Background: Previous analyses derived the relative risk (RR) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight. Objectives: The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight. Design: Data were obtained from investigators of 10 cohort studies with both weight-for-age category (<−3 SDs, −3 to <−2 SDs, −2 to <−1 SD, and >−1 SD) and cause of death information. All 10 studies contributed information on weight-for-age and risk of diarrhea, pneumonia, and all-cause mortality; however, only 6 studies contributed information on deaths because of measles, and only 3 studies contributed information on deaths because of malaria or fever. With use of weighted random effects models, we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition. Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys. With use of the RR and prevalence information, we then calculated the fraction of deaths by cause attributable to undernutrition. Results: The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality. Overall, 52.5% of all deaths in young children were attributable to undernutrition, varying from 44.8% for deaths because of measles to 60.7% for deaths because of diarrhea. Conclusion: A significant proportion of deaths in young children worldwide is attributable to low weight-for-age, and efforts to reduce malnutrition should be a policy priority.

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). 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. 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. 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 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 Health Epidemiology Reference Group.

Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Non-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0-2years of age. Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Bill & Melinda Gates Foundation.

Mild-to-moderate zinc deficiency may be relatively common worldwide, but the public health importance of this degree of zinc deficiency is not well defined. The purpose of this review was to provide a conceptual framework for evaluating the public health importance of maternal zinc deficiency as it relates to fetal growth and development, complications of pregnancy, labor and delivery, and maternal and infant health. The mechanisms through which zinc deficiency could influence health outcomes are well described. The results of experimental studies conducted in animal models have motivated concern about the potential health effects of mild-to-moderate maternal zinc deficiency. Observational studies in human populations have produced strong associations between poor maternal zinc status and various indicators of poor pregnancy outcome, but supplementation trials have not produced strong, or even consistent results. Supplementation trials are needed to define the public health importance of maternal zinc deficiency worldwide.

Objective: To provide a better understanding of dietary intakes of pregnant women in low- and middle-income countries.Design: Systematic review was performed to identify relevant studies which reported nutrient intakes or food consumption of pregnant women in developing countries. Macronutrient and micronutrient intakes were compared by region and the FAO/WHO Estimated Average Requirements. Food consumption was summarized by region.Setting: Developing countries in Africa, Asia, and the Caribbean and Central/South America.Subjects: Pregnant women in the second or third trimester of their pregnancies.Results: From a total of 1499 retrieved articles, sixty-two relevant studies were analysed. The ranges of mean/median intakes of energy, fat, protein and carbohydrate were relatively higher in women residing in the Caribbean and Central/South America than in Africa and Asia. Percentages of energy from carbohydrate and fat varied inversely across studies in all regions, whereas percentage of energy from protein was relatively stable. Among selected micronutrients, folate and Fe intakes were most frequently below the Estimated Average Requirements, followed by Ca and Zn. Usual dietary patterns were heavily cereal based across regions.Conclusions: Imbalanced macronutrients, inadequate micronutrient intakes and predominantly plant-based diets were common features of the diet of pregnant women in developing countries. Cohesive public health efforts involving improving access to nutrient-rich local foods, micronutrient supplementation and fortification are needed to improve the nutrition of pregnant women in developing countries.

Undernutrition is highly prevalent in many areas in which morbidity and mortality from malaria is unacceptably high. That undernutrition exacerbates diarrhea and respiratory infections is widely demonstrated; however, research suggests that it may exacerbate, palliate, or have little effect on malaria outcomes. This review examines the global burden of malaria associated with various nutrient deficiencies as well as underweight status in children 0–4 years of age. Although the association is complex and requires additional research, improved nutritional status lessens the severity of malaria episodes and results in fewer deaths due to malaria. Deficiencies in vitamin A, zinc, iron, folate, as well as other micronutrients are responsible for a substantial proportion of malaria morbidity and mortality. It is recommended that nutrition programs be integrated into existing malaria intervention programs.