Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Estimating the global impact of poor quality of care on maternal and neonatal outcomes in 81 low- and middle-income countries: A modeling study.

BACKGROUND: In low-resource settings where disease burdens remain high and many health facilities lack essentials such as drugs or commodities, functional equipment, and trained personnel, poor quality of care often results and the impact can be profound. In this paper, we systematically quantify the potential gain of addressing quality of care globally using country-level data about antenatal, childbirth, and postnatal care interventions. METHODS AND FINDINGS: In this study, we created deterministic models to project health outcomes if quality of care was addressed in a representative sample of 81 low- and middle-income countries (LMICs). First, available data from health facility surveys (e.g., Service Provision Assessment [SPA] and Service Availability and Readiness Assessment [SARA]) conducted 2007-2016 were linked to household surveys (e.g., Demographic and Health Surveys [DHS] and Multiple Indicator Cluster Surveys [MICS]) to estimate baseline coverage for a core subset of 19 maternal and newborn health interventions. Next, models were constructed with the Lives Saved Tool (LiST) using country-specific baseline levels in countries with a linked dataset (n = 17) and sample medians applied as a proxy in countries without linked data. Lastly, these 2016 starting baseline levels were raised to reach targets in 2020 as endline based upon country-specific utilization (e.g., proportion of women who attended 4+ antenatal visits, percentage of births delivered in a health facility) from the latest DHS or MICS population-based reports. Our findings indicate that if high-quality health systems could effectively deliver this subset of evidence-based interventions to mothers and their newborns who are already seeking care, there would be an estimated 28% decrease in maternal deaths, 28% decrease in neonatal deaths, and 22% fewer stillbirths compared to a scenario without any change or improvement in quality of care. Totals of 86,000 (range, 77,800-92,400) maternal and 0.67 million (range, 0.59 million-0.75 million) neonatal lives could be saved, and 0.52 million (range, 0.48 million-0.55 million) stillbirths could be prevented across the 81 countries in the calendar year 2020 when adequate quality care is provided at current levels of utilization. Limitations include the paucity of data to individually assess quality of care for each intervention in all LMICs and the necessary assumption that quality of care being provided among the subset of countries with linked datasets is comparable or representative of LMICs overall. CONCLUSIONS: Our findings suggest that efforts to close the quality gap would still produce substantial benefits at current levels of access or utilization. With estimated mortality rate declines of 21%-32% on average, gains from this first step would be significant if quality was improved for selected antenatal, intrapartum, and postnatal interventions to benefit pregnant women and newborns seeking care. Interventions provided at or around the time of childbirth are most critical and accounted for 64% of the impact overall estimated in this quality improvement analysis.

Validity of self-reported receipt of iron supplements during pregnancy: implications for coverage measurement.

BACKGROUND: Iron-deficiency anemia during pregnancy is an underlying cause of maternal deaths, and reducing risk through routine iron supplementation is a key component of antenatal care (ANC) programs in most low- and middle income countries. Supplementation coverage during pregnancy is estimated from maternal self-reports in population-based household surveys, yet recall bias and social desirability bias lead to errors of unknown magnitude. METHODS: We linked data from household and health facility surveys from 16 countries to estimate input-adjusted coverage of iron supplementation during pregnancy. We assessed the validity of reported receipt of iron supplements in client exit interviews using direct observation as the gold standard across 9 countries with a recent Service Provision Assessment (SPA). Using a sample of 227 women who participated in the Nepal Oil Massage Study (NOMS), we also assessed the validity of self-reported receipt of iron folic acid (IFA) supplements. We used Poisson regression models to explore the association between client and health facility characteristics and agreement of self-reported receipt of iron supplements compared to direct observation. RESULTS: Across the 16 countries, iron supplements were in supply at most of the 9215 sampled health facilities offering ANC services (91%). We estimated that between 48 and 93% of women attended at least one ANC visit at a health facility with iron supplements available. The specificity of recall of receipt of iron supplementation immediately following a visit was 79.3% and the sensitivity was 88.7% for the entire sample. Individual-level accuracy was high (Area under the curve > 0.7) and population bias low (0.75 < inflation factor < 1.25) across all countries. By contrast, in the NOMS sub-study, the accuracy of self-reported receipt of IFA supplements after 1-2 years was poor (sensitivity 86.1%, specificity 34.3%). Adjusted regression analyses indicated that older age and higher level of education were associated with poorer agreement between self-reports and direct observation. CONCLUSIONS: These findings suggest the need for caution when using self-reported measures with an extended recall period. Further validation studies using conditions similar to widely used population-based household surveys are warranted.

Reproductive, maternal, newborn, and child health: key messages from Disease Control Priorities 3rd Edition.

As part of Disease Control Priorities 3rd Edition, the World Bank will publish a volume on Reproductive, Maternal, Newborn, and Child Health that identifies essential cost-effective health interventions that can be scaled up to reduce maternal, newborn, and child deaths, and stillbirths. This Review summarises the volume's key findings and estimates the effect and cost of expanded implementation of these interventions. Recognising that a continuum of care from the adolescent girl, woman, or mother to child is needed, the volume includes details of preventive and therapeutic health interventions in integrated packages: Maternal and Newborn Health and Child Health (along with folic acid supplementation, a key reproductive health intervention). Scaling up all interventions in these packages from coverage in 2015 to hypothetically immediately achieve 90% coverage would avert 149 000 maternal deaths, 849 000 stillbirths, 1 498 000 neonatal deaths, and 1 515 000 additional child deaths. In alternative calculations that consider only the effects of reducing the number of pregnancies by provision of contraceptive services as part of a Reproductive Health package, meeting 90% of the unmet need for contraception would reduce global births by almost 28 million and consequently avert deaths that could have occurred at 2015 rates of fertility and mortality. Thus, 67 000 maternal deaths, 440 000 neonatal deaths, 473 000 child deaths, and 564 000 stillbirths could be averted from avoided pregnancies. Particularly effective interventions in the Maternal and Newborn Health and Child Health packages would be management of labour and delivery, care of preterm births, and treatment of serious infectious diseases and acute malnutrition. Nearly all of these essential interventions can be delivered by health workers in the community or in primary health centres, which can increase population access to needed services. The annual incremental cost of immediately scaling up these essential interventions would be US$6·2 billion in low-income countries, $12·4 billion in lower-middle-income countries, and $8·0 billion in upper-middle-income countries. With the additional funding, greater focus on high-effect integrated interventions and innovations in service delivery, such as task shifting to other groups of health workers and supply and demand incentives, can help rectify major gaps in accessibility and quality of care. In recent decades, reduction of avoidable maternal and child deaths has been a global priority. With continued priority and expansion of essential reproductive, maternal, newborn, and child health interventions to high coverage, equity, and quality, as well as interventions to address underlying problems such as women's low status in society and violence against women, these deaths and substantial morbidity can be largely eliminated in another generation.

Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect.

The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries. In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor. Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes. The scaling up of breastfeeding to a near universal level could prevent 823,000 annual deaths in children younger than 5 years and 20,000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor.

Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001-2020.

OBJECTIVE: To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance. METHODS: We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs - expressed in 2010 United States dollars (US$) - of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization. FINDINGS: We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$ 330 billion and US$ 9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$ 820 billion. CONCLUSION: By preventing significant costs and potentially increasing economic productivity among some of the world's poorest countries, the impact of immunization goes well beyond health.

Nutrition Interventions in the Lives Saved Tool (LiST).

The Lives Saved Tool (LiST) was initially developed in 2003 to estimate the impact of increasing coverage of efficacious interventions on under-5 mortality. Over time, the model has been expanded to include more outcomes (neonatal mortality, maternal mortality, stillbirths) and interventions. The model has also added risk factors, such as stunting and wasting, and over time has attempted to capture a full range of nutrition and nutrition-related interventions (e.g., antenatal supplementation, breastfeeding promotion, child supplemental feeding, acute malnutrition treatment), practices (e.g., age-appropriate breastfeeding), and outcomes (e.g., stunting, wasting, birth outcomes, maternal anemia). This article reviews the overall nutrition-related structure, assumptions, and outputs that are currently available in LiST. This review focuses on the new assumptions and structure that have been added to the model as part of the current effort to expand and improve the nutrition modeling capability of LiST. It presents the full set of linkages in the model that relate to nutrition outcomes, as well as the research literature used to support those linkages.

Metrics for Identifying Food Security Status and the Population with Potential to Benefit from Nutrition Interventions in the Lives Saved Tool (LiST).

Background: The Lives Saved Tool (LiST) uses the poverty head-count ratio at $1.90/d as a proxy for food security to identify the percentage of the population with the potential to benefit from balanced energy supplementation and complementary feeding (CF) interventions, following the approach used for the Lancet's 2008 series on Maternal and Child Undernutrition. Because much work has been done in the development of food security indicators, a re-evaluation of the use of this indicator was warranted.Objective: The aim was to re-evaluate the use of the poverty head-count ratio at $1.90/d as the food security proxy indicator in LiST.Methods: We carried out a desk review to identify available indicators of food security. We identified 3 indicators and compared them by using scatterplots, Spearman's correlations, and Bland-Altman plot analysis. We generated LiST projections to compare the modeled impact results with the use of the different indicators.Results: There are many food security indicators available, but only 3 additional indicators were identified with the data availability requirements to be used as the food security indicator in LiST. As expected, analyzed food security indicators were significantly positively correlated (P < 0.001), but there was generally poor agreement between them. The disparity between the indicators also increases as the values of the indicators increase. Consequently, the choice of indicator can have a considerable effect on the impact of interventions modeled in LiST, especially in food-insecure contexts.Conclusions: There was no single indicator identified that is ideal for measuring the percentage of the population who is food insecure for LiST. Thus, LiST will use the food security indicators that were used in the meta-analyses that produced the effect estimates. These are the poverty head-count ratio at $1.90/d for CF interventions and the prevalence of a low body mass index in women of reproductive age for balanced energy supplementation interventions.

New Option in the Lives Saved Tool (LiST) Allows for the Conversion of Prevalence of Small-for-Gestational-Age and Preterm Births to Prevalence of Low Birth Weight.

Background: The Lives Saved Tool (LiST) is a software model that estimates the health impact of scaling up interventions on maternal and child health. One of the outputs of the model is an estimation of births by fetal size [appropriate-for-gestational-age (AGA) or small-for-gestational-age (SGA)] and by length of gestation (term or preterm), both of which influence birth weight. LiST uses prevalence estimates of births in these categories rather than of birth weight categories, because the causes and health consequences differ between SGA and preterm birth. The World Health Assembly nutrition plan, however, has set the prevalence of low birth weight (LBW) as a key indicator, with a specific goal of a 30% reduction in LBW prevalence by 2025.Objective: The objective of the study is to develop an algorithm that will allow LiST users to estimate changes in prevalence of LBW on the basis of changes in coverage of interventions and the resulting impact on prevalence estimates of SGA and preterm births.Methods: The study used 13 prospective cohort data sets from low- and middle-income countries (LMICs; 4 from sub-Saharan Africa, 5 from Asia, and 4 from Latin America), with reliable measures of gestational age and birth weight. By calculating the proportion of LBW births among SGA and preterm births in each data set and meta-analyzing those estimates, we calculated region-specific pooled rates of LBW among SGA and preterm births.Results: In Africa, 0.4% of term-AGA, 36.7% of term-SGA, 49.3% of preterm-AGA, and 100.0% of preterm-SGA births were LBW. In Asia, 1.0% of term-SGA, 47.0% of term-SGA, 36.7% of preterm-AGA, and 100.0% of preterm-SGA births were LBW. In Latin America, 0.4% of term-AGA, 34.4% of term-SGA, 32.3% of preterm-AGA, and 100.0% of preterm-SGA births were LBW.Conclusions: The simple conversion factor proposed here allows for the estimation of LBW within LiST for most LMICs. This will allow LiST users to approximate the impact of their health programs on LBW prevalence via the impact on SGA and preterm prevalence.

Estimating Lives Saved by Achieving Dietary Micronutrient Adequacy, with a Focus on Vitamin A Intervention Programs in Cameroon.

Background: We previously compared the potential effects of different intervention strategies for achieving dietary vitamin A (VA) adequacy. The Lives Saved Tool (LiST) permits estimates of lives saved through VA interventions but currently only considers periodic VA supplements (VASs).Objective: We aimed to adapt the LiST method for estimating the mortality impact of VASs to estimate the impact of other VA interventions (e.g., food fortification) on child mortality and to estimate the number of lives saved by VA interventions in 3 macroregions in Cameroon.Methods: We used national dietary intake data to predict the effects of VA intervention programs on the adequacy of VA intake. LiST parameters of population affected fraction and intervention coverage were replaced with estimates of prevalence of inadequate intake and effective coverage (proportion achieving adequate VA intake). We used a model of liver VA stores to derive an estimate of the mortality reduction from achieving dietary VA adequacy; this estimate and a conservative assumption of equivalent mortality reduction for VAS and VA intake were applied to projections for Cameroon.Results: There were 2217-3048 total estimated VA-preventable deaths in year 1, with 58% occurring in the North macroregion. The relation between effective coverage and lives saved differed by year and macroregion due to differences in total deaths, diarrhea burden, and prevalence of low VA intake. Estimates of lives saved by VASs (the intervention common to both methods) were similar with the use of the adapted method (in 2012: North, 743-1021; South, 280-385; Yaoundé and Douala, 146-202) and the "usual" LiST method (North: 697; South: 381; Yaoundé and Douala: 147).Conclusions: Linking effective coverage estimates with an adapted LiST method permits estimation of the effects of combinations of VA programs (beyond VASs only) on child mortality to aid program planning and management. Rigorous program monitoring and evaluation are necessary to confirm predicted impacts.

Predicting high risk births with contraceptive prevalence and contraceptive method-mix in an ecologic analysis.

BACKGROUND: Increased contraceptive use has been associated with a decrease in high parity births, births that occur close together in time, and births to very young or to older women. These types of births are also associated with high risk of under-five mortality. Previous studies have looked at the change in the level of contraception use and the average change in these types of high-risk births. We aim to predict the distribution of births in a specific country when there is a change in the level and method of modern contraception. METHODS: We used data from full birth histories and modern contraceptive use from 207 nationally representative Demographic and Health Surveys covering 71 countries to describe the distribution of births in each survey based on birth order, preceding birth space, and mother's age at birth. We estimated the ecologic associations between the prevalence and method-mix of modern contraceptives and the proportion of births in each category. Hierarchical modelling was applied to these aggregated cross sectional proportions, so that random effects were estimated for countries with multiple surveys. We use these results to predict the change in type of births associated with scaling up modern contraception in three different scenarios. RESULTS: We observed marked differences between regions, in the absolute rates of contraception, the types of contraceptives in use, and in the distribution of type of birth. Contraceptive method-mix was a significant determinant of proportion of high-risk births, especially for birth spacing, but also for mother's age and parity. Increased use of modern contraceptives is especially predictive of reduced parity and more births with longer preceding space. However, increased contraception alone is not associated with fewer births to women younger than 18 years or a decrease in short-spaced births. CONCLUSIONS: Both the level and the type of contraception are important factors in determining the effects of family planning on changes in distribution of high-risk births. The best predictions for how birth risk changes with increased modern contraception and for different contraception methods allow for more nuanced predictions specific to each country and can aid better planning for the scaling up of modern contraception.

Effects of deworming on child and maternal health: a literature review and meta-analysis.

BACKGROUND: Soil-transmitted helminth infections are widespread. Many studies have been published on the topic of deworming. The Lives Saved Tool (LiST) is a software package that uses a deterministic mathematical model to estimate the effect of scaling up interventions on maternal and child health outcomes. This review investigates the scope of available evidence for benefits of deworming treatments in order to inform a decision about possible inclusion of deworming as an intervention in LiST. METHODS: We searched PubMed, the Cochrane Library, and Google Scholar. We included studies that reported pre/post data in children younger than 5 years or pregnant women for outcomes related to mortality and growth. We excluded studies that compared different anthelminthic treatments but did not include a placebo or non-treatment group, and those that did not report post-intervention outcomes. We categorized articles by treated population (children younger than 5 years and pregnant women), experimental versus observational, mass drug administration (MDA) versus treatment, and reported outcome. RESULTS: We identified 58 relevant trials; 27 investigated children younger than 5 years and 11 investigated pregnant women; one reported on both children younger than 5 years and pregnant women. We conducted meta-analyses of relevant outcomes in children younger than 5 years. CONCLUSIONS: Deworming did not show consistent benefits for indicators of mortality, anemia, or growth in children younger than five or women of reproductive age. We do not recommend including the effect of deworming in the LiST model.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

BACKGROUND: In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. METHODS: The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. RESULTS: Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. CONCLUSIONS: Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Modelling stunting in LiST: the effect of applying smoothing to linear growth data.

BACKGROUND: The Lives Saved Tool (LiST) is a widely used resource for evidence-based decision-making regarding health program scale-up in low- and middle-income countries. LiST estimates the impact of specified changes in intervention coverage on mortality and stunting among children under 5 years of age. We aimed to improve the estimates of the parameters in LiST that determine the rate at which the effects of interventions to prevent stunting attenuate as children get older. METHODS: We identified datasets with serial measurements of children's lengths or heights and used random effects models and restricted cubic splines to model the growth trajectories of children with at least six serial length/height measurements. We applied WHO growth standards to both measured and modelled (smoothed) lengths/heights to determine children's stunting status at multiple ages (1, 6, 12, 24 months). We then calculated the odds ratios for the association of stunting at one age point with stunting at the next ("stunting-to-stunting ORs") using both measured and smoothed data points. We ran analyses in LiST to compare the impact on intervention effect attenuation of using smoothed rather than measured stunting-to-stunting ORs. RESULTS: A total of 21,786 children with 178,786 length/height measurements between them contributed to our analysis. The odds of stunting at a given age were strongly related to whether a child is stunted at an earlier age, using both measured and smoothed lengths/heights, although the relationship was stronger for smoothed than measured lengths/heights. Using smoothed lengths/heights, we estimated that children stunted at 1 month have 45 times the odds of being stunted at 6 months, with corresponding odds ratios of 362 for the period 6 to 12 months and 175 for the period 12 to 24 months. Using the odds ratios derived from the smoothed data in LiST resulted in a somewhat slower attenuation of intervention effects over time, but substantial attenuation was still observed in the LiST outputs. For example, in Mali the effect of effectively eliminating SGA births reduced prevalence of stunting at age 59 months from 44.4% to 43.7% when using odds ratios derived from measured lengths/heights and from 44.4% to 41.9% when using odds ratios derived from smoothed lengths/heights. CONCLUSIONS: Smoothing of children's measured lengths/heights increased the strength of the association between stunting at a given age and stunting at an earlier age. Using odds ratios based on smoothed lengths/heights in LiST resulted in a small reduction in the attenuation of intervention effects with age and thus some increase in the estimated benefits, and may better reflect the true benefits of early nutritional interventions.

Can available interventions end preventable deaths in mothers, newborn babies, and stillbirths, and at what cost?

Progress in newborn survival has been slow, and even more so for reductions in stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and ten or fewer stillbirths per 1000 births in every country by 2035 will necessitate accelerated scale-up of the most effective care targeting major causes of newborn deaths. We have systematically reviewed interventions across the continuum of care and various delivery platforms, and then modelled the effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of the quality gap through the provision of effective care for all women and newborn babies delivering in facilities could prevent an estimated 113,000 maternal deaths, 531,000 stillbirths, and 1·325 million neonatal deaths annually by 2020 at an estimated running cost of US$4·5 billion per year (US$0·9 per person). Increased coverage and quality of preconception, antenatal, intrapartum, and postnatal interventions by 2025 could avert 71% of neonatal deaths (1·9 million [range 1·6-2·1 million]), 33% of stillbirths (0·82 million [0·60-0·93 million]), and 54% of maternal deaths (0·16 million [0·14-0·17 million]) per year. These reductions can be achieved at an annual incremental running cost of US$5·65 billion (US$1·15 per person), which amounts to US$1928 for each life saved, including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect is attributable to facility-based care which, although more expensive than community-based strategies, improves the likelihood of survival. Most of the running costs are also for facility-based care (US$3·66 billion or 64%), even without the cost of new hospitals and country-specific capital inputs being factored in. The maximum effect on neonatal deaths is through interventions delivered during labour and birth, including for obstetric complications (41%), followed by care of small and ill newborn babies (30%). To meet the unmet need for family planning with modern contraceptives would be synergistic, and would contribute to around a halving of births and therefore deaths. Our analysis also indicates that available interventions can reduce the three most common cause of neonatal mortality--preterm, intrapartum, and infection-related deaths--by 58%, 79%, and 84%, respectively.

Advancing social and economic development by investing in women's and children's health: a new Global Investment Framework.

A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.

Patterns in coverage of maternal, newborn, and child health interventions: projections of neonatal and under-5 mortality to 2035.

BACKGROUND: Urgent calls have been made for improved understanding of changes in coverage of maternal, newborn, and child health interventions, and their country-level determinants. We examined historical trends in coverage of interventions with proven effectiveness, and used them to project rates of child and neonatal mortality in 2035 in 74 Countdown to 2015 priority countries. METHODS: We investigated coverage of all interventions for which evidence was available to suggest effective reductions in maternal and child mortality, for which indicators have been defined, and data have been obtained through household surveys. We reanalysed coverage data from 312 nationally-representative household surveys done between 1990 and 2011 in 69 countries, including 58 Countdown countries. We developed logistic Loess regression models for patterns of coverage change for each intervention, and used k-means cluster analysis to divide interventions into three groups with different historical patterns of coverage change. Within each intervention group, we examined performance of each country in achieving coverage gains. We constructed models that included baseline coverage, region, gross domestic product, conflict, and governance to examine country-specific annual percentage coverage change for each group of indicators. We used the Lives Saved Tool (LiST) to predict mortality rates of children younger than 5 years (henceforth, under 5) and in the neonatal period in 2035 for Countdown countries if trends in coverage continue unchanged (historical trends scenario) and if each country accelerates intervention coverage to the highest level achieved by a Countdown country with similar baseline coverage level (best performer scenario). RESULTS: Odds of coverage of three interventions (antimalarial treatment, skilled attendant at birth, and use of improved sanitation facilities) have decreased since 1990, with a mean annual decrease of 5·5% (SD 2·7%). Odds of coverage of four interventions--all related to the prevention of malaria--have increased rapidly, with a mean annual increase of 27·9% (7·3%). Odds of coverage of other interventions have slowly increased, with a mean annual increase of 5·3% (3·5%). Rates of coverage change varied widely across countries; we could not explain the differences by measures of gross domestic product, conflict, or governance. On the basis of LiST projections, we predicted that the number of Countdown countries with an under-5 mortality rate of fewer than 20 deaths per 1000 livebirths per year would increase from four (5%) of the 74 in 2010, to nine (12%) by 2035 under the historical trends scenario, and to 15 (20%) under the best performer scenario. The number of countries with neonatal mortality rates of fewer than 11 per 1000 livebirths per year would increase from three (4%) in 2010, to ten (14%) by 2035 under the historical trends scenario, and 67 (91%) under the best performer scenario. The number of under-5 deaths per year would decrease from an estimated 7·6 million in 2010, to 5·4 million (28% decrease) if historical trends continue, and to 2·3 million (71% decrease) under the best performer scenario. INTERPRETATION: Substantial reductions in child deaths are possible, but only if intensified efforts to achieve intervention coverage are implemented successfully within each of the Countdown countries. FUNDING: The Bill & Melinda Gates Foundation.

Interventions to address deaths from childhood pneumonia and diarrhoea equitably: what works and at what cost?

Global mortality in children younger than 5 years has fallen substantially in the past two decades from more than 12 million in 1990, to 6·9 million in 2011, but progress is inconsistent between countries. Pneumonia and diarrhoea are the two leading causes of death in this age group and have overlapping risk factors. Several interventions can effectively address these problems, but are not available to those in need. We systematically reviewed evidence showing the effectiveness of various potential preventive and therapeutic interventions against childhood diarrhoea and pneumonia, and relevant delivery strategies. We used the Lives Saved Tool model to assess the effect on mortality when these interventions are applied. We estimate that if implemented at present annual rates of increase in each of the 75 Countdown countries, these interventions and packages of care could save 54% of diarrhoea and 51% of pneumonia deaths by 2025 at a cost of US$3·8 billion. However, if coverage of these key evidence-based interventions were scaled up to at least 80%, and that for immunisations to at least 90%, 95% of diarrhoea and 67% of pneumonia deaths in children younger than 5 years could be eliminated by 2025 at a cost of $6·715 billion. New delivery platforms could promote equitable access and community platforms are important catalysts in this respect. Furthermore, several of these interventions could reduce morbidity and overall burden of disease, with possible benefits for developmental outcomes.