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Objective Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal.Design This is a secondary observational analysis of trial data (registration number NCT01177111).Setting Rural Sarlahi district, Nepal.Participants 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017.Outcome measures The outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios.Result The prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90).Conclusion The prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.

BACKGROUND:An estimated 49.5 million children under five years of age are wasted. There is a lack of robust studies on effective interventions to prevent wasting. The aim of this study was to identify and prioritise the main outstanding research questions in relation to wasting prevention to inform future research agendas. METHOD:A research prioritisation exercise was conducted following the Child Health and Nutrition Research Initiative method. Identified research gaps were compiled from multiple sources, categorised into themes and streamlined into forty research questions by an expert group. A survey was then widely circulated to assess research questions according to four criteria. An overall research priority score was calculated to rank questions. FINDINGS:The prioritised questions have a strong focus on interventions. The importance of the early stages of life in determining later experiences of wasting was highlighted. Other important themes included the identification of at-risk infants and young children early in the progression of wasting and the roles of existing interventions and the health system in prevention. DISCUSSION:These results indicate consensus to support more research on the pathways to wasting encompassing the in-utero environment, on the early period of infancy and on the process of wasting and its early identification. They also reinforce how little is known about impactful interventions for the prevention of wasting. CONCLUSION:This exercise provides a five-year investment case for research that could most effectively improve on-the-ground programmes to prevent child wasting and inform supportive policy change.

Reducing neonatal and child mortality is a key component of the health-related sustainable development goal (SDG), but most low and middle income countries lack data to monitor child mortality on an annual basis. We tested a mortality monitoring system based on the continuous recording of pregnancies, births and deaths by trained community-based volunteers (CBV).This project was implemented in 96 clusters located in three districts of the Northern Region of Ghana. Community-based volunteers (CBVs) were selected from these clusters and were trained in recording all pregnancies, births, and deaths among children under 5 in their catchment areas. Data collection lasted from January 2012 through September 2013. All CBVs transmitted tallies of recorded births and deaths to the Ghana Birth and deaths registry each month, except in one of the study districts (approximately 80% reporting). Some events were reported only several months after they had occurred. We assessed the completeness and accuracy of CBV data by comparing them to retrospective full pregnancy histories (FPH) collected during a census of the same clusters conducted in October-December 2013. We conducted all analyses separately by district, as well as for the combined sample of all districts. During the 21-month implementation period, the CBVs reported a total of 2,819 births and 137 under-five deaths. Among the latter, there were 84 infant deaths (55 neonatal deaths and 29 post-neonatal deaths). Comparison of the CBV data with FPH data suggested that CBVs significantly under-estimated child mortality: the estimated under-5 mortality rate according to CBV data was only 2/3 of the rate estimated from FPH data (95% Confidence Interval for the ratio of the two rates = 51.7 to 81.4). The discrepancies between the CBV and FPH estimates of infant and neonatal mortality were more limited, but varied significantly across districts.In northern Ghana, a community-based data collection systems relying on volunteers did not yield accurate estimates of child mortality rates. Additional implementation research is needed to improve the timeliness, completeness and accuracy of such systems. Enhancing pregnancy monitoring, in particular, may be an essential step to improve the measurement of neonatal mortality.

BACKGROUND:Millions of children worldwide suffer and die from conditions for which effective interventions exist. While there is ample evidence regarding these diseases, there is a dearth of information on the social factors associated with child mortality. METHODS:The 2014 Verbal and Social Autopsy Study was conducted based on a nationally representative sample of 3,254 deaths that occurred in children under the age of five and were reported on the birth history component of the 2013 Nigerian Demographic and Health Survey. We conducted a descriptive analysis of the preventive and curative care sought and obtained for the 2,057 children aged 1-59 months who died in Nigeria and performed regional (North vs. South) comparisons. RESULTS:A total of 1,616 children died in the northern region, while 441 children died in the South. The majority (72.5%) of deceased children in the northern region were born to mothers who had no education, married at a young age, and lived in the poorest two quintiles of households. When caregivers first noticed that their child was ill, a median of 2 days passed before they sought or attempted to seek healthcare for their children. The proportion of children who reached and departed from their first formal healthcare provider alive was greater in the North (30.6%) than in the South (17.9%) (p

Nigeria's under-five mortality rate is the eighth highest in the world. Identifying the causes of under-five deaths is crucial to achieving Sustainable Development Goal 3 by 2030 and improving child survival. National and international bodies collaborated in this study to provide the first ever direct estimates of the causes of under-five mortality in Nigeria. Verbal autopsy interviews were conducted of a representative sample of 986 neonatal and 2,268 1-59 month old deaths from 2008 to 2013 identified by the 2013 Nigeria Demographic and Health Survey. Cause of death was assigned by physician coding and computerized expert algorithms arranged in a hierarchy. National and regional estimates of age distributions, mortality rates and cause proportions, and zonal- and age-specific mortality fractions and rates for leading causes of death were evaluated. More under-fives and 1-59 month olds in the South, respectively, died as neonates (N = 24.1%, S = 32.5%, p

[This corrects the article DOI: 10.1371/journal.pmed.1002056.].

Gretchen Stevens and colleagues present the GATHER statement, which seeks to promote good practice in the reporting of global health estimates.

Under the Global Forum for Health Research, the Child Health and Nutrition Research Initiative (CHNRI) began its operations in 1999 and became a Swiss foundation in 2006. The vision of CHNRI was to improve child health and nutrition of all children in low– and middle–income countries (LMIC) through research that informs health policy and practice. Specific objectives included expanding global knowledge on childhood disease burden and cost-effectiveness of interventions, promoting priority setting in research, ensuring inclusion of institutions and scientists in LMIC in setting priorities, promoting capacity development in LMIC and stimulating donors and countries to increase resources for research. CHNRI created a knowledge network, funded research through multiple rounds of a global competitive process and published research papers and policy briefs. A signature effort was to develop a systematic methodology for prioritizing health and nutrition research investments. The “CHNRI method” has been extensively applied to global health problems and is now the most commonly used method for prioritizing health research questions.

In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013–2025.

This study was one of a set of verbal/social autopsy (VASA) investigations undertaken by the WHO/UNICEF–supported Child Health Epidemiology Reference Group to estimate the causes and determinants of neonatal and child deaths in high priority countries. The study objective was to help explain the lack of decrease in neonatal mortality in Niger from 2007 to 2010, a period during which child mortality was decreasing.

Physician assessment historically has been the most common method of analyzing verbal autopsy (VA) data. Recently, the World Health Organization endorsed two automated methods, Tariff 2.0 and InterVA–4, which promise greater objectivity and lower cost. A disadvantage of the Tariff method is that it requires a training data set from a prior validation study, while InterVA relies on clinically specified conditional probabilities. We undertook to validate the hierarchical expert algorithm analysis of VA data, an automated, intuitive, deterministic method that does not require a training data set.

The World Health Organization (WHO) currently coordinates rotavirus diarrhea and invasive bacterial disease (IBD) surveillance at 178 sentinel sites in 60 countries. However, only 78 sites participate in both surveillance systems using a common sentinel site. Here, we explored the feasibility of extending a WHO-IBD surveillance platform to generate data on the burden of rotaviral diarrhea and its epidemiological characteristics to prepare the countries to measure the impact of rotaviral vaccine. A six-month (July to December, 2012) surveillance, managed by IBD team, collected stool samples and clinical data from under-five children with acute watery diarrhea at an IBD sentinel site. Samples were tested for rotavirus antigen by ELISA and genotyped by PCR at the regional reference laboratory (RRL). Specimens were collected from 79% (n=297) of eligible cases (n=375); 100% of which were tested for rotavirus by ELISA and 54% (159/297) of them were positive. At RRL, all the cases were confirmed by PCR and genotyped (99%; 158/159). The typing results revealed the predominance of G12 (40%; 64/159) genotype, followed by G1 (31%; 50/159) and G9 (19%; 31/159). All in all, this exploratory surveillance collected the desired demographic and epidemiological data and achieved almost all the benchmark indicators of WHO, starting from enrollment number to quality assurance through a number of case detection, collection, and testing of specimens and genotyping of strains at RRL. The success of this WHO-IBD site in achieving these benchmark indicators of WHO can be used by WHO as a proof-of-concept for considering integration of rotavirus surveillance with WHO-IBD platforms, specifically in countries with well performing IBD site and no ongoing rotavirus surveillance.

Improving the counting of stillbirths and neonatal deaths is important to tracking Sustainable Development Goal 3.2 and improving vital statistics in low- and middle-income countries (LMICs). However, the validity of self-reported stillbirths and neonatal deaths in surveys is often threatened by misclassification errors between the two birth outcomes. We assessed the extent and correlates of stillbirths being misclassified as neonatal deaths by comparing two recent and linked population surveys conducted in Malawi, one being a full birth history (FBH) survey, and the other a follow-up verbal/social autopsy (VASA) survey. We found that one-fifth of 365 neonatal deaths identified in the FBH survey were classified as stillbirths in the VASA survey. Neonatal deaths with signs of movements in the last few days before delivery reported were less likely to be misclassified stillbirths (OR = 0.08, p

BackgroundFoodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases.Methods and findingsWe synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990-2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5-2.9 billion) cases, over one million (95% UI 0.89-1.4 million) deaths, and 78.7 million (95% UI 65.0-97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23-36%) of cases caused by diseases in our study, or 582 million (95% UI 401-922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5-37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70-251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52-177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49-6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne.ConclusionsFoodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings.

To address inadequate coverage of oral rehydration salts (ORS) and zinc supplements for the treatment of diarrhea among children under–five, the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program was carried out from 2011–2013 in Gujarat and from 2011–2014 in Uttar Pradesh (UP), India. The program focused on improving the diarrhea treatment practices of public and private sector providers. We conducted cross–sectional household surveys in program districts at baseline and endline and constructed state–specific logistic regression models with generalized estimating equations to assess changes in ORS and zinc treatment during the program period. Between baseline and endline, zinc coverage increased from 2.5% to 22.4% in Gujarat and from 3.1% to 7.0% in UP; ORS coverage increased from 15.3% to 39.6% in Gujarat but did not change in UP. In comparison to baseline, children with diarrhea in the two–weeks preceding the endline survey had higher odds of receiving zinc treatment in both Gujarat (odds ratio, OR = 11.2; 95% confidence interval (CI) 6.4–19.3) and UP (OR = 2.4; 95% CI 1.4–3.9), but the odds of receiving ORS only increased in Gujarat (OR = 3.6; 95% CI 2.7–4.8; UP OR = 0.9; 95% CI 0.7–1.2). Seeking care outside the home, especially from a public sector source, was associated with higher odds of receiving ORS and zinc. Conclusions During the duration of the DAZT program, there were modest improvements in the treatment of diarrhea among young children. Future programs should build upon and accelerate this trend with continued investment in public and private sector provider training and supply chain sustainability, in addition to targeted care–giver demand generation activities.

There is limited evidence on adherence to the recommended dose and duration of zinc supplementation for diarrheal episodes in children under five years of age. In selected districts of Uttar Pradesh, India, we sought to assess adherence to the nationally advised zinc treatment regimen (ie, 10 mg/day for ages 2–6 months and 20 mg/day for ages 7–59 months for 14 days) among caregivers of zinc–prescribed children. We identified and conducted follow–up visits to children advised zinc for the treatment of diarrhea. At the initial visit, we collected data on the treatment instructions received from providers. Caregivers were asked to record treatments administered on a pictorial tracking form and were asked to retain all packaging for collection at follow–up. We quantified the average dose and duration of zinc therapy and built logistic regression models to assess the factors associated with caregiver adherence to national guidelines. Caregivers administered zinc for an average of 10.7 days (standard deviation (SD) = 3.9 days; median = 13 days), and 47.8% continued treatment for the complete 14 days. Among children receiving zinc syrups and tablets respectively, the age appropriate dose was received by 30.8% and 67.3%. Adherence to age appropriate dose and continuation of zinc for 14 days were highly associated with having received appropriate provider instructions. Our results indicate moderate–to–good adherence to national zinc treatment guidelines for diarrhea among caregivers in rural India. Our findings also highlight the importance of provider guidance in ensuring adherence to zinc dose and duration. Programs aiming to scale–up zinc treatment for childhood diarrhea should train providers to successfully communicate dosing instructions to caregivers, while also addressing the tendency of caregivers to terminate treatment once a child appears to have recovered from an acute diarrheal episode.

Recent studies, partly based on murine models, suggest childhood immunization and vitamin A supplements may confer protection against malaria infection, although strong evidence to support these theories in humans has so far been lacking. We analyzed national survey data from children aged 6–59 months in four sub-Saharan African countries over an 18-month time period, to determine the risk of Plasmodium spp. parasitemia (n=8390) and Plasmodium falciparum HRP-2 (PfHRP-2)-related antigenemia (n=6121) following vitamin A supplementation and standard vaccination. Bacille Calmette Guerin-vaccinated children were more likely to be PfHRP-2 positive (relative risk [RR]=4.06, 95% confidence interval [CI]=2.00–8.28). No association was identified with parasitemia. Measles and polio vaccination were not associated with malaria. Children receiving vitamin A were less likely to present with parasitemia (RR=0.46, 95% CI=0.39–0.54) and antigenemia (RR=0.23, 95% CI=0.17–0.29). Future studies focusing on climate seasonality, placental malaria and HIV are needed to characterize better the association between vitamin A and malaria infection in different settings.

Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods.We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1-3.3 billion) cases and 599,000 (95% UI 472,000-802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468-1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154-380 million), Shigella spp. (188 million; 95% UI 94-379 million) and Giardia lamblia (179 million; 95% UI 125-263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783-266,561), enteropathogenic E. coli (121,455; 95% UI 103,657-143,348), ETEC (73,041; 95% UI 55,474-96,984) and Shigella (64,993; 95% UI 48,966-92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age.Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.

BACKGROUND:Deficiencies in essential vitamins and minerals-also termed hidden hunger-are pervasive and hold negative consequences for the cognitive and physical development of children. METHODS:This analysis evaluates the change in hidden hunger over time in the form of one composite indicator-the Hidden Hunger Index (HHI)-using an unweighted average of prevalence estimates from the Nutrition Impact Model Study for anemia due to iron deficiency, vitamin A deficiency, and stunting (used as a proxy indicator for zinc deficiency). Net changes from 1995-2011 and population weighted regional means for various time periods are measured. FINDINGS:Globally, hidden hunger improved (-6.7 net change in HHI) from 1995-2011. Africa was the only region to see a deterioration in hidden hunger (+1.9) over the studied time period; East Asia and the Pacific performed exceptionally well (-13.0), while other regions improved only slightly. Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anemia due to iron deficiency persisted and even increased. INTERPRETATION:This analysis is critical for informing and tracking the impact of policy and programmatic efforts to reduce micronutrient deficiencies, to advance the global nutrition agenda, and to achieve the Millennium Development Goals (MDGs). However, there remains an unmet need to invest in gathering frequent, nationally representative, high-quality micronutrient data as we renew our efforts to scale up nutrition, and as we enter the post-2015 development agenda. FUNDING:Preparation of this manuscript was funded by Sight and Life. There was no funding involved in the study design, data collection, analysis, or decision to publish.

As community case management of childhood illness expands in low-income countries, there is a need to assess the quality of care provided by community health workers. This study had the following objectives: 1) examine methods of recruitment of sick children for assessment of quality of care, 2) assess the validity of register review (RR) and direct observation only (DO) compared to direct observation with re-examination (DO+RE), and 3) assess the effect of observation on community health worker performance.We conducted a survey to assess the quality of care provided by Ethiopian Health Extension Workers (HEWs). The sample of children was obtained through spontaneous consultation, HEW mobilization, or recruitment by the survey team. We assessed patient characteristics by recruitment method. Estimates of indicators of quality of care obtained using RR and DO were compared to gold standard estimates obtained through DO+RE. Sensitivity, specificity, and the area under receiver operator characteristic curve (AUC) were calculated to assess the validity of RR and DO. To assess the Hawthorne effect, we compared estimates from RR for children who were observed by the survey team to estimates from RR for children who were not observed by the survey team.Participants included 137 HEWs and 257 sick children in 103 health posts, plus 544 children from patient registers. Children mobilized by HEWs had the highest proportion of severe illness (27%). Indicators of quality of care from RR and DO had high sensitivity for most indicators, but specificity was low. The AUC for different indicators from RR ranged from 0.47 to 0.76, with only one indicator above 0.75. The AUC of indicators from DO ranged from 0.54 to 1.0, with three indicators above 0.75. The differences between estimates of correct care for observed versus not observed children were small.Mobilization by HEWs and recruitment by the survey teams were feasible, but potentially biased, methods of obtaining sick children. Register review and DO underestimated performance errors. Our data suggest that being observed had only a small positive effect on the performance of HEWs.

Programs aimed at reducing the burden of diarrhea among children under-five in low-resource settings typically allocate resources to training community-level health workers, but studies have suggested that provider knowledge does not necessarily translate into adequate practice. A diarrhea management program implemented in Bihar, Gujarat and Uttar Pradesh, India trained private sector rural medical practitioners (RMPs) and public sector Accredited Social Health Activists (ASHAs) and Anganwadi workers (AWWs) in adequate treatment of childhood diarrhea with oral rehydration salts (ORS) and zinc. We used cross-sectional program evaluation data to determine the association between observed diarrhea treatment practices and reported knowledge of ORS and zinc among each provider cadre.We conducted principal components analysis on providers' responses to diarrhea treatment questions in order to generate a novel scale assessing ORS/zinc knowledge. We subsequently regressed a binary indicator of whether ORS/zinc was prescribed during direct observation onto the resulting knowledge scores, controlling for other relevant knowledge predictors.There was a positive association between ORS/zinc knowledge score and prescribing ORS and zinc to young children with diarrhea among private sector RMPs (aOR: 2.32; 95% CI: 1.29-4.17) and public sector ASHAs and AWWs (aOR 2.48; 95% CI: 1.90-3.24). Controlling for knowledge score, receipt of training in the preceding 6 months was a good predictor of adequate prescribing in the public but not the private sector. In the public sector, direct access to ORS and zinc supplies was also highly associated with prescribing.To enhance the management of childhood diarrhea in India, programmatic activities should center on increasing knowledge of ORS and zinc among public and private sector providers through biannual trainings but should also focus on ensuring sustained access to an adequate supply chain.

Ethiopia has scaled up its community-based programs over the past decade by training and deploying health extension workers (HEWs) in rural communities throughout the country. Consequently, child mortality has declined substantially, placing Ethiopia among the few countries that have achieved the United Nations' fourth Millennium Development Goal. As Ethiopia continues its efforts, results must be assessed regularly to provide timely feedback for improvement and to generate further support for programs. More specifically the expansion of HEWs at the community level provides a unique opportunity to build a system for real-time monitoring of births and deaths, linked to a civil registration and vital statistics system that Ethiopia is also developing. We tested the accuracy and completeness of births and deaths reported by trained HEWs for monitoring child mortality over 15 -month periods.HEWs were trained in 93 randomly selected rural kebeles in Jimma and West Hararghe zones of the Oromia region to report births and deaths over a 15-month period from January, 2012 to March, 2013. Completeness of number of births and deaths, age distribution of deaths, and accuracy of resulting under-five, infant, and neonatal mortality rates were assessed against data from a large household survey with full birth history from women aged 15-49. Although, in general HEWs, were able to accurately report events that they identified, the completeness of number of births and deaths reported over twelve-month periods was very low and variable across the two zones. Compared to household survey estimates, HEWs reported only about 30% of births and 21% of under-five deaths occurring in their communities over a twelve-month period. The under-five mortality rate was under-estimated by around 30%, infant mortality rate by 23% and neonatal mortality by 17%. HEWs reported disproportionately higher number of deaths among the very young infants than among the older children.Birth and death data reported by HEWs are not complete enough to support the monitoring of changes in childhood mortality. HEWs can significantly contribute to the success of a CRVS in Ethiopia, but cannot be relied upon as the sole source for identification of vital events. Further studies are needed to understand how to increase the level of completeness.

BackgroundNeonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.Methods and findingsWe searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9-11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1-28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm ConclusionsNeonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis. Please see later in the article for the Editors' Summary.

BackgroundChild undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies.MethodsPooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (-2≤ZResults53 809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality.ConclusionsAll degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases.

Diarrhea morbidity and mortality remain important child health problems in low- and middle-income countries. The treatment of diarrhea and accurate measurement of treatment coverage are critical if child mortality is going to continue to decline. In this review, we examine diarrhea treatment coverage indicators collected in two large-scale community-based household surveys--the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS). Current surveys do not distinguish between children with mild diarrhea episodes and those at risk for dehydration. Additional disease severity questions may improve the identification of cases of severe diarrhea but research is needed to identify indicators with the highest sensitivity and specificity. We also review the current treatment indicators in these surveys and highlight three areas for improvement and research. First, specific questions on fluids other than oral rehydration salts (ORS) should be eliminated to refocus the treatment of dehydration on ORS and to prevent confusion between prevention and treatment of dehydration. Second, consistency across surveys and throughout translations is needed for questions about the caregiver behavior of "offering" the sick child fluid and food. Third, breastfeeding should be separated from other fluid and food questions to capture the frequency and duration of nursing sessions offered during the illness. Research is also needed to assess the accuracy of the current zinc indicator to determine if caregivers are correctly recalling zinc treatment for current and recent diarrhea episodes.

The unified global efforts to mitigate the high burden of vitamin and mineral deficiency, known as hidden hunger, in populations around the world are crucial to the achievement of most of the Millennium Development Goals (MDGs). We developed indices and maps of global hidden hunger to help prioritize program assistance, and to serve as an evidence-based global advocacy tool. Two types of hidden hunger indices and maps were created based on i) national prevalence data on stunting, anemia due to iron deficiency, and low serum retinol levels among preschool-aged children in 149 countries; and ii) estimates of Disability Adjusted Life Years (DALYs) attributed to micronutrient deficiencies in 136 countries. A number of countries in sub-Saharan Africa, as well as India and Afghanistan, had an alarmingly high level of hidden hunger, with stunting, iron deficiency anemia, and vitamin A deficiency all being highly prevalent. The total DALY rates per 100,000 population, attributed to micronutrient deficiencies, were generally the highest in sub-Saharan African countries. In 36 countries, home to 90% of the world's stunted children, deficiencies of micronutrients were responsible for 1.5-12% of the total DALYs. The pattern and magnitude of iodine deficiency did not conform to that of other micronutrients. The greatest proportions of children with iodine deficiency were in the Eastern Mediterranean (46.6%), European (44.2%), and African (40.4%) regions. The current indices and maps provide crucial data to optimize the prioritization of program assistance addressing global multiple micronutrient deficiencies. Moreover, the indices and maps serve as a useful advocacy tool in the call for increased commitments to scale up effective nutrition interventions.

Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future.

BackgroundDiarrhea remains one of the leading causes of morbidity and mortality among children under 5 years of age, but in many low and middle-income countries where vital registration data are lacking, updated estimates with regard to the proportion of deaths attributable to diarrhea are needed.MethodsWe conducted a systematic literature review to identify studies reporting diarrhea proportionate mortality for children 1-59 mo of age published between 1980 and 2009. Using the published proportionate mortality estimates and country level covariates we constructed a logistic regression model to estimate country and regional level proportionate mortality and estimated uncertainty bounds using Monte-Carlo simulations.FindingsWe identified more than 90 verbal autopsy studies from around the world to contribute data to a single-cause model. We estimated diarrhea proportionate mortality for 84 countries in 6 regions and found diarrhea to account for between 10.0% of deaths in the Americas to 31.3% of deaths in the South-east Asian region.DiscussionDiarrhea remains a leading cause of death for children 1-59 mo of age. Published literature can be used to create a single-cause mortality disease model to estimate mortality for countries lacking vital registration data.

Diarrhea is a leading cause of morbidity among children under 5 years of age in low- and middle-income countries yet the additional effects and sequelae, such as cognitive impairment associated with diarrhea, have not been quantified.We quantified the association between diarrhea prevalence and cognitive outcomes while controlling for linear growth in 4 study populations. Cognition was assessed using different methods across sites and was expressed in standardized units. We built linear regression models for each study with standardized cognitive score as the outcome and diarrhea prevalence as the main predictor variable. We then conducted meta-analyses of the regression coefficients to generate pooled estimates of the association between diarrhea prevalence and cognition whilst controlling for anthropometric status and other covariates.Diarrhea was not a significant predictor of cognitive score in any site in the regression models or in the meta-analyses (Coefficient = 0.07; 95% CI: -0.1, 0.2). The length for age Z- score was negatively related to cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably similar across sites (Coefficient Range: 0.168-0.186).We did not demonstrate an association between diarrhea and cognition with stunting included in the model. The links between diarrhea, stunting, and cognition provide additional rationale for accelerating interventions to reduce diarrhea.

BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children

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.

Multiple micronutrient deficiencies are highly prevalent among preschool children and often lead to anemia and growth faltering. Given the limited success of supplementation and health education programs, fortification of foods could be a viable and sustainable option. We report results from a community based double-masked, randomized trial among children 1-4 years evaluating the effects of micronutrients (especially of zinc and iron) delivered through fortified milk on growth, anemia and iron status markers as part of a four group study design, running two studies simultaneously.Enrolled children (n = 633) were randomly allocated to receive either micronutrients fortified milk (MN = 316) or control milk (Co = 317). Intervention of MN milk provided additional 7.8 mg zinc, 9.6 mg iron, 4.2 microg selenium, 0.27 mg copper, 156 microg vitamin A, 40.2 mg vitamin C, and 7.5 mg vitamin E per day (three serves) for one year. Anthropometry was recorded at baseline, mid- and end-study. Hematological parameters were estimated at baseline and end-study. Both groups were comparable at baseline. Compliance was over 85% and did not vary between groups. Compared to children consuming Co milk, children consuming MN milk showed significant improvement in weight gain (difference of mean: 0.21 kg/year; 95% confidence interval [CI] 0.12 to 0.31, p

Recent reviews suggest common infectious diseases continue to be a major cause of death among preschool children in developing countries. Identification of feasible strategies to combat this disease burden is an important public health need. We evaluated the efficacy of adding prebiotic oligosaccharide and probiotic Bifidobacterium lactis HN019 to milk, in preventing diarrhea, respiratory infections and severe illnesses, in children aged 1-4 years as part of a four group study design, running two studies simultaneously.In a community based double-masked, randomized controlled trial, children 1-3 years of age, willing to participate, were randomly allocated to receive either control milk (Co; n = 312) or the same milk fortified with 2.4 g/day of prebiotic oligosaccharide and 1.9x10(7) colony forming unit (c.f.u)/day of probiotic Bifidobacterium lactis HN019 (PP; n = 312). Children were followed up for 1 year providing data for 1-4 years. Biweekly household surveillance was conducted to gather information on compliance and morbidity. Both study groups were comparable at baseline; compliance to intervention was similar. Overall, there was no effect of prebiotic and probiotic on diarrhea (6% reduction, 95% Confidence Interval [CI]: -1 to 12%; p = 0.08). Incidence of dysentery episodes was reduced by 21% (95% CI: 0 to 38%; p = 0.05). Incidence of pneumonia was reduced by 24% (95% CI: 0 to 42%; p = 0.05) and severe acute lower respiratory infection (ALRI) by 35% (95% CI: 0 to 58%; p = 0.05). Compared to children in Co group, children in PP group had 16% (95% CI: 5 to 26%, p = 0.004) and 5% (95% CI: 0 to 10%; p = 0.05) reduction in days with severe illness and high fever respectively.Milk can be a good medium for delivery of prebiotic and probiotic and resulted in significant reduction of dysentery, respiratory morbidity and febrile illness. Overall, impact of diarrhea was not significant. These findings need confirmation in other settings.

BackgroundTo evaluate a delivery strategy for newborn interventions in rural Bangladesh.MethodsA cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality.FindingsA total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80-1.30) at baseline and 0.87 (95% CI: 0.68-1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported.ConclusionLack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management.Trial registrationClinicaltrials.gov NCT00198627.