Dietary patterns and cognitive achievement among school children in socio-cultural context, a case of Montevideo, Uruguay.

PURPOSE: The benefits of a healthy diet on children´s cognition have been described in several studies. However, many previous studies have analyzed the effect on general cognitive domains (e.g. intelligence), used measures based almost exclusively on local examinations, and rarely consider social context. OBJECTIVE: The objective of the present study was to examine the relationship between two diet patterns and contextualized cognitive performance measures of children aged 6-8 years from low-average income neighborhoods in Montevideo, Uruguay. METHODS: 270 first-grade children with complete data participated in the study. Consumption of foods was determined via two averaged 24-h dietary recalls with the mother. Two dietary patterns were identified via principal component analysis: "processed (high calorie) foods" and "nutrient dense". Children´s cognitive performance, including general cognitive abilities, achievement in mathematics and reading, and discrepancy scores between predicted and actual achievement was assessed with the Woodcock-Muñoz Cognitive and Achievement scales. The association of dietary patterns and cognitive endpoints was analyzed in multilevel models, clustered by children´s school. Sociodemographic and biological variables were used as covariates. RESULTS: The nutrient dense foods pattern, characterized by higher consumption of dark leafy and red-orange vegetables, eggs, beans & peas, potatoes, was associated with better performance in reading, with beta coefficient 3.28 (95% CI 0.02, 6.54). There was also an association between the nutrient dense foods factor and the Discrepancy in reading, 2.52 (0.17, 4.87). Processed (high calorie) foods pattern, characterized by higher consumption of breads, processed meats, fats and oils, sweetened beverages, and sweetened yogurt/dairy products; reduced intake of milk, pastries and pizza dinners was not associated with cognitive performance. CONCLUSIONS: Nutrient dense food pattern was positively associated with children's reading achievement. A nutrient-rich diet may benefit written language acquisition at the beginning of schooling.

Reducing the complexity of high-dimensional environmental data: An analytical framework using LASSO with considerations of confounding for statistical inference.

PURPOSE: Frameworks for selecting exposures in high-dimensional environmental datasets, while considering confounding, are lacking. We present a two-step approach for exposure selection with subsequent confounder adjustment for statistical inference. METHODS: We measured cognitive ability in 338 children using the Woodcock-Muñoz General Intellectual Ability (GIA) score, and potential associated features across several environmental domains. Initially, 111 variables theoretically associated with GIA score were introduced into a Least Absolute Shrinkage and Selection Operator (LASSO) in a 50% feature selection subsample. Effect estimates for selected features were subsequently modeled in linear regressions in a 50% inference (hold out) subsample, first adjusting for sex and age and later for covariates selected via directed acyclic graphs (DAGs). All models were adjusted for clustering by school. RESULTS: Of the 15 LASSO selected variables, eleven were not associated with GIA score following our inference modeling approach. Four variables were associated with GIA scores, including: serum ferritin adjusted for inflammation (inversely), mother's IQ (positively), father's education (positively), and hours per day the child works on homework (positively). Serum ferritin was not in the expected direction. CONCLUSIONS: Our two-step approach moves high-dimensional feature selection a step further by incorporating DAG-based confounder adjustment for statistical inference.

Contribution of household drinking water intake to arsenic and lead exposure among Uruguayan schoolchildren.

BACKGROUND: Food and water are common exposure sources of arsenic and lead among children. Whereas dietary sources of these toxicants are fairly well-studied, the contribution of drinking water to toxicant exposures is not well characterized in many populations, particularly in the Global South. OBJECTIVE: To assess the extent to which consumption of household drinking water contributes to arsenic and lead exposure among Uruguayan schoolchildren with low-level exposure. METHODS: Children, aged 5-8 years, were enrolled into the Salud Ambiental Montevideo study during 2009-2013 from schools in Montevideo, Uruguay. Participants reported water intake as part of two 24-h dietary recalls. Concentrations of arsenic were measured in first morning void urine samples, and adjusted for urinary specific gravity. Lead concentrations were measured in venous blood samples. Drinking water samples were collected from participants' homes and toxicant concentrations measured. Data analyses involved a triangulation approach. First, multivariable linear regressions estimated the associations between toxicant exposure through drinking water, calculated for each child as the product of water intake and water toxicant concentration, and the respective toxicant biomarker concentrations among children with complete data on all variables (Sample A; n = 40). Second, regressions were repeated for participants with complete data on all variables except water intakes (Sample B; n = 195), after water intakes were imputed. Finally, models were constructed for participants of Sample B (n = 195) based on drinking water intakes assumed to be fixed at 25th, 50th, 75th percentile intakes of participants in sample A. RESULTS: Toxicant exposure via drinking water intake was low. The triangulation approach revealed no associations between toxicant exposure through household water intake and the respective toxicant biomarker concentrations. CONCLUSION: Studies with larger samples and repeated measures are needed to confirm these findings. Nevertheless, it appears that at low water toxicant concentrations, typical water consumption is not a major contributor to children's exposure.

Lead exposure and indices of height and weight in Uruguayan urban school children, considering co-exposure to cadmium and arsenic, sex, iron status and dairy intake.

Child growth depends on complex factors including diet, nutritional status, socioeconomic, and sanitary conditions, and exposure to environmental chemicals. Lead exposure is known to impair growth in young children but effects in school-age children are less clear. The effects of co-exposure to low-level lead and other toxic metals on child growth are not well understood. We examined cross-sectional associations of blood lead (BLL) with growth indices (Z scores of body mass index for age, BAZ, and height for age, HAZ) in Uruguayan urban school children (n = 259; ~7 y). Potential differences in these associations in children with lower vs. higher urinary inorganic arsenic metabolites (U-As), urinary cadmium (U-Cd), sex (42% girls), iron deficiency (ID, 39% children), or intake of dairy foods below recommended levels were examined. BLL was measured using AAS, U-As using HPLC-HGICP-MS, and U-Cd using ICP-MS. Dietary information was obtained by two 24-h recalls completed by caregivers. Children's linear growth was within age and sex-appropriate reference values. Overweight (BAZ > 1 2 SD) was found in 20.1%, and obesity (BAZ > 2 SD) in 18.5%, of children. Ranges (5th, 95th percentile) of biomarker concentrations were: BLL, 0.8-7.8 µg/dL; U-Cd, 0.01-0.2 µg/L, and U-As, 4.0-27.3 µg/L. BLL was inversely associated with HAZ ([95% CI]: 0.10 [-0.17, -0.03]) in covariate-adjusted models. Although this association was slightly more pronounced in girls, children without ID, and children with lower U-As, there was little evidence of effect modification due to overlapping CIs in stratified models. BLLs were not associated with BAZ, except for a suggestion of a negative relationship in girls (-0.10 [-0.23, 0.02]) but not boys [0.001 [-0.11, 0.12]). Our findings indicate that exposure to low levels of lead was associated with lower HAZ in apparently normally growing urban school children. Larger future studies should help elucidate if these associations persist over time and across populations.

Associations of dietary intakes and serum levels of folate and vitamin B-12 with methylation of inorganic arsenic in Uruguayan children: Comparison of findings and implications for future research.

BACKGROUND: In the human body, inorganic arsenic (iAs) is methylated via the one-carbon cycle to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of iAs and MMA, and higher proportions of DMA in urine indicate efficient methylation; formation of DMA is thought to detoxify iAs and MMA. Studies on folate, vitamin B-12 and iAs methylation yield mixed findings, depending on whether folate and vitamin B-12 were assessed from diet, supplements, or using a blood biomarker. OBJECTIVE: First, to compare the associations of serum concentrations and estimated intake of folate and vitamin B-12 with indicators of iAs methylation. Second, to highlight the implications of these different B-vitamin assessment techniques on the emerging evidence of the impact of dietary modifications on iAs methylation. METHODS: The study was conducted among ~7-year-old children from Montevideo, Uruguay. Serum folate and vitamin B-12 levels were measured on the Horiba ABX Pentra 400 analyzer; urinary arsenic was measured using High-Performance Liquid Chromatography on-line with Inductively Coupled Plasma Mass Spectrometry. Dietary intakes were assessed using the average of two 24-h dietary recalls. Linear regressions assessed the associations of serum levels, and dietary intakes of folate (n = 237) and vitamin B-12 (n = 217) with indicators of iAs methylation. Models were adjusted for age, sex, body mass index, total urinary arsenic, and rice intake. RESULTS: Serum folate and vitamin B-12 levels were above the adequacy threshold for 99% of the participants. No associations were observed between serum folate, serum vitamin B-12, or vitamin B-12 intake and iAs methylation. Folate intake was inversely associated with urinary %MMA [ß (95% confidence interval): -1.04 (-1.89, -0.18)]. CONCLUSION: Additional studies on the role of B-vitamins in iAs methylation are needed to develop a deeper understanding of the implications of assessing folate and vitamin B-12 intake compared to the use of biomarkers. Where possible, both methods should be employed because they reflect different exposure windows and inherent measurement error, and if used individually, will likely continue to contribute to lack of consensus.

Executive functions in school children from Montevideo, Uruguay and their associations with concurrent low-level arsenic exposure.

OBJECTIVE: Arsenic is a known childhood neurotoxicant, but its neurotoxicity at low exposure levels is still not well established. The aim of our cross-sectional study was to test the association between low-level arsenic exposure and executive functions (EF) among children in Montevideo. We also assessed effect modification by arsenic methylation capacity, a susceptibility factor for the health effects of arsenic, and by B-vitamin intake, which impacts arsenic methylation. METHODS: Arsenic exposure was assessed as the specific gravity-adjusted sum of urinary arsenic metabolites (U-As) among 255 ~ 7 year-old children, and methylation capacity as the proportion of urinary monomethylarsonic acid (%MMA). Arsenic concentrations from kitchen water samples at participants' homes were assessed. B-vitamin intake was calculated from the average of two 24-hour dietary recalls. EF was measured using three tests from the Cambridge Neuropsychological Test Automated Battery- Stockings of Cambridge (SOC), Intra-dimensional/extra-dimensional shift task (IED), and Spatial Span (SSP). Generalized linear models assessed the association between U-As and EF measures; models were adjusted for age, sex, maternal education, possessions score, Home Observation for Measurement of the Environment Inventory score, season, and school clusters. Additional analyses were conducted to address issues of residual confounding and sample size. A "B-vitamin index" was calculated using principal component analysis. Effect modification by the index and urinary %MMA was assessed in strata split at the respective medians of these variables. RESULTS: The median (range) U-As and water arsenic levels were 9.9 µg/L (2.2, 47.7) and 0.45 µg/L (0.1, 18.9) respectively, indicating that exposure originated mainly from other sources. U-As was inversely associated with the number of stages completed (ß = -0.02; 95% CI: -0.03, -0.002) and pre-executive shift errors (ß = -0.08; 95% CI: -0.14, -0.02) of the IED task, and span length of the SSP task (ß = -0.01; 95% CI: -0.02, -0.004). There was no clear pattern of effect modification by B-vitamin intake or urinary %MMA. CONCLUSION: Low-level arsenic exposure may adversely affect executive function among children but additional, including longitudinal, studies are necessary to confirm these findings.

Vitamin B-6 Intake Is Modestly Associated with Arsenic Methylation in Uruguayan Children with Low-Level Arsenic Exposure.

BACKGROUND: Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. OBJECTIVES: Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (<50 µg/L in water; urinary arsenic 5-50 µg/L). METHODS: We conducted a cross-sectional study in 290 ∼7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. RESULTS: Median (range) arsenic concentrations in urine and water were 9.9 (2.2-48.7) and 0.45 (0.1-18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0-33.8), 9.7% (2.6-24.8), and 79.1% (58.5-95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19-2.56), 1.0 (0.30-2.24), 8.6 (3.5-23.3), and 0.67 (0.25-1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75-466) and 1.7 (0.34-8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (ß = -1.60; 95% CI: -3.07, -0.15). No other statistically significant associations were observed. CONCLUSIONS: Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.

Low level arsenic exposure, B-vitamins, and achievement among Uruguayan school children.

OBJECTIVES: Millions of children globally, including the U.S., are exposed to low levels of arsenic from water and food. Arsenic is a known neurotoxicant at high levels but its effects at lower exposure levels are understudied. Arsenic methylation capacity, influenced by B-vitamin intake and status, potentially influences arsenic toxicity. In a cross-secitonal study of 5-8 year-old children from Montevideo, we assessed the relationship between urinary arsenic (U-As) and academic achievement, and tested for effect modification by B-vitamin intake, status, and arsenic methylation capacity. METHODS: Broad math and reading scores were calculated based on six subtests (calculation, math facts fluency, applied problems, sentence reading fluency, letter word identification, passage comprehension) from the Woodcock-Muñoz Achievement Battery. B-vitamin intake was assessed from two non-consecutive 24-h dietary recalls, serum folate and vitamin B-12 levels were measured in a subset of participants. Arsenic methylation capacity was measured as the proportion of urinary monomethylarsonic acid (%MMA). Multiple imputation using chained equations was conducted to account for missing covariate and exposure data. Ordinal regressions assessed associations between U-As and achievement score tertiles in the complete case and imputed samples. A "B-vitamin index" was calculated using principal component analysis. Interactions by urinary %MMA and the B-vitamin index were assessed. RESULTS: Median specific gravity adjusted U-As was 11.7 µg/L (range: 2.6, 50.1). We found no association between U-As and broad math and reading scores, nor effect modification by %MMA or B-vitamins. CONCLUSION: At low-levels of exposure, U-As does not appear to affect children's academic achievement.

Sobrepeso, obesidad y niveles de presión arterial en niños de nivel 5 de jardines de infantes públicos de Montevideo: prevalencia y factores asociados / Overweight, obesity and high-blood pressure in 5 year-old children in 5 public preschool centers in Montevideo: prevalence and associated factors / Sobrepeso, obesidade e níveis de pressão arterial em crianças de nível 5 de jardins de infância públicos de Montevidéu: prevalência e fatores associados

Resumen: Introducción: en Uruguay, en los últimos años, se ha constatado un incremento en la prevalencia de sobrepeso y obesidad. La evidencia científica ha demostrado que las condiciones en la primera infancia son determinantes. Objetivo: determinar la prevalencia de sobrepeso, obesidad y los niveles de presión arterial (PA) braquial e identificar factores de riesgo asociados en niños de nivel 5 que concurren a jardines públicos de Montevideo. Método: estudio transversal (7/2016-6/2017) en una muestra representativa de 771 niños de nivel 5 de jardines públicos de Montevideo. Se relevó historia y comportamiento alimentario, actividad física, hábitos de sueño, peso y talla materna. En cada niño se registró antropometría y PA braquial. Resultados: la prevalencia de sobrepeso u obesidad fue 40,6% (IC95%: 37,4-44,3), obesidad 16,5% (IC95%: 13,9-19,1) y obesidad abdominal 12,9% (IC95%: 11,0-15,8). Reportaron sobrepeso 29,4% de las madres y obesidad 21,9%. Se observó sedentarismo en 58,3%, exposición prolongada a pantallas en 60,4% y escasas horas de sueño en 40,9%. El consumo frecuente de alfajores, obleas y bizcochos en el desayuno, de embutidos entre semana, la preferencia de alimentos con publicidad, y el reporte de sobrepeso u obesidad materna se asociaron con obesidad infantil. Los niños con sobrepeso, obesidad u obesidad abdominal presentaron mayores niveles de PA braquial. Conclusiones: la prevalencia de sobrepeso y obesidad en niños de nivel 5 de jardines públicos de Montevideo es elevada. El sobrepeso, la obesidad materna y los hábitos en relación con la alimentación, actividad física y sueño se asocian con su presencia.

Summary: Introduction: in recent years, Uruguay has seen an increase of the prevalence of overweight and obesity. Scientific evidence has shown that early childhood conditions are determinant. Objective: to determine the prevalence of overweight, obesity and brachial blood pressure levels and identify associated risk factors in 5-year-old children who attend public preschool centers in Montevideo. Method: transversal study (7/2016-6/2017) in a representative sample of 771 5-year-old children from preschool centers in Montevideo. We assessed their history, eating habits, physical activity, sleeping habits, weight and maternal size. We recorded anthropometry and brachial blood pressure for each child. Results: the prevalence of overweight or obesity was 40.6% (CI 95%: 37.4- 44.3), obesity 16.5% (CI 95%: 13.9-19.1) and abdominal obesity 12.9% (CI 95%: 11.0-15.8). 29.4% of mothers reported overweight and 21.9% of them reported obesity. Sedentary lifestyle was found in 58.3%, long screen viewing in 60.4% and inadequate sleep in 40.9%. Frequent consumption of pastries, wafers and biscuits for breakfast, cold cuts during week days, preference of food they see in advertisements, and reported maternal overweight or obesity were associated to child obesity. Children with overweight and/or abdominal obesity evidenced higher levels of brachial blood pressure. Conclusions: prevalence of overweight and obesity in 5-year-old children from public preschool centers in Montevideo is high. Maternal overweight and obesity and habits in connection with eating, physical activity and amount of sleep are associated with this condition.

Resumo: Introdução: nos últimos anos observou-se um aumento da prevalência de sobrepeso e obesidade no Uruguai. A evidência científica mostra que as condições de vida na primeira infância são determinantes. Objetivo: determinar a prevalência de sobrepeso, obesidade e os niveles de pressão arterial (PA) braquial e identificar fatores de risco associados em crianças com 5 anos que frequentam jardines de infância públicos em Montevidéu. Métodos: estudo transversal (7/2016-6/2017) em uma amostra representativa de 771 crianças com 5 anos de jardins de infância públicos de Montevidéu. Foram coletados dados sobre a história e o comportamento alimentar, atividade física, hábitos de sono e peso e altura materna. Os dados antropométricos e PA braquial de todas as crianças foram registrados. Resultados: a prevalência de sobrepeso ou obesidade foi de 40,6% (I.C.95%:37,4-44,3), obesidade 16,5% (I.C.95%:13,9-19,1) e obesidade abdominal 12,9% (I.C.95%:11,0-15,8). 29,4% das mães informaram sobrepeso e 21,9% obesidade. Observou-se sedentarismo em 58,3%, exposição prolongada a telas de equipamentos eletrônicos em 60,4% e poucas horas de sono em 40,9%. O consumo frequente de alfajores, obleias e pães com altos teores de açúcar e gordura no café da manhã, de embutidos nos dias de semana, preferência de alimentos com publicidade, e a informação de sobrepeso ou obesidade materna estava associado a obesidade infantil. As crianças com sobrepeso, obesidade e/ou obesidade abdominal apresentaram niveles mais altos de PA braquial. Conclusões: a prevalência de sobrepeso e obesidade em crianças com 5anos de jardins de infância públicos de Montevidéu é elevada. O sobrepeso e obesidade materna e os hábitos relacionados à alimentação, atividade física e sono, estão associados à sua presença.

A cross-sectional study of urinary cadmium concentrations in relation to dietary intakes in Uruguayan school children.

BACKGROUND: Cadmium (Cd) exposure has adverse health effects in children. Diet contributes to Cd exposure, but dietary components could affect body Cd levels. OBJECTIVE: To examine associations between diet and urinary Cd (U-Cd) in children. METHODS: In this cross-sectional study conducted in Montevideo, Uruguay, Cd exposure of 5-8 year old children (n = 279 with complete data) was assessed in first morning urine (U-Cd), a marker of long-term exposure, measured by ICP-MS and adjusted for specific gravity. Distribution of U-Cd was (median [5%, 95%]: 0.06 [0.02, 0.17] µg/L); data were natural-log-transformed (ln) for statistical analyses. Serum ferritin (SF), an indicator of iron stores, was measured in fasting samples. Trained nutritionists completed two non-consecutive 24-h dietary recalls with both child and caregiver present. Measures of iron, zinc, calcium and fiber intake, and the consumption of grains, root vegetables, milk, and foods rich in heme iron (white and read meats) and non-heme iron (legumes, spinach, broccoli, tomatoes, dried fruit) were derived. Multivariable ordinary least squares (OLS) and ordinal regressions were used to examine associations among tertiles of water Cd, SF, diet, and U-Cd. OLS models were further stratified by sex. RESULTS: In covariate-adjusted models, SF was not related to ln-U-Cd. Children in highest tertile of iron and zinc intake had lower ln-U-Cd: (-0.23 [-0.42, -0.03]) and (-0.25 [-0.44, -0.05]), respectively, compared to the reference group. Children consuming higher amounts of foods rich in heme iron had slightly lower ln-U-Cd (-0.17 [-0.36, 0.03]). High grain consumption was related to higher ln-U-Cd (0.25 [0.06, 0.45]). CONCLUSIONS: Diets rich in grains were related to higher urinary Cd levels among children living in the context of low Cd pollution. Higher intake of iron and zinc was related to lower Cd levels. Given that urinary Cd is mainly a marker of long-term exposure, these findings should be further corroborated.

Association of Low Lead Levels with Behavioral Problems and Executive Function Deficits in Schoolers from Montevideo, Uruguay.

The negative effect of lead exposure on children's intelligence is well-documented. Less is known about the impact of lead on the use of executive functions to self-regulate behavior. We measured blood lead level (BLL) in a sample of first grade children from Montevideo, Uruguay (n = 206, age 6.7 ± 0.5 years, 59.7% boys). Behavior was assessed with teacher versions of the Conners Rating Scale (CRS) and the Behavior Rating Inventory of Executive Functions (BRIEF). Mean BLL was 4.2 ± 2.1 µg/dL; 10% had mild-to-severe ratings of Attentional Deficit with Hyperactivity Disorder (ADHD) (T score > 65). In negative binomial regression, BLL was not associated with CRS sub-scales, but was associated with a poorer ability to inhibit inappropriate behaviors, prevalence ratio (PR) [95% CI]: 1.01 [1.00, 1.03] as measured by the BRIEF. In covariate-adjusted models, the association with BLL was attenuated. When stratified by sex, the covariate-adjusted association between BLL, hyperactivity, poorer inhitibion, emotional control, and behavioral regulation was marginally significant for girls but not boys. In summary, among children with low lead-exposure, we found some, but nonetheless modest, evidence of a relationship between higher BLL and child behavior. If confirmed by larger studies and other objective measures of behavior, such links could have implications for learning and social interaction, particularly among girls.

Drinking water lead, iron and zinc concentrations as predictors of blood lead levels and urinary lead excretion in school children from Montevideo, Uruguay.

The global burden of water-based lead (Pb) exposure on children is largely unknown; however, the importance of water sources as a path of Pb exposure is receiving increased attention due to recent prominent exposure events related to corroded plumbing infrastructure in the US. This study investigated the contribution of Pb in household drinking and cooking water to Pb levels in blood (PbB) and urine (PbU) within 353 early school-aged children from Montevideo, Uruguay. Additionally, the analysis considered the child's iron status and the water content of iron (WFe) and zinc (WZn) in relation to water Pb and blood/urine Pb concentrations. Lead concentrations for both PbB and PbU were fairly low (M ±â€¯SD: 4.2 ±â€¯2.1 µg/dL; Median [5%, 95%]: 1.9 [0.6, 5.1 µg/L, respectively]); however 21% of the sample had a PbB >5 µg/dL but ≤ 10 µg/dL. Overall, there was little evidence of an association between water metal concentrations and children's PbB/PbU. However, when the sample was stratified by children's iron status, WPb was positively related to PbU, but negatively related to PbB in iron-replete children, even after adjusting for WFe and WZn. In iron-deficient children, there was no elevation in PbU with increasing WPb. In this sample of children with low Pb levels, there were no overwhelming relationships between WPb and either PbB or PbU, however, there was some evidence that iron-replete status promotes excretion of WPb.

Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children.

Oxidative stress (OS) is an important consequence of exposure to toxic metals but it is unclear to what extent low-level metal exposures contribute to OS in children. We examined the cross-sectional association between urinary concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers of OS: F2-8α isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also tested effect modification by dietary intakes. Of the 211 children aged 6-8 years living in Montevideo who were eligible for the study because they had at least one OS marker measured via ELISA, 143 were included in a complete-case analysis. Urinary metals were measured with inductively coupled plasma mass spectrometry (ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride generation ICP-MS (As-metabolites); concentrations were log2-transformed. All urinary markers were adjusted for specific gravity of urine. Two 24-h dietary recalls were conducted to estimate children's dietary intakes, including total fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary least square (OLS) and weighted quantile sum (WQS) regressions were used to estimate the association between metals and each OS marker as outcome. Metal exposure was generally low: median urinary As, Cd, Pb 9.6 µg/L, 0.06 µg/L and 1.9 µg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG 39.6 ng/mL. Log2-transformed urinary As concentrations were positively associated with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models which also took account of exposure to Cd and Pb. In WQS, a mixture index was also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in index value), mostly driven by As exposure. There was little evidence of effect modification by dietary antioxidants. In sum, even at low-level, As exposure is associated with detectable oxidative damage to the DNA.

A cross-sectional study of general cognitive abilities among Uruguayan school children with low-level arsenic exposure, potential effect modification by methylation capacity and dietary folate.

BACKGROUND: Few studies have evaluated the association between low-level arsenic (As) exposure and cognitive performance among children. OBJECTIVES: In this cross-sectional study, we assessed the association between low-level As exposure and cognitive performance among 5-8 year-old children in Montevideo, and tested effect modification by As methylation capacity and children's dietary folate intake. METHODS: We measured total urinary As (UAs) concentrations and the proportion of monomethylarsonic acid (MMA) in the urine of 328 children. Seven subtests of the standardized Woodcock-Muñoz cognitive battery were used to assess cognitive performance, from which, the general intellectual abilities (GIA) score was derived. Total folate intake was estimated from two 24-h dietary recalls. Linear regression analyses were performed. Effect modification was assessed by stratifying at the median %MMA value and tertiles of total folate intake calculated as micrograms (µg) of dietary folate equivalents (dfe). RESULTS: The median UAs was 11.9 µg/l (range = 1.4-93.9), mean folate intake was 337.4 (SD = 123.3) µg dfe, and median %MMA was 9.42 (range = 2.6-24.8). There was no association between UAs and cognitive abilities, and no consistent effect modification by %MMA. UAs was associated inversely with concept formation, and positively with cognitive efficiency and numbers reversed subtest in the lowest folate intake tertile; UAs was also positively associated with sound integration in the second tertile and concept formation in the highest tertile of folate intake. There was no consistent pattern of effect modification by %MMA or folate intake. CONCLUSION: There was no association between low-level As exposure and general cognitive abilities.

Nutritional status and diet as predictors of children's lead concentrations in blood and urine.

Lead exposure remains an important public health problem. Contaminated foods may act as a source of lead exposure, while certain nutrients may reduce lead absorption. We examined the cross-sectional associations of dietary patterns and the intake of several nutrients and foods with blood (Pb-B) and urinary (Pb-U) lead concentrations in children (5-8y) from Montevideo, Uruguay. From two 24-hour recalls completed by caregivers, we derived the mean daily intake of select nutrients and food groups (dairy, milk, fruit, root vegetables, foods rich in heme and non-heme iron), as well as "nutrient dense" and "processed" food patterns. Pb-B (n=315) was measured using atomic absorption spectrometry; Pb-U (n=321) using ICP-MS. Pb-U was adjusted for specific gravity and log-transformed to approximate a normal distribution. Iron deficiency (ID) and dietary variables were tested as predictors of Pb-B and log-Pb-U in covariate-adjusted regressions. Median [5%, 95%] Pb-B and Pb-U were 3.8 [0.8-7.8] µg/dL and 1.9 [0.6-5.1] µg/L, respectively; ~25% of Pb-B above current U.S. CDC reference concentration of 5µg/dL. ID was associated with 0.75µg/dL higher Pb-B, compared to non-ID (p<0.05). Consumption of root vegetables was not associated with Pb-B or log-Pb-U. Higher scores on the nutrient-dense pattern were related with higher Pb-Bs, possibly due to consumption of green leafy vegetables. Dietary intake of iron or iron-rich foods was not associated with biomarkers of lead. Conversely, children consuming more calcium, dairy, milk and yogurt had lower Pb-B and log-Pb-U. Our findings appear consistent with existing recommendations on including calcium-rich, but not iron- or vitamin-C-rich foods in the diets of lead-exposed children, especially where the consumption of these foods is low.

Low-level arsenic exposure: Nutritional and dietary predictors in first-grade Uruguayan children.

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9µg/L) and household water (water As: median 0.45µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity.

Association of blood lead levels with urinary F2-8α isoprostane and 8-hydroxy-2-deoxy-guanosine concentrations in first-grade Uruguayan children.

Oxidative stress (OS) is a potential molecular mechanism for lead-induced toxicities, yet, we have limited understanding of the relation between low-level lead (Pb) exposure and OS, especially in children. This cross-sectional study examines the association between blood lead level (BLL) and two OS markers-urinary F2-8α isoprostane or isoprostane (a marker of lipid peroxidation) and 8-hydroxy-2-deoxy-Guanosine or 8-OH-dG (a marker of DNA damage) in 211 children, aged 5-8 years, from Montevideo, Uruguay. The role of dietary intakes of vitamin C and zinc in modifying the relation between BLL and OS was also examined. The mean (SD) BLL of the study children was 4.7 (2.2) µg/dL, with 30.2% children having BLL ≥5 µg/dL, the current reference level set by the US Centre for Disease Control for identifying, monitoring and management of children with elevated BLL. In covariate-adjusted analysis, there was a weak positive association between BLL and urinary isoprostane (adjusted for specific gravity) [ß=0.09, p<0.1]. No association was found between children's BLL and urinary 8-OH-dG. Interactions between dietary intakes of vitamin C or zinc and BLL on OS biomarkers were not consistent. However, when BLL and vitamin C or BLL and zinc were modeled together, BLL was independently associated with isoprostane concentration [ß=0.10, p<0.05] but vitamin C or zinc intake was not. These findings suggest that there may be a potential adverse effect of BLL on OS in children with low-level Pb exposure. There is a need to study the effects of Pb on other OS measures, as well as the role of OS in mediating low-level Pb toxicity on functional outcomes.