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.

Maternal and child nutrition in the Lives Saved Tool: Results of a recent update.

Background: The Lives Saved Tool (LiST) is a mathematical modelling tool for estimating the survival, health, and nutritional impacts of scaling intervention coverage in low- and middle-income countries (LMICs). Various nutrition interventions are included in LiST and are regularly (and independently) reviewed and updated as new data emerge. This manuscript describes our latest in-depth review of nutrition evidence, focusing on intervention efficacy, appropriate population-affected fractions, and new interventions for potential inclusion in the LiST model. Methods: An external advisory group (EAG) was assembled to review evidence from systematic reviews on intervention-outcome (I-O) pairs for women and children under five years of age. GRADE quality was assigned to each pair based on a LiST-specific checklist to facilitate consistent decisions during the consideration. For existing interventions with new information, the EAG was asked to recommend whether to update the default efficacy values and population-affected fractions. For the new interventions, the EAG decided whether there was sufficient evidence of benefit, and in affirmative cases, information on the efficacy and affected fraction values that could be used. Decisions were based on expert group consensus. Results: Overall, the group reviewed 53 nutrition-related I-O pairs, including 25 existing and 28 new ones. Efficacy and population-affected fractions were updated for seven I-O pairs; three pairs were updated for efficacy estimates only, three were updated for population-affected fractions only; and nine new I-O pairs were added to the model, bringing the total of nutrition-related I-O pairs to 34. Included in the new I-O pairs were two new nutrition interventions added to LIST: zinc fortification and neonatal vitamin A supplementation. Conclusions: For modelling tools like LiST to be useful, it is crucial to update interventions, efficacy and population-affected fractions as new evidence becomes available. The present updates will enable LiST users to better estimate the potential health, nutrition, and survival benefits of investing in nutrition.

Current levels of coverage of iron and folic acid fortification are insufficient to meet the recommended intake for women of reproductive age in low- and middle-income countries.

BACKGROUND: Food fortification can be an effective intervention to improve maternal and child health. Folic acid fortification can reduce neural tube defects due to folate deficiency. Iron fortification is effective to reduce maternal anemia due to iron deficiency. The paper describes the methods for estimating current coverage levels for iron fortification and folic acid fortification and estimates current impact of fortification in low- and middle-income countries (LMICs) using the Lives Saved Tool (LiST). METHODS: The database was obtained from Global Fortification Data Exchange. We used the following indicators from the database: food intake, fortification standard, percent of food produced in industrial mills, and percent of industrially milled food that is fortified. Together with the recommended dietary allowances for women of reproductive age (WRA), we calculated percentage of WRA getting recommended intake through fortification and used the percentage as an estimate for fortification coverage. We then used LiST to estimate the health impact of fortification on maternal and child health. RESULTS: Folic acid was fortified in 72 countries, with a median coverage of 43%. Iron was fortified in 87 countries, with a median coverage of 23%. Forty-six LMICs fortified either folic acid, iron, or both. And the weighted coverage of folic acid fortification and iron fortification were 34% and 19%, respectively. A greater percentage of WRA got appropriate levels of folic acid and iron via fortification in higher income countries. Based on LiST projection, it is estimated that in 2021, over 4 million anemia cases among WRA will be averted due to consumption of iron fortified food. About 1900 stillbirths and 3000 neonatal deaths due to neural tube defects will be averted due to consumption of folic acid fortified food. CONCLUSIONS: We estimated the coverage of folic acid fortification and iron fortification in LMICs and included them in the most recent version of LiST. Trends in coverage will be included in LiST as data become available. Our analysis shows that while most LMICs have fortification programs, currently the effects of these programs are limited either through low levels of fortification in industrialized food, low consumption of fortified food or both.

Factors associated with the decline in under-five diarrhea mortality in India: a LiST analysis.

BACKGROUND: India has achieved 86% reduction in the number of under-five diarrheal deaths from 1980 to 2015. Nonetheless diarrhea is still among the leading causes of under-five deaths. The aim of this analysis was to study the contribution of factors that led to decline in diarrheal deaths in the country and the effect of scaling up of intervention packages to address the remaining diarrheal deaths. METHODS: We assessed the attribution of different factors and intervention packages such as direct diarrhea case management interventions, nutritional factors and WASH interventions which contributed to diarrhea specific under-five mortality reduction (DSMR) during 1980 to 2015 using the Lives Saved Tool (LiST). The potential impact of scaling up different packages of interventions to achieve universal coverage levels by year 2030 on reducing the number of remaining diarrheal deaths were estimated. RESULTS: The major factors associated with DSMR reduction in under-fives during 1980 to 2015, were increase in ORS use, reduction in stunting prevalence, improved sanitation, changes in age appropriate breastfeeding practices, increase in the vitamin-A supplementation and persistent diarrhea treatment. ORS use and reduction in stunting were the two key interventions, each accounting for around 32% of the lives saved during this period. Scaling up the direct diarrhea case management interventions from the current coverage levels in 2015 to achieve universal coverage levels by 2030 can save around 82 000 additional lives. If the universal targets for nutritional factors and WASH interventions can be achieved, an additional 23 675 lives can potentially be saved. CONCLUSIONS: While it is crucial to improve the coverage and equity in ORS use, an integrated approach to promote nutrition, WASH and direct diarrhea interventions is likely to yield the highest impact on reducing the remaining diarrheal deaths in under-five children.

Factors associated with the decline in under five diarrhea mortality in Tanzania from 1980-2015.

BACKGROUND: Tanzania has made great progress in reducing diarrhea mortality in under- five children. We examined factors associated with the decline and projected the impact of scaling up interventions or reducing risk factors on diarrhea deaths. METHODS: We reviewed economic, health, and diarrhea-related policies, reports and programs implemented during 1980 to 2015. We used the Lives Saved Tool to determine the percentage reduction in diarrhea-specific mortality attributable to changes in coverage of the interventions and risk factors, including direct diarrhea-related interventions, nutrition, and water, sanitation and hygiene (WASH). We projected the number of diarrhea deaths that could be prevented in 2030, assuming near universal coverage of different intervention packages. RESULTS: Diarrhea-specific mortality among under-five children in Tanzania declined by 89% from 35.3 deaths per 1000 live births in 1980 to 3.9 deaths per 1000 live births in 2015. Factors associated with diarrhea-specific under-five mortality reduction included oral rehydration solution (ORS) use, changes in stunting prevalence, vitamin A supplementation, rotavirus vaccine, change in wasting prevalence and change in age-appropriate breastfeeding practices. Universal coverage of direct diarrhea, nutrition and WASH interventions has the potential reduce the diarrhea-specific mortality rate by 90%. CONCLUSIONS: Scaling up of a few key childhood interventions such as ORS and nutrition, and reducing the prevalence of stunting would address the remaining diarrhea-specific under-five mortality by 2030.

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.

Quality of antenatal care service provision in health facilities across sub-Saharan Africa: Evidence from nationally representative health facility assessments.

BACKGROUND: Utilization of antenatal care (ANC) services has increased over the past two decades. Continued gains in maternal and newborn health will require an understanding of both access and quality of ANC services. We linked health facility and household survey data to examine the quality of service provision for five ANC interventions across health facilities in sub-Saharan Africa. METHODS: Using data from 20 nationally representative health facility assessments - the Service Provision Assessment (SPA) and the Service Availability and Readiness Assessment (SARA), we estimated facility level readiness to deliver five ANC interventions: tetanus toxoid vaccine for pregnant women, intermittent preventive treatment for malaria in pregnancy (IPTp), syphilis detection and treatment in pregnancy, iron supplementation and hypertensive disease case management. Facility level indicators were stratified by health facility type, managing authority and location, then linked to estimates of ANC utilization in that stratum from the corresponding Demographic and Health Surveys (DHS) to generate population level estimates of the 'likelihood of appropriate care'. Finally, the association between estimates of the 'likelihood of appropriate care' from the linking approach and estimates of coverage levels from the DHS were assessed. FINDINGS: A total of 10 534 health facilities were surveyed in the 20 health facility assessments, of which 8742 reported offering ANC services and were included in the analysis. Health facility readiness to deliver IPTp, iron supplementation, and tetanus toxoid vaccination was higher (median: 84.1%, 84.9% and 82.8% respectively) than readiness to deliver hypertensive disease case management and syphilis detection and treatment (median: 23.0% and 19.9% respectively). Coverage of at least 4 ANC visits ranged from 24.8% to 75.8%. Estimates of the likelihood of appropriate care derived from linking health facility and household survey data showed marked gaps for all interventions, particularly hypertensive disease case management and syphilis detection and treatment. There was fairly good concordance between our estimates of high likelihood of appropriate care and DHS estimates of coverage for iron supplementation, IPTp, and tetanus toxoid vaccination. CONCLUSION: Linking household surveys to health facility assessments revealed marked gaps in population-level coverage of quality ANC interventions and underscored the need for a double-pronged approach to increase ANC utilization and improve the quality of ANC services.

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.

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.

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.

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.

Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

Maternal undernutrition contributes to 800,000 neonatal deaths annually through small for gestational age births; stunting, wasting, and micronutrient deficiencies are estimated to underlie nearly 3·1 million child deaths annually. Progress has been made with many interventions implemented at scale and the evidence for effectiveness of nutrition interventions and delivery strategies has grown since The Lancet Series on Maternal and Child Undernutrition in 2008. We did a comprehensive update of interventions to address undernutrition and micronutrient deficiencies in women and children and used standard methods to assess emerging new evidence for delivery platforms. We modelled the effect on lives saved and cost of these interventions in the 34 countries that have 90% of the world's children with stunted growth. We also examined the effect of various delivery platforms and delivery options using community health workers to engage poor populations and promote behaviour change, access and uptake of interventions. Our analysis suggests the current total of deaths in children younger than 5 years can be reduced by 15% if populations can access ten evidence-based nutrition interventions at 90% coverage. Additionally, access to and uptake of iodised salt can alleviate iodine deficiency and improve health outcomes. Accelerated gains are possible and about a fifth of the existing burden of stunting can be averted using these approaches, if access is improved in this way. The estimated total additional annual cost involved for scaling up access to these ten direct nutrition interventions in the 34 focus countries is Int$9·6 billion per year. Continued investments in nutrition-specific interventions to avert maternal and child undernutrition and micronutrient deficiencies through community engagement and delivery strategies that can reach poor segments of the population at greatest risk can make a great difference. If this improved access is linked to nutrition-sensitive approaches--ie, women's empowerment, agriculture, food systems, education, employment, social protection, and safety nets--they can greatly accelerate progress in countries with the highest burden of maternal and child undernutrition and mortality.

Scaling up diarrhea prevention and treatment interventions: a Lives Saved Tool analysis.

BACKGROUND: Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated. METHODS AND FINDINGS: We use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions. CONCLUSION: Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4) by 2015.