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Maternal mortality, as a largely avoidable cause of death, is an important focus of international development efforts, and a target for Millennium Development Goal (MDG) 5. However, data weaknesses have made monitoring progress problematic. In 2006, a new maternal mortality working group was established to develop improved estimation methods and make new estimates of maternal mortality for 2005, and to analyse trends in maternal mortality since 1990. We developed and used a range of methods, depending on the type of data available, to produce comparable country, regional, and global estimates of maternal mortality ratios for 2005 and to assess trends between 1990 and 2005. We estimate that there were 535 900 maternal deaths in 2005, corresponding to a maternal mortality ratio of 402 (uncertainty bounds 216–654) deaths per 100 000 livebirths. Most maternal deaths in 2005 were concentrated in sub-Saharan Africa (270 500, 50%) and Asia (240 600, 45%). For all countries with data, there was a decrease of 2·5% per year in the maternal mortality ratio between 1990 and 2005 (p<0·0001); however, there was no evidence of a significant reduction in maternal mortality ratios in sub-Saharan Africa in the same period. Although some regions have shown some progress since 1990 in reducing maternal deaths, maternal mortality ratios in sub-Saharan Africa have remained very high, with little evidence of improvement in the past 15 years. To achieve MDG5 targets by 2015 will require sustained and urgent emphasis on improved pregnancy and delivery care throughout the developing world.

Historically, the main focus of studies of childhood mortality has been the infant and under-five mortality rates. Neonatal mortality (deaths <28 days of age) has received limited attention, although such deaths account for about 41% of all child deaths. To better assess progress, we developed annual estimates for neonatal mortality rates (NMRs) and neonatal deaths for 193 countries for the period 1990-2009 with forecasts into the future. We compiled a database of mortality in neonates and children (<5 years) comprising 3,551 country-years of information. Reliable civil registration data from 1990 to 2009 were available for 38 countries. A statistical model was developed to estimate NMRs for the remaining 155 countries, 17 of which had no national data. Country consultation was undertaken to identify data inputs and review estimates. In 2009, an estimated 3.3 million babies died in the first month of life-compared with 4.6 million neonatal deaths in 1990-and more than half of all neonatal deaths occurred in five countries of the world (44% of global livebirths): India 27.8% (19.6% of global livebirths), Nigeria 7.2% (4.5%), Pakistan 6.9% (4.0%), China 6.4% (13.4%), and Democratic Republic of the Congo 4.6% (2.1%). Between 1990 and 2009, the global NMR declined by 28% from 33.2 deaths per 1,000 livebirths to 23.9. The proportion of child deaths that are in the neonatal period increased in all regions of the world, and globally is now 41%. While NMRs were halved in some regions of the world, Africa's NMR only dropped 17.6% (43.6 to 35.9). Neonatal mortality has declined in all world regions. Progress has been slowest in the regions with high NMRs. Global health programs need to address neonatal deaths more effectively if Millennium Development Goal 4 (two-thirds reduction in child mortality) is to be achieved.

We sought to assess the current status of global data on death registration and to examine several indicators of data completeness and quality. We summarized the availability of death registration data by year and country. Indicators of data quality were assessed for each country and included the timeliness, completeness and coverage of registration and the proportion of deaths assigned to ill-defined causes. At the end of 2003 data on death registration were available from 115 countries, although they were essentially complete for only 64 countries. Coverage of death registration varies from close to 100% in the WHO European Region to less than 10% in the African Region. Only 23 countries have data that are more than 90% complete, where ill-defined causes account for less than 10% of total of causes of death, and where ICD-9 or ICD-10 codes are used. There are 28 countries where less than 70% of the data are complete or where ill-defined codes are assigned to more than 20% of deaths. Twelve high-income countries in western Europe are included among the 55 countries with intermediate-quality data. Few countries have good-quality data on mortality that can be used to adequately support policy development and implementation. There is an urgent need for countries to implement death registration systems, even if only through sample registration, or enhance their existing systems in order to rapidly improve knowledge about the most basic of health statistics: who dies from what?

Monitoring development indicators has become a central interest of international agencies and countries for tracking progress towards the Millennium Development Goals. In this review, which also provides an introduction to a collection of articles, we describe the methodology used by the United Nations Inter-agency Group for Child Mortality Estimation to track country-specific changes in the key indicator for Millennium Development Goal 4 (MDG 4), the decline of the under-five mortality rate (the probability of dying between birth and age five, also denoted in the literature as U5MR and (5)q(0)). We review how relevant data from civil registration, sample registration, population censuses, and household surveys are compiled and assessed for United Nations member states, and how time series regression models are fitted to all points of acceptable quality to establish the trends in U5MR from which infant and neonatal mortality rates are generally derived. The application of this methodology indicates that, between 1990 and 2010, the global U5MR fell from 88 to 57 deaths per 1,000 live births, and the annual number of under-five deaths fell from 12.0 to 7.6 million. Although the annual rate of reduction in the U5MR accelerated from 1.9% for the period 1990-2000 to 2.5% for the period 2000-2010, it remains well below the 4.4% annual rate of reduction required to achieve the MDG 4 goal of a two-thirds reduction in U5MR from its 1990 value by 2015. Thus, despite progress in reducing child mortality worldwide, and an encouraging increase in the pace of decline over the last two decades, MDG 4 will not be met without greatly increasing efforts to reduce child deaths.

Mortality estimates for many populations are derived using model life tables, which describe typical age patterns of human mortality. We propose a new system of model life tables as a means of improving the quality and transparency of such estimates. A flexible two-dimensional model was fitted to a collection of life tables from the Human Mortality Database. The model can be used to estimate full life tables given one or two pieces of information: child mortality only, or child and adult mortality. Using life tables from a variety of sources, we have compared the performance of new and old methods. The new model outperforms the Coale-Demeny and UN model life tables. Estimation errors are similar to those produced by the modified Brass logit procedure. The proposed model is better suited to the practical needs of mortality estimation, since both input parameters are continuous yet the second one is optional.

The present paper examines, describes and documents country-specific trends in under-five mortality rates (i.e., mortality among children under five years of age) in the 1990s. Our analysis updates previous studies by UNICEF, the World Bank and the United Nations. It identifies countries and WHO regions where sustained improvement has occurred and those where setbacks are evident. A consistent series of estimates of under-five mortality rate is provided and an indication is given of historical trends during the period 1950-2000 for both developed and developing countries. It is estimated that 10.5 million children aged 0-4 years died in 1999, about 2.2 million or 17.5% fewer than a decade earlier. On average about 15% of newborn children in Africa are expected to die before reaching their fifth birthday. The corresponding figures for many other parts of the developing world are in the range 3-8% and that for Europe is under 2%. During the 1990s the decline in child mortality decelerated in all the WHO regions except the Western Pacific but there is no widespread evidence of rising child mortality rates. At the country level there are exceptions in southern Africa where the prevalence of HIV is extremely high and in Asia where a few countries are beset by economic difficulties. The slowdown in the rate of decline is of particular concern in Africa and South-East Asia because it is occurring at relatively high levels of mortality, and in countries experiencing severe economic dislocation. As the HIV/AIDS epidemic continues in Africa, particularly southern Africa, and in parts of Asia, further reductions in child mortality become increasingly unlikely until substantial progress in controlling the spread of HIV is achieved.

We present three cases of eosinophilic granulomatosis with polyangiitis (EGPA) where patients experienced relapse of eosinophilic sinusitis without peripheral eosinophilia while on remission maintenance therapy with mepolizumab (MPZ), an anti-interleukin (IL)-5 monoclonal antibody. Despite the initial control of symptoms with high-dose prednisolone (PSL) and MPZ, patients experienced a relapse of nasal obstruction and eosinophilic infiltration in nasal mucosal biopsies. Notably, relapses occurred despite normal peripheral eosinophil counts, indicating the localized nature of eosinophilic inflammation. While IL-5 inhibitors effectively reduce peripheral blood eosinophils, eosinophilic sinusitis may persist due to local factors such as IL-4-mediated inflammation. IL-4 has been implicated in promoting eosinophil migration into nasal tissues, suggesting that IL-5 inhibitors alone may not sufficiently suppress eosinophilic infiltration in such cases. These findings highlight the importance of considering the possibility of eosinophilic sinusitis relapse in EGPA patients treated with IL-5 inhibitors and reduced glucocorticoid doses. Further research is warranted to elucidate the mechanisms underlying local eosinophilic inflammation and optimize treatment strategies for EGPA patients.

Good public-health decisionmaking is dependent on reliable and timely statistics on births and deaths (including the medical causes of death). All high-income countries, without exception, have national civil registration systems that record these events and generate regular, frequent, and timely vital statistics. By contrast, these statistics are not available in many low-income and lower-middle-income countries, even though it is in such settings that premature mortality is most severe and the need for robust evidence to back decisionmaking most critical. Civil registration also has a range of benefits for individuals in terms of legal status, and the protection of economic, social, and human rights. However, over the past 30 years, the global health and development community has failed to provide the needed technical and financial support to countries to develop civil registration systems. There is no single blueprint for establishing and maintaining such systems and ensuring the availability of sound vital statistics. Each country faces a different set of challenges, and strategies must be tailored accordingly. There are steps that can be taken, however, and we propose an approach that couples the application of methods to generate better vital statistics in the short term with capacity-building for comprehensive civil registration systems in the long run.

The increased attention to tracking progress towards the Millennium Development Goals (MDG), including Goal 4 of reducing child mortality, has drawn attention to a number of interrelated technical, operational and political challenges and to the underlying weaknesses of country health information systems upon which reliable monitoring depends. Assessments of child mortality published in 2005, for almost all low-income countries, are based on an extrapolation of the trends observed during the 1990s, rather than on the empirical data for more recent years. The validity of the extrapolation depends on the quality and quantity of the data used, and many countries lack suitable data. In the long run, it is hoped that vital registration or sample registration systems will be established to monitor vital events in a sustainable way. However, in the short run, tracking child mortality in high-mortality countries will continue to rely on household surveys and extrapolations of historical trends. This will require more collaborative efforts both to collect data through initiatives to strengthen health information systems at the country level, and to harmonize the estimation process. The latter objective requires the continued activity of a coordinating group of international agencies and academics that aims to produce transparent estimates -- through the consistent application of an agreed-upon methodology --for monitoring at the international level.