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.

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.

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries. Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future. Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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.

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.

Gaps in the implementation of antenatal syphilis detection and treatment in health facilities across sub-Saharan Africa.

BACKGROUND: Syphilis in pregnancy is an under-recognized public health problem, especially in sub-Saharan Africa which accounts for over 60% of the global burden of syphilis. If left untreated, more than half of maternal syphilis cases will result in adverse pregnancy outcomes including stillbirth and fetal loss, neonatal death, prematurity or low birth weight, and neonatal infections. Achieving universal coverage of antenatal syphilis screening and treatment has been the focus of the global campaign for the elimination of mother-to-child transmission of syphilis. However, little is known about the availability of antenatal syphilis screening and treatment across sub-Saharan Africa. The objective of this study was to estimate the 'likelihood of appropriate care' for antenatal syphilis screening and treatment by analyzing health facility surveys and household surveys conducted from 2010 to 2015 in 12 sub-Saharan African countries. METHODS: In this secondary data analysis, we linked indicators of health facility readiness to provide antenatal syphilis detection and treatment from Service Provision Assessments (SPAs) and Service Availability and Readiness Assessments (SARAs) to indicators of ANC use from the Demographic and Health Surveys (DHS) to compute estimates of the 'likelihood of appropriate care'. RESULTS: Based on data from 5,593 health facilities that reported offering antenatal care (ANC) services, the availability of syphilis detection and treatment in ANC facilities ranged from 2% to 83%. The availability of syphilis detection and treatment was substantially lower in ANC facilities in West Africa compared to the other sub-regions. Levels of ANC attendance were high (median 94.9%), but only 27% of ANC attendees initiated care at less than 4 months gestation. We estimated that about one in twelve pregnant women received ANC early (<4 months) at a facility ready to provide syphilis detection and treatment (median 8%, range 7-32%). The largest implementation bottleneck identified was low health facility readiness, followed by timeliness of the first ANC visit. CONCLUSIONS: While access was fairly high, the low levels of likelihood of antenatal syphilis detection and treatment identified reinforce the need to improve the availability of syphilis rapid diagnostic tests and treatment and the timeliness of antenatal care-seeking across sub-Saharan Africa.

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.

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.

The estimated mortality impact of vaccinations forecast to be administered during 2011-2020 in 73 countries supported by the GAVI Alliance.

INTRODUCTION: From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS: The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS: By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION: Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits.

Mathematical models in the evaluation of health programmes.

Modelling is valuable in the planning and evaluation of interventions, especially when a controlled trial is ethically or logistically impossible. Models are often used to calculate the expected course of events in the absence of more formal assessments. They are also used to derive estimates of rare or future events from recorded intermediate points. When developing models, decisions are needed about the appropriate level of complexity to be represented and about model structure and assumptions. The degree of rigor in model development and assessment can vary greatly, and there is a danger that existing beliefs inappropriately influence judgments about model assumptions and results.

Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment.