Perspective on Emerging Micronutrient Deficiencies in Latin America and the Caribbean.

The moral imperative of public health systems is to maximize the health and welfare of the population to the extent possible. Constraints often include a lack of resources, political will, popular acceptance, or an acceptable safety margin. Major agencies have established iron, iodine, and vitamin A as the principal elements for micronutrients, with folate and zinc on the second plane. As the armamentarium of interventions to favor micronutrient nutrition, for example, preventive health measures, dietary improvement, forms of fortification, and nutrient supplements, is offered in public health policy. The utility of their merger with other nutrients, emergent nutrients, has been considered. The Latin America and Caribbean Region has unique characteristics. The scientific and epidemiology considerations for action in the Region's health concern on 4 emergent nutrient deficiencies of public health-vitamins D and E, essential fatty acids, and choline-are reviewed.

Plain language titleMicronutrient Deficiencies of Interest in Latin America and the CaribbeanPlain language summaryThe diets consumed in the diverse corners and societies in the nations of Latin America and the Caribbean area do not fully supply the vitamins and minerals needed by people of all ages and conditions. Some public health actions are being taken, but only against a limited selection of such nutrients as iron, vitamin A, iodine, and folic acid. The composition of diets and environmental conditions across the region suggests that 4 additional nutrients might be candidates for public health efforts. These include vitamin D, vitamin E, certain large fatty acid molecules, and choline.

Human milk microbial species are associated with infant head-circumference during early and late lactation in Guatemalan mother-infant dyads.

Human milk contains abundant commensal bacteria that colonize and establish the infant's gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, 'early' (6-46 days postpartum, n = 29) or 'late' (109-184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ -1 SD (early: n = 18; late: n = 14) and HCAZ < -1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ -1 SD and HCAZ < -1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ -1 SD and HCAZ < -1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR < 0.05) between HCAZ ≥ -1 SD and HCAZ < -1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ -1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ < -1 SD group at late lactation had more differentially abundant taxa associated with environmentally and 'potentially opportunistic' species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.

Nutrient Density as a Dimension of Dietary Quality: Findings of the Nutrient Density Approach in a Multi-Center Evaluation.

The nutrient adequacy of a diet is typically assessed by comparing estimated nutrient intakes with established average nutrient requirements; this approach does not consider total energy consumed. In this multinational survey investigation in Indonesia, Mexico, and South Africa, we explore the applications of the "critical nutrient-density approach"-which brings energy requirements into the equation-in the context of public health epidemiology. We conducted 24 h dietary recalls in convenience samples of normal-weight (BMI 18.5-25 kg/m2) or obese (BMI > 30 kg/m2), low-income women in three settings (n = 290). Dietary adequacy was assessed both in absolute terms and using the nutrient density approach. No significant differences in energy and nutrient intakes were observed between normal-weight and obese women within any of the three samples (p > 0.05). Both the cut-point method (% of EAR) and critical nutrient density approach revealed a high probability of inadequate intakes for several micronutrients but with poor concordance between the two methods. We conclude that it may often require some approximate estimate of the habitual energy intake from an empirical source to apply a true critical nutrient density reference for a population or subgroup. This will logically signify that there would be more "problem nutrients" in the diets examined with this nutrient density approach, and efforts toward improved food selection or food- or biofortification will frequently be indicated.

Infant Anthropometry and Growth Velocity Before 6 Months are Associated with Breastfeeding Practices and the Presence of Subclinical Mastitis and Maternal Intestinal Protozoa in Indigenous Communities in Guatemala.

BACKGROUND: The possibility that maternal health status and breastfeeding practices contribute to growth faltering before 6 mo is underexplored. OBJECTIVES: This longitudinal study investigated whether indicators of subclinical mastitis (SCM) and breast inflammation, maternal fecal-oral contamination, and/or breastfeeding practices were associated with infant anthropometry or growth velocity before 6 mo. METHODS: Indigenous Mam-Mayan mother-infant dyads (n = 140) were recruited. Breast milk was collected at early (<6 wk) and established (4-6 mo) lactation when maternal and infant anthropometry were measured. Milk Na:K ratio as an indicator of SCM and concentrations of 4 proinflammatory cytokines were measured. Maternal stool samples were examined for the presence of intestinal parasites including nonpathogenic protozoa (Endolimax nana, Iodamoeba bütschlii, Entamoeba coli, Blastocystis hominis). Questionnaires characterized breastfeeding and hygiene practices. Multiple linear regression identified factors associated with infant growth attainment [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and head circumference-for-age z-score (HCAZ)] and growth velocity (expressed as change per day from early to established lactation). Multiple logistic regression identified factors associated with increased odds of underweight, stunting, and low head circumference at both lactation stages. RESULTS: A higher Na:K ratio, individual nonpathogenic protozoa, and specific breastfeeding and hygiene practices were associated with impaired growth before 6 wk and at 4-6 mo in exclusively breastfed infants. Growth velocity for weight was inversely associated with Entamoeba coli but cranial growth was associated positively with Iodamoeba bütschlii whereas feeding colostrum in early lactation was protective and decreased the odds of an HCAZ < -2 SD. Finally, the presence of SCM in early lactation increased the likelihood of both WAZ < -2 SD and LAZ < -2 SD by 6 wk. CONCLUSIONS: Prevention of SCM can improve early infant weight, but measures that promote the feeding of colostrum and reduce exposure to fecal-oral contamination might be required to minimize infant growth faltering in breastfed infants.

Distinct Changes Occur in the Human Breast Milk Microbiome Between Early and Established Lactation in Breastfeeding Guatemalan Mothers.

Human breast milk contains a diverse community of bacteria, but as breast milk microbiome studies have largely focused on mothers from high income countries where few women breastfeed to 6 months, the temporal changes in the breast milk microbiome that occur during later lactation stages have not been explored. For this cross-sectional study, microbiota from breast milk samples of Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala were analyzed. All mothers delivered vaginally and breastfed their infants for 6 months. Breast milk from 76 unrelated mothers was used to compare two lactation stages, either "early" (6-46 days post-partum, n = 33) or "late" (109-184 days post-partum, n = 43). Breast milk microbial communities were assessed using 16S ribosomal RNA gene sequencing and lactation stages were compared using DESeq2 differential abundance analysis. A total of 1,505 OTUs were identified, including 287 which could be annotated as putative species. Among several maternal factors, lactation stage explained microbiome variance and inertia in ordination with the most significance (p < 0.001). Differential abundance analysis identified 137 OTUs as significantly higher in either early or late lactation. These included a general shift from Staphylococcus and Streptococcus species in early lactation to Sphingobium and Pseudomonas species in late lactation. Species enriched in early lactation included putative commensal bacteria known to colonize the infant oral and intestinal tracts whereas species enriched in late lactation had a uniform functional trait associated with aromatic compound degradation. Differentially abundant species also included several species which have not previously been reported within breast milk, such as Janthinobacterium agaricidamnosum, Novosphingobium clariflavum, Ottowia beijingensis, and Flavobacterium cucumis. These discoveries describe temporal changes to the breast milk microbiome of healthy Guatemalan mothers from early to late lactation. Collectively, these findings illustrate how studying under-represented human populations might advance our understanding of factors that modulate the human milk microbiome in low and middle income countries (LMIC).

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.

Vision of Research on Human Linear Growth.

The human body grows in length from conception to the maximal adult height over two decades. The shortest male population averages ∼150 cm and the tallest ∼183 cm. Nonetheless the dimensions of head and trunk are highly comparable, with the vast difference in the leg length. Stunting is a personal condition in which an individual has a standing height-for-age (HAZ) of less than two standard deviations of the standard curve median. It is associated with increased mortality, morbidity, and functional deficits. The process of losing relative stature is known as linear growth retardation, first attributed to chronic protein deficiency, then to an assortment of micronutrient deficiencies, and most recently to inflammation from unhygienic environmental conditions. Public health intervention trials responding to each of these possibilities have failed to produce true reversal responses measured in the 10s of centimeters. As to biological insights, there is no convenient way to separate weight from length growth with sonographic monitoring, but a third of infants can be born stunted. Normative growth (standard curves) competes with epigenetic adaptation (programming) as the beacon for in utero growth. Major investments into field trials allow us to discard multiple micronutrients and water/sanitation/hygiene interventions as measures to reverse established stunting. The preponderance of evidence is against catch-up growth during puberty. Future publications will be in the conceptual domain, resolving metrics, while the full range of stimuli and exposures impeding growth will be elucidated. Advances in measurement techniques in anthropometry and immunology and endocrinology will be mobilized to the literature.

Anthropometry before Day 46 and Growth Velocity before 6 Months of Guatemalan Breastfed Infants Are Associated with Subclinical Mastitis and Milk Cytokines, Minerals, and Trace Elements.

BACKGROUND: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland, but its association with human milk composition and infant growth is not well described. OBJECTIVES: We investigated whether SCM, milk cytokines, and/or estimated intakes of milk minerals and trace elements were associated with infant anthropometry or growth velocity before 6 mo. METHODS: Breast milk was collected from Mam-Mayan mothers (n = 114) at both early (2-46 d) and established (4-6 mo) lactation. Concentrations of 9 elements (sodium, potassium, calcium, magnesium, copper, iron, manganese, selenium, zinc) analyzed by inductively-coupled plasma mass spectrometry were used to estimate infants' daily intakes. Concentrations of 4 cytokines were measured. Milk concentrations and infants' estimated elemental intakes and anthropometric measurements during early and established lactation were compared by SCM status. Multiple regression was used to identify factors associated with infant growth attainment (<46 d) for infant weight- (WAZ), length- (LAZ), and head circumference-for-age (HCAZ) and weight-for-length (WLZ) z scores and with growth velocity (expressed as Δ/d) from early to established lactation. RESULTS: SCM prevalence was higher in early (30%) than established (10%) lactation. Breast milk of SCM mothers had higher cytokine concentrations and higher magnesium in early and higher selenium concentrations in both early and established lactation (Padj < 0.0121). At day 46, regression models showed inverse associations of SCM with WLZ and IL-1ß with LAZ (Padj < 0.0150). In contrast, linear growth velocity was positively associated with IL-1ß measured in early lactation (Padj < 0.0124), whereas cranial growth velocity was positively associated with IL-8 measured during established lactation ( Padj < 0.0124). CONCLUSIONS: Despite a high prevalence of inadequate intakes, only infants' intake of milk magnesium during early lactation was associated with linear growth velocity in breastfed infants <6 mo. Evidence shows that SCM, breast-milk cytokines, and infants' estimated intakes of select elements are independently associated with growth attainment and growth velocity during lactation.

Endocannabinoid Metabolome Characterization of Milk from Guatemalan Women Living in the Western Highlands.

BACKGROUND: Recognized as the gold-standard ideal fare, human milk has a unique composition that meets infants' needs throughout development. Endocannabinoids and endocannabinoid-like compounds [endocannabinoid metabolome (ECM)] are endogenous lipid mediators derived from long-chain polyunsaturated fatty acids. Based on animal models, it has been proposed that endocannabinoid arachidonoyl glycerol (AG) plays a role in establishing the suckling response during lactation. In addition, endocannabinoid ethanolamides have been shown to stimulate food intake. The mechanisms of action and the role of the ECM in human milk are not fully understood. OBJECTIVES: The present study aimed to characterize and quantify the ECM in human milk samples from an underserved population in Guatemala. METHODS: Human milk samples were collected from lactating women (n = 26) for ECM characterization and quantification. Samples were taken at 3 different time points between 4 and 6 mo of lactation during maternal fasting. Human milk samples were analyzed by liquid chromatography-mass spectrometry. Identified members of the ECM were: arachidonoyl ethanolamide, palmitoyl ethanolamide (PEA), oleoyl ethanolamide, docosahexaenoyl ethanolamide, eicoapentaenoyl ethanolamide, eicosenoyl ethanolamide, AG, palmitoyl glycerol, oleoyl glycerol, docosahexaenoyl glycerol, eicosapentaenoyl glycerol, eicosenoyl glycerol, arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). RESULTS: Overall, concentrations in the ethanolamide group were lower than the glycerols. A time effect was observed for ARA, DHA, EPA, and PEA across the 3 time points (P ≤ 0.05). CONCLUSIONS: Our study identified the ECM in mature human milk and provides the first report for a population with health disparities within a developing country. The few studies available have been conducted in developed countries. Hypotheses for future studies can be developed based on this study's data to help elucidate specific roles for members of the ECM and how this biological system modulates infant health and development.

Infant growth faltering linked to subclinical mastitis, maternal faecal-oral contamination, and breastfeeding.

Infant growth faltering occurs in breastfed infants <6 months of age. The possibility that maternal health status contributes to this growth faltering is underexplored. We investigated whether (a) subclinical mastitis (SCM), an asymptomatic inflammation of the breast, (b) maternal intestinal nematode and protozoan infections, indicators of faecal-oral contamination, or (c) poor breastfeeding practices increased the odds of stunting (length-for-age z-score < -2SD), underweight (weight-for-age z-score < -2SD), or low head circumference (head circumference-for-age z-score < -2SD) in breastfed infants in rural indigenous communities in Guatemala. Mother-infant dyads (n = 105) were subdivided into those with and without SCM (milk Na:K ratio > 0.6). Maternal and infant anthropometry were measured at the time of breast milk collection. Maternal stool samples were examined for the presence of intestinal nematodes and protozoa. Questionnaires were used to characterize breastfeeding practices (exclusivity and frequency) and support, hygiene (latrine use and household faucet), and infant diarrhoea. SCM occurred in 14% of women and was associated with increased odds of infant stunting (odds ratio [OR] = 4.3; confidence interval [CI] [1.1, 15.8]), underweight (OR = 9.2; CI [1.8, 48.0]), and low head circumference (OR = 15.9; CI [2.6, 96.9]). Maternal pathogenic protozoa and nematodes were uncommon (<4%), but nonpathogenic protozoa were common (e.g., Entamoeba coli [39%]). Entamoeba coli increased the likelihood (OR = 3.3; CI [1.02, 10.6]) of low head circumference, whereas higher breastfeeding frequency lowered its odds (OR = 0.74, CI [0.56, 0.97]). Prevention of SCM may improve early infant growth, but public health measures that increase breastfeeding frequency and reduce faecal-oral contamination may be required to minimize low head circumference.

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.

Subclinical mastitis (SCM) and proinflammatory cytokines are associated with mineral and trace element concentrations in human breast milk.

The possibility that either subclinical mastitis (SCM), an inflammatory condition of the breast, or elevations in breast milk proinflammatory cytokines alter breast milk mineral and trace element composition in humans has not been investigated. In this cross-sectional study, breast milk samples (n=108) were collected from Guatemalan Mam-Mayan mothers at one of three stages of lactation (transitional, early and established), and categorized as SCM (Na:K >0.6) or non-SCM (Na:K ≤0.6). Milk concentrations of 12 minerals (calcium, copper, iron, magnesium, manganese, phosphorus, potassium, rubidium, selenium, sodium, strontium, and zinc) and 4 proinflammatory cytokines (IL-1ß, IL-6, IL-8, TNF-α) were measured by inductively coupled plasma mass spectrometry (ICP-MS), Lachat analyzer or Luminex multiplex bead cytokine assay. SCM was more prevalent during transitional (30%) than early (15.6%) and established (8.9%) lactation. Analysis of variance revealed that breast milk minerals differed by stage of lactation and SCM status. Breast milk minerals with the exception of magnesium were lower in established lactation, whereas SCM was associated with higher selenium and lower phosphorus. Regression models that controlled for lactation stage also confirmed that SCM was associated with lower milk phosphorus and higher milk selenium concentrations. Furthermore, cytokine concentrations were independently associated with several mineral concentrations: IL-1ß with higher phosphorus and iron, IL-6 with higher calcium, magnesium, copper and manganese, IL-8 with higher calcium and zinc, and TNF-α with lower iron and manganese. We conclude that milk mineral and trace element concentrations are affected not only by the presence of SCM but also by proinflammatory cytokines in breast milk.

Comparative performance of NEMS-S Surveys in latino food stores in the greater boston area

The dietary practices of diverse population groups, associated with the nutritional transition and the rapid demographic changes occurring globally require more attention to the food preferences of migrant groups such as Latinos living in the United States United States of America (US). This work aimed at the performance of an instrument utilized to measure availability of healthy food options in Latino stores located in the town of Somerville, state of Massachusetts. The methodology included the application of two versions: Guatemalan and US of the Nutrition Environment Measures Survey for Stores (NEMS-S), for the assessment of the availability of healthy food options in three Latino stores. Data were analyzed using descriptive statistics. The results indicated that foods sold in Latino stores were identified more successfully with the Guatemalan-NEMS-S than with the US NEMS-S. There was a general lack of healthy food options found when using the US survey, as well as a relatively narrow selection of fruits and vegetables. As conclusion, it was found that the US NEMS-S tended to identify a lower number of healthy food options, as compared to a larger number of similar options when a culturally-appropriate survey was used. These findings illustrate a manner in which a culture-specific instrument perform more appropriately than similar instruments adapted for other population groups, especially when the results are to be applied to support development of healthy food policies(AU)

Las prácticas alimentarias de diversos grupos de población, asociadas a la transición nutricional, y a los rápidos cambios demográficos que se producen a nivel mundial, exigen más atención a las preferencias alimentarias de grupos migrantes, como por ejemplo Latinos en los Estados Unidos de Norteamérica (EU). Este trabajo documenta los resultados de aplicar un instrumento para medir disponibilidad de alimentos saludables en tres tiendas latinas ubicadas en la ciudad de Somerville, estado de Massachusetts. La metodología utilizada incluyó la aplicación de dos versiones: guatemalteca y EU de la Encuesta para Medir Ambiente Nutricional en Tiendas (NEMS-S, siglas en inglés), para evaluar la disponibilidad de alimentos saludables. Los datos se analizaron con estadísticas descriptivas. Los resultados indicaron que los alimentos vendidos en las tiendas latinas fueron identificados con más acierto con el NEMS-S guatemalteco que con el NEMS-S de EU. Con este último instrumento, se obtuvo un número menor de opciones saludables y una selección limitada de frutas y de vegetales. Como conclusión, se encontró que el NEMS-S de EU identificaba un menor número de opciones de alimentos saludables, en comparación con el instrumento culturalmente apropiado. Estos hallazgos ilustran la importancia de utilizar instrumentos específicos para determinar disponibilidad de alimentos saludables, especialmente cuando los resultados se utilicen para apoyar el desarrollo de políticas alimentarias(AU)