Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission.

Objectives: Natural killer (NK) cells make important contributions to anti-malarial immunity through antibody-dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear. Methods: We compared the functions and phenotypes of NK cells from malaria-exposed and malaria-naive donors, and then varied the erythrocyte genetic background, Plasmodium falciparum strain and opsonising plasma used in ADCC to observe their impacts on NK cell degranulation as measured by CD107a mobilisation. Results: Natural killer cells from malaria-exposed adult Ugandan donors had enhanced ADCC, but an impaired pro-inflammatory response to cytokine stimulation, compared to NK cells obtained from malaria-naive adult North American donors. Cellular phenotypes from malaria-exposed donors reflected this specialisation for ADCC, with a compartment-wide downregulation of the Fc receptor γ-chain and enrichment of highly differentiated CD56dim and CD56neg populations. NK cell degranulation was enhanced in response to opsonised P. falciparum schizonts cultured in sickle cell heterozygous erythrocytes relative to wild-type erythrocytes, and when using opsonising plasma collected from donors living in a high transmission area compared to a lower transmission area despite similar levels of 3D7 schizont-specific IgG levels. However, degranulation was lowered in response to opsonised field isolate P. falciparum schizonts isolated from clinical malaria infections, compared to the 3D7 laboratory strain typically used in these assays. Conclusion: This work highlights important host and parasite factors that contribute to ADCC efficacy that should be considered in the design of ADCC assays.

Randomized trial to compare acceptability of magnesium sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care.

INTRODUCTION: In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance. OBJECTIVE: To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia. DESIGN: Randomized Open Label Clinical Trial. METHODS: The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician's decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15-20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students' t-test. RESULTS: Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2-2), vs 4(CI: 4-5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm). TRIAL REGISTRATION: Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).

Implementation challenges in preeclampsia care: perspectives from health care professionals in urban Uganda.

BACKGROUND: Sub-Saharan Africa bears the burden of 70% of maternal deaths worldwide, of which ∼10% are attributable to hypertensive disorders of pregnancy, primarily complications of preeclampsia. In other global settings, outcomes of pregnancies affected by preeclampsia are improved with timely and effective medical care. OBJECTIVE: This study aimed to explore the perspectives of local health care professionals on how preeclampsia care is currently delivered in the study setting and what challenges they experience in providing prompt and safe care. We identified specific objectives of exploring stakeholder perceptions of (1) recognizing preeclampsia and (2) timely intervention when preeclampsia is diagnosed. We also explored the wider system factors (eg, cultural, financial, and logistic challenges) that health care professionals perceived as affecting their ability to deliver optimal preeclampsia care. STUDY DESIGN: Individual semistructured interviews were conducted with health care professionals and stakeholders. The findings were analyzed using thematic analysis. RESULTS: Thirty-three participants contributed to the study, including doctors and midwives with varying degrees of clinical experience and external stakeholders. The following 5 key themes emerged: delayed patient presentation, recognizing the unwell patient with preeclampsia, the challenges of the existing triage system, stakeholder disconnect, and ways of learning from each other. Health care professionals referenced an important psychosocial perspective associated with preeclampsia in the study setting, which may influence the likelihood of seeking care through traditional healers rather than hospital-based routes. CONCLUSION: We identify the key barriers to improving maternal and neonatal outcomes of preeclampsia, described at both the institutional level and within the wider setting. The study provides invaluable contextual information that suggests that a systems-based approach to health care quality improvement may be effective in reducing rates of maternal and neonatal morbidity and mortality.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.

The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis.

Background: Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with HIV-unexposed uninfected (HUU). Immunization of pregnant women living with HIV (PWLWH) could reduce the severity and burden of infectious diseases for HEU in early infancy. Methods: We conducted a systematic review of safety and immunogenicity of vaccines administered to PWLWH and meta-analyses to test the overall effect of immunogenicity comparing pregnant women without HIV (PWWH) to PWLWH. We searched MEDLINE, Embase, Web of Science, Virtual Health Library and Cochrane databases in accordance with PRISMA guidelines for randomized controlled trials and observational studies. Review articles, case series, conference abstracts, and animal studies were excluded. Studies were included from inception to 6th September 2023, with no language restrictions. Random effects meta-analyses were performed for immunogenicity using Review manager (RevMan) analysis software version 5.4.1, Geometric Mean Titer (GMT) values were transformed to obtain the mean and standard deviation within RevMan, the effect size was computed and reported as mean difference with respective 95% confidence intervals. The review was registered with PROSPERO CRD42021289081. Findings: We included 12 articles, comprising 3744 pregnant women, 1714 were PWLWH given either influenza, pneumococcal or an investigational Group B streptococcal (GBS) vaccine. Five studies described safety outcomes, and no increase in adverse events was reported in PWLWH compared to PWWH. The GMT increase from baseline to 28-35 weeks post vaccination in HA units ranged from 12.4 (95% CI: 9.84-14.9) to 238.8 (95% CI: 0.35-477.9). Meta-analyses of influenza vaccines showed the pooled geometric mean difference in Hemagglutination Inhibition (HAI) titers post vaccination was 56.01 (95% CI: 45.01-67.01), p < 0.001. The increase was less in PWLWH when compared with PWWH: -141.76 (95% CI: -194.96, -88.55), p < 0.001. Interpretation: There are limited data on the safety and immunogenicity of vaccines given to PWLWH making policy consideration in this group difficult when new vaccines are introduced. With new vaccines on the horizon, PWLWH need to be included in studies to promote vaccine confidence for this special population. Funding: This work was funded by Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].

Prevalence and Factors Associated with Anxiety Disorders Among Pregnant Women at Mulago National Referral Hospital, Uganda.

Background: Anxiety disorders in pregnancy are common and represent a global concern. However, data regarding the magnitude of anxiety among pregnant women in Uganda are limited, and yet, these data could pave way for implementing effective mitigation measures. We determined the prevalence of anxiety disorders and associated factors among pregnant women at Mulago Hospital Uganda. Methods: A cross-sectional study was conducted among pregnant women attending antenatal care clinic at Mulago Hospital between September and November 2015. Systematic sampling was used to enroll eligible women. An interviewer-administered demographic questionnaire and the Hamilton Anxiety Rating Scale for Antenatal Anxiety (HAMA-A) scale were used to assess demographic features and anxiety, respectively. Women with HAMA-A score ≥17 were considered to have anxiety disorder. Factors associated with anxiety disorders were determined using multivariate logistic regression. Results: A total of 501 pregnant women were enrolled into the study; the prevalence of anxiety disorders was 13% (n=65; 95% CI: 9.8-15.7%). Factors that were significantly associated with anxiety disorders were low income of the participants (adjusted odds ratio [AOR]=2.65, 95% CI: 1.16-6.06), bad relationship with spouse (AOR = 2.50, 95% CI: 1.01-5.82) and history of hypertension in previous pregnancy (AOR = 4.17, 95% CI: 1.68-10.37). Conclusion: Approximately one in ten women surveyed exhibited anxiety disorders. Anxiety disorders were associated with low-income levels, bad spousal relationships, and a history of hypertension during previous pregnancies. Multidisciplinary approaches that integrate mental health support, social services, and partner involvement may help address anxiety disorders in pregnancy and contribute to improved maternal and child outcomes.

Healthcare provider experiences interacting with survivors of intimate partner violence: a qualitative study to inform survivor-centered approaches.

BACKGROUND: Intimate partner violence (IPV) remains a pervasive form of gender-based violence (GBV) that is largely undisclosed, especially among women seeking healthcare services in Uganda. Prioritizing survivor needs may improve IPV disclosure. This study explores healthcare worker experiences from provider-patient interactions with survivors seeking antenatal care services (ANC) in Uganda. METHODS: In-depth interviews were conducted among twenty-eight experienced healthcare providers in a rural and an urban-based ANC clinic in Eastern and Central Uganda. Providers were asked what they viewed as the needs and fears of women identified as having experienced any form of IPV. Iterative, inductive/deductive thematic analysis was conducted to discover themes regarding perceived needs, fears, and normalizing violence experienced by IPV survivors. RESULTS: According to healthcare providers, IPV survivors are unaware of available support services, and have need for support services. Providers reported that some survivors were afraid of the consequences of IPV disclosure namely, community stigma, worries about personal and their children's safety, retaliatory abuse, fear of losing their marriage, and partners' financial support. Women survivors also blamed themselves for IPV. Contextual factors underlying survivor concerns included the socio-economic environment that 'normalizes' violence, namely, some cultural norms condoning violence, and survivors' unawareness of their human rights due to self-blame and shame for abuse. CONCLUSIONS: We underscore a need to empower IPV survivors by prioritizing their needs. Results highlight opportunities to create a responsive healthcare environment that fosters IPV disclosure while addressing survivors' immediate medical and psychosocial needs, and safety concerns. Our findings will inform GBV prevention and response strategies that integrate survivor-centered approaches in Uganda.

Obstetric referrals, complications and health outcomes in maternity wards of large hospitals during the COVID-19 pandemic: a mixed methods study of six hospitals in Guinea, Nigeria, Uganda and Tanzania.

OBJECTIVES: The COVID-19 pandemic affected provision and use of maternal health services. This study describes changes in obstetric complications, referrals, stillbirths and maternal deaths during the first year of the pandemic and elucidates pathways to these changes. DESIGN: Prospective observational mixed-methods study, combining monthly routine data (March 2019-February 2021) and qualitative data from prospective semi-structured interviews. Data were analysed separately, triangulated during synthesis and presented along three country-specific pandemic periods: first wave, slow period and second wave. SETTING: Six referral maternities in four sub-Saharan African countries: Guinea, Nigeria, Tanzania and Uganda. PARTICIPANTS: 22 skilled health personnel (SHP) working in the maternity wards of various cadres and seniority levels. RESULTS: Percentages of obstetric complications were constant in four of the six hospitals. The percentage of obstetric referrals received was stable in Guinea and increased at various times in other hospitals. SHP reported unpredictability in the number of referrals due to changing referral networks. All six hospitals registered a slight increase in stillbirths during the study period, the highest increase (by 30%-40%) was observed in Uganda. Four hospitals registered increases in facility maternal mortality ratio; the highest increase was in Guinea (by 158%), which had a relatively mild COVID-19 epidemic. These increases were not due to mortality among women with COVID-19. The main pathways leading to these trends were delayed care utilisation and disruptions in accessing care, including sub-optimal referral linkages and health service closures. CONCLUSIONS: Maternal and perinatal survival was negatively affected in referral hospitals in sub-Saharan Africa during COVID-19. Routine data systems in referral hospitals must be fully used as they hold potential in informing adaptations of maternal care services. If combined with information on women's and care providers' needs, this can contribute to ensuring continuation of essential care provision during emergency.

Glycocalyx-Sodium Interaction in Vascular Endothelium.

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.

Source-tracking ESBL-producing bacteria at the maternity ward of Mulago hospital, Uganda.

INTRODUCTION: Escherichia coli, Klebsiella pneumoniae and Enterobacter (EKE) are the leading cause of mortality and morbidity in neonates in Africa. The management of EKE infections remains challenging given the global emergence of carbapenem resistance in Gram-negative bacteria. This study aimed to investigate the source of EKE organisms for neonates in the maternity environment of a national referral hospital in Uganda, by examining the phenotypic and molecular characteristics of isolates from mothers, neonates, and maternity ward. METHODS: From August 2015 to August 2016, we conducted a cross-sectional study of pregnant women admitted for elective surgical delivery at Mulago hospital in Kampala, Uganda; we sampled (nose, armpit, groin) 137 pregnant women and their newborns (n = 137), as well as health workers (n = 67) and inanimate objects (n = 70 -beds, ventilator tubes, sinks, toilets, door-handles) in the maternity ward. Samples (swabs) were cultured for growth of EKE bacteria and isolates phenotypically/molecularly investigated for antibiotic sensitivity, as well as ß-lactamase and carbapenemase activity. To infer relationships among the EKE isolates, spatial cluster analysis of phenotypic and genotypic susceptibility characteristics was done using the Ridom server. RESULTS: Gram-negative bacteria were isolated from 21 mothers (15%), 15 neonates (11%), 2 health workers (3%), and 13 inanimate objects (19%); a total of 131 Gram-negative isolates were identified of which 104 were EKE bacteria i.e., 23 (22%) E. coli, 50 (48%) K. pneumoniae, and 31 (30%) Enterobacter. Carbapenems were the most effective antibiotics as 89% (93/104) of the isolates were susceptible to meropenem; however, multidrug resistance was prevalent i.e., 61% (63/104). Furthermore, carbapenemase production and carbapenemase gene prevalence were low; 10% (10/104) and 6% (6/104), respectively. Extended spectrum ß-lactamase (ESBL) production occurred in 37 (36%) isolates though 61 (59%) carried ESBL-encoding genes, mainly blaCTX-M (93%, 57/61) implying that blaCTX-M is the ideal gene for tracking ESBL-mediated resistance at Mulago. Additionally, spatial cluster analysis revealed isolates from mothers, new-borns, health workers, and environment with similar phenotypic/genotypic characteristics, suggesting transmission of multidrug-resistant EKE to new-borns. CONCLUSION: Our study shows evidence of transmission of drug resistant EKE bacteria in the maternity ward of Mulago hospital, and the dynamics in the ward are more likely to be responsible for transmission but not individual mother characteristics. The high prevalence of drug resistance genes highlights the need for more effective infection prevention/control measures and antimicrobial stewardship programs to reduce spread of drug-resistant bacteria in the hospital, and improve patient outcomes.

Impact of high human genetic diversity in Africa on immunogenicity and efficacy of RTS,S/AS01 vaccine.

In modern medicine, vaccination is one of the most effective public health strategies to prevent infectious diseases. Indisputably, vaccines have saved millions of lives by reducing the burden of many serious infections such as polio, tuberculosis, measles, pneumonia, and tetanus. Despite the recent recommendation by the World Health Organization (WHO) to roll out RTS,S/AS01, this malaria vaccine still faces major challenges of variability in its efficacy partly due to high genetic variation in humans and malaria parasites. Immune responses to malaria vary between individuals and populations. Human genetic variation in immune system genes is the probable cause for this heterogeneity. In this review, we will focus on human genetic factors that determine variable responses to vaccination and how variation in immune system genes affect the immunogenicity and efficacy of the RTS,S/AS01 vaccine.

No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda.

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major angiogenic factor that plays an important role in the formation of blood vessels during embryonic development. VEGFA has been implicated in the pathophysiology of pre-eclampsia (PE), since pre-eclamptic women present with reduced levels of free circulating VEGFA. The 3' untranslated region (3'-UTR) of the VEGFA gene consists of elements that regulate the transcription and hence expression of the VEGFA protein in circulation. Hence it is suggested that variations thereof could underlie the reduced VEGFA levels observed in pre-eclamptic women. The purpose of this study was to investigate presence of the + 936C/T polymorphism, a common single nucleotide polymorphism (SNP) in the 3'-UTR of the VEGFA gene, and determine its association with PE among pregnant women in Uganda. RESULTS: There was no significant difference observed in the allele and genotype frequencies of the + 936C/T 3' UTR-VEGFA polymorphism between pre-eclamptic and normotensive pregnant women (P > 0.05). Additionally, there was no significant difference in the median plasma levels of free VEGFA among women with the wild type, CT and TT genotypes of the + 936C/T VEGFA polymorphism (median = 0.84 pg/mL (IQR = 0.39-1.41) Vs 1.05 (0.61-1.18) Vs 1.05 (1.05-1.05) respectively, p-value = 0.7161). CONCLUSIONS: These study findings indicate that the + 936C/T 3' UTR-VEGFA polymorphism had no significant association with increased susceptibility to PE among women in Uganda. Further studies with a larger sample size are recommended.

Prediction of pre-eclampsia at St. Mary's hospital lacor, a low-resource setting in northern Uganda, a prospective cohort study.

BACKGROUND: Pre-eclampsia is the second leading cause of maternal death in Uganda. However, mothers report to the hospitals late due to health care challenges. Therefore, we developed and validated the prediction models for prenatal screening for pre-eclampsia. METHODS: This was a prospective cohort study at St. Mary's hospital lacor in Gulu city. We included 1,004 pregnant mothers screened at 16-24 weeks (using maternal history, physical examination, uterine artery Doppler indices, and blood tests), followed up, and delivered. We built models in RStudio. Because the incidence of pre-eclampsia was low (4.3%), we generated synthetic balanced data using the ROSE (Random Over and under Sampling Examples) package in RStudio by over-sampling pre-eclampsia and under-sampling non-preeclampsia. As a result, we got 383 (48.8%) and 399 (51.2%) for pre-eclampsia and non-preeclampsia, respectively. Finally, we evaluated the actual model performance against the ROSE-derived synthetic dataset using K-fold cross-validation in RStudio. RESULTS: Maternal history of pre-eclampsia (adjusted odds ratio (aOR) = 32.75, 95% confidence intervals (CI) 6.59-182.05, p = 0.000), serum alkaline phosphatase(ALP) < 98 IU/L (aOR = 7.14, 95% CI 1.76-24.45, p = 0.003), diastolic hypertension ≥ 90 mmHg (aOR = 4.90, 95% CI 1.15-18.01, p = 0.022), bilateral end diastolic notch (aOR = 4.54, 95% CI 1.65-12.20, p = 0.003) and body mass index of ≥ 26.56 kg/m2 (aOR = 3.86, 95% CI 1.25-14.15, p = 0.027) were independent risk factors for pre-eclampsia. Maternal age ≥ 35 years (aOR = 3.88, 95% CI 0.94-15.44, p = 0.056), nulliparity (aOR = 4.25, 95% CI 1.08-20.18, p = 0.051) and white blood cell count ≥ 11,000 (aOR = 8.43, 95% CI 0.92-70.62, p = 0.050) may be risk factors for pre-eclampsia, and lymphocyte count of 800 - 4000 cells/microliter (aOR = 0.29, 95% CI 0.08-1.22, p = 0.074) may be protective against pre-eclampsia. A combination of all the above variables predicted pre-eclampsia with 77.0% accuracy, 80.4% sensitivity, 73.6% specificity, and 84.9% area under the curve (AUC). CONCLUSION: The predictors of pre-eclampsia were maternal age ≥ 35 years, nulliparity, maternal history of pre-eclampsia, body mass index, diastolic pressure, white blood cell count, lymphocyte count, serum ALP and end-diastolic notch of the uterine arteries. This prediction model can predict pre-eclampsia in prenatal clinics with 77% accuracy.

Prediction of stillbirth low resource setting in Northern Uganda.

BACKGROUND: Women of Afro-Caribbean and Asian origin are more at risk of stillbirths. However, there are limited tools built for risk-prediction models for stillbirth within sub-Saharan Africa. Therefore, we examined the predictors for stillbirth in low resource setting in Northern Uganda. METHODS: Prospective cohort study at St. Mary's hospital Lacor in Northern Uganda. Using Yamane's 1967 formula for calculating sample size for cohort studies using finite population size, the required sample size was 379 mothers. We doubled the number (to > 758) to cater for loss to follow up, miscarriages, and clients opting out of the study during the follow-up period. Recruited 1,285 pregnant mothers at 16-24 weeks, excluded those with lethal congenital anomalies diagnosed on ultrasound. Their history, physical findings, blood tests and uterine artery Doppler indices were taken, and the mothers were encouraged to continue with routine prenatal care until the time for delivery. While in the delivery ward, they were followed up in labour until delivery by the research team. The primary outcome was stillbirth 24 + weeks with no signs of life. Built models in RStudio. Since the data was imbalanced with low stillbirth rate, used ROSE package to over-sample stillbirths and under-sample live-births to balance the data. We cross-validated the models with the ROSE-derived data using K (10)-fold cross-validation and obtained the area under curve (AUC) with accuracy, sensitivity and specificity. RESULTS: The incidence of stillbirth was 2.5%. Predictors of stillbirth were history of abortion (aOR = 3.07, 95% CI 1.11-8.05, p = 0.0243), bilateral end-diastolic notch (aOR = 3.51, 95% CI 1.13-9.92, p = 0.0209), personal history of preeclampsia (aOR = 5.18, 95% CI 0.60-30.66, p = 0.0916), and haemoglobin 9.5 - 12.1 g/dL (aOR = 0.33, 95% CI 0.11-0.93, p = 0.0375). The models' AUC was 75.0% with 68.1% accuracy, 69.1% sensitivity and 67.1% specificity. CONCLUSION: Risk factors for stillbirth include history of abortion and bilateral end-diastolic notch, while haemoglobin of 9.5-12.1 g/dL is protective.

Why mothers die at a busy tertiary urban hospital in Kampala, Uganda: a comprehensive review of maternal deaths 2016-2018 and implications for quality improvement to reduce deaths.

Background: Reviewing maternal deaths and drawing out lessons for clinical practice is part of an effective cohesive intervention strategy to reduce future deaths. Objective: To review maternal deaths at the National Referral hospital in Kampala over a 3-year period (2016-2018) to determine causes of death, extent of preventability, proportion of deaths notified and audited as per national guidelines. Methods: Trained-multidisciplinary panels (obstetricians and senior midwives) conducted retrospective reviews of maternal deaths that occurred. Results: Major causes of deaths: obstetric haemorrhage (158/350; 45%), hypertensive disorders of pregnancy (87/350; 25%) and infection (95/350; 27%). Overall, 294/350 (84%) of maternal deaths were considered preventable. In 95% (332/350) of cases, delays within healthcare facilities were identified (64%; 226/350). We note that only 115/350 (33%) cases had been audited. This proportion did not change during the studied period. In 48% (167/350) of cases, notification to the Ministry of Health occurred, but only 11% of deaths (39/350) were notified within the recommended 24-hours. Conclusions: A high proportion (84%) of deaths were preventable. Significant delays to care occurred within health-care facilities. Results suggest that a well-supported, and timely maternal death review process with targeted and pragmatic interventions might be effective in reducing maternal deaths in this setting.

Learning from maternal deaths due to uterine rupture: review of cases from peri-urban Uganda.

BACKGROUND: Maternal deaths from uterine rupture continue to occur globally, with particularly high rates in sub-Saharan Africa. Maternal death reviews have been shown to be an effective part of cohesive strategies to prevent future deaths. OBJECTIVE: This study aimed to conduct maternal death reviews for all deaths following uterine rupture in the study center, to assess preventability, and to synthesize key learning points that may help to prevent future maternal deaths following uterine rupture. STUDY DESIGN: Thorough case reviews of all maternal deaths from 2016 to 2018 at the study center (a national referral hospital in urban Uganda) were conducted by trained multidisciplinary panels of obstetricians and midwives. Medical records of women who died following uterine rupture (n=37, 10.6% of all maternal deaths) were extracted for further analysis. RESULTS: Most maternal deaths due to uterine rupture (36/37, 97%) were preventable, with most having been still potentially preventable after the women reached the study center (24/36, 67%). Obstructed labor was the leading cause of uterine rupture, accounting for 73% (27/37) of cases. Previous cesarean delivery was confirmed in 38% (14/37) of cases. The incidence of grand multiparity was 11% (4/37), and 11% (4/37) were primiparous. Most women (28/37, 76%) died within 24 hours of admission. On arrival at the study center, 19 (51%) were critically ill. Exploratory laparotomy was performed in 54% (20/37) of cases, and a further 35% (13/37) died while awaiting laparotomy. Four women died shortly after arrival at the study center (within 1 hour) and received basic resuscitative treatment; 27% (10/37) of women who died had received antenatal planning or preparation. CONCLUSION: Most deaths due to uterine rupture were preventable. The key lessons that emerged from the reviews were: (1) careful birth preparation and complication awareness for women with known risk factors, (2) early recognition of obstructed labor, (3) close monitoring of obstetrical interventions known to be associated with uterine rupture, and (4) treating incipient or suspected uterine rupture as a time-critical obstetrical emergency. The recommendations emerging from our narrative reviews are suitable for implementation in low-resource obstetrical settings, where high numbers of deaths involving uterine rupture occur.

The influence of fasting and post-load glucose levels on maternal and neonatal outcomes in women with hyperglycaemia in pregnancy in Uganda: A prospective observational cohort study.

AIMS: The study aims to evaluate the strength of fasting versus post-load glucose levels in predicting adverse outcomes in women with hyperglycaemia in pregnancy (HIP). METHODS: Women attending antenatal clinics in urban and peri-urban Uganda had oral glucose tolerance test between 24 and 28 weeks of gestation to screen for HIP, and were followed up to collect data on maternal and neonatal outcomes. Univariable and multivariable Poisson regression models were used to estimate the relative risk adverse outcome associated with fasting hyperglycaemia alone post-load hyperglycaemia alone, or elevation of both fasting and post-load glucose levels. RESULTS: We included 3206 participants in the final analysis. HIP was associated with increased risk of Caesarean section, large for gestaional age babies, and neonatal intensive care admission. The risk was highest (2.54-fold compared to normal glycaemic women) when both FBG and post-load glucose levels were elevated. After adjustment for potential confounders, having elevated post-load glucose alone was not associated with increased risk of any of the outcomes, but elevated FBG alone increased the risk of Caesarian section by 1.36-fold. CONCLUSION: Fasting hyperglycemia appears to be more strongly associated with adverse pregnancy outcomes than post-load hyperglycaemia, but the risk is even higher in women with elevation of both fasting and post-load glucose levels.

Protocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study.

BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl's Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes.

Preventing death following unsafe abortion: a case series from urban Uganda.

BACKGROUND: Maternal deaths from unsafe abortion continue to occur globally, with particularly high rates in Sub-Saharan Africa where most abortions are classified as unsafe. Maternal death reviews are an effective part of cohesive strategies to prevent future deaths while abortion remains illegal. OBJECTIVE: This study aimed to conduct maternal death reviews for all deaths occurring following unsafe abortion during the study period, to assess preventability, and to synthesize key learning points that may help to prevent future maternal deaths following unsafe abortions. STUDY DESIGN: Full case reviews of all maternal deaths (350 cases from Jan 2016 to Dec 2018) at the study center (a national referral hospital in urban Uganda) were conducted by specially trained multidisciplinary panels of obstetricians and midwives. We extracted the reviews of women who died following unsafe abortions (13 [2.6%]) for further analysis. RESULTS: Most maternal deaths owing to unsafe abortion were found to be preventable. The key recommendations that emerged from the reviews were (1) that clinicians should maintain a high index of suspicion for delayed presentation and rapid decompensation in cases where unsafe abortion has occurred, (2) that a low threshold for early intravenous antibiotic therapy should be applied, and (3) that any admission with complications following an unsafe abortion merits review by an experienced clinician as soon as possible. CONCLUSION: Postabortion care is part of essential emergency medical care and should be provided with high standards, especially in areas where there is limited or no legal access to abortion care. Implementing the recommended learning points is likely to be feasible even in low-resource obstetrical settings and, given the high rates of preventability found in maternal deaths owing to unsafe abortion, is likely to be effective.