Direct maternal morbidity and the risk of pregnancy-related deaths,stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries

BackgroundMaternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.Methods and findingsThis is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman’s self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes.Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.ConclusionsOur findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.Trial registrationThe study is not a clinical trial.     

Malaria mortality rates in South Asia and in Africa: implications for malaria control

Malaria mortality in human populations varies greatly under different circumstances. The intense malaria transmission conditions found in many parts of tropical Africa, the much lower malaria inoculation rates currently sustained in areas of southern Asia, and the epidemic outbreaks of malaria occasionally seen on both continents, present highly contrasting patterns of malaria-related mortality. Here Harsha Alles, Kamini Mendis and Richard Carter examine malaria-related mortality under different circumstances and discuss implications for the management of malaria in these settings. They emphasize the power of rapid case treatment to save lives at risk under virtually all circumstances of malaria transmission.     

Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study

BackgroundData on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions.Methods and findingsWe used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related.Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates.ConclusionsThis study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children.

Jackie Kleynhans and colleagues investigate whether introduction of the pneumococcal conjugate vaccine may have reduced all-cause pneumonia mortality in South Africa.     

Hospital factors associated with maternal and neonatal outcomes of deliveries to patients with a previous cesarean delivery: an ecological study

Background:Recommendations for deliveries of pregnant patients with a previous cesarean delivery and the type of hospitals deemed safe for these deliveries have evolved in recent years, although no studies have examined hospital factors and associated safety. We sought to evaluate maternal and neonatal outcomes among patients with a previous cesarean delivery by hospital tier and volume.Methods:We carried out an ecological study of singleton live births delivered at term gestation to patients with a previous cesarean delivery in all Canadian hospitals (excluding Quebec), 2013–2019. We obtained data from the Discharge Abstract Database of the Canadian Institute for Health Information. The primary outcomes were severe maternal morbidity or mortality (SMMM), and serious neonatal morbidity or mortality (SNMM). We used regression modelling to examine hospital tier (tier 4 hospitals being those that provide the highest level of care) and volume; we also identified hospitals with high rates of SMMM and SNMM using within-tier comparisons and comparisons with the overall rate.Results:We included 235 442 deliveries to patients with a previous cesarean delivery; SMMM and SNMM rates were 14.6 per 1000 deliveries and 4.6 per 1000 live births, respectively. Among patients with a parity of 1, SMMM rates were lower in tier 1 hospitals (adjusted incidence rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.52–0.89) and higher in tier 4 hospitals (adjusted IRR 1.41, 95% CI 1.05–1.91) than in tier 2 hospitals; SNMM rates did not differ by hospital tier. Rates of SNMM increased with increasing hospital volume (adjusted IRR 1.02, 95% CI 1.00–1.04) and increasing rates of vaginal birth after cesarean delivery (adjusted IRR 1.02, 95% CI 1.01–1.04). Most hospitals had relatively low SMMM and SNMM rates, although a few hospitals in each tier and volume category had significantly higher rates than others.Interpretation:Adverse maternal and neonatal outcomes among patients with a previous cesarean delivery showed no clear pattern of decreasing SMMM and SNMM with increasing tiers of service and hospital volume. All hospitals, irrespective of tier or size, should continually review their rates of adverse maternal and neonatal outcomes.

The approach to delivery for patients with a previous cesarean delivery has undergone substantial changes over the last few decades in Canada, the United States and elsewhere. Rates of vaginal birth after cesarean delivery (VBAC) in Canada increased rapidly, from less than 5% of deliveries in the late 1970s to peak at more than 35% in the mid-1990s.^1–4 However, this trend reversed sharply after studies in the mid-1990s showed that attempted VBAC (as opposed to elective repeat cesarean delivery) was associated with higher rates of severe maternal morbidity and of fetal and infant morbidity and mortality.^5–9 The decline has partly reversed after the release of a guideline from the Society of Obstetricians and Gynaecologists of Canada (SOGC) in 2005, and the National Institutes of Health Consensus Development Conference in 2010, which affirmed that patients with 1 previous transverse lower-segment cesarean section and no contraindications could be offered a trial of labour with appropriate discussion of risks and benefits.^10,11Recommendations regarding hospitals deemed safe for delivering patients with a previous cesarean delivery have also evolved. The 1998 and 1999 guidelines of the American College of Obstetricians and Gynecologists (ACOG) required hospitals attempting trials of labour to have “ready availability of emergency care” or “immediate availability of emergency care.”^12,13 After the publication of these guidelines, about 30% of hospitals in the US stopped offering trial-of-labour services to patients with a previous cesarean delivery because they could not provide immediate surgical and anesthesia services, which compelled many patients who had opted for a trial of labour to travel to hospitals far from their homes and families.^14–16 More recently, guidelines have attempted to balance clinical safety with the challenges associated with such social disruption. The current ACOG guideline states that a trial of labour can be attempted in a level 1 maternity care facility (i.e., a hospital providing basic obstetric services), which has “the ability to begin emergency cesarean delivery within a time interval that best incorporates maternal and fetal risks and benefits.”¹⁷ Similarly, the current SOGC guideline states that hospitals providing trial-of-labour services should have “the resources to perform an emergency cesarean section.”¹⁸ This change in recommendations has led to an increase in the number of hospitals that offer trials of labour, though concerns about inadequate access to such delivery options persist.^19,20Although clinical guidelines regarding hospitals deemed safe for delivering patients with a previous cesarean delivery have changed in recent years, to our knowledge, no studies have evaluated hospital factors and associated safety issues. We sought to evaluate maternal and infant outcomes of deliveries to patients with a previous cesarean delivery by tier of obstetric service and hospital delivery volume.     

An ecological study of the determinants of differences in 2009 pandemic influenza mortality rates between countries in Europe

Background

Pandemic A (H1N1) 2009 mortality rates varied widely from one country to another. Our aim was to identify potential socioeconomic determinants of pandemic mortality and explain between-country variation.

Methodology

Based on data from a total of 30 European countries, we applied random-effects Poisson regression models to study the relationship between pandemic mortality rates (May 2009 to May 2010) and a set of representative environmental, health care-associated, economic and demographic country-level parameters. The study was completed by June 2010.

Principal Findings

Most regression approaches indicated a consistent, statistically significant inverse association between pandemic influenza-related mortality and per capita government expenditure on health. The findings were similar in univariable [coefficient: –0.00028, 95% Confidence Interval (CI): –0.00046, –0.00010, p = 0.002] and multivariable analyses (including all covariates, coefficient: –0.00107, 95% CI: –0.00196, –0.00018, p = 0.018). The estimate was barely insignificant when the multivariable model included only significant covariates from the univariate step (coefficient: –0.00046, 95% CI: –0.00095, 0.00003, p = 0.063).

Conclusions

Our findings imply a significant inverse association between public spending on health and pandemic influenza mortality. In an attempt to interpret the estimated coefficient (–0.00028) for the per capita government expenditure on health, we observed that a rise of 100 international dollars was associated with a reduction in the pandemic influenza mortality rate by approximately 2.8%. However, further work needs to be done to unravel the mechanisms by which reduced government spending on health may have affected the 2009 pandemic influenza mortality.     

Modelling children's anthropometric status using Bayesian distributional regression merging socio-economic and remote sensed data from South Asia and sub-Saharan Africa

A history of insufficient nutritional intake is reflected by low anthropometric measures and can lead to growth failures, limited mental development, poor health outcomes and a higher risk of dying. Children below five years are among those most vulnerable and, while improvements in the share of children affected by insufficient nutritional intake has been observed, both sub-Saharan Africa and South Asia have a disproportionately high share of growth failures and large disparities at national and sub-national levels. In this study, we use a Bayesian distributional regression approach to develop models for the standard anthropometric measures, stunting and wasting. This approach allows us to model both the mean and the standard deviation of the underlying response distribution. Accordingly, the whole distribution of the anthropometric measures can be evaluated. This is of particular importance, considering the fact that (severe) growth failures of children are defined having a z-score below −2 (−3), emphasising the need to extend the analysis beyond the conditional mean. In addition, we merge individual data taken from the Demographic and Health Surveys with remote sensed data for a large sample of 38 countries located in sub-Saharan Africa and South Asia for the period 1990–2016, in order to combine individual and household specific characteristics with geophysical and environmental characteristics, and to allow for a comparison over time. Our results show besides gender differences across space, and strong non-linear effects of included socio-economic characteristics, in particular for maternal education and the wealth of the household that, surprisingly, in the presence of socio-economic characteristics, remote sensed data does not contribute to variations in growth failures, and including a pure spatial effect excluding remote sensed data leads to even better results. Further, while all regions showed improvements towards the target of the Sustainable Development Goals (SDGs), our analysis identifies hotspots of growth failures at sub-national levels within India, Nigeria, Niger, and Madagascar, emphasising the need to accelerate progress to reach the target set by the SDGs.     

HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon

Background

The disease burden of human immunodeficiency virus (HIV) - acquired immunodeficiency syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders in this region. The objectives of this study were to determine whether Western neuropsychological (NP) methods are appropriate for use in Cameroon, and to evaluate cognitive function in a sample of HIV-infected adults.

Methods

We used a battery of 19 NP measures in a cross-sectional study with 44 HIV+ adults and 44 demographically matched HIV- controls, to explore the validity of these NP measures in Cameroon, and evaluate the effect of viral infection on seven cognitive ability domains.

Results

In this pilot study, the global mean z-score on the NP battery showed worse overall cognition in the HIV+ individuals. Significantly lower performance was seen in the HIV+ sample on tests of executive function, speed of information processing, working memory, and psychomotor speed. HIV+ participants with AIDS performed worse than those with less advanced HIV disease.

Conclusions

Similar to findings in Western cohorts, our results in Cameroon suggest that HIV infection, particularly in advanced stages, is associated with worse performance on standardized, Western neurocognitive tests. The tests used here appear to be promising for studying NeuroAIDS in sub-Saharan Africa.     

Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa

Background

Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up.

Methods and Findings

Treatment-naïve patients starting combination ART in five programmes in Côte d''Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9–6.5%) to 10.9% (9.6–12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9–11.6%) to 16.9% (15.0–19.1%), with relative increases in mortality ranging from 27% to 73% across programmes.

Conclusions

Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.     

Structural determinants of child mortality in sub-Saharan Africa: A cross-national study of economic and social influences from 1970 to 1997

This cross-national study seeks to understand the lagging child mortality declines in sub-Saharan Africa by using World Bank data to investigate social and economic factors at three points in time: 1970, 1985, and 1997. Women's education, foreign debt-to-export ratio, and GNP per capita are among the strongest correlates of under five mortality over time. Cross-sectional and longitudinal results suggest that female education is the best overall predictor of child mortality. Average national income does not emerge as a strong predictor, particularly since 1985. Increasing levels of foreign debt are associated with a substantial excess mortality burden. In 1997, the effect of adult HIV prevalence on child mortality was moderate and statistically significant. The study concludes that, although future gains in social factors such as female education will likely be beneficial, without simultaneously addressing high levels of foreign debt and high HIV prevalence, it may be difficult to improve child mortality rates across sub-Saharan Africa.     

Melanin and HIV in sub-Saharan Africa

HIV is common in sub-Saharan Africa. Sexually transmitted bacterial and fungal infections increase the chance of HIV infection. Melanin can prevent the penetration of skin and mucus membranes by microorganisms, and soluble melanin can inhibit HIV replication. We suggest that melanin may reduce the incidence of HIV infection through venereally acquired skin lesions, thus reducing the risk of sero-conversion and slow the progress to AIDS. Indigenous sub-Saharan peoples are highly melanized, but there is pigment variation between populations. We show that skin reflectance, a negative correlate of melanin, is positively associated with adult rate of HIV in sub-Saharan countries. There is no such relationship in populations outside sub-Saharan Africa. We suggest that melanin concentration in black people may correlate with resistance to HIV infection.     

Malaria and urbanization in sub-Saharan Africa

There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.     

An ecological reassessment of the southern African carnivore guild: a case study from Member 4, Sterkfontein, South Africa

The southern African late Pliocene to early Pleistocene carnivore guild was much larger than that of the present day. Understanding how this guild may have functioned is important for the reconstruction of carnivore-hominin interactions and to assess the potential for hominin scavenging in southern Africa. In modern ecosystems, the coexistence of larger carnivore species is constrained by several factors, which include high levels of interspecific competition. Here, the composition of the fossil carnivore guild is examined using Sterkfontein Member 4 (Cradle of Humankind, South Africa) as a case study. Sterkfontein Member 4 contains 10 larger carnivore taxa (body mass > 21.5 kg) and may also contain two Australopithecus species. Two possible causes of higher numbers of carnivore species in the South African fossil record are initially considered. First, that there is a bias introduced through comparing assemblages of differing sizes; second, carnivore biodiversity may have been artificially inflated due to previous taxonomic splitting of carnivore species, such as Crocuta. These possibilities are rejected and modern ecological data are used to construct a simple spatial model to determine how many carnivores could have co-existed. Although the resulting model indicates that the carnivore taxa present in Member 4 could have co-occurred, modern ecological studies indicate that it is highly unlikely that they would have co-existed simultaneously. Considering the complex depositional processes that operate in the southern African cave sites, it is proposed that the larger carnivore guild observed in the Sterkfontein Member 4 fossil assemblage is a palimpsest created by time-averaging. In light of this, we suggest that sites which have a large number of carnivore taxa should be examined for time-averaging, while those sites which have relatively few species may be a better reflection of carnivore communities.     

Sex differences in obesity rates in poor countries: Evidence from South Africa

Globally, men and women face markedly different risks of obesity. In all but of handful of (primarily Western European) countries, obesity is much more prevalent among women than men. We examine several potential explanations for this phenomenon. We analyze differences between men and women in reports and effects of potential underlying causes of obesity—childhood and adult poverty, depression, and attitudes about obesity. We evaluate the evidence for each explanation using data collected in an urban African township in the Cape Town metropolitan area. Three factors explain the greater obesity rates we find among women. Women who were nutritionally deprived as children are significantly more likely to be obese as adults, while men who were deprived as children face no greater risk. In addition, women of higher adult socioeconomic status are significantly more likely to be obese, which is not true for men. These two factors - childhood circumstances and adult SES - can fully explain the difference in obesity rates between men and women that we find in our sample. More speculatively, in South Africa, women's perceptions of an ‘ideal’ female body are larger than men's perceptions of the ‘ideal’ male body, and individuals with larger ‘ideal’ body images are significantly more likely to be obese.     

Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa

Background

The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.

Methods and Findings

We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year.

Conclusions

The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up. Please see later in the article for the Editors'' Summary     

Biotechnology and sustainable development in sub-Saharan Africa

Whether development is defined by the long-standing economic parameter of per capita gross national product (GNP) or by the newly introduced Human Development Index (HDI), which is not based exclusively on per capita GNP, the countries of sub-Saharan Africa rank at or near the bottom of the developing world. Agriculture and agro-based processing are the mainstays of the economies of the majority of these countries. Because of this, and also because many of the diseases endemic in these countries are communicable, the application of modern biotechnology (including genetic engineering, tissue culture and monoclonal antibody technology) and related biotechnologies could play an important part in creating sustainable development in the region. There is, therefore, an urgent need to train more of the region's indigenous citizens, and to equip more laboratories, in modern biotechnology. It is suggested that, in order to accelerate the harnessing of the fruits of biotechnology, more countries in the region should affiliate with the International Centre for Genetic Engineering and Biotechnology (ICGEB). It is further suggested that a regional equivalent of the ICGEB be built and the services of non-governmental biotechnology organizations used.The author is with Nnamdi Azikiwe University, P. M. B. 5025, Awka, Nigeria. Address correspondence to P. M. B. 1457, Enugu, Nigeria