Micronutrient supplementation of lactating Guatemalan women acutely increases infants' intake of riboflavin, thiamin, pyridoxal, and cobalamin, but not niacin, in a randomized crossover trial.

BACKGROUND: Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. OBJECTIVES: We compared acute effects of maternal lipid-based nutrient supplement (LNS) consumption (n = 22 nutrients, 175%-212% of the RDA intake for the nutrients examined), as a single dose or at spaced intervals during 8 h, on milk concentrations and infant intake from milk of B-vitamins. METHODS: This randomized crossover trial in Quetzaltenango, Guatemala included 26 mother-infant dyads 4-6 mo postpartum who were randomly assigned to receive 3 treatments in a random order: bolus 30-g dose of LNS (Bolus); 3 × 10-g doses of LNS (Divided); and no LNS (Control), with control meals. Mothers attended three 8-h visits during which infant milk consumption was measured and milk samples were collected at every feed. Infant intake was assessed as $\mathop \sum \nolimits_{i\ = \ 1}^n ( {{\rm{milk\ volum}}{{\rm{e}}_{{\rm{feed\ }}n}} \times \ {\rm{nutrient\ concentratio}}{{\rm{n}}_{{\rm{feed}}\ n}}} )$ over 8 h. RESULTS: Maternal supplementation with the Bolus or Divided dose increased least-squares mean (95% CI) milk and infant intakes of riboflavin [milk: Bolus: 154.4 (138.2, 172.5) µg · min-1 · mL-1; Control: 84.5 (75.8, 94.3) µg · min-1 · mL-1; infant: Bolus: 64.5 (56.1, 74.3) µg; Control: 34.5 (30.0, 39.6) µg], thiamin [milk: Bolus: 10.9 (10.1, 11.7) µg · min-1 · mL-1; Control: 7.7 (7.2, 8.3) µg · min-1 · mL-1; infant: Bolus: 5.1 (4.4, 6.0) µg; Control: 3.4 (2.9, 4.0) µg], and pyridoxal [milk: Bolus: 90.5 (82.8, 98.9) µg · min-1 · mL-1; Control: 60.8 (55.8, 66.3) µg · min-1 · mL-1; infant: Bolus: 39.4 (33.5, 46.4) µg; Control: 25.0 (21.4, 29.2) µg] (all P < 0.001). Only the Bolus dose increased cobalamin in milk [Bolus: 0.054 (0.047, 0.061) µg · min-1 · mL-1; Control: 0.041 (0.035, 0.048) µg · min-1 · mL-1, P = 0.039] and infant cobalamin intake [Bolus: 0.023 (0.020, 0.027) µg; Control: 0.015 (0.013, 0.018) µg, P = 0.001] compared with Control. Niacin was unaffected. CONCLUSIONS: Maternal supplementation with LNS as a Bolus or Divided dose was similarly effective at increasing milk riboflavin, thiamin, and pyridoxal and infant intakes, whereas only the Bolus dose increased cobalamin. Niacin was unaffected in 8 h. This trial was registered at clinicaltrials.gov as NCT02464111.

Several problem nutrients are identified in the complementary diet of 6 to 11 month old breastfed children in Western Guatemala.

BACKGROUND AND OBJECTIVES: The failure of infants in developing countries to meet nutrient intake recommendations is well documented. The objective of this study was to assess the nutritional adequacy and identify problem nutrients of the diets of Guatemalan infants with continued breastfeeding. METHODS AND STUDY DESIGN: A single previous-day dietary recall was collected from a convenience sample of 94 mothers of infants aged 6-11 mo attending a public health clinic in the urban area of Quetzaltenango, Guatemala. Energy and nutrient content of complementary feeding (CF) and breastmilk, modelled by subtracting estimated energy intakes from CF from energy requirements, were calculated and nutrient adequacy of the diet was assessed. Nutrient densities and critical nutrient densities of CF were computed to identify "problem nutrients" and main food sources of these nutrients. RESULTS: Complementary diets were adequate for protein, but likely to be inadequate for pantothenic acid and vitamins C, A, D, E, and K, as well as calcium, iron and zinc. In the worst-case scenario, i.e. for small girls with limited energy allowances, riboflavin, niacin, vitamin B-6 and magnesium were identified as "problem nutrients" as well. Formula milk, cow milk and Incaparina® were main food sources of "problem nutrients". CONCLUSIONS: The intake of micronutrients during the first six months of the recommend CF period in Guatemala has a number of notable inadequacies, but the gaps are narrower than traditionally reported for this age group in low-income settings.

Perspective: What Makes It So Difficult to Mitigate Worldwide Anemia Prevalence?

Anemia can be related to decreased production or increased loss of erythrocytes, or both, leading to many underlying and often overlapping causes. A largely cereal-based diet with plenty of phytates, polyphenols, and other ligands that inhibit intestinal iron absorption predominated in preindustrial Europe and predominates in present-day developing countries alike. In both situations, we find poor hygienic conditions, which frequently lead to anemia of inflammation. The large number of possible causes and their interaction shows why it is so difficult to mitigate anemia prevalence. Diagnostic biomarkers are required to differentiate the different types of anemia and to treat them appropriately. Some of them are well established in adults [e.g., concentrations of serum ferritin, soluble transferrin receptor (sTfR), and serum iron or the ratio of sTfR to log ferritin]. Others, such as serum hepcidin, hold considerable promise, although they are not yet widely used. A particular issue is to establish reference values for biomarkers in infants and children at different ages. The fact that resource-rich postindustrial societies have a very low prevalence of iron-deficiency anemia offers hope that common types of anemia can be eliminated. In contrast, inborn forms of anemia, such as thalassemia, and anemias related to underlying diseases (e.g., bleeding tumors or peptic ulcers, gynecologic blood losses, or renal diseases) require an operational health system to be addressed appropriately.

Vitamin D status among indigenous Mayan (Kekchi) and Afro-Caribe (Garifuna) adolescents from Guatemala: a comparative description between two ethnic groups residing on the Rio Dulce at the Caribbean coast in Izabal Province, Guatemala.

OBJECTIVE: To assess vitamin D status and the influence of risk factors such as skin pigmentation and time spent outdoors on hypovitaminosis D among Guatemalan Kekchi and Garifuna adolescents. DESIGN: Cross-sectional study, with convenient sampling design. Blood samples, anthropometric and behavioural data were all collected during the dry season. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by RIA. SETTING: Communities of Rio Dulce and Livingston, Izabal Province, Caribbean coast of Guatemala, with latitude and longitude of 15°49'N and 88°45'W for Livingston and 15°46'N and 88°49'W for Rio Dulce, respectively. SUBJECTS: Eighty-six adolescents, divided evenly by sex and ethnicity, with mean age of 14 years. RESULTS: Mean (sd) 25(OH)D value was 27·8 (7·2) ng/ml for the total group, with 25·8 (5·9) and 29·8 (7·9) ng/ml, respectively, in Kekchis and Garifunas (P=0·01). Use of vitamin D supplementation, clothing practices and sun protection were not statistically different between groups. Skin area exposed on the day of data collection ranged from 20·0 % minimum to 49·4 % maximum, with mean (sd) exposure of 32·0 (8.5) %. With univariate regression analysis, age (P=0·034), sex (P=0·044), ethnicity (P=0·010), time spent outdoors (P=0·006) and percentage skin area exposed (P=0·001) were predictive. However, multivariate analysis indicated that only sex (P=0·034) and percentage skin area exposed (P=0·044) remained as predictors of 25(OH)D. CONCLUSIONS: Despite residing in an optimal geographic location for sunlight exposure, nearly 65 % of study adolescents were either insufficient or deficient in vitamin D. Correction and long-term prevention of this nutritional problem may be instrumental in avoiding adverse effects in adulthood attributed to low 25(OH)D during adolescence.

Minerals and Trace Elements in Human Breast Milk Are Associated with Guatemalan Infant Anthropometric Outcomes within the First 6 Months.

BACKGROUND: Breast milk is the recommended source of nutrients for infant growth, but its adequacy to meet infants' mineral and trace element needs is unknown. OBJECTIVES: We used breast-milk mineral and trace element concentrations of Guatemalan mothers at 3 lactation stages to estimate total daily intakes and to determine whether intakes were associated with early infant growth. METHODS: In this cross-sectional study, breast-milk samples were collected from Mam-Mayan mothers during transitional (5-17 d, n = 56), early (18-46 d, n = 75), and established (4-6 mo, n = 103) lactation; z scores for weight (WAZ), length (LAZ), and head circumference (HCAZ) were measured. Concentrations of 11 minerals (calcium, potassium, magnesium, sodium, copper, iron, manganese, rubidium, selenium, strontium, and zinc) were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). WHO equations were used to calculate the estimated energy requirement, which was divided by the energy density of breast milk to estimate daily milk volume, and this number was multiplied by breast-milk mineral concentrations to estimate intakes. Principal component analyses identified clusters of minerals; principal components (PCs) were used in regression analyses for anthropometric outcomes. RESULTS: Estimated breast-milk intakes during established lactation were insufficient to compensate for the lower milk sodium, copper, manganese, and zinc concentrations in male infants and the lower sodium, iron and manganese concentrations in female infants. Estimated intakes of calcium, magnesium, potassium, sodium, and selenium were below the Institute of Medicine Adequate Intake for both sexes at all 3 stages of lactation. In early lactation, multiple linear regressions showed that PC1 (calcium, magnesium, potassium, rubidium, and strontium intakes) was positively associated with WAZ, LAZ, and HCAZ. In established lactation, the same PC with sodium added was positively associated with all 3 anthropometric outcomes; a second PC (PC2: zinc, copper, and selenium intakes) was associated with WAZ and LAZ but not HCAZ. CONCLUSIONS: Breast milk may be inadequate in selected minerals and trace elements where higher estimated intakes were associated with greater infant growth.

The Nutritional Contribution of Foods and Beverages Provided by Government-Sponsored Day Care Centers in Guatemala.

BACKGROUND: Meals served at government-run day care centers must be nutritionally adequate to ensure good health and proper development of preschool-aged children. They can provide a controlled opportunity to complement the daily diet of children in vulnerable populations. OBJECTIVE: To determine the nutrient adequacy and leading food sources of nutrients provided by the diet served in government-sponsored day care centers. METHODS: Estimated daily energy and nutrient intakes of a theoretical 40-day day care center menu were calculated, and the nutrient adequacy was assessed. Nutrient densities and critical nutrient densities of the menu were computed to identify nutrient inadequacies. Furthermore, main sources of nutrients were identified, and energy and nutrient distributions were examined by meal time. RESULTS: The menu provides approximately 90% of daily energy requirement and more than 100% of Recommended Nutrient Intakes (RNIs), with the exception of vitamin D and calcium. Sugar was the first leading source of energy, whereas milk was the first leading contributor of vitamin D. CONCLUSION: Within an environment of budgetary constraints, the Guatemalan government developed and advocated an exemplary menu offering for children in the vulnerable preschool period. We have demonstrated that, if prepared and served as planned, the items from the official, standard menu would supply most of the nutrients needed. High vitamin A intake related to the mandated national fortification program is a potential problem. From the analysis, it was found that vitamin D emerges as the most prominent candidate for a problem nutrient of deficient intake.

Can iron supplementation be reconciled with benefits and risks in areas hyperendemic for malaria?

Malaria is associated with about a million fatalities annually, largely among young children in zones of intense malarial transmission. The last thing needed would be measures that might increase the severity of clinical malaria. Thus, the finding in a field trial on Pemba Island, Tanzania, that routine oral iron supplementation produced adverse effects in iron-sufficient subjects had a ripple effect throughout the international public health community; it has effectively paralyzed efforts to redress iron-deficiency anemia in malaria-endemic regions. From a Hippocratic perspective, we consider the de facto moratorium on oral supplementation in such circumstance as a prudent interim measure. Public health programs to combat iron-deficiency anemia cannot be denied indefinitely to malaria-endemic populations, but the universal campaigns of iron provision cannot simply resume in the manner of the past. Contemporary biological and epidemiological understanding of the coevolution of humans and their pathogens should be able to provide guidance within the context of the essential and harmful aspects of iron. From these evolutionary standpoints, we identify a series of unresolved dilemmas. Toward a way forward, we highlight the pros and cons, as well as possible directions toward short-term strengthening, within three domains: tailored oral iron compounds, iron administration targeted only to iron-deficient individuals through screening, and prudent use of antimalarial prophylaxis. Although the tension between the essentiality of iron for humans and its role in pathogen virulence looms through every consideration, this recognition is a starting point toward the weighing of appropriate options balancing benefits and safety.

Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores.

BACKGROUND: The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria. OBJECTIVE: To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds--ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM)--in women with marginal iron stores. METHODS: Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men. RESULTS: The serum iron and NTBI responses to ferrous sulfate were significantly greater than those to water and the other two iron compounds. Serum iron responses to IPM did not differ from those to water alone. CONCLUSIONS: The administration of the two "slow-release" iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron-NTBI relationship is steeper in men than in women.

Update on zinc biology.

Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation.

Stunting rates in infants and toddlers born in metropolitan Quetzaltenango, Guatemala.

OBJECTIVE: Guatemala has the highest prevalence of stunting (54% of children under age 5 years) in the Americas and the fifth highest in the world. The aim of this study was to describe the stunting prevalence and the association with early feeding practices, morbidity patterns, and socioeconomic status (SES) in a sample of infants and toddlers from urban Quetzaltenango. METHODS: We recruited 299 children (149 boys), ages 6-23 mo from two public health clinics in metropolitan Quetzaltenango. Data on SES, early feeding practices, and morbidity were collected by means of a single face-to-face interview. Recumbent spine length was measured according to standardized procedures and height-for-age (HAZ) z-scores were calculated. HAZ <-2 SD of the World Health Organization's 2006 Growth Standards was considered stunting. Multiple logistic regression analysis was used to examine determinants of stunting. RESULTS: The overall mean HAZ z-score was -1.89 ± 1.11 and 135 (45%) children were stunted. The results of the crude odds ratios showed that place of interview (suburban), being male, being ages 13-18 mo, being born at home, having a mother with a low level of education, being of Mayan (indigenous) ethnicity, having a mother with short stature, and having ever received iron supplementation were strongly and significantly (P < 0.05) associated with stunting. None of the other variables, such as supplement use and morbidity rates, contributed to the predictive model. We did not observe an association between early feeding practices or morbidity and stunting. CONCLUSION: The stunting prevalence exceeds the cut-off of 40% stunting, indicating a community with a high level of malnutrition.

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men.

BACKGROUND: Oral iron supplementation with ferrous sulfate (FeSO4) at dosage levels suggested by the international guidelines poses a safety hazard to young children with malaria. Exposure to loosely bound iron in the circulation has been advanced as a potential factor. OBJECTIVE: To evaluate the kinetics of circulating concentrations of plasma iron and non-transferrin-bound iron (NTBI) in response to oral iron administration in healthy adults. METHODS: Plasma samples were collected at 90-minute intervals over a period of 270 minutes from 10 healthy Guatemalan men after oral administration of water or 100 mg of iron from each of three iron compounds: FeSO4, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), and iron polymaltose. The four tests were administered in an individually randomized sequence. Serum iron concentration was measured spectrophotometrically by the ferrozine method, and NTBI concentration was measured by a fluorometric competitive binding assay. The kinetic response and the maximal and cumulative changes in circulating concentrations of the biomarkers of interest were compared. RESULTS: Serum iron and NTBI responses to oral administration of FeSO4 were significantly greater than responses to plain water or the other two iron compounds. NTBI concentrations after NaFeEDTA or iron polymaltose ingestion were not different from those determined after water intake. CONCLUSIONS: Administration of two iron compounds of proven bioavailability, but with complex absorption characteristics, is associated with a negligible NTBI response, potentially mitigating the safety concerns associated with iron supplementation in malarial areas.

Targeted provision of oral iron: the evolution of a practical screening option.

Universal oral iron supplementation, undertaken according to 1998 WHO guidelines, produced adverse consequences among some children in malaria-endemic areas. Prompted by the Pemba trial, which revealed excessive hospitalizations and deaths, WHO advised that iron supplementation in such regions be accompanied by previous screening for iron deficiency. This agenda, however, poses issues of cost, benefit, acceptability, technical feasibility, and reliability of such screening. The cost of equipment and personnel is balanced against savings from iron supplements spared and treatment for morbidity averted. Costs aside, the most efficacious acceptable screening approach for avoiding hospitalization and deaths must be fielded. Screening before supplementation can be used to assess hematological, iron, and possible inflammatory status to differentiate the source of decreased hemoglobin concentration. Iron deficiency has often been inferred from hematological status markers. The need for extraction of blood, albeit capillary in origin, and high assay costs limit the use of validated methods in screening. Noninvasive methods, i.e., not requiring the extraction of blood, provide the most acceptable and potentially least expensive approach for determining hematological or iron status. Although a noninvasive technique for iron and inflammatory status would be the ideal, it is unattained. Field-friendly, skin-probe hemoglobin devices, derived from instruments for clinical settings, are being developed and tested for eventual rollout in malarial areas. Given a firm grounding for the theoretical requirements needed to advance the screening agenda, evaluation and monitoring of the performance of screening devices can proceed hand in hand.

Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men.

BACKGROUND: Urinary biomarkers are used in assessment of severe, clinical oxidative stress. Little is known, however, about their diagnostic value within the normative range. OBJECTIVE: To evaluate the response of urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) as indicators of systemic oxidation in response to short-term oral iron and antioxidant supplementation. METHODS: Five healthy adult men participated in the pilot study phase and 12 in the definitive intervention trial. For 7 days each, separated by 12-day washouts, the subjects received different treatment regimens, consisting of 120 mg of iron, 120 mg of iron in refined palm oil, and 120 mg of iron in palm oil combined with one of the two doses of Carotino Tocotrienol Carotene Mixed Concentrate (CTCMC). Creatinine-normalized urinary TBARS and 8-OHdG concentrations were quantified in samples taken from subjects with and without active supplementation. Temporal and correlative associations between TBARS and 8-OHdG were explored. RESULTS: Daily intake of supplemental iron failed to produce any increment in urinary excretion of TBARS or 8-OHdG. However, a significant within-individual correlation between the urinary biomarkers was observed (Spearman r = 0.697, p < .0001, n = 466). Both doses of CTCMC significantly lowered urinary excretion of both oxidation indicators. CONCLUSIONS: Despite the lack of effect of oral iron on the biomarkers of systemic oxidation, they show a strong and significant mutual association within the nonpathological range of oxidative stress in healthy male adults.