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Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9-11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.

BACKGROUND: Several recent reviews of the methods used to set research priorities have identified the CHNRI method (acronym derived from the "Child Health and Nutrition Research Initiative") as an approach that clearly became popular and widely used over the past decade. In this paper we review the first 50 examples of application of the CHNRI method, published between 2007 and 2016, and summarize the most important messages that emerged from those experiences. METHODS: We conducted a literature review to identify the first 50 examples of application of the CHNRI method in chronological order. We searched Google Scholar, PubMed and so-called grey literature. RESULTS: Initially, between 2007 and 2011, the CHNRI method was mainly used for setting research priorities to address global child health issues, although the first cases of application outside this field (eg, mental health, disabilities and zoonoses) were also recorded. Since 2012 the CHNRI method was used more widely, expanding into the topics such as adolescent health, dementia, national health policy and education. The majority of the exercises were focused on issues that were only relevant to low- and middle-income countries, and national-level applications are on the rise. The first CHNRI-based articles adhered to the five recommended priority-setting criteria, but by 2016 more than two-thirds of all conducted exercises departed from recommendations, modifying the CHNRI method to suit each particular exercise. This was done not only by changing the number of criteria used, but also by introducing some entirely new criteria (eg, "low cost", "sustainability", "acceptability", "feasibility", "relevance" and others). CONCLUSIONS: The popularity of the CHNRI method in setting health research priorities can be attributed to several key conceptual advances that have addressed common concerns. The method is systematic in nature, offering an acceptable framework for handling many research questions. It is also tra

BACKGROUND: China has achieved Millennium Development Goal 4 to reduce under-5 mortality rate by two-thirds between 1990 and 2015. In this study, we estimated the national and subnational levels and causes of child mortality in China annually from 1996 to 2015 to draw implications for achievement of the SDGs for China and other low-income and middle-income countries. METHODS: In this systematic analysis, we adjusted empirical data on levels and causes of child mortality collected in the China Maternal and Child Health Surveillance System to generate representative estimates at the national and subnational levels. In adjusting the data, we considered the sampling design and probability, applied smoothing techniques to produce stable trends, fitted livebirth and age-specific death estimates to natvional estimates produced by the UN for international comparison, and partitioned national estimates of infrequent causes produced by independent sources to the subnational level. FINDINGS: Between 1996 and 2015, the under-5 mortality rate in China declined from 50·8 per 1000 livebirths to 10·7 per 1000 livebirths, at an average annual rate of reduction of 8·2%. However, 181 600 children still died before their fifth birthday, with 93 400 (51·5%) deaths occurring in neonates. Great inequity exists in child mortality across regions and in urban versus rural areas. The leading causes of under-5 mortality in 2015 were congenital abnormalities (35 700 deaths, 95% uncertainty range [UR] 28 400-45 200), preterm birth complications (30 900 deaths, 24 200-40 800), and injuries (26 600 deaths, 21 000-33 400). Pneumonia contributed to a higher proportion of deaths in the western region of China than in the eastern and central regions, and injury was a main cause of death in rural areas. Variations in cause-of-death composition by age were also examined. The contribution of preterm birth complications to mortality decreased after the neonatal period; congenital abnormalities remained an

BACKGROUND: Substantial progress in reducing the child mortality rate has been made globally in the last two decades. However, for China, the number of children dying from preventable diseases is still very large. It is important to have regularly updated information on the distribution of causes of death (COD) in children to inform policy and research. In this study, we aim to estimate the COD spectrum in children younger than five years old from 2009 to 2015 with a focus on the year 2015 and to provide an updated COD prediction model for China. METHODS: Updated data of under-five mortality rates (U5MRs) and the number of live births at national and provincial levels were obtained from United Nation's Inter-agency Group for Child Mortality Estimation (UN IGME), Institute for Health Metrics and Evaluation (IHME), and United Nations Population Division (UNPD). Then, we conducted a systematic review across four Chinese and English bibliographic databases and identified high-quality community-based longitudinal studies of COD in children younger than five years in China. We developed a number of single-cause models to predict the number of child death for main COD in different age groups at both national and provincial levels. The jackknife procedure was applied to construct the 95% Uncertainty Ranges (URs). RESULTS: From 2009 to 2015, the under-five mortality rates have declined by 37.1%. The leading causes of death in 2015 were preterm birth complications (17.4%), birth asphyxia (15.2%), congenital abnormalities (14.1%), accidents (13.5%) and pneumonia (12.4%) for children under five years old. The COD spectrum varied substantially across Chinese provinces with different development levels. The leading cause in children under five years in the wealthier provinces (with lower U5MRs) was congenital abnormalities (up to 18.9%), while in the poorer provinces (with higher U5MRs), pneumonia was the dominant COD (up to 23.4%). CONCLUSIONS: This study updates and validates t

Evidence supporting the impact of therapeutic zinc supplementation on the duration and severity of diarrhea among children under five is largely derived from studies conducted in South Asia. China experiences a substantial portion of the global burden of diarrhea, but the impact of zinc treatment among children under five has not been well documented by previously published systematic reviews on the topic. We therefore conducted a systematic literature review, which included an exhaustive search of the Chinese literature, in an effort to update previously published estimates of the effect of therapeutic zinc. We conducted systematic literature searches in various databases, including the China National Knowledge Infrastructure (CNKI), and abstracted relevant data from studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool select outcomes and to generate estimates of percentage difference and relative risk comparing outcomes between zinc and control groups. We identified 89 Chinese and 15 non-Chinese studies for the review, including studies in 10 countries from all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469 zinc and 9353 control). None of the included Chinese studies had previously been included in published pooled effect estimates. Chinese and non-Chinese studies reported the effect of therapeutic zinc supplementation on decreased episode duration, stool output, stool frequency, hospitalization duration and proportion of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese studies yielded an overall 26% (95% CI: 20%-32%) reduction in the estimated relative risk of diarrhea lasting beyond three days among zinc-treated children. Studies conducted in and outside China report reductions in morbidity as a result of oral therapeutic zinc supplementation for acute diarrhea among children under five years of age. The WHO recommendation for zinc treatment of diarrhea episodes should be suppo

BACKGROUND: Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC). METHODS: Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥ 3) and maternal age (<18 years, 18-<35 years, ≥ 35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed. RESULTS: Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥ 3/age 18-<35 years, and preterm and neonatal mortality for parity ≥ 3/≥ 35 years. CONCLUSIONS: Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥ 3 / age ≥ 35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman's reproductive period. FUNDING: Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Healt

BACKGROUND: Between 1990 and 2006, China reduced its under-five mortality rate (U5MR) from 64.6 to 20.6 per 1000 live births and achieved the fourth United Nation's Millennium Development Goal nine years ahead of target. This study explores the contribution of social, economic and political determinants, health system and policy determinants, and health programmes and interventions to this success. METHODS: For each of the years between 1990 and 2006, we obtained an estimate of U5MR for 30 Chinese provinces from the annual China Health Statistics Yearbook. For each year, we also obtained data describing the status of 8 social, 10 economic, 2 political, 9 health system and policy, and six health programmes and intervention indicators for each province. These government data are not of the same quality as some other health information sources in modern China, such as articles with primary research data available in Chinese National Knowledge Infrastructure (CNKI) and Wan Fang databases, or Chinese Maternal and Child Mortality Surveillance system. Still, the comparison of relative changes in underlying indicators with the undisputed strong general trend of childhood mortality reduction over 17 years should still capture the main effects at the macro-level. We used multivariate random effect regression models to determine the effect of 35 indicators individually and 5 constructs defined by factor analysis (reflecting effects of social, economic, political, health systems and policy, and health programmes) on the reduction of U5MR in China. RESULTS: In the univariate regression applied with a one-year time lag, social determinants of health construct showed the strongest crude association with U5MR reduction (R(2) = 0.74), followed by the constructs for health programmes and interventions (R(2) = 0.65), economic (R(2) = 0.47), political (R(2) = 0.28) and health system and policy determinants (R(2) = 0.26), respectively. Similarly, when multivariate regression was applied

Igor Rudan and colleagues report the results of their consensus building exercise that identified health research priorities to help reduce child mortality from pneumonia.

Background: Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age or exposure level, can inform the selection and targeting of specific interventions and programs, and increase cost-effectiveness. Methods and Findings: For 26 selected risk factors, expert working groups conducted comprehensive reviews of data on risk-factor exposure and hazard for 14 epidemiological subregions of the world, by age and sex. Age-sex-subregion-population attributable fractions were estimated and applied to the mortality and burden of disease estimates from the World Health Organization Global Burden of Disease database. Where possible, exposure levels were assessed as continuous measures, or as multiple categories. The proportion of risk-factor-attributable burden in different population subgroups, defined by age, sex, and exposure level, was estimated. For major cardiovascular risk factors (blood pressure, cholesterol, tobacco use, fruit and vegetable intake, body mass index, and physical inactivity) 43%-61% of attributable disease burden occurred between the ages of 15 and 59 y, and 87% of alcohol-attributable burden occurred in this age group. Most of the disease burden for continuous risks occurred in those with only moderately raised levels, not among those with levels above commonly used cut-points, such as those with hypertension or obesity. Of all disease burden attributable to being underweight during childhood, 55% occurred among children 1-3 standard deviations below the reference population median, and the remainder occurred among severely malnourished children, who were three or more standard deviations below median. Conclusions: Many major global risks are widely spread in a population, rather than restricted to a minority. Population-based strategies that seek to shift the whole distribution of risk factors often have the potential to produce substantial reduc