a proved risk factor for surgical site infection (SSI), cesarean section (CS) is an important operation to target because of its massive impact on maternal and neonatal health. There is currently insufficient published data available on the patient and facility-based context around SSI after CS to establish a true and clear understanding of this infectious category. The objective of this study was to collect accurate and valid data on the incidence of SSI after CS and the circumstances around SSI in two Kenyan hospitals. Hypothesis: Our primary analysis focused on the consequences of timing of peri-operative antimicrobial prophylaxis. We hypothesized that patients who were given antibiotics pre-operatively would show lower SSI rates than those given the agents post-operatively. Methods: This was an Institutional Review Board-approved observational study of 609 women who had CS operations at two Kenyan hospitals from September to December 2015. Thika provided antimicrobial prophylaxis prior to incision for all patients, and Kiambu provided only post-operative prophylaxis. It should be noted that this difference was the result of a previous intervention at Thika and not a part of this observational study. Results: Patients at the two hospitals had similar pre-operative characteristics indicating a relatively healthy population. The median age was 26 ± 6 years (range 18-43) at Thika and 26 ± 5 (18-44) at Kiambu. Median parity was 1 ± 1 (range 0-7) at Thika and 1 ± 1 (0-10). Patients also went through a comparable number of antenatal care visits (median 4 ± 1 at both hospitals). The number of patients with prolonged rupture of the membranes was 103 (34.4%) at Thika and 99 (32.9%) at Kiambu. There was a slightly higher number of patients with meconium-stained liquor at Kiambu Hospital (115) than at Thika (74). The SSI rate was 4.0% (12/299; 11 superficial, 1 deep) at Thika and 9.3% (28/301; 18 superficial, 7 deep, 3 organ/space) at Kiambu. Conclusions: The data show a striking difference between SSI rates in patients who were given properly timed pre-operative antibiotics and patients who were given only post-operative antibiotics. Administration of post-operative antibiotics is currently the norm in much of SSA, and there is strong evidence that many of the infectious problems encountered in this population would be reduced by the provision of antibiotic prophylaxis prior to the incision.

Implementation of surgical site infection surveillance in low- and middle-income countries: A position statement for the International Society for Infectious Diseases.

Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include 1. Collecting valid, high-quality data; 2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities; 3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors; 4. Prioritizing IPC training for healthcare workers in LMICs to conduct broad-based surveillance and to develop and implement locally applicable IPC programs; and 5. Developing a highly accurate and objective international system for defining SSIs, which can be translated globally in a straightforward manner. Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports developing sustainable IPC programs in LMICs. This entails 1. Identifying index operations for targeted surveillance; 2. Identifying IPC "champions" and empowering healthcare workers; 3. Using multimodal improvement measures; 4. Positioning hand hygiene programs as the basis for IPC initiatives; 5. Use of telecommunication devices for surveillance and healthcare outcome follow-ups. Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.

Burden of surgical site infection following cesarean section in sub-Saharan Africa: a narrative review.

Cesarean section (CS) is the most common operative procedure performed in sub-Saharan Africa (SSA), accounting for as much as 80% of the surgical workload. In contrast to CSs performed in high-income countries, CSs performed in SSA are accompanied by high morbidity and mortality rates. This operation is the most important known variable associated with an increased probability of postpartum bacterial infection. The objective of this review was to assess surgical outcomes related to CS in SSA. PubMed (including Medline), CINAHL, Embase, and the World Health Organization's Global Health Library were searched without date or language restrictions. A total of 26 studies reporting surgical site-infection rates after CS were identified, representing 14,063 women from 14 countries. The vast majority (76.7%) of CSs performed were emergency operations. The overall CS rate for women included in this review was 12.4% (range: 1.0%-41.9%). Only 17 of 26 total studies reported a significant proportion of women receiving antimicrobials of any kind. The surgical site-infection rate was 15.6% and the wound-infection rate 10.3%.

Changing use of surgical antibiotic prophylaxis in Thika Hospital, Kenya: a quality improvement intervention with an interrupted time series design.

INTRODUCTION: In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals. METHODS: We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design. RESULTS: From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these. CONCLUSION: Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.

Interventional studies for preventing surgical site infections in sub-Saharan Africa - A systematic review.

BACKGROUND: There is a great need for safe surgical services in sub-Saharan Africa, but a major difficulty of performing surgery in this region is the high risk of post-operative surgical site infection (SSI). METHODS: We aimed to systematically review which interventions had been tested in sub-Saharan Africa to reduce the risk of SSI and to synthesize their findings. We searched Medline, Embase and Global Health databases for studies published between 1995 and 2010 without language restrictions and extracted data from full-text articles. FINDINGS: We identified 24 relevant articles originating from nine countries in sub-Saharan Africa. The methodological quality of these publications was diverse, with inconsistency in definitions used for SSI, period and method of post-operative follow-up and classification of wound contamination. Although it was difficult to synthesise information between studies, there was consistent evidence that use of single-dose pre-operative antibiotic prophylaxis could reduce, sometimes dramatically, the risk of SSI. Several studies indicated that alcohol-based handrubs could provide a low-cost alternative to traditional surgical hand-washing methods. Other studies investigated the use of drains and variants of surgical technique. There were no African studies found relating to several other promising SSI prevention strategies, including use of checklists and SSI surveillance. CONCLUSIONS: There is extremely limited research from sub-Saharan Africa on interventions to curb the occurrence of SSI. Although some of the existing studies are weak, several high-quality studies have been published in recent years. Standard methodological approaches to this subject are needed.