Polycyclic aromatic hydrocarbons in silicone wristbands of Uruguayan children: measurement and exposure source exploration.

Polycyclic aromatic hydrocarbons (PAHs) pose health risks to children, potentially resulting in stunted growth, obesity, and cognitive deficits, but lack of reliable and noninvasive means to measure PAHs results in poor understanding of exposure patterns and sources in this vulnerable population. In this study, 24 children aged ∼7 years (9 boys and 15 girls) from Montevideo, Uruguay wore silicone wristbands for 8 days to monitor the exposure of 27 PAHs. Wristbands were extracted using a modified ethyl acetate tandem solid phase extraction clean up and then analyzed via gas chromatography with tandem mass spectrometry. This analysis has reported LODs for 27 PAHs between 0.05 and 3.91 µg L-1. Eighteen PAHs were detected in >50% of the samples with concentration medians ranging 1.2-16.3 ng g-1 of wristband. Low molecular weight PAHs (2-3 rings) such as naphthalene and its alkyl derivatives were highly correlated (0.7-0.9) in the wristbands, suggesting exposure from related sources. Exposure source exploration focused on secondhand tobacco smoke, potentially through caregivers who reported on smoking habits in an associated survey. A principal components analysis (PCA) was conducted to examine patterns in PAH compounds detected in the wristbands; subsequently, the resulting components were compared according to current smoking among caregivers. The PCA analysis revealed a grouping of participants based on higher exposure of 1-methyl naphthalene, pyrene, fluoranthene, 1-methylphenanthrene, dibenzothiophene and 2-phenyl naphthalene. The derived components did relate with parental smoking, suggesting that some participants experienced exposure to a common source of certain PAHs outside of parental smoking. This is the first study to assess PAH exposure in young children from South America. Using wristbands, our study indicates exposure to multiple, potentially harmful chemicals. Wristbands could provide a comprehensive picture of PAH exposure in children, complementing other non-invasive biomonitoring approaches.

Temperature stability of urinary F2-isoprostane and 8-hydroxy-2'-deoxyguanosine.

Background: Clinical and epidemiological studies employ long-term temperature storage but the effect of temperature on the stability of oxidative stress (OS) markers is unknown. We investigated the effects of storage at -20 °C and -80 °C over 4-9 months on F2-isoprostanes (F2-IsoP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in urine of children, a population group among whom the measurement of these markers is still limited. Methods: Paired spot urine samples from 87 children aged 8.9-16.9 years (52.9% boys) were analyzed. Samples were preserved with 0.005% (w/v) butylated hydroxytoluene, portioned and stored within 2.5 h (median) of collection. Samples were analyzed in duplicate or triplicate using commercial ELISA kits and their correlations were evaluated. Results: F2-IsoP and 8-OHdG showed high correlations (Spearman rho of 0.90 and 0.97, respectively; P < 0.0001) with storage at -20 °C and -80 °C. There was a strong agreement among categories of values for F2-IsoP (Kappa = 0.76 ± 0.08, agreement = 83.9%, P < 0.0001) and 8-OHdG: (Kappa = 0.83 ± 0.08, agreement = 88.4%, P < 0.0001). The correlation between the temperatures for F2-IsoP concentrations was also high when stored for <4 (0.93), 4 (0.93), and 5 months (0.88), all P < 0.0001. For 8-OHdG, Spearman correlations at <8, 8, and 9 months of storage at -20 °C and -80 °C were 0.95, 0.98, and 0.96 (all P < 0.0001), respectively. Conclusions: Urine storage with BHT for up to nine months at a temperature of -20 °C to -80 °C yields highly comparable concentrations of F2-IsoP and 8-OHdG.

Blood lead levels and math learning in first year of school: An association for concern.

Lead is a well-known neurotoxicant that continues to affect children's cognition and behavior. With the aim to examine the associations of lead exposure with math performance in children at the beginning of formal schooling, we conducted a cross-sectional study of first-grade students from 11 schools in Montevideo, Uruguay. Math abilities were assessed with tests from the Batería III Woodcock-Muñoz (Calculation, Math Facts Fluency, Applied Problems, Math Calculation Skills and Broad Maths). Separate generalized linear models (GLM) tested the association of blood lead level (BLL) and each math ability, adjusting for key covariates including age and sex, maternal education, household assets and Home Observation for Measurement of the Environment Inventory score. In a complete-case of 252 first-grade students (age 67-105 months, 45% girls), mean ± SD blood lead level was 4.0 ± 2.2 µg/dL. Covariate-adjusted logistic models were used to examine the association between childhood BLLs and the odds of low math performance. BLL was negatively associated with scores on the Calculation test (ß (95% CI): -0.18 (-0.33, -0.03)), Math Calculation Skills (-1.26 (-2.26, -0.25)), and Broad Maths cluster scores (-0.88 (-1.55, -0.21)). Similarly, performance on the Calculation test, as well as cluster scores for Broad Maths and Math Calculation Skills differed between children with BLLs <5 and ≥ 5 µg/dL (p < 0.01), being lower in children with higher BLLs. Finally, considering the likelihood of low test performance, each 1 µg/dL higher B-Pb was related to 27% higher likelihood for Maths Facts Fluency, 30% for Broad Math and Math Calculation Skills, and 31% for Calculation (p < 0.05). These results suggest that lead exposure is negatively associated with several basic skills that are key to math learning. These findings further suggest that the cognitive deficits related to lead exposure impact student achievement at very early stages of formal education.

Secular trends in blood lead concentrations of school-age children in Montevideo, Uruguay from 2009 to 2019.

Lead exposure continues to be a public health problem globally, yet very few countries perform systematic biomonitoring or surveillance of children's blood lead levels (BLLs). Secular trends in children's BLLs have not been well characterized outside North America and Europe. In 2009-19, we conducted a series of non-representative cross-sectional surveys in Montevideo, Uruguay, enrolling children living in areas of the city with known or suspected lead contamination. Lead was measured with atomic absorption spectrometry on fasting venous blood samples. Of the 856 children representing independent (non-sibling) observations, 759 had BLL measures. Other missing data were imputed. Using linear and logistic regression models, we estimated the covariate-adjusted year to year difference in mean BLL and the likelihood of having BLL ≥5 and BLL ≥3.5 µg/dL. At the start of the study, mean ± SD BLL was 4.8 ± 2.6 µg/dL, and at the end 1.4 ± 1.4 µg/dL. The prevalence of BLL ≥5 and BLL ≥3.5 µg/dL also differed markedly between 2009 and 2019 (30.8% vs. 2.7% and 53.8% vs. 5.8%). Similarly, where 80.8% of children had BLL ≥2 µg/dL in 2011, in 2019 that number was 19.3%. The estimated year to year difference in BLL was ∼0.3 µg/dL. Despite this progress, pediatric lead exposure remains a problem in Montevideo. In years 2015-19, between 19 and 48% of school children had BLL ≥2 µg/dL, a level at which adverse neurobehavioral outcomes continue to be reported in the literature. Continued prevention and risk-reduction efforts are needed in Montevideo, including systematic surveillance of BLLs in all children.

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.

Pyrethroid and Chlorpyrifos Pesticide Exposure, General Intellectual Abilities, and Executive Functions of School Children from Montevideo, Uruguay.

Children's developing brains are susceptible to pesticides. Less is known about the effect of exposure to chlorpyrifos and pyrethroids on executive functions (EF). We measured urinary 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos, and urinary 3-phenoxybenzoic acid (3-PBA), a general, nonspecific metabolite of pyrethroids in first-grade children from Montevideo, Uruguay (n = 241, age 80.6 ± 6.4 months, 58.1% boys). EFs were assessed with the Intra-dimensional/Extra-dimensional shift (IED), Spatial Span (SSP), and Stockings of Cambridge (SOC) tests from the Cambridge Neuropsychological Test Automated (CANTAB) Battery. General intellectual ability (GIA) was assessed using the Woodcock-Muñoz Cognitive battery. Median (range) urinary TCPy and 3-PBA levels were 16.7 (1.9, 356.9) ng/mg of creatinine and 3.3 (0.3, 110.6) ng/mg of creatinine, respectively. In multivariable generalized linear models, urinary TCPy was inversely associated with postdimensional errors on the IED task ß [95% CI]: -0.11 [-0.17, -0.06]. Urinary 3-PBA was inversely associated with the total number of trials -0.07 [-0.10, -0.04], and the total number of errors -0.12 [-0.18, -0.07] on the IED task. When TCPy and 3-PBA were modeled together, the associations did not differ from single-metabolite models. We found no evidence of effect modification by blood lead level (BLL). Pesticide exposure may affect EF performance in urban children.

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.

A Call for Biomonitoring Systems in Latin America and the Caribbean: Considerations for Potentially Toxic Metals/Metalloids.

The Latin America and the Caribbean (LAC) region makes up 8.4% of the world's population. Human biomonitoring (HBM) programs, which can shed light on population-level exposure to environmental contaminants such as toxic metals and thus, improve the health of the populations are inexistent in LAC countries. We call for the creation of HBM programs in the region and identify three viable design options for HBM at the individual level, through national surveys, newborn blood collection, and biobanks. We highlight some of challenges to the implementation of HBM programs, including financial and human resources, technical constrains (laboratory), sample, and data logistics. Finally, we provide the case studies of Brazil, Chile, Mexico, and Uruguay, to illustrate a range of responses to toxic metal exposure in non-occupational populations. Although different in many respects, the individual country responses share two commonalities: 1) academic centers drive the research to raise awareness of governmental entities; 2) reference levels are adapted from international norms rather than arising from the studied populations. Well-designed and sufficiently funded biomonitoring systems need to be established in each country of the LAC region. HBM programs are key to promoting human health by informing the public and contributing to policy processes that establish sustainable environmental controls and health prevention programs.

Do Neighborhood Factors Modify the Effects of Lead Exposure on Child Behavior?

Lead exposure and neighborhoods can affect children's behavior, but it is unclear if neighborhood characteristics modify the effects of lead on behavior. Understanding these modifications has important intervention implications. Blood lead levels (BLLs) in children (~7 years) from Montevideo, Uruguay, were categorized at 2 µg/dL. Teachers completed two behavior rating scales (n = 455). At one-year follow-up (n = 380), caregivers reported child tantrums and parenting conflicts. Multilevel generalized linear models tested associations between BLLs and behavior, with neighborhood disadvantage, normalized difference vegetation index (NDVI), and distance to nearest greenspace as effect modifiers. No effect modification was noted for neighborhood disadvantage or NDVI. Children living nearest to greenspace with BLLs < 2 µg/dL were lower on behavior problem scales compared to children with BLLs ≥ 2 µg/dL. When furthest from greenspace, children were similar on behavior problems regardless of BLL. The probability of daily tantrums and conflicts was ~20% among children with BLLs < 2 µg/dL compared to ~45% among children with BLLs ≥ 2 µg/dL when closest to greenspace. Furthest from greenspace, BLLs were not associated with tantrums and conflicts. Effect modification of BLL on child behavior by distance to greenspace suggests that interventions should consider both greenspace access and lead exposure prevention.

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.

A mixed methods study examining neighborhood disadvantage and childhood behavior problems in Montevideo, Uruguay.

BACKGROUND: Neighborhood disadvantage (ND) is a risk factor for child behavior problems (CBPs), but is understudied outside the United States and Europe. Our mixed methods study aims to (1) create a culturally meaningful measure of ND, (2) test cross-sectional associations between ND and CBPs and (3) qualitatively explore life in the neighborhoods of families participating in the Salud Ambiental Montevideo (SAM) study. METHODS: The quantitative study (Study 1) comprised 272, ~7-year-old children with geolocation and complete data on twelve behavioral outcomes (Conner's Teachers Rating Scale - Revised Short Form: CTRS-R:S and Behavioral Rating Inventory of Executive Functioning: BRIEF). A ND factor was created at the census segment level (1,055 segments) with 19 potential indicators of ND downloaded from the Municipality of Montevideo Geographic Services. Children were assigned ND scores based on the location of their household within a census segment. Multilevel models tested associations between ND and all CBP scales, controlling for confounders at the individual level. The qualitative study (Study 2) comprised 10 SAM caregivers. Photovoice alongside semi-structured interviews in Spanish were used to foster conversations about neighborhood quality, activities, and raising children. Thematic analysis with inductive coding was used to summarize qualitative study findings. RESULTS: The ND factor consisted of 12 census-based indicators related to education, employment, ethnicity, housing quality, and age characteristics, but unrelated to home ownership and some ethnicity variables. In multivariable models, ND was associated with greater conduct problems (ß = 1.37, p < .05), poor shifting (ß = 1.56, p < .01) and emotional control problems (ß = 2.36, p < .001). Photovoice and semi-structured interviews yielded four themes: physical disorder, recreation, safety and crime, and community resources. Residents discussed improving waste management and transportation, updating playgrounds, and ensuring neighborhood safety. CONCLUSIONS: ND in Montevideo comprised a unique set of census indicators. ND was primarily related to behavioral regulation problems. Hypothesized pathways whereby ND affects CBPs are discussed.

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.

Catching flame retardants and pesticides in silicone wristbands: Evidence of exposure to current and legacy pollutants in Uruguayan children.

Children are exposed to many potentially toxic compounds in their daily lives and are vulnerable to the harmful effects. To date, very few non-invasive methods are available to quantify children's exposure to environmental chemicals. Due to their ease of implementation, silicone wristbands have emerged as passive samplers to study personal environmental exposures and have the potential to greatly increase our knowledge of chemical exposures in vulnerable population groups. Nevertheless, there is a limited number of studies monitoring children's exposures via silicone wristbands. In this study, we implemented this sampling technique in ongoing research activities in Montevideo, Uruguay which aim to monitor chemical exposures in a cohort of elementary school children. The silicone wristbands were worn by 24 children for 7 days; they were quantitatively analyzed using gas chromatography with tandem mass spectrometry for 45 chemical pollutants, including polychlorinated biphenyls (PCBs), pesticides, polybrominated diphenyl ethers (PBDEs), organophosphorus flame retardants (OPFRs), and novel halogenated flame-retardant chemicals (NHFRs). All classes of chemicals, except NHFRs, were identified in the passive samplers. The average number of analytes detected in each wristband was 13 ±3. OPFRs were consistently the most abundant class of analytes detected. Median concentrations of ΣOPFRs, ΣPBDEs, ΣPCBs, and dichlorodiphenyltrichloroethane (DDT) and its metabolites (dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD)) were 1020, 3.00, 0.52 and 3.79 ng/g wristband, respectively. Two major findings result from this research; differences in trends of two OPFRs (TCPP and TDCPP) are observed between studies in Uruguay and the United States, and the detection of DDT, a chemical banned in several countries, suggests that children's exposure profiles in these settings may differ from other parts of the world. This was the first study to examine children's exposome in South America using silicone wristbands and clearly points to a need for further studies.

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.

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.