Predicting blood lead in uruguayan children: Individual- vs neighborhood-level ensemble learners.

Predicting childhood blood lead levels (BLLs) has had mixed success, and it is unclear if individual- or neighborhood-level variables are most predictive. An ensemble machine learning (ML) approach to identify the most relevant predictors of BLL ≥2µg/dL in urban children was implemented. A cross-sectional sample of 603 children (~7 years of age) recruited between 2009-2019 from Montevideo, Uruguay participated in the study. 77 individual- and 32 neighborhood-level variables were used to predict BLLs ≥2µg/dL. Three ensemble learners were created: one with individual-level predictors (Ensemble-I), one with neighborhood-level predictors (Ensemble-N), and one with both (Ensemble-All). Each ensemble learner comprised four base classifiers with 50% training, 25% validation, and 25% test datasets. Predictive performance of the three ensemble models was compared using area under the curve (AUC) for the receiver operating characteristic (ROC), precision, sensitivity, and specificity on the test dataset. Ensemble-I (AUC: 0.75, precision: 0.56, sensitivity: 0.79, specificity: 0.65) performed similarly to Ensemble-All (AUC: 0.75, precision: 0.63, sensitivity: 0.79, specificity: 0.69). Ensemble-N (AUC: 0.51, precision: 0.0, sensitivity: 0.0, specificity: 0.50) severely underperformed. Year of enrollment was most important in Ensemble-I and Ensemble-All, followed by household water Pb. Three neighborhood-level variables were among the top 10 important predictors in Ensemble-All (density of bus routes, dwellings with stream/other water source and distance to nearest river). The individual-level only model performed best, although precision was improved when both neighborhood and individual-level variables were included. Future predictive models of lead exposure should consider proximal predictors (i.e., household characteristics).

Companion animals and child development outcomes: longitudinal and cross-sectional analysis of a UK birth cohort study.

BACKGROUND: Research into the impact of social relationships on childhood and adolescent health and wellbeing has been largely limited to children's relationships with other humans, while studies into the impact of pet ownership are sparse and have generally not adjusted for potential confounders. This study aimed to investigate the association between pet ownership and a range of developmental outcomes in childhood and adolescence. METHODS: Data were self-reports and direct assessments of approx. 14,000 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable regression models adjusting for confounding factors examined associations between developmental outcome measures (emotional health, behavioural development, cognitive development, language development, educational attainment) and concurrent pet ownership, including species, and also longitudinal pet ownership history and pet-interaction where possible. Analyses model numbers using multiple imputation varied from n = 393-8963. RESULTS: In cross-sectional analyses, owning a dog (b = 0.24, [0.06-0.41], p = .004) and owning other/miscellaneous pets (b = 0.18, [0.03-0.33], p = .021) at age 3 were associated with higher prosocial behaviour score. Owning a pet was associated with a higher non-verbal communication score at age 2 (cross-sectional, b = 0.18, [0.04-0.32], p = .014), and a higher language development score at age 5 (cross-sectional, b = 1.01, [0.18-1.83], p = .017). However, pet ownership was associated with lower educational attainment across a number of academic subjects and timepoints, in both cross-sectional and longitudinal analyses. It was also cross-sectionally linked to hyperactivity at age 3 and conduct problems at age 3 and 11. Furthermore, at age 8, cross-sectional analysis showed that children who owned any pets (OR [95% CI]: 0.85 [0.73-0.98], p= ·026) or cats (0.83, [0.73-0.95], p= ·006) had lower odds of high self-esteem (scholastic competence). CONCLUSIONS: Using a large, well-designed longitudinal study and adjusting for key confounders, we found little evidence of cross-sectional or longitudinal associations between pet ownership and emotional health or cognitive outcomes in children. There may, however, be some cross-sectional and longitudinal association with poorer educational attainment and a positive impact on social interactions as seen through associations with enhanced language development and prosocial behaviour. This study demonstrates the importance of adjustment for confounding variables and suggests that, contrary to popular belief, positive impacts of pet ownership on childhood development may be mainly limited to social behaviour and language development.

Diet quality and blood lead levels in Uruguayan first graders.

OBJECTIVE: Foods are a potential source of lead but also contain nutrients that counteract the intestinal absorption of lead. Translatable evidence is needed to better understand the relationship between whole diets and blood lead levels (BLLs) in children. In this cross-sectional study we investigated the association between dietary variety, adequacy, moderation, and overall diet quality with children's BLLs. METHODS: First graders (~ 7 years) from Montevideo, Uruguay were evaluated in years 2009-13 (Phase I, n = 303) and 2015-19 (Phase II, n = 443). Lead was measured in fasting blood via atomic absorption spectrometry and primary caregivers completed two non-consecutive 24-h recalls. Indices of dietary variety (maximum score of 20), adequacy (maximum 40), moderation (maximum 30), and overall diet quality were calculated from food and nutrient intakes averaged over two recall days. The indices were adapted from the Diet Quality Index-International based on dietary recommendations for children. Missing covariate data were imputed. The associations between diet quality measures and BLLs were modeled separately in Phase I and II with multivariable linear models, testing for sex differences via interaction terms and stratified models. RESULTS: The median[IQR] BLLs were 3.8[2.6, 4.9] and 1.3[0.7, 3.6] µg/dL in study Phases I and II, respectively. All diet quality scores were <60 % of the maximum values and daily intakes of key food groups fell below recommended levels. There was little evidence of an association between measures of diet quality and children's BLLs overall. On the other hand, higher diet variety, adequacy, and overall diet quality were associated with slightly higher BLLs among girls in Phase I only. CONCLUSIONS: In the context of low lead exposure and food consumption patterns that fall short of recommended levels, the relation of diet quality to children's BLLs may depend on lead exposure levels.

The mediating role of air pollutants in the association between education and lung function among the elderly, the HAPIEE study.

BACKGROUND: Chronic exposure to air pollutants harms human health, and at a geographical level, concentrations of air pollutants are often associated with socioeconomic disadvantage. OBJECTIVES: The aim of this study was to investigate the effects of educational attainment and air pollution on lung function in older adults, and whether air pollution may mediate the effect of education. METHODS: The study included 6381 individuals (mean age 58.24 ± 7.14 years) who participated in the Czech HAPPIE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) study. Participants' residential addresses were linked to air pollution data, including mean exposures to PM10 (particulate matter of aerodynamic diameter below 10 µm) and NO2 (nitrogen dioxide). We used path analysis to link educational attainment and air pollutants to a standardized measure of the Forced Expiratory Volume in the first second (FEV1). RESULTS: Higher levels of participants' education were associated with lower exposures to PM10 and NO2. Individuals with tertiary education had higher standardized FEV1 than individuals with primary education (88 % vs 95 %). Path analysis revealed a direct positive effect of education on FEV1, while about 12 % of the relationship between education and lung function was mediated by PM10 and NO2. CONCLUSIONS: Education (typically completed at young ages) appeared to have a protective effect on lung function later in life, and a small part of this effect was mediated by air pollution.

Association between breakfast skipping and blood levels of lead and cadmium in children and adolescents aged 6-17 years: Results from the National Health and Nutrition Examination Survey 2013-2018.

INTRODUCTION: Previous research suggests that fasting increases lead absorption in the gastrointestinal tract, and that regularly eating meals may reduce blood lead. However, there is insufficient evidence linking breakfast status and blood-metal levels in children. We assessed the cross-sectional association between breakfast consumption status and children and adolescent's blood levels of lead and cadmium. We also explored blood hemoglobin, serum ferritin, and age group as potential effect modifiers of these associations. METHODS: This analysis included children and adolescents aged 6-17 years who participated in the National Health and Nutrition Examination Survey (NHANES) cycles 2013-2018 with complete data on breakfast consumption status (consumers vs. skippers), blood metals, and covariates (N=3722). Blood metal variables were log-transformed. Crude and covariate-adjusted, survey-weighted linear regression models were conducted for each blood metal outcome. Potential effect modification was explored using stratification. RESULTS: Overall fewer participants reported skipping breakfast (n=719) than eating breakfast (n=3003). Mean (SE) concentrations of blood lead and cadmium (µg/L) were 0.63 (0.01) µg/dL and 0.13 (0.00) µg/L, respectively. Children and adolescents who skipped breakfast were more likely to be female (51.2%), older (mean 12.2 years, SE = 0.1), have a higher body mass index (mean 22.8 kg/m2, SE = 0.2), and a lower income-poverty ratio (mean 1.7, SE = 0.1) than breakfast consumers. No associations between breakfast consumption and any of the blood metals were found. When stratified by age (≤ 10, 11-13, and 14-17 years), children aged 11-13 years who consumed breakfast had lower log-transformed blood lead levels [ß = -0.14 µg/L; 95% CI: (-0.25, -0.03)] compared to children of the same age who skipped breakfast. CONCLUSION: Children 11-13 years-old who were breakfast consumers had lower blood lead levels compared to children of the same age who skipped breakfast. Our results support that encouraging breakfast consumption among school-age children may contribute to lower blood lead levels.

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.

Heavy Metal Remediation by Dry Mycelium Membranes: Approaches to Sustainable Lead Remediation in Water.

Lead contamination poses significant and lasting health risks, particularly in children. This study explores the efficacy of dried mycelium membranes, distinct from live fungal biomass, for the remediation of lead (Pb(II)) in water. Dried mycelium offers unique advantages, including environmental resilience, ease of handling, biodegradability, and mechanical reliability. The study explores Pb(II) removal mechanisms through sorption and mineralization by dried mycelium hyphae in aqueous solutions. The sorption isotherm studies reveal a high Pb(II) removal efficiency, exceeding 95% for concentrations below 1000 ppm and ∼63% above 1500 ppm, primarily driven by electrostatic interactions. The measured infrared peak shifts and the pseudo-second-order kinetics for sorption suggests a correlation between sorption capacity and the density of interacting functional groups. The study also explores novel surface functionalization of the mycelium network with phosphate to enhance Pb(II) removal, which enables remediation efficiencies >95% for concentrations above 1500 ppm. Scanning electron microscopy images show a pH-dependent formation of Pb-based crystals uniformly deposited throughout the entire mycelium network. Continuous cross-flow filtration tests employing a dried mycelium membrane demonstrate its efficacy as a microporous membrane for Pb(II) removal, reaching remediation efficiency of 85-90% at the highest Pb(II) concentrations. These findings suggest that dried mycelium membranes can be a viable alternative to synthetic membranes in heavy metal remediation, with potential environmental and water treatment applications.

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.

An Industry-Relevant Metal Mixture, Iron Status, and Reported Attention-Related Behaviors in Italian Adolescents.

BACKGROUND: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10-14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale-Long Form, Parent Rating Scales Revised-Short Form, and Teacher Rating Scales Revised-Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [ß=0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (ß=0.04; 95% CrI: 0.00, 0.08), and 4.1% (ß=0.04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. https://doi.org/10.1289/EHP12988.

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.

Dietary Predictors of Urinary Biomarkers of Pyrethroids in the General Population - A Scoping Review.

BACKGROUND: Pyrethroid pesticides are ubiquitous environmental contaminants, contributing to chronic and potentially harmful exposure among the general population. Although studies have measured pesticide residues on agricultural products, the link between food intake and concentrations of pyrethroid biomarkers in urine remains unclear. OBJECTIVE: This scoping review aims to analyze peer-reviewed publications investigating dietary predictors of pyrethroid exposure through urinary biomarkers. We assess existing evidence, identify research gaps, and highlight current limitations. METHODS: We conducted a comprehensive search using PubMed and Google Scholar. Eligible studies examined associations between diets, food items or dietary components, and measured urinary pyrethroid biomarkers. No geographical restriction was applied to our search. Results were summarized in themes referring to study characteristics, relevant outcomes, biomarker measurement, dietary assessment and statistical analyses. RESULTS: We identified 20 relevant articles. Most studies presented evidence on associations between the consumption of organic diets or food items and reduced concentrations of 3-phenobenzoic acid metabolites in urine. There was less evidence for diet affecting other pyrethroid-specific biomarkers. Dietary assessment methodologies and recall periods varied, as did the number and timing of urine collections. Many studies did not control for potential alternative pyrethroid sources, exposure to other pesticides, or demographic and socioeconomic characteristics. CONCLUSION: Researchers should consider standardized dietary assessment, chemical analyses of foods consumed, adequate recall time, and food preparation methods. Consistency in biomarker measurement, including urine collection time and corrections for specific gravity or creatinine, is needed. Ensuring the validity of such studies also requires larger samples and appropriate control for confounders.

Air Pollution and Chronic Eye Disease in Adults: A Scoping Review.

PURPOSE: We conducted a scoping review of studies examining ambient air pollution as a risk factor for chronic eye disease influencing the lens, retina, and intraocular pressure in adults. METHODS: Terms related to air pollution and eye disease outcomes were used to search for publications on Embase, Web of Science Core Collection, Global Health, PubMed, and the Cochrane Central Register of Controlled Trials from January 1, 2010, through April 11, 2022. RESULTS: We identified 27 articles, focusing on the following non-mutually exclusive outcomes: cataract (n = 9), presbyopia (n = 1), retinal vein occlusion or central retinal arteriolar and venular equivalents (n = 5), intraocular pressure (IOP) (n = 3), glaucoma (n = 5), age-related macular degeneration (AMD) (n = 5), diabetic retinopathy (n = 2), and measures of retinal morphology (n = 3). Study designs included cross-sectional (n = 16), case-control (n = 4), and longitudinal (n = 7). Air pollutants were measured in 50% and 95% of the studies on lens and retina or IOP, respectively, and these exposures were assigned to geographic locations. Most research was conducted in global regions with high exposure to air pollution. Consistent associations suggested a possibly increased risk of cataract and retina-associated chronic eye disease with increasing exposure to particulate matter (PM2.5-PM10), NO2, NOx, and SO2. Associations with O3 were less consistent. CONCLUSIONS: Accumulating research suggests air pollution may be a modifiable risk factor for chronic eye diseases of the lens and retina. The number of studies on each specific lens- or retina-related outcome is limited. Guidelines regarding the role of air pollution in chronic eye disease do not exist.

Assessing the mediating role of iron status on associations between an industry-relevant metal mixture and verbal learning and memory in Italian adolescents.

BACKGROUND: Metals, including lead (Pb), manganese (Mn), chromium (Cr) and copper (Cu), have been associated with neurodevelopment; iron (Fe) plays a role in the metabolism and neurotoxicity of metals, suggesting Fe may mediate metal-neurodevelopment associations. However, no study to date has examined Fe as a mediator of the association between metal mixtures and neurodevelopment. OBJECTIVE: We assessed Fe status as a mediator of a mixture of Pb, Mn, Cr and Cu in relation to verbal learning and memory in a cohort of Italian adolescents. METHODS: We used cross-sectional data from 383 adolescents (10-14 years) in the Public Health Impact of Metals Exposure Study. Metals were quantified in blood (Pb) or hair (Mn, Cr, Cu) using ICP-MS, and three markers of Fe status (blood hemoglobin, serum ferritin and transferrin) were quantified using luminescence assays or immunoassays. Verbal learning and memory were assessed using the California Verbal Learning Test for Children (CVLT-C). We used Bayesian Kernel Machine Regression Causal Mediation Analysis to estimate four mediation effects: the natural direct effect (NDE), natural indirect effect (NIE), controlled direct effect (CDE) and total effect (TE). Beta (ß) coefficients and 95 % credible intervals (CIs) were estimated for all effects. RESULTS: The metal mixture was jointly associated with a greater number of words recalled on the CVLT-C, but these associations were not mediated by Fe status. For example, when ferritin was considered as the mediator, the NIE for long delay free recall was null (ß = 0.00; 95 % CI = -0.22, 0.23). Conversely, the NDE (ß = 0.23; 95 % CI = 0.01, 0.44) indicated a beneficial association of the mixture with recall that operated independently of Fe status. CONCLUSION: An industry-relevant metal mixture was associated with learning and memory, but there was no evidence of mediation by Fe status. Further studies in populations with Fe deficiency and greater variation in metal exposure are warranted.

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.

Neighborhood disadvantage and adolescent behavior problems: how do inferences differ across definitions of disadvantage?

BACKGROUND: Various definitions of neighborhood disadvantage (ND) exist, yet evidence is lacking on how ND operationalization may impact scientific inference. METHODS: We used data from wave 6 of the Fragile Families study, excluding those without census tract or behavior problem data (n = 2363). Outcomes included five scales from the caregiver-reported Child Behavior Checklist (CBCL) and a self-reported delinquency scale. ND was defined in four ways: (1) a modified Sampson definition which included four neighborhood poverty variables; (2) a poverty-only definition which only included percent households below poverty; (3) an overextended definition which added a mediator between the ND-behavior relationship, and (4) an expanded definition which added six additional ND variables to the modified Sampson definition. Using effect estimates from generalized linear models, differences were calculated using percent change-in-estimate, with the modified Sampson as the referent. RESULTS: Effect estimates were similar for the modified Sampson and expanded definitions (< 5% difference). The poverty-only definition differed from the modified Sampson unsystematically. Estimates for the overextended definition were consistently larger compared to modified Sampson (10-37% greater). The expanded and modified Sampson definitions produced similar results. CONCLUSION: Poverty-only and overextended ND definitions should be interpreted with caution.

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.

Predicting Low-Level Childhood Lead Exposure in Metro Atlanta Using Ensemble Machine Learning of High-Resolution Raster Cells.

Low-level lead exposure in children is a major public health issue. Higher-resolution spatial targeting would significantly improve county and state-wide policies and programs for lead exposure prevention that generally intervene across large geographic areas. We use stack-ensemble machine learning, including an elastic net generalized linear model, gradient-boosted machine, and deep neural network, to predict the number of children with venous blood lead levels (BLLs) ≥2 to <5 µg/dL and ≥5 µg/dL in ~1 km2 raster cells in the metro Atlanta region using a sample of 92,792 children ≤5 years old screened between 2010 and 2018. Permutation-based predictor importance and partial dependence plots were used for interpretation. Maps of predicted vs. observed values were generated to compare model performance. According to the EPA Toxic Release Inventory for air-based toxic release facility density, the percentage of the population below the poverty threshold, crime, and road network density was positively associated with the number of children with low-level lead exposure, whereas the percentage of the white population was inversely associated. While predictions generally matched observed values, cells with high counts of lead exposure were underestimated. High-resolution geographic prediction of lead-exposed children using ensemble machine learning is a promising approach to enhance lead prevention efforts.

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.

Associations of an industry-relevant metal mixture with verbal learning and memory in Italian adolescents: The modifying role of iron status.

BACKGROUND: Biomarker concentrations of metals are associated with neurodevelopment, and these associations may be modified by nutritional status (e.g., iron deficiency). No prior study on associations of metal mixtures with neurodevelopment has assessed effect modification by iron status. OBJECTIVES: We aimed to quantify associations of an industry-relevant metal mixture with verbal learning and memory among adolescents, and to investigate the modifying role of iron status on those associations. METHODS: We used cross-sectional data from 383 Italian adolescents (10-14 years) living in proximity to ferroalloy industry. Verbal learning and memory was assessed using the California Verbal Learning Test for Children (CVLT-C), and metals were quantified in hair (manganese, copper, chromium) or blood (lead) using inductively coupled plasma mass spectrometry. Serum ferritin, a proxy for iron status, was measured using immunoassays. Covariate-adjusted associations of the metal mixture with CVLT subtests were estimated using Bayesian Kernel Machine Regression, and modification of the mixture associations by ferritin was examined. RESULTS: Compared to the 50th percentile of the metal mixture, the 90th percentile was associated with a 0.12 standard deviation [SD] (95% CI = -0.27, 0.50), 0.16 SD (95% CI = -0.11, 0.44), and 0.11 SD (95% CI = -0.20, 0.43) increase in the number of words recalled for trial 5, long delay free, and long delay cued recall, respectively. For an increase from its 25th to 75th percentiles, copper was beneficially associated the recall trials when other metals were fixed at their 50th percentiles (for example, trial 5 recall: ß = 0.31, 95% CI = 0.14, 0.48). The association between copper and trial 5 recall was stronger at the 75th percentile of ferritin, compared to the 25th or 50th percentiles. CONCLUSIONS: In this metal mixture, copper was beneficially associated with neurodevelopment, which was more apparent at higher ferritin concentrations. These findings suggest that metal associations with neurodevelopment may depend on iron status, which has important public health implications.