Systematic review and meta-analysis of arsenic concentration in drinking water sources of Iran.

Recent studies have found arsenic contamination of drinking water in some parts of Iran, as in many other countries. Thus, a comprehensive systematic review is necessary to assess the distribution and concentration of arsenic in drinking water sources. For this purpose, articles published from the first identification until December 2023, were retrieved from various national and international databases. Of all the studies examined (11,726), 137 articles were selected for review based on their conceptual relationship to this survey. A review of the extracted studies presented that ICP methods (ICP-MS, ICP-OES, 56%) and atomic absorption spectrophotometry (AAS, 34.1%) were the two most commonly used techniques for the analysis of arsenic in water samples. The order of arsenic content in the defined study areas is descending, as follows: northwest ˃ southeast ˃ southwest ˃ northeast. A review of studies performed in Iran depicted that provinces such as Kurdistan, Azerbaijan, and Kerman have the highest arsenic concentrations in water resources. Accordingly, the maximum concentration of arsenic was reported in Rayen, Kerman, and ranged from < 0.5-25,000 µg/L. The primary cause of elevated arsenic levels in water resources appears to be geologic structure, including volcanic activity, biogeochemical processes, sulfur-bearing volcanic rocks, Jurassic shale, the spatial coincidence of arsenic anomalies in tube wells and springs, and, to some extent, mining activities. The findings of the presented survey indicate that it is essential to take serious measures at the national level to minimize the health risks of arsenic contamination from drinking water consumption.

Pro-vegetarian dietary patterns and mortality by all-cause and specific causes in an older Mediterranean population.

PURPOSE: Pro-vegetarian (PVG) dietary patterns have shown health benefits, although the evidence concerning their association with mortality is scarce, particularly in older populations. We investigated the effect of three defined PVG patterns on all-cause, cardiovascular disease (CVD) and cancer mortality risk in an older Mediterranean population. METHODS: We analysed baseline data from 597 adults aged 65 and older who participated in a population-based cross-sectional study, and mortality during a 12-year period. We used a validated food frequency questionnaire to estimate the adherence in tertiles to three evidence-based PVG dietary patterns: a general PVG pattern (gPVG) and two specific variations (healthful -hPVG, and unhealthful -uPVG). The gPVG pattern incorporated data from 12 food groups, consisting of 7 plant-based and 5 animal-based. The hPVG and uPVG versions included information from 18 food groups (4 food groups added and the splitting of 2 food groups). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for relevant covariates. RESULTS: After the 12-years follow-up period, moderate adherence to hPVG pattern was associated with lower all-cause and CVD mortality whereas greater adherence to uPVG pattern was associated with higher all-cause and CVD mortality. Compared with those in the lowest tertile, participants in the second tertile of adherence to the hPVG pattern showed a significant lower risk of all-cause mortality (HR = 0.59; 95%CI: 0.43, 0.82) and CVD mortality (HR = 0.47; 0.28, 0.78). Participants in the highest tertile of adherence to the uPVG showed an increased mortality risk of all-cause (HR = 1.53; 1.07, 2.19) and CVD (HR = 2.10; 1.19, 3.70). No significant associations were found between adherence to any of the PVG dietary patterns and cancer mortality. CONCLUSION: Moderate adherence to a healthy PVG pattern reduced the long-term mortality risk for all-cause and CVD in an older Mediterranean population, while higher adherence to an unhealthy PVG pattern increased the risk of all-cause and CVD mortality.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Pro-vegetarian dietary patterns and essential and heavy metal exposure in children of 4-5-years from the INfancia y medio Ambiente cohort (INMA).

Dietary patterns provide a comprehensive assessment of food consumption, including essential nutrients and potential exposure to environmental contaminants. While pro-vegetarian (PVG) dietary patterns have shown health benefits in adults, their effects on children are less well studied. This study aims to explore the association between children's adherence to the most common PVG dietary patterns and their exposure to metals, assessed through urine concentration. In our study, we included a population of 723 children aged 4-5-years from the INfancia y Medio Ambiente (INMA) cohort in Spain. We calculated three predefined PVG dietary patterns, namely general (gPVG), healthful (hPVG), and unhealthful (uPVG), using dietary information collected through a validated Food Frequency Questionnaire. Urinary concentrations of various essential and heavy metals (Co, Cu, Zn, Se, Mo, Pb, and Cd) were measured using mass spectrometry. Additionally, urinary arsenic speciation, including arsenobetaine (AsB), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and inorganic arsenic (iAs), was measured. The sum of urinary MMA and iAs was used to assess iAs exposure. We estimated primary (PMI) and secondary iAs methylation (SMI) indices. To explore the association between PVG dietary patterns in quintiles and metal exposure, we utilized multiple-adjusted linear regression models and the quantile g-computation approach. Compared with the lowest quintile, participants in the highest quintile of gPVG showed a 22.7% lower urinary Co (95% confidence interval (CI): -38.7; -1.98) and a 12.6% lower Se (95%CI: -22.9; -1.00) concentrations. Second quintile of adherence to hPVG was associated with a 51.7% lower urinary iAs + MMA concentrations (95%CI: -74.3; -8.61). Second quintile of adherence to an uPVG was associated with a 13.6% lower Se levels (95%CI: -22.9; -2.95) while the third quintile to this pattern was associated with 17.5% lower Mo concentrations (95%CI: -29.5; -2.95). The fourth quintile of adherence to gPVG was associated with a 68.5% higher PMI and a 53.7% lower SMI. Our study showed that adherence to a gPVG dietary pattern in childhood may modestly reduce the intakes of some essential metals such as Co and Se. Further investigations are warranted to explore any potential health implications.

Environmental pollution by heavy metals within the area influenced by the Tungurahua volcano eruption - Ecuador.

Volcanic eruptions can have long-lasting negative effects on nearby environments and communities, especially those relying on agriculture. The Tungurahua and Sangay volcanoes in Ecuador's highlands pose a significant risk to the region's agricultural economy and inhabitants. The most recent eruption of the Tungurahua volcano spanned from September 1999 to March 2016. Volcanic ash is known to contain both non-essential and essential elements for plant growth, but excessive amounts of the latter can also be toxic and disrupt physiological processes. Additionally, the use of pesticides and fertilizers introduces additional elements to agricultural soils, which can potentially transfer to edible plants and raise health concerns for consumers. Despite this, little is known about the impact of the Tungurahua volcano's latest eruption on soil deposition of micronutrient and heavy metals and their potential transfer to the food chain. To address this knowledge gap, we conducted a study to explore the impact of the Tungurahua volcano's latest eruption on soil deposition of Cd, Cr, Ni, Pb, As, Fe, Cu, Mn, and Zn, as well as the physicochemical characteristics of cultivated and uncultivated soil samples and vegetables in the cantons most affected by volcanic ash. According to our findings, the physicochemical properties, micronutrient, and heavy metal concentrations of both cultivated and uncultivated soils differ and, in some cases, exceeded the maximum limits established, which could affect the health of the soil as well as of human beings through the trophic chain. This study provides valuable information for monitoring the chemical and physical properties of soil and vegetables in areas affected by the Tungurahua volcanic activity and agriculture, aiding in understanding their impact on the environment, agriculture, and potential health risks associated with locally grown crops in rural Ecuadorian communities.

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire birth cohort study.

Prenatal exposure to metals/metalloids, even at common US population levels, may pose risks to fetal health, and affect children's lung function. Yet, the combined effects of simultaneous prenatal exposures on children's lung function remain largely unexplored. This study analyzed 11 metals (As speciation, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Sn, Zn) in maternal urine during weeks 24-28 of gestation and evaluated lung function, including forced vital capacity (FVC) and forced expiratory volume in the first second of expiration (FEV1), in 316 US mother-child pairs at around age 7. We used Bayesian Kernel Machine Regression (BKMR), weighted quantile sum regression (WQSR), and multiple linear regression to examine the association between metal mixture exposure and children's lung function, adjusting for maternal smoking, child age, sex, and height. In BKMR models assessing combined exposure effects, limited evidence of metal non-linearity or interactions was found. Nevertheless, Co, As species, and Pb showed a negative association, while Mo exhibited a positive association with children's FVC and FEV1, with other metals held constant at their medians. The weighted index, from WQSR analysis assessing the cumulative impact of all metals, highlighted prenatal Mo with the highest positive weight, and Co, As, and Sb with the most substantial negative weights on children's FVC and FEV1. Urinary Co and Pb were negatively associated with FVC (ß = -0.09, 95% confidence interval (CI) (-0.18; -0.01) and ß = -0.07, 95% CI (-0.13; 0.00), respectively). Co was also negatively associated with FEV1 (ß = -0.09, 95% CI (-0.18; 0.00). There was a negative association between As and FVC, and a positive association between Mo and both FVC and FEV1, though with wide confidence intervals. Our findings suggest that prenatal trace element exposures may impact children's lung function, emphasizing the importance of reducing toxic exposures and maintaining adequate nutrient levels.

Dietary Exposure to Essential and Non-essential Elements During Infants' First Year of Life in the New Hampshire Birth Cohort Study.

Even the low levels of non-essential elements exposure common in the US may have health consequences especially early in life. However, little is known about the infant's dynamic exposure to essential and non-essential elements. This study aims to evaluate exposure to essential and non-essential elements during infants' first year of life and to explore the association between the exposure and rice consumption. Paired urine samples from infants enrolled in the New Hampshire Birth Cohort Study (NHBCS) were collected at approximately 6 weeks (exclusively breastfed) and at 1 year of age after weaning (n = 187). A further independent subgroup of NHBCS infants with details about rice consumption at 1 year of age also was included (n = 147). Urinary concentrations of 8 essential (Co, Cr, Cu, Fe, Mn, Mo, Ni, and Se) and 9 non-essential (Al, As, Cd, Hg, Pb, Sb, Sn, V, and U) elements were determined as a measure of exposure. Several essential (Co, Fe, Mo, Ni, and Se) and non-essential (Al, As, Cd, Hg, Pb, Sb, Sn, and V) elements had higher concentrations at 1 year than at 6 weeks of age. The highest increases were for urinary As and Mo with median concentrations of 0.20 and 1.02 µg/L at 6 weeks and 2.31 and 45.36 µg/L at 1 year of age, respectively. At 1 year of age, As and Mo urine concentrations were related to rice consumption. Further efforts are necessary to minimize exposure to non-essential elements while retaining essential elements to protect and promote children's health. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-022-00489-x.

Dietary intake of polychlorinated dibenzo-p-dioxins and furans, adiposity and obesity status.

INTRODUCTION: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited. OBJECTIVE: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population. METHODS: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models. RESULTS: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (ß-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (ß-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015). CONCLUSION: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results.

Arsenic exposure and respiratory outcomes during childhood in the INMA study.

Ingested inorganic arsenic (iAs) is a human carcinogen that is also linked to other adverse health effects, such as respiratory outcomes. Yet, among populations consuming low-arsenic drinking water, the impact of iAs exposure on childhood respiratory health is still uncertain. For a Spanish child study cohort (INfancia y Medio Ambiente-INMA), low-arsenic drinking water is usually available and ingestion of iAs from food is considered the major source of exposure. Here, we explored the association between iAs exposure and children's respiratory outcomes assessed at 4 and 7 years of age (n = 400). The summation of 4-year-old children's urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of iAs exposure (∑As) (median of 4.92 µg/L). Children's occurrence of asthma, eczema, sneeze, wheeze, and medication for asthma and wheeze at each assessment time point (i.e., 4- and 7-year) was assessed with maternal interviewer-led questionnaires. Crude and adjusted Poisson regression models using Generalized Estimating Equation (GEE) were performed to account for the association between natural logarithm transformed (ln) urinary ∑As in µg/L at 4 years and repeated assessments of respiratory symptoms at 4 and 7 years of age. The covariates included in the models were child sex, maternal smoking status, maternal level of education, sub-cohort, and children's consumption of vegetables, fruits, and fish/seafood. The GEE-splines function using Poisson regression showed an increased trend of the overall expected counts of respiratory symptoms with high urinary ∑As. The adjusted expected counts (95% confidence intervals) at ln-transformed urinary ∑As 1.57 (average concentration) and 4.00 (99th percentile concentration) were 0.63 (0.36, 1.10) and 1.33 (0.61, 2.89), respectively. These exploratory findings suggest that even relatively low-iAs exposure levels, relevant to the Spanish and other populations, may relate to an increased number of respiratory symptoms during childhood.

Associations of maternal urinary arsenic concentrations during pregnancy with childhood cognitive abilities: The HOME study.

Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exist from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal maternal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women's urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to ∑As. We assessed children's cognitive function (n = 260) longitudinally at 1-, 2-, and 3-years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of ∑As with estimated score (ß) differences and 95% confidence interval (CI) of -1.8 from -4.1 to 0.5 and -2.5 from -5.1 to 0.0, respectively. This trend was stronger and reached statistical significance among children whose mothers had lower iAs methylation capacity and low urinary arsenobetaine concentrations. Our findings suggest that arsenic exposure levels relevant to the general US population may affect children's cognitive abilities.

Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population.

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (ß coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown. Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.

Serum concentrations of persistent organic pollutants mixture during pregnancy and anogenital distance in 8-year-old children from the INMA-Asturias cohort.

BACKGROUND: During pregnancy, women are commonly exposed to several endocrine-disrupting chemicals, including persistent organic pollutants (POPs). These compounds can transfer to the fetus through the placenta. Prenatal POP exposure is related to altered fetal genital and reproductive tract development. However, the relationship between exposure to POP mixtures and anogenital distance (AGD) is poorly investigated. This study investigated the association between prenatal exposure to POP mixtures and AGD in 8-year-old children. METHODS: Data were collected from the INMA-Asturias cohort. Maternal serum POP concentrations were measured during the first trimester of pregnancy. Anoscrotal distance (AGDAS) and anopenile distance (AGDAP) in males and anofourchetal distance (AGDAF) and anoclitoral distance (AGDAC) in females were recorded in 362 8-years-olds. Conventional linear regression, and the novel weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) models were applied to assess the relationships between AGD and POPs exposure stratified by sex. RESULTS: Among males, in the linear regression, b-hexachlorocyclohexane, PCB138, PCB153, and PCB180 were inversely associated with the anogenital index (AGI)AS (-0.06 mm/kg (95% confidence interval [CI]: -0.11, -0.02), -0.07 mm/kg (95% CI: -0.14, -0.01), -0.07 mm/kg (95% CI: -0.13, -0.01), and -0.08 mm/kg (95% CI: -0.14, -0.02), respectively). Among females, polybrominated diphenyl ether (PBDE)47 and PBDE154 were positively associated with increased AGIAF (0.02 mm/kg (95% CI: 0.00, 0.03) and 0.09 mm/kg (95% CI: 0.01, 0.17), respectively). BKMR confirmed these associations. WQSR found a negative combined effect of the POP mixture on AGD, and PCB138, PCB153, and PCB180 (weighted 0.18, 0.13, and 0.09, respectively) were identified as the most impacting chemicals. In females, WQSR found a positive combined effect and determined PBDE47 (weighted 0.35) as the most impacting. CONCLUSIONS: Maternal exposure to a POP mixture was negatively associated with AGD in male children and positively associated with AGD in female children, thus providing evidence of the adverse effects of POPs on genital development.

Infant infections, respiratory symptoms, and allergy in relation to timing of rice cereal introduction in a United States cohort.

Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of infections, respiratory symptoms, and allergy. Among 572 infants from the New Hampshire Birth Cohort Study, we used generalized estimating equation, adjusted for maternal smoking during pregnancy, marital status, education attainment, pre-pregnancy body mass index, maternal age at enrollment, infant birth weight, and breastfeeding history. Among 572 infants, each month earlier of introduction to rice cereal was associated with increased risks of subsequent upper respiratory tract infections (relative risk, RR = 1.04; 95% CI: 1.00-1.09); lower respiratory tract infections (RR = 1.19; 95% CI: 1.02-1.39); acute respiratory symptoms including wheeze, difficulty breathing, and cough (RR = 1.10; 95% CI: 1.00-1.22); fever requiring a prescription medicine (RR = 1.22; 95% CI: 1.02-1.45) and allergy diagnosed by a physician (RR = 1.20; 95% CI: 1.06-1.36). No clear associations were observed with gastrointestinal symptoms. Our findings suggest that introduction of rice cereal earlier may influence infants' susceptibility to respiratory infections and allergy.

Dietary Exposure to Toxic Elements and the Health of Young Children: Methodological Considerations and Data Needs.

Concerns have been raised regarding toxic-element (arsenic, cadmium, lead, and mercury) contamination of commercially available infant foods around the world. Young children are vulnerable to the effects of toxic elements, based on higher absorption levels and potentially poorer detoxification capacities. Toxic-element exposures in early life exact high societal costs, but it is unclear how much dietary exposure to these elements contributes to adverse health outcomes. Well-designed epidemiological studies conducted in different geographical and socioeconomic contexts need to estimate dietary toxicant exposure in young children and to determine whether causal links exist between toxicants in children's diets and health outcomes. This commentary outlines the methodological considerations and data needs to advance such research.

Exposure to metal mixture and growth indicators at 4-5 years. A study in the INMA-Asturias cohort.

BACKGROUND: Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4-5 years of age. METHODS: We used urine metal concentrations as biomarkers of exposure in 328 children enrolled in the Spanish INMA-Asturias cohort. Anthropometric measurements (arm, head, and waist circumferences, standing height, and body mass index) and parental sociodemographic variables were collected through face-to-face interviews by trained study staff. Linear regressions were used to estimate the independent effects and were adjusted for each metal in the mixture. We applied Bayesian kernel machine regression to examine non-linear associations and potential interactions. RESULTS: In linear regression, urinary levels of cadmium were associated with reduced arm circumference (ßadjusted = -0.44, 95% confidence interval [CI]: -0.73, -0.15), waist circumference (ßadjusted = -1.29, 95% CI: -2.10, -0.48), and standing height (ßadjusted = -1.09, 95% CI: -1.82, -0.35). Lead and cobalt concentrations were associated with reduced standing height (ßadjusted = -0.64, 95% CI: -1.20, -0.07) and smaller head circumference (ßadjusted = -0.29, 95% CI: -0.49, -0.09), respectively. However, molybdenum was positively associated with head circumference (ßadjusted = 0.22, 95% CI: 0.01, 0.43). BKMR analyses showed strong linear negative associations of cadmium with arm and head circumference and standing height. BKMR analyses also found lead and cobalt in the metal mixture were related to reduce standing height and head circumference, and consistently found molybdenum was related to increased head circumference. CONCLUSION: Our findings suggest that exposure to metal mixtures impacts growth indicators in children.

Exposure to a mixture of metals and growth indicators in 6-11-year-old children from the 2013-16 NHANES.

Lead (Pb), mercury (Hg) and fluoride (F) exposure during childhood is of concern owing to their toxicity. Also, evidence suggests that high and low exposure levels to manganese (Mn) and selenium (Se) during this vulnerable period are associated with an increased risk of adverse health effects. A reduced growth is associated with high Pb and F exposure; however, little is known about their impact on children's body size, and there is a lack of consensus on the effects of Hg, Mn, and Se exposure on children's anthropometric measures. This is particularly true for childhood metal co-exposures at levels relevant to the general population. We investigated the joint effects of exposure to a metal mixture (Pb, Mn, Hg, and Se in blood and F in plasma) on 6-11-year-old US children's anthropometry (n = 1,634). Median F, Pb, Mn, Hg, and Se concentrations were 0.3 µmol/L, 0.5 µg/dL, 10.2 µg/L, 0.3 µg/L, and 178.0 µg/L, respectively. The joint effects of the five metals were modeled using Bayesian kernel machine and linear regressions. Pb and Mn showed opposite directions of associations with all outcome measured, where Pb was inversely associated with anthropometry. For body mass index and waist circumference, the effect estimates for Pb and Mn appeared stronger at high and low concentrations of the other metals of the mixture, respectively. Our findings suggest that metal co-exposures may influence children's body mass and linear growth indicators, and that such relations may differ by the exposure levels of the components of the metal mixture.

Prenatal exposure to arsenic and lung function in children from the New Hampshire Birth Cohort Study.

Prenatal arsenic exposure is associated with an increased risk of lung cancer along with multiple non-carcinogenic outcomes, including respiratory diseases in arsenic-contaminated areas. Limited epidemiologic data exist on whether in utero arsenic exposure influences lung development and subsequent respiratory health. We investigated the association between gestational arsenic exposure and childhood lung function in the New Hampshire Birth Cohort Study. Urinary arsenic speciation including inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine was measured in maternal urine samples collected during pregnancy and spirometry was performed in offspring at a median age of 7.4 years. Forced vital capacity (FVC), forced expiratory volume in the first second of exhalation (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) standardized z-scores were assessed in linear models as dependent variables with the log2-transformed summation of urinary arsenic species (ΣAs = iAs + MMA + DMA) corrected for specific gravity as an independent variable and with adjustment for maternal smoking status, children's age, sex and height. Among the 358 children in the study, a doubling of ΣAs was associated with a -0.08 (ß) decrease in FVC z-scores (95% confidence interval (CI) from -0.14 to -0.01) and -0.10 (ß) (95% CI from -0.18 to -0.02) decrease in FEV1 z-scores. The inverse association appeared stronger among those mothers with lower secondary methylation index (urinary DMA/MMA), especially among girls. No association was observed for FEF25-75 z-scores. Our results suggest that gestation arsenic exposure at levels relevant to the general US population during the vulnerable period of lung formation may adversely affect lung function in childhood.

A Secure and Reusable Software Architecture for Supporting Online Data Harmonization.

Retrospective data harmonization across multiple research cohorts and studies is frequently done to increase statistical power, provide comparison analysis, and create a richer data source for data mining. However, when combining disparate data sources, harmonization projects face data management and analysis challenges. These include differences in the data dictionaries and variable definitions, privacy concerns surrounding health data representing sensitive populations, and lack of properly defined data models. With the availability of mature open-source web-based database technologies, developing a complete software architecture to overcome the challenges associated with the harmonization process can alleviate many roadblocks. By leveraging state-of-the-art software engineering and database principles, we can ensure data quality and enable cross-center online access and collaboration. This paper outlines a complete software architecture developed and customized using the Django web framework, leveraged to harmonize sensitive data collected from three NIH-support birth cohorts. We describe our framework and show how we successfully overcame challenges faced when harmonizing data from these cohorts. We discuss our efforts in data cleaning, data sharing, data transformation, data visualization, and analytics, while reflecting on what we have learned to date from these harmonized datasets.

Toenails as a biomarker of exposure to arsenic: A review.

This systematic review summarizes the current evidence related to the reliability of toenail total arsenic concentrations (thereafter "arsenic") as a biomarker of long-term exposure. Specifically, we reviewed literature on consistency of repeated measures over time, association with other biomarkers and metal concentrations, factors influencing concentrations, and associations with health effects. We identified 129 papers containing quantitative original data on arsenic in toenail samples covering populations from 29 different countries. We observed geographic differences in toenail arsenic concentrations, with highest median or mean concentrations in Asian countries. Arsenic-contaminated drinking water, occupational exposure or living in specific industrial areas were associated with an increased toenail arsenic content. The effects of other potential determinants and sources of arsenic exposure including diet, gender and age on the concentrations in toenails need further investigations. Toenail arsenic was correlated with the concentrations in hair and fingernails, and with urine arsenic mainly among highly exposed populations with a toenail mean or median ≥1 µg/g. Overall, there is a growing body of evidence suggesting that arsenic content from a single toenail sample may reflect long-term internal dose-exposure. Toenail arsenic can serve as a reliable measure of toxic inorganic arsenic exposure in chronic disease research, particularly promising for cancer and cardiovascular conditions.

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.