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Maternal health is a big issue and is central to sustainable development. Each year, about 210 million women become pregnant and about 140 million newborn babies are delivered—the sheer scale of maternal health alone makes maternal well being and survival vital concerns. In this Series paper, we adopt primarily a numerical lens to illuminate patterns and trends in outcomes, but recognise that understanding of poor maternal health also warrants other perspectives, such as human rights. Our use of the best available evidence highlights the dynamic burden of maternal health problems. Increased diversity in the magnitude and causes of maternal mortality and morbidity between and within populations presents a major challenge to policies and programmes aiming to match varying needs with diverse types of care across different settings. This diversity, in turn, contributes to a widening gap or differences in levels of maternal mortality, seen most acutely in vulnerable populations, predominantly in sub-Saharan Africa. Strong political and technical commitment to improve equity-sensitive information systems is required to monitor the gap in maternal mortality, and robust research is needed to elucidate major interactions between the broad range of health problems. Diversity and divergence are defining characteristics of poor maternal health in the 21st century. Progress on this issue will be an ultimate judge of sustainable development.

In addition to the inherent importance of education and its essential role in economic growth, education and health are strongly related. We updated previous systematic assessments of educational attainment, and estimated the contribution of improvements in women's education to reductions in child mortality in the past 40 years. We compiled 915 censuses and nationally representative surveys, and estimated mean number of years of education by age and sex. By use of a first-differences model, we investigated the association between child mortality and women's educational attainment, controlling for income per person and HIV seroprevalence. We then computed counterfactual estimates of child mortality for every country year between 1970 and 2009. The global mean number of years of education increased from 4·7 years (95% uncertainty interval 4·4–5·1) to 8·3 years (8·0–8·6) for men (aged ≥25 years) and from 3·5 years (3·2–3·9) to 7·1 years (6·7 −7·5) for women (aged ≥25 years). For women of reproductive age (15–44 years) in developing countries, the years of schooling increased from 2·2 years (2·0–2·4) to 7·2 years (6·8–7·6). By 2009, in 87 countries, women (aged 25–34 years) had higher educational attainment than had men (aged 25–34 years). Of 8·2 million fewer deaths in children younger than 5 years between 1970 and 2009, we estimated that 4·2 million (51·2%) could be attributed to increased educational attainment in women of reproductive age. The substantial increase in education, especially of women, and the reversal of the gender gap have important implications not only for health but also for the status and roles of women in society. The continued increase in educational attainment even in some of the poorest countries suggests that rapid progress in terms of Millennium Development Goal 4 might be possible. Bill & Melinda Gates Foundation.

New momentum for civil registration and vital statistics (CRVS) is building, driven by the confluence of growing demands for accountability and results in health, improved equity, and rights-based approaches to development challenges, and by the immense potential of innovation and new technologies to accelerate CRVS improvement. Examples of country successes in strengthening of hitherto weak systems are emerging. The key to success has been to build collaborative partnerships involving local ownership by several sectors that span registration, justice, health, statistics, and civil society. Regional partners can be important to raise awareness, set regional goals and targets, foster country-to-country exchange and mutual learning, and build high-level political commitment. These regional partners continue to provide a platform through which country stakeholders, development partners, and technical experts can share experiences, develop and document good practices, and propose innovative approaches to tackle CRVS challenges. This country and regional momentum would benefit from global leadership, commitment, and support.

Breast and cervical cancer are important causes of mortality in women aged ≥15 years. We undertook annual age-specific assessments of breast and cervical cancer in 187 countries. We systematically collected cancer registry data on mortality and incidence, vital registration, and verbal autopsy data for the period 1980–2010. We modelled the mortality-to-incidence (MI) ratio using a hierarchical model. Vital registration and verbal autopsy were supplemented with incidence multiplied by the MI ratio to yield a comprehensive database of mortality rates. We used Gaussian process regression to develop estimates of mortality with uncertainty by age, sex, country, and year. We used out-of-sample predictive validity to select the final model. Estimates of incidence with uncertainty were also generated with mortality and MI ratios. Global breast cancer incidence increased from 641 000 (95% uncertainty intervals 610 000–750 000) cases in 1980 to 1 643 000 (1 421 000–1 782 000) cases in 2010, an annual rate of increase of 3·1%. Global cervical cancer incidence increased from 378 000 (256 000–489 000) cases per year in 1980 to 454 000 (318 000–620 000) cases per year in 2010—a 0·6% annual rate of increase. Breast cancer killed 425 000 (359 000–453 000) women in 2010, of whom 68 000 (62 000–74 000) were aged 15–49 years in developing countries. Cervical cancer death rates have been decreasing but the disease still killed 200 000 (139 000–276 000) women in 2010, of whom 46 000 (33 000–64 000) were aged 15–49 years in developing countries. We recorded pronounced variation in the trend in breast cancer mortality across regions and countries. More policy attention is needed to strengthen established health-system responses to reduce breast and cervical cancer, especially in developing countries. Susan G Komen for the Cure and the Bill & Melinda Gates Foundation.

Understanding potential patterns in future population levels is crucial for anticipating and planning for changing age structures, resource and health-care needs, and environmental and economic landscapes. Future fertility patterns are a key input to estimation of future population size, but they are surrounded by substantial uncertainty and diverging methodologies of estimation and forecasting, leading to important differences in global population projections. Changing population size and age structure might have profound economic, social, and geopolitical impacts in many countries. In this study, we developed novel methods for forecasting mortality, fertility, migration, and population. We also assessed potential economic and geopolitical effects of future demographic shifts. We modelled future population in reference and alternative scenarios as a function of fertility, migration, and mortality rates. We developed statistical models for completed cohort fertility at age 50 years (CCF50). Completed cohort fertility is much more stable over time than the period measure of the total fertility rate (TFR). We modelled CCF50 as a time-series random walk function of educational attainment and contraceptive met need. Age-specific fertility rates were modelled as a function of CCF50 and covariates. We modelled age-specific mortality to 2100 using underlying mortality, a risk factor scalar, and an autoregressive integrated moving average (ARIMA) model. Net migration was modelled as a function of the Socio-demographic Index, crude population growth rate, and deaths from war and natural disasters; and use of an ARIMA model. The model framework was used to develop a reference scenario and alternative scenarios based on the pace of change in educational attainment and contraceptive met need. We estimated the size of gross domestic product for each country and territory in the reference scenario. Forecast uncertainty intervals (UIs) incorporated uncertainty propagated from past data inputs, model estimation, and forecast data distributions. The global TFR in the reference scenario was forecasted to be 1·66 (95% UI 1·33–2·08) in 2100. In the reference scenario, the global population was projected to peak in 2064 at 9·73 billion (8·84–10·9) people and decline to 8·79 billion (6·83–11·8) in 2100. The reference projections for the five largest countries in 2100 were India (1·09 billion [0·72–1·71], Nigeria (791 million [594–1056]), China (732 million [456–1499]), the USA (336 million [248–456]), and Pakistan (248 million [151–427]). Findings also suggest a shifting age structure in many parts of the world, with 2·37 billion (1·91–2·87) individuals older than 65 years and 1·70 billion (1·11–2·81) individuals younger than 20 years, forecasted globally in 2100. By 2050, 151 countries were forecasted to have a TFR lower than the replacement level (TFR <2·1), and 183 were forecasted to have a TFR lower than replacement by 2100. 23 countries in the reference scenario, including Japan, Thailand, and Spain, were forecasted to have population declines greater than 50% from 2017 to 2100; China's population was forecasted to decline by 48·0% (−6·1 to 68·4). China was forecasted to become the largest economy by 2035 but in the reference scenario, the USA was forecasted to once again become the largest economy in 2098. Our alternative scenarios suggest that meeting the Sustainable Development Goals targets for education and contraceptive met need would result in a global population of 6·29 billion (4·82–8·73) in 2100 and a population of 6·88 billion (5·27–9·51) when assuming 99th percentile rates of change in these drivers. Our findings suggest that continued trends in female educational attainment and access to contraception will hasten declines in fertility and slow population growth. A sustained TFR lower than the replacement level in many countries, including China and India, would have economic, social, environmental, and geopolitical consequences. Policy options to adapt to continued low fertility, while sustaining and enhancing female reproductive health, will be crucial in the years to come. Bill & Melinda Gates Foundation.

During the past decade, renewed global and national efforts to combat malaria have led to ambitious goals. We aimed to provide an accurate assessment of the levels and time trends in malaria mortality to aid assessment of progress towards these goals and the focusing of future efforts. We systematically collected all available data for malaria mortality for the period 1980–2010, correcting for misclassification bias. We developed a range of predictive models, including ensemble models, to estimate malaria mortality with uncertainty by age, sex, country, and year. We used key predictors of malaria mortality such as Plasmodium falciparum parasite prevalence, first-line antimalarial drug resistance, and vector control. We used out-of-sample predictive validity to select the final model. Global malaria deaths increased from 995 000 (95% uncertainty interval 711 000–1 412 000) in 1980 to a peak of 1 817 000 (1 430 000–2 366 000) in 2004, decreasing to 1 238 000 (929 000–1 685 000) in 2010. In Africa, malaria deaths increased from 493 000 (290 000–747 000) in 1980 to 1 613 000 (1 243 000–2 145 000) in 2004, decreasing by about 30% to 1 133 000 (848 000–1 591 000) in 2010. Outside of Africa, malaria deaths have steadily decreased from 502 000 (322 000–833 000) in 1980 to 104 000 (45 000–191 000) in 2010. We estimated more deaths in individuals aged 5 years or older than has been estimated in previous studies: 435 000 (307 000–658 000) deaths in Africa and 89 000 (33 000–177 000) deaths outside of Africa in 2010. Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met. The Bill & Melinda Gates Foundation.

Girls' and women's health is in transition and, although some aspects of it have improved substantially in the past few decades, there are still important unmet needs. Population ageing and transformations in the social determinants of health have increased the coexistence of disease burdens related to reproductive health, nutrition, and infections, and the emerging epidemic of chronic and non-communicable diseases (NCDs).

Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Increasing demand for better quality data and more investment to strengthen civil registration and vital statistics (CRVS) systems will require increased emphasis on objective, comparable, cost-effective monitoring and assessment methods to measure progress. We apply a composite index (the vital statistics performance index [VSPI]) to assess the performance of CRVS systems in 148 countries or territories during 1980–2012 and classify them into five distinct performance categories, ranging from rudimentary (with scores close to zero) to satisfactory (with scores close to one), with a mean VSPI score since 2005 of 0·61 (SD 0·31). As expected, the best performing systems were mostly in the European region, the Americas, and Australasia, with only two countries from east Asia and Latin America. Most low-scoring countries were in the African or Asian regions. Globally, only modest progress has been made since 2000, with the percentage of deaths registered increasing from 36% to 38%, and the percentage of children aged under 5 years whose birth has been registered increasing from 58% to 65%. However, several individual countries have made substantial improvements to their CRVS systems in the past 30 years by capturing more deaths and improving accuracy of cause-of-death information. Future monitoring of the effects of CRVS strengthening will greatly benefit from application of a metric like the VSPI, which is objective, costless to compute, and able to identify components of the system that make the largest contributions to good or poor performance.

Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection. In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850). We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% (95% uncertainty interval [UI] 17·3–76·1) and 44·0% (26·5–65·0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% (49·8–93·6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% (24·4–51·3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% (69·7–97·5) for ancestral, alpha, and delta variants, and 88·9% (84·7–90·9) for omicron BA.1 at 40 weeks. Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings. Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.