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.

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.

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.

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.

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.

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.

Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity.

BACKGROUND: Malaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity. Several studies have shown that KIR and HLA-C genes influence the immune response to viral infections, but few studies have examined the role of KIR and HLA-C in malaria infection, and these have used low-resolution genotyping. The aim of this study was to determine whether genetic variation in KIR and their HLA-C ligands differ in Ugandan populations with historically varied malaria transmission intensity using more comprehensive genotyping approaches. METHODS: High throughput multiplex quantitative real-time PCR method was used to genotype KIR genetic variants and copy number variation and a high-throughput real-time PCR method was developed to genotype HLA-C1 and C2 allotypes for 1344 participants, aged 6 months to 10 years, enrolled from Ugandan populations with historically high (Tororo District), medium (Jinja District) and low (Kanungu District) malaria transmission intensity. RESULTS: The prevalence of KIR3DS1, KIR2DL5, KIR2DS5, and KIR2DS1 genes was significantly lower in populations from Kanungu compared to Tororo (7.6 vs 13.2%: p = 0.006, 57.2 vs 66.4%: p = 0.005, 33.2 vs 46.6%: p < 0.001, and 19.7 vs 26.7%: p = 0.014, respectively) or Jinja (7.6 vs 18.1%: p < 0.001, 57.2 vs 63.8%: p = 0.048, 33.2 vs 43.5%: p = 0.002, and 19.7 vs 30.4%: p < 0.001, respectively). The prevalence of homozygous HLA-C2 was significantly higher in populations from Kanungu (31.6%) compared to Jinja (21.4%), p = 0.043, with no significant difference between Kanungu and Tororo (26.7%), p = 0.296. CONCLUSIONS: The KIR3DS1, KIR2DL5, KIR2DS5 and KIR2DS1 genes may partly explain differences in transmission intensity of malaria since these genes have been positively selected for in places with historically high malaria transmission intensity. The high-throughput, multiplex, real-time HLA-C genotyping PCR method developed will be useful in disease-association studies involving large cohorts.

Level of and factors associated with awareness of gestational diabetes mellitus among pregnant women attending antenatal care at Kawempe National Referral Hospital: a cross sectional study.

BACKGROUND: The burden of Gestational diabetes mellitus (GDM) is significantly increasing worldwide and the disorder causes substantial short term and long-term adverse effects both to the mother and the unborn baby. Public health measures to increase awareness of GDM among pregnant women may aid in prevention of the disease through life style modification, screening, early diagnosis and management but very few studies have assessed awareness of GDM among pregnant women in sub Saharan Africa and none of these are from Uganda. This study therefore sought to evaluate the level of and factors associated with awareness of GDM among pregnant women attending antenatal care at Kawempe National Referral Hospital (KNRH), the busiest obstetric unit in Uganda, so as to assess their health sensitization needs. METHODS: This was a cross-sectional study. We recruited 403 participants at 30 weeks of gestation and above after giving written informed consent. Systematic sampling was used to select participants and data was collected using pretested interviewer-administered questionnaires. The collected data was entered in Epidata version 4.2 and exported to Stata for analysis. Continuous variables were summarized using mean and standard deviation. Categorical variables were summarized using frequencies and proportions. Factors associated with awareness were assessed at both bivariate and multivariate levels. RESULTS: Four hundred three pregnant women were recruited, majority (35.5 %) were between 20 and 24 years and their mean age was 26.6 years. Only 125 (31 %) participants were aware of GDM. Age and educational level were significantly associated with awareness of GDM. Women aged 35 years and above were more likely to be aware of GDM (OR = 2.34 (95 % CI = 1.14-4.81) p = 0.021. Women with primary education or no education were less likely to be aware (OR = 0.48 (CI 0.24-0.96) p = 0.038. CONCLUSIONS: Awareness of GDM was poor among study participants. There is need to improve the health education programs in order to increase awareness of GDM among women attending ANC at KNRH. Women below 35 years of age and those with primary education or less should be specifically targeted when giving health education sessions so as to increase their awareness of GDM.

Antenatal management and maternal/fetal outcomes associated with hyperglycaemia in pregnancy (HIP) in Uganda; a prospective cohort study.

BACKGROUND: Hyperglycaemia in pregnancy (HIP) is associated with complications for both mother and baby. The prevalence of the condition is likely to increase across Africa as the continent undergoes a rapid demographic transition. However, little is known about the management and pregnancy outcomes associated with HIP in the region, particularly less severe forms of hyperglycaemia. It is therefore important to generate local data so that resources may be distributed effectively. The aim of this study was to describe the antenatal management and maternal/fetal outcomes associated with HIP in Ugandan women. METHODS: A prospective cohort study of 2917 pregnant women in five major hospitals in urban/semi-urban central Uganda. Women were screened with oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Cases of gestational diabetes (GDM) and diabetes in pregnancy (DIP) were identified (WHO 2013 diagnostic criteria) and received standard care. Data was collected on maternal demographics, anthropometrics, antenatal management, umbilical cord c-peptide levels, and pregnancy outcomes. RESULTS: Two hundred and seventy-six women were diagnosed with HIP (237 classified as GDM and 39 DIP). Women had between one and four fasting capillary blood glucose checks during third trimester. All received lifestyle advice, one quarter (69/276) received metformin therapy, and one woman received insulin. HIP was associated with large birthweight (unadjusted relative risk 1.30, 95% CI 1.00-1.68), Caesarean delivery (RR 1.34, 95% CI 1.14-1.57) and neonatal hypoglycaemia (RR 4.37, 95% CI 1.36-14.1), but not perinatal mortality or preterm birth. Pregnancy outcomes were generally worse for women with DIP compared with GDM. CONCLUSION: HIP is associated with significant adverse pregnancy outcomes in this population, particularly overt diabetes in pregnancy. However pregnancy outcomes in women with milder forms of hyperglycaemia are similar to those with normoglycaemic pregnancies. Intervention strategies are required to improve current monitoring and management practice, and more research needed to understand if this is a cost-effective way of preventing poor perinatal outcomes.

Decision-to-delivery interval of emergency cesarean section in Uganda: a retrospective cohort study.

BACKGROUND: In many low and medium human development index countries, the rate of maternal and neonatal morbidity and mortality is high. One factor which may influence this is the decision-to-delivery interval of emergency cesarean section. We aimed to investigate the maternal risk factors, indications and decision-to-delivery interval of emergency cesarean section in a large, under-resourced obstetric setting in Uganda. METHODS: Records of 344 singleton pregnancies delivered at ≥24 weeks throughout June 2017 at Mulago National Referral Hospital were analysed using Cox proportional hazards models and multivariate logistic regression models. RESULTS: An emergency cesarean section was performed every 104 min and the median decision-to-delivery interval was 5.5 h. Longer interval was associated with preeclampsia and premature rupture of membranes/oligohydramnios. Fetal distress was associated with a shorter interval (p < 0.001). There was no association between decision-to-delivery interval and adverse perinatal outcomes (p > 0.05). Mothers waited on average 6 h longer for deliveries between 00:00-08:00 compared to those between 12:00-20:00 (p < 0.01). The risk of perinatal death was higher in neonates where the decision to deliver was made between 20:00-02:00 compared to 08:00-12:00 (p < 0.01). CONCLUSION: In this setting, the average decision-to-delivery interval is longer than targets adopted in high development index countries. Decision-to-delivery interval varies diurnally, with decisions and deliveries made at night carrying a higher risk of adverse perinatal outcomes. This suggests a need for targeting the improvement of service provision overnight.

Trends and determinants of adolescent childbirth in Uganda- analysis of rural and urban women using six demographic and health surveys, 1988-2016.

INTRODUCTION: Uganda has high adolescent pregnancy. The details of adolescent childbirth and urban/rural patterns are scarce. We investigated the levels, time trends and determinants of adolescent childbirth in Uganda separately for urban and rural women. METHODS: We estimated the percentage of women 20-24 years at each of the six Uganda Demographic and Health Surveys (1988/89, 1995, 2000/01, 2006, 2011 and 2016) who reported a live childbirth before age 20 years ("adolescent childbirth"), and examined change over time using t-test. A modified multivariable Poisson regression was used to examine determinants of having adolescent childbirth on the 2016 survey. RESULTS: Among these women, 67.5, 66.4, 70.1, 62.3, 57.3 and 54.1% reported an adolescent childbirth in 1988/89, 1995, 2000/01, 2006, 2011 and 2016 surveys, respectively. Between 1988/89 to 2000/01, there was no evidence of change (+ 2.6% point (pp), p = 0.170), unlike between the 2000/01 and 2016 surveys when a significant decline occurred (- 16.0 pp., p < 0.001). First childbirth < 18 years of age declined by - 13.5 pp. (p < 0.001) between 2000/01 and 2016. There was no change over time in the percentage of adolescents 18-19.9 years of age having first childbirth. Among rural residents, childbirth < 18 years declined from 43.8% in 1988/89 to 32.7% in 2016 (- 11.1 pp., p < 0.001), in urban it declined from 28.3 to 18.2% (- 10.1 pp., p = 0.006). There was an increase over time in the percentage of women, both rural and urban, who wanted to delay their first pregnancy. Independent determinants of reporting an adolescent childbirth in both urban and rural residents were: no education/incomplete primary and younger age at first sex. Additional determinants for rural women were residence in Eastern region, Muslim religion, and poor household wealth index. CONCLUSION: In the 30-year period examined, adolescent childbirth in Uganda declined from highs of 7 in 10 to approximately 5 in 10 women, with more wanting to delay the pregnancy. The decline started after the 2000/01 survey and affected predominantly younger adolescent childbirth < 18 years among both rural and urban residence women. Efforts need to be intensified to sustain the decline in adolescent pregnancies. Targeted and specific strategies for urban and rural areas might be required.

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia.

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.

A need to accelerate health research productivity in an African University: the case of Makerere University College of Health Sciences.

BACKGROUND: In the last decade, Makerere University College of Health Sciences (MakCHS) has taken strides in research and training to improve healthcare through collaborative training and research programs. However, there is limited data on the trends of MakCHS faculty contributions to research and on faculty growth to take leading roles in health research. This paper reviews MakCHS faculty research publications over 15.5 years and outlines possible strategies to enhance faculty research outputs. METHODS: We used a mixed methods approach. A systematic review of research publications by faculty at MakCHS (PubMed and Google Scholar from January 1, 2000, to June 30, 2015) to quantify the number of research articles, areas researched, authorship contribution by MakCHS faculty, source of funding, as well as affiliated local and international collaborations. Graphs were used to shown trends in publications and leadership of authorship by faculty. Annual individual faculty research productivity was presented as publication per capita. Qualitative data on high priority needs to improve research outputs was collected through focus group discussions (FGDs) with faculty members, and analysed manually into emerging themes. RESULTS: Of 298 faculty at MakCHS at 2015, 89 (30%) were female and 229 (77%) were junior and mid-level faculty (senior lecturer and below). The PubMed and Google Scholar searches yielded 6927 published articles, of which 3399 (49%) full-text articles were downloaded for analysis, 426/3825 (11%) available as titles/abstracts only, and 598/4423 (14%) were excluded. Only 614 articles were published in 2014, giving a publication per capita of 2.1 for any authorship, and 0.3 for first and last authorship positions. MakCHS faculty increasingly contributed as first, second, third, and last authors. Up to 57% of research was in infectious diseases, followed by non-communicable diseases (20%) and non-communicable maternal child health (11%). Priority needs to improve research outputs, as expressed by faculty, were (1) an institutionally led faculty career development program, (2) skills building in research methods and scientific writing, (3) protected time for research related activities, (4) opportunities for collaborative research, and (5) use of individual development plans. CONCLUSION: Faculty research productivity was low and dominated by infectious diseases and non-communicable disease research. There is a need for structured institutional support to optimise faculty research outputs. Only with increased research productivity will MakCHS and other academic institutions be able to make a significant contribution in addressing national health challenges.

Maternal near misses from two referral hospitals in Uganda: a prospective cohort study on incidence, determinants and prognostic factors.

BACKGROUND: Maternal near misses occur more often than maternal deaths and could enable more comprehensive analysis of risk factors, short-term outcomes and prognostic factors of complications during pregnancy and childbirth. The study determined the incidence, determinants and prognostic factors of severe maternal outcomes (near miss or maternal death) in two referral hospitals in Uganda. METHODS: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, where cases of severe pregnancy and childbirth complications were included. The clinical conditions included abortion-related complications, obstetric haemorrhage, hypertensive disorders, obstructed labour, infection and pregnancy-specific complications such as febrile illness, anemia and premature rupture of membranes. Near miss cases were defined according to the WHO criteria. Multivariate logistic regression analysis was conducted to identify prognostic factors for severe maternal outcomes. RESULTS: Of 3100 women with severe obstetric complications, 130 (4.2%) were maternal deaths and 695 (22.7%) were near miss cases. Severe pre-eclampsia was the commonest morbidity (incidence ratio (IR) 7.0%, case-fatality rate (CFR) 2.3%), followed by postpartum haemorrhage (IR 6.7%, CFR 7.2%). Uterine rupture (IR 5.5%) caused the highest CFR (17.9%), followed by eclampsia (IR 0.4%, CFR 17.8%). The three groups (maternal deaths, near misses and non-life-threatening obstetric complications) differed significantly regarding gravidity and education level. The commonest diagnostic criteria for maternal near miss were admission to the high dependency unit (HDU) or to the intensive care unit (ICU). Thrombocytopenia, circulatory collapse, referral to a more specialized unit, intubation unrelated to anaesthesia, and cardiopulmonary resuscitation were predictive of maternal death (p < 0.05). Gravidity (ARR 1.4, 95% C1 1.0-1.2); elevated serum lactate levels (ARR 4.5, 95% CI 2.3-8.7); intubation for conditions unrelated to general anaesthesia (ARR 2.6 (95% CI 1.2-5.7), cardiovascular collapse (ARR 4.9, 95% CI 2.5-9.5); transfusion of 4 or more units of blood (ARR 1.9, 95% CI 1.1-3.1); being an emergency referral (ARR 2.6, 95% CI 1.2-5.6); and need for cardiopulmonary resuscitation (ARR 6.1, 95% CI 3.2-11.7), were prognostic factors. CONCLUSIONS: The analysis of near misses is a useful tool in the investigation of severe maternal morbidity. The prognostic factors for maternal death, if instituted, might save many women with obstetric complications.

The burden of maternal morbidity and mortality attributable to hypertensive disorders in pregnancy: a prospective cohort study from Uganda.

BACKGROUND: Hypertensive disorders of pregnancy are a major cause of morbidity and mortality. The objective was to estimate the disease burden attributable to hypertensive disorders of pregnancy in two referral hospitals in Uganda. METHODS: Through a prospective cohort study conducted in Jinja and Mulago hospitals in Uganda from March 1, 2013 and February 28, 2014, hypertension-related cases were analyzed. Maternal near miss cases were defined according to the WHO criteria. Maternal deaths were also analyzed. The maternal near miss incidence ratio, the case-specific severe maternal outcome ratio, the case-specific maternal mortality ratio and the case-fatality ratio were computed. RESULTS: Of 403 women with hypertensive disorders of pregnancy, 218 (54.1 %) had severe preeclampsia, 172 (42.7 %) had eclampsia, and 13 had chronic hypertension or Hemolysis, elevated liver enzymes or low platelets (HELLP) syndrome. The case-specific maternal near miss incidence ratios was 8.60 per 1,000 live births for all hypertensive disorders, 3.06 per 1,000 live births for severe preeclampsia and 5.11 per 1,000 live births for eclampsia. The case-specific severe maternal outcome ratio was 9.37 per 1,000 live births for all hypertensive disorders, and was 3.25 per 1,000 live births for severe preeclampsia and 5.61 per 1,000 live births for eclampsia. The case-specific maternal mortality ratio was 780 per 100,000 live births for all hypertensive disorders, and was 1940 per 100,000 live births for severe preeclampsia and 501 per 100,000 live births for eclampsia. The case-fatality ratio was 5.1 % overall (for all hypertensive disorders), but was 8 times higher for eclampsia compared to severe preeclampsia. Cyanosis, abnormal respiration, oliguria, circulatory collapse, coagulopathy, thrombocytopenia, and elevated serum lactate were significantly associated with severe maternal outcomes. CONCLUSION: There is high morbidity attributable to hypertensive disorders in pregnancy. Since some of the complications associated with morbidity can be recognized early, it is possible to prevent severe morbidity through early intervention with delivery, antihypertensive therapy and prophylactic magnesium sulphate treatment. The findings highlight the feasibility of implementing a facility-based surveillance system for severe maternal morbidity due to hypertensive disorders.

Still births, neonatal deaths and neonatal near miss cases attributable to severe obstetric complications: a prospective cohort study in two referral hospitals in Uganda.

BACKGROUND: Neonatal near miss cases occur more often than neonatal deaths and could enable a more comprehensive analysis of risk factors, short-term outcomes and prognostic factors in neonates born to mothers with severe obstetric complications. The objective was to assess the incidence, presentation and perinatal outcomes of severe obstetric morbidity in two referral hospitals in Central Uganda. METHODS: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, in which all newborns from cases of severe pregnancy and childbirth complications were eligible for inclusion. The obstetric conditions included obstetric haemorrhage, hypertensive disorders, obstructed labour, chorioamnionitis and pregnancy-specific complications such as malaria, anemia and premature rupture of membranes. Still births, neonatal deaths and neonatal near miss cases (defined using criteria that employed clinical features, presence of organ-system dysfunction and management provided to the newborns were compiled). Stratified and multivariate logistic regression analysis was conducted to identify risk factors for perinatal death. RESULTS: Of the 3100 mothers, 192 (6.2%) had abortion complications. Of the remainder, there were 2142 (73.1%) deliveries, from whom the fetal outcomes were 257 (12.0%) still births, 369 (17.2%) neonatal deaths, 786 (36.7%) neonatal near misses and 730 (34.1%) were newborns with no or minimal life threatening complications. Of the 235 babies admitted to the neonatal intensive care unit (NICU), the main reasons for admission were prematurity for 64 (26.8%), birth asphyxia for 59 (23.7%), and grunting respiration for 26 (11.1%). Of the 235 babies, 38 (16.2%) died in the neonatal period, and of these, 16 died in the first 24 hours after admission. Ruptured uterus caused the highest case-specific mortality of 76.8%, and led to 16.9% of all newborn deaths. Across the four groups, there were significant differences in mean birth weight, p = 0.003. CONCLUSIONS: Antepartum hemorrhage, ruptured uterus, severe preeclampsia, eclampsia, and the syndrome of Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP syndrome), led to statistically significant attributable risk of newborn deaths (still birth or neonatal deaths). Development of severe maternal outcomes, the mothers having been referred, and gravidity of 5 or more were significantly associated with newborn deaths.

Gaps in continuity of care: patients' perceptions of the quality of care during labor ward handover in Mulago hospital, Uganda.

BACKGROUND: Client satisfaction is a common outcome measure for quality of care and goal for quality improvement in healthcare. We assessed women's perceptions of the structure, process and outcome of intrapartum care in Mulago hospital, specifically, labor ward duty shift handovers. METHODS: Data was collected through 40 in-depth interviews conducted on two occasions: during the time of hospitalization and within 4-6 months after childbirth. Participants were women who delivered at the hospital, of whom some had life-threatening obstetric complications. Data was analyzed by thematic analysis. RESULTS: Maternity duty handovers were associated with patient dissatisfaction, particularly the process of hand-over, the decision-making that follows handovers and failure of communication of information to patients and their caretakers. Consequently, duty handovers were perceived inadequate. They were described as gaps in the continuity of care, and contributed to poor quality of care, birth trauma and mothers' dissatisfaction with the childbirth experience. CONCLUSION: The handover process and practices should be standardized using protocols and checklists. Health workers need training on handover practices, team work and communication skills (so as to improve patient-health provider and provider-provider interaction.

Male partners' perceptions of maternal near miss obstetric morbidity experienced by their spouses.

BACKGROUND: Severe obstetric complications have potential negative impact on the family and household of the survivors, with potential negative effects during (and in the aftermath of) the traumatic obstetric events. The objective was to gain deeper understanding of how severe obstetric complications are perceived by male partners, and their impact on the livelihoods of the family and community. METHODS: Data was collected through 25 in-depth narrative interviews with male partners of women with severe obstetric morbidity. The interviews occurred 4-12 months after the traumatic childbirth events. To gain a deeper understanding of the meanings and spouses attach to the experiences, we employed the notions of social capital and resilience. RESULTS: Male partners' perceptions and experiences were mostly characterized by losses, dreams and dilemmas, disempowerment and alienation, seclusion and self isolation or reliance on the social networks. During the aftermath of the events, there was disruption of the livelihoods of the partners and the whole family. CONCLUSION: While a maternal near miss obstetric event might appear as a positive outcome for the survivors, partners and caregivers of women who experience severe obstetric morbidity are deeply affected by the experiences of this life-threatening episode.

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

Pregnancy, parturition and preeclampsia in women of African ancestry.

Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health.