Sonja Y. Hess

Preventive Zinc Supplementation among Infants, Preschoolers, and Older Prepubertal Children

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by ∼20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by ∼15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on childrens behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

Indicators of zinc status at the population level: a review of the evidence

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Use of Serum Zinc Concentration as an Indicator of Population Zinc Status

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individuals serum zinc concentration does not reliably predict that persons response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a populations risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Recent Advances in Knowledge of Zinc Nutrition and Human Health

Zinc deficiency increases the risk and severity of a variety of infections, restricts physical growth, and affects specific outcomes of pregnancy. Global recognition of the importance of zinc nutrition in public health has expanded dramatically in recent years, and more experience has accumulated on the design and implementation of zinc intervention programs. Therefore, the Steering Committee of the International Zinc Nutrition Consultative Group (IZiNCG) completed a second IZiNCG technical document that reexamines the latest information on the intervention strategies that have been developed to enhance zinc nutrition and control zinc deficiency. In particular, the document reviews the current evidence regarding preventive zinc supplementation and the role of zinc as adjunctive therapy for selected infections, zinc fortification, and dietary diversification or modification strategies, including the promotion and protection of breastfeeding and biofortification. The purposes of this introductory paper are to summarize new guidelines on the assessment of population zinc status, as recommended by the World Health Organization (WHO), the United Nations Childrens Fund (UNICEF), the International Atomic Energy Agency (IAEA), and IZiNCG, and to provide an overview on several new advances in zinc metabolism. The following papers will then review the intervention strategies individually.

Effects of maternal zinc supplementation on pregnancy and lactation outcomes.

Observational studies in human populations suggest that maternal zinc deficiency during pregnancy may cause adverse pregnancy outcomes for the mother and fetus. Therefore, we reviewed the current evidence from studies of zinc supplementation, with or without other micronutrients, during pregnancy and lactation to assess its impact on maternal, fetal, and infant health. A meta-analysis of supplementation trials indicates a 14% reduction in premature delivery among zinc-supplemented women. Most studies found no significant impact of maternal zinc supplementation on infant birthweight, but a subset of studies conducted in underweight or zinc-deficient women suggests that there may be a positive effect of zinc supplementation in such women. However, the number of relevant studies is limited, and more information is needed to confirm these observations. The results for other pregnancy outcomes are inconsistent, and the number of available studies is small. Likewise, the impact of maternal zinc supplementation during pregnancy on infant postnatal growth and risk of infection is variable, and few studies are available. Thus, more research will be needed to allow definitive conclusions to be drawn, especially for the second half of infancy and later childhood. Studies found no adverse effects of maternal zinc supplementation on iron status during pregnancy. More information is required on other potential adverse effects, particularly with regard to a possible modifying effect of preexisting maternal zinc status. In view of the possible benefits of zinc supplementation for reducing the risk of premature delivery, the possible positive impact of zinc supplementation on infant birthweight among undernourished women, and the lack of reported adverse effects, zinc should be included in maternal supplements given during pregnancy in populations at risk for zinc deficiency.

A national study of the prevalence of overweight and obesity in 6-12 y-old Swiss children: body mass index, body-weight perceptions and goals.

Objectives: To estimate the prevalence of overweight and obesity in Swiss children and to obtain information on weight perceptions and weight control practices in this population.Design: Cross-sectional, three-stage, probability-proportionate-to-size cluster sampling.Setting: Middle schools throughout Switzerland.Subjects: A representative national sample of 595 6–12 y-old schoolchildren.Intervention: Measurement of weight and height; interview on weight perceptions and weight control practices.Results: Body mass index (BMI) was calculated and used as an indicator of overweight. The BMIs of the Swiss children were compared with US, UK, French and Swiss reference data. Depending on which reference data were used, the prevalence of obesity varied between 9.7 and 16.1% and the prevalence of overweight varied between 21.7 and 34.2%. Girls were significantly more likely to consider themselves too fat (26% and 15%, respectively) and to report currently trying to lose weight (30% and 18%, respectively) compared to boys (P<0.05).Conclusions: The prevalence of overweight in Swiss children, and its attendant health and social consequences, are important public health concerns.Sponsorship: The Swiss Foundation for Nutrition Research, Zürich, Switzerland.European Journal of Clinical Nutrition (2000) 54, 568–572

Impact of Zinc Fortification on Zinc Nutrition

Food fortification is increasingly recognized as an effective approach to improve a populations micronutrient status. The present report provides a critical review of the scientific evidence currently available on the impact of zinc fortification on zinc nutrition. The available studies clearly show that zinc fortification can increase dietary zinc intake and total daily zinc absorption. Most absorption studies also indicate that adding zinc to food does not adversely affect the absorption of other minerals, such as iron. Despite the positive effect of zinc fortification on total zinc absorption, only a few studies have found positive impacts of zinc fortification on serum zinc concentrations or functional indicators of zinc status. The reasons for these inconsistent results are uncertain but may relate to the choice of food vehicles, the age group and zinc status of the study populations, or particular aspects of the study design. Thus, additional research is needed to determine the impact of zinc fortification, with or without other micronutrients, in populations at risk for zinc deficiency. Because of the benefits of increasing intake in populations at high risk for zinc deficiency, the documented increase in total zinc absorption that occurs following zinc fortification, the absence of any adverse effects, and the relatively low cost of adding zinc, public health planners should consider including zinc in mass and targeted fortification programs in such populations. Because of the limited available information on program impact, it will be important to evaluate the outcomes of such programs.

Monitoring the adequacy of salt iodization in Switzerland: a national study of school children and pregnant women

Background: Several countries with long-standing salt iodization programs, including Switzerland, have recently reported declining and/or low urinary iodine (UI) levels in their populations. In Switzerland, in response to studies indicating low UI levels in children and pregnant women, the salt iodine level was increased in 1998 from 15 to 20 mg/kg.Objective: Our objective was to evaluate iodine nutrition in a national sample of Swiss school children and pregnant women 8–16 months after the increase in the salt iodine level.Design: A 3-stage probability proportionate to size cluster sampling method was used to obtain a representative national sample of 600 children aged 6–12 y and 600 pregnant women. We then measured UI in both groups, thyrotropin (TSH) in pregnant women and thyroid volume by ultrasound to determine goiter prevalence in school children.Results: The median UI (range) of the children and pregnant women was 115 μg/l (5–413) and 138 μg/l (5–1881), respectively. The median blood TSH concentration (range) of pregnant women was 0.6 mU/l (0.2–2.1). Based on the current WHO/ICCIDD normative data for thyroid volume, none of the children were goitrous, using either age/sex-specific or BSA/sex-specific cutoffs.Conclusions: The iodine status of the Swiss population is once again adequate, illustrating the value of periodic monitoring and prudent adjustments to the iodine level in salt. This approach could serve as a model for countries struggling to maintain dietary iodine intake in the face of shifting dietary habits and changes in the food supply.Sponsorship: Swiss Foundation for Nutrition Research, Zürich, Switzerland; Foundation for Micronutrients in Medicine, Rapperswil, Switzerland; and Swiss Federal Institute of Technology in Zürich, Switzerland.European Journal of Clinical Nutrition (2001) 55, 162–166

Small-Quantity Lipid-Based Nutrient Supplements, Regardless of Their Zinc Content, Increase Growth and Reduce the Prevalence of Stunting and Wasting in Young Burkinabe Children: A Cluster-Randomized Trial

Small-quantity lipid-based nutrient supplements (SQ-LNS) are promising home fortification products, but the optimal zinc level needed to improve growth and reduce morbidity is uncertain. We aimed to assess the impact of providing SQ-LNS with varied amounts of zinc, along with illness treatment, on zinc-related outcomes compared with standard care. In a placebo-controlled, cluster-randomized trial, 34 communities were stratified to intervention (IC) or non-intervention cohorts (NIC). 2435 eligible IC children were randomly assigned to one of four groups:1) SQ-LNS without zinc, placebo tablet; 2) SQ-LNS containing 5mg zinc, placebo tablet; 3) SQ-LNS containing 10mg zinc, placebo tablet; or 4) SQ-LNS without zinc and 5mg zinc tablet from 9–18 months of age. During weekly morbidity surveillance, oral rehydration salts were provided for reported diarrhea and antimalarial therapy for confirmed malaria. Children in NIC (n = 785) did not receive SQ-LNS, tablets, illness surveillance or treatment. At 9 and 18 months, length, weight and hemoglobin were measured in all children. Reported adherence was 97±6% for SQ-LNS and tablets. Mean baseline hemoglobin was 89±15g/L. At 18 months, change in hemoglobin was greater in IC than NIC (+8 vs -1g/L, p<0.0001), but 79.1% of IC were still anemic (vs. 91.1% in NIC). Final plasma zinc concentration did not differ by group. During the 9-month observation period, the incidence of diarrhea was 1.10±1.03 and of malaria 0.54±0.50 episodes per 100 child-days, and did not differ by group. Length at 18 months was significantly greater in IC compared to NIC (77.7±3.0 vs. 76.9±3.4cm; p<0.001) and stunting prevalence was significantly lower in IC (29.3%) than NIC (39.3%; p<0.0001), but did not differ by intervention group within IC. Wasting prevalence was also significantly lower in IC (8.7%) than in NIC (13.5%; p = 0.0003). Providing SQ-LNS daily with or without zinc, along with malaria and diarrhea treatment, significantly increased growth and reduced stunting, wasting and anemia prevalence in young children. Trial Registration ClinicalTrials.gov NCT00944281

The impact of common micronutrient deficiencies on iodine and thyroid metabolism: the evidence from human studies

Deficiencies of micronutrients are highly prevalent in low-income countries. Inadequate intake of iodine impairs thyroid function and results in a spectrum of disorders. Other common deficiencies of micronutrients such as iron, selenium, vitamin A, and possibly zinc may interact with iodine nutrition and thyroid function. Randomised controlled intervention trials in iodine- and iron-deficient populations have shown that providing iron along with iodine results in greater improvements in thyroid function and volume than providing iodine alone. Vitamin A supplementation given alone or in combination with iodised salt can have a beneficial impact on thyroid function and thyroid size. Despite numerous studies of the effect of selenium on iodine and thyroid metabolism in animals, most published randomised controlled intervention trials in human populations failed to confirm an impact of selenium supplementation on thyroid metabolism. Little evidence is available on interactions between iodine and zinc metabolism.