Adequate zinc nutrition is essential for adequate growth, immunocompetence and neurobehavioral development, but limited information on population zinc status hinders the expansion of interventions to control zinc deficiency. The present analyses were conducted to: (1) estimate the country-specific prevalence of inadequate zinc intake; and (2) investigate relationships between country-specific estimated prevalence of dietary zinc inadequacy and dietary patterns and stunting prevalence. National food balance sheet data were obtained from the Food and Agriculture Organization of the United Nations. Country-specific estimated prevalence of inadequate zinc intake were calculated based on the estimated absorbable zinc content of the national food supply, International Zinc Nutrition Consultative Group estimated physiological requirements for absorbed zinc, and demographic data obtained from United Nations estimates. Stunting data were obtained from a recent systematic analysis based on World Health Organization growth standards. An estimated 17.3% of the world’s population is at risk of inadequate zinc intake. Country-specific estimated prevalence of inadequate zinc intake was negatively correlated with the total energy and zinc contents of the national food supply and the percent of zinc obtained from animal source foods, and positively correlated with the phytate: zinc molar ratio of the food supply. The estimated prevalence of inadequate zinc intake was correlated with the prevalence of stunting (low height-for-age) in children under five years of age (r = 0.48, P<0.001). These results, which indicate that inadequate dietary zinc intake may be fairly common, particularly in Sub-Saharan Africa and South Asia, allow inter-country comparisons regarding the relative likelihood of zinc deficiency as a public health problem. Data from these analyses should be used to determine the need for direct biochemical and dietary assessments of population zinc status, as part of nationally representative nutritional surveys targeting countries estimated to be at high risk.

Increasing concentrations of atmospheric carbon dioxide (CO2) lower the content of zinc and other nutrients in important food crops. Zinc deficiency is currently responsible for large burdens of disease globally, and the populations who are at highest risk of zinc deficiency also receive most of their dietary zinc from crops. By modelling dietary intake of bioavailable zinc for the populations of 188 countries under both an ambient CO2 and elevated CO2 scenario, we sought to estimate the effect of anthropogenic CO2 emissions on the global risk of zinc deficiency. We estimated per capita per day bioavailable intake of zinc for the populations of 188 countries at ambient CO2 concentrations (375-384 ppm) using food balance sheet data for 2003-07 from the Food and Agriculture Organization. We then used previously published data from free air CO2 enrichment and open-top chamber experiments to model zinc intake at elevated CO2 concentrations (550 ppm, which is the concentration expected by 2050). Estimates developed by the International Zinc Nutrition Consultative Group were used for country-specific theoretical mean daily per-capita physiological requirements for zinc. Finally, we used these data on zinc bioavailability and population-weighted estimated average zinc requirements to estimate the risk of inadequate zinc intake among the populations of the different nations under the two scenarios (ambient and elevated CO2). The difference between the population at risk at elevated and ambient CO2 concentrations (ie, population at new risk of zinc deficiency) was our measure of impact. The total number of people estimated to be placed at new risk of zinc deficiency by 2050 was 138 million (95% CI 120-156). The people likely to be most affected live in Africa and South Asia, with nearly 48 million (32-63) residing in India alone. Global maps of increased risk show significant heterogeneity. Our results indicate that one heretofore unquantified human health effect associated with anthropogenic CO2 emissions will be a significant increase in the human population at risk of zinc deficiency. Our country-specific findings can be used to help guide interventions aimed at reducing this vulnerability. Bill & Melinda Gates Foundation, Winslow Foundation.

The prevalence of inadequate zinc intake in a population can be estimated by comparing the zinc content of the food supply with the population’s theoretical requirement for zinc. However, assumptions regarding the nutrient composition of foods, zinc requirements, and zinc absorption may affect prevalence estimates. These analyses were conducted to: (1) evaluate the effect of varying methodological assumptions on country-specific estimates of the prevalence of dietary zinc inadequacy and (2) generate a model considered to provide the best estimates. National food balance data were obtained from the Food and Agriculture Organization of the United Nations. Zinc and phytate contents of these foods were estimated from three nutrient composition databases. Zinc absorption was predicted using a mathematical model (Miller equation). Theoretical mean daily per capita physiological and dietary requirements for zinc were calculated using recommendations from the Food and Nutrition Board of the Institute of Medicine and the International Zinc Nutrition Consultative Group. The estimated global prevalence of inadequate zinc intake varied between 12–66%, depending on which methodological assumptions were applied. However, country-specific rank order of the estimated prevalence of inadequate intake was conserved across all models (r = 0.57–0.99, P<0.01). A “best-estimate” model, comprised of zinc and phytate data from a composite nutrient database and IZiNCG physiological requirements for absorbed zinc, estimated the global prevalence of inadequate zinc intake to be 17.3%. Given the multiple sources of uncertainty in this method, caution must be taken in the interpretation of the estimated prevalence figures. However, the results of all models indicate that inadequate zinc intake may be fairly common globally. Inferences regarding the relative likelihood of zinc deficiency as a public health problem in different countries can be drawn based on the country-specific rank order of estimated prevalence of inadequate zinc intake.

Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. SQ-LNS provision decreased stunting (length-for-age z score < −2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < −2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < −2) by 18%, acute malnutrition (WLZ < −2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < −2) by 13%, and small head size (head circumference-for-age z score < −2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12–14% lower prevalence of stunting, wasting, and underweight; were 16–19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown. Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old. We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates. We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10). LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718.