Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (ß = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (ß = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (ß = -0.04; 95 %CI: -0.07, -0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Associations of gestational exposure to air pollution with maternal vitamin D levels: a meta-analysis.

OBJECTIVE: Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce. We investigated the association between air pollution during pregnancy and maternal vitamin D levels. METHODS: A total of 15,935 pregnant women from 5 birth cohorts in Europe and U.S were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants' residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception. RESULTS: We found an association between PM2.5 and higher odds of suboptimal vitamin D levels (i.e., below 20 ng/mL) (odds ratio per 5 µg/m3 increase in PM2.5, 1.43 95%CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels. CONCLUSIONS: PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.

The effects of heavy metal exposure on brain and gut microbiota: A systematic review of animal studies.

The gut-brain axis is a crucial interface between the central nervous system and the gut microbiota. Recent evidence shows that exposure to environmental contaminants, such as heavy metals, can cause dysbiosis in gut microbiota, which may affect the gut-brain communication, impacting aspects of brain function and behavior. This systematic review of the literature aims to evaluate whether deleterious effects on brain function due to heavy metal exposure could be mediated by changes in the gut microbiota profile. Animal studies involving exposure to heavy metals and a comparison with a control group that evaluated neuropsychological outcomes and/or molecular outcomes along with the analysis of microbiota composition were reviewed. The authors independently assessed studies for inclusion, extracted data and assessed risk of bias using the protocol of Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) for preclinical studies. A search in 3 databases yielded 16 eligible studies focused on lead (n = 10), cadmium (n = 1), mercury (n = 3), manganese (n = 1), and combined exposure of lead and manganese (n = 1). The animal species were rats (n = 7), mice (n = 4), zebrafish (n = 3), carp (n = 1) and fruit fly (n = 1). Heavy metals were found to adversely affect cognitive function, behavior, and neuronal morphology. Moreover, heavy metal exposure was associated with changes in the abundance of specific bacterial phyla, such as Firmicutes and Proteobacteria, which play crucial roles in gut health. In some studies, these alterations were correlated with learning and memory impairments and mood disorders. The interplay of heavy metals, gut microbiota, and brain suggests that heavy metals can induce direct brain alterations and indirect effects through the microbiota, contributing to neurotoxicity and the development of neuropsychological disorders. However, the small number of papers under review makes it difficult to draw definitive conclusions. Further research is warranted to unravel the underlying mechanisms and evaluate the translational implications for human health.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

Associated factors with mycotoxin exposure in Spanish population.

Human exposure to mycotoxins is a global concern since filamentous fungi can contaminate food and feed from crops to ready-to-eat meals. Human urine biomonitoring is a widely used technique to evaluate mycotoxins exposure, as an alternative to food correlation studies. The aim of this study is to describe human exposure to mycotoxins and to investigate the associated sociodemographic, lifestyle and dietary variables. Participants were 540 women from the Valencia (Spain) cohort of the Spanish Childhood and Environment Project (INMA). A validated multi-mycotoxin method using HPLC-Q-TOF-MS was applied to determine the concentration of ten selected mycotoxins: Enniatin A, Enniatin B, Enniatin A1, Enniatin B1, Beauvericine, Aflatoxin B1, Aflatoxin B2, Aflatoxin G1, Aflatoxin G2 and Ochratoxin A. A simultaneous untargeted screening of mycotoxins and their metabolites has been performed. Mycotoxins associations were assessed by bivariate and multivariate regression models using participants' sociodemographic, lifestyle and dietary data collected through questionnaires. Mycotoxins were detected in 81% of urine samples. The method quantified mycotoxins concentrations in up to 151 samples. Most quantified mycotoxins were: Enniatin B [% of detection (concentration range)] = 26% (1.0-39.7 ng/mg) and Enniatin B1 = 7% (0.5-14.4 ng/mg). Besides the ten-targeted mycotoxins, other mycotoxins and metabolites were studied, and higher incidence was observed for Deepoxy-deoxynivalenol (45%), Ochratoxin B (18%) and Ochratoxin α (17%). Higher mycotoxins concentrations were associated with rural areas as well as with participants belonged to lower social class, beer, light sodas and fruit juice consumers. On the contrary, higher processed meat intake was related to lower mycotoxins' levels. Studies are required to better evaluate the exposure to mycotoxins from food and their environmental relationships.

Creatine Kinase Is Decreased in Childhood Asthma.

Rationale: The identification of novel molecules associated with asthma may provide insights into the mechanisms of disease and their potential clinical implications. Objectives: To conduct a screening of circulating proteins in childhood asthma and to study proteins that emerged from human studies in a mouse model of asthma. Methods: We included 2,264 children from eight birth cohorts from the Mechanisms of the Development of ALLergy project and the Tucson Children's Respiratory Study. In cross-sectional analyses, we tested 46 circulating proteins for association with asthma in the selection stage and carried significant signals forward to a validation and replication stage. As CK (creatine kinase) was the only protein consistently associated with asthma, we also compared whole blood CK gene expression between subjects with and without asthma (n = 249) and used a house dust mite (HDM)-challenged mouse model to gain insights into CK lung expression and its role in the resolution of asthma phenotypes. Measurements and Main Results: As compared with the lowest CK tertile, children in the highest tertile had significantly lower odds for asthma in selection (adjusted odds ratio, 95% confidence interval: 0.31; 0.15-0.65; P = 0.002), validation (0.63; 0.42-0.95; P = 0.03), and replication (0.40; 0.16-0.97; P = 0.04) stages. Both cytosolic CK forms (CKM and CKB) were underexpressed in blood from asthmatics compared with control subjects (P = 0.01 and 0.006, respectively). In the lungs of HDM-challenged mice, Ckb expression was reduced, and after the HDM challenge, a CKB inhibitor blocked the resolution of airway hyperresponsiveness and reduction of airway mucin. Conclusions: Circulating concentrations and gene expression of CK are inversely associated with childhood asthma. Mouse models support a possible direct involvement of CK in asthma protection via inhibition of airway hyperresponsiveness and reduction of airway mucin.

Prenatal and child vitamin D levels and allergy and asthma in childhood.

BACKGROUND: Early-life vitamin D deficiency may impair immune system development contributing to allergy and asthma onset. Findings from prospective studies are inconsistent. OBJECTIVE: To examine whether maternal and child vitamin D levels are associated with allergic and asthma-related symptoms throughout childhood in a Spanish birth cohort. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) levels were measured in the serum of pregnant women (N = 2525) and children (N = 803). Information on allergic and asthma-related symptoms was obtained from repeated questionnaires from 1 to 9 years. RESULTS: A total of 19% of mothers and 24% of children had deficient 25(OH)D3 levels (<20 ng/ml). Higher child 25(OH)D3 levels at 4 years were associated with lower odds of atopic eczema from 4 to 9 years (adjusted odds ratio = 0.90; 95% CI = 0.84-0.97 per 5 ng/ml). Higher maternal and child 25(OH)D3 levels were associated with a lower prevalence of late-onset wheezing at the limit of statistical significance (adjusted relative risk ratio (RRRadj) = 0.86; 95% CI = 0.74-1.00 and RRRadj = 0.76; 95% CI = 0.58-1.02 per 5 ng/ml, respectively). All the remaining associations were null. CONCLUSION: Child 25(OH)D3 levels at pre-school age are associated with a reduced odds of atopic eczema in later childhood and both maternal and child levels may reduce the prevalence of late-onset wheezing. IMPACT: In this Spanish birth cohort, with a total of 19% of mothers and 24% of children with deficient levels of vitamin D, higher child vitamin D at 4 years of age was associated with reduced odds of atopic eczema up to 9 years. There was also some evidence that higher maternal and child vitamin D levels reduced the prevalence of late-onset wheezing. Although these findings need replication, they may imply optimal vitamin D levels at pre-school age to prevent atopic eczema.

Development and Validation of LC-Q-TOF-MS Methodology to Determine Mycotoxin Biomarkers in Human Urine.

Mycotoxin contamination of foodstuffs is a health concern worldwide and monitoring human exposure to mycotoxins is a key concern. Most mycotoxins and their metabolites are excreted in urine, but a reliable detection method is required, considering the low levels present in this biological sample. The aim of this work is to validate a sensitive methodology capable of simultaneously determining ten targeted mycotoxins as well as detecting untargeted ones by using Liquid Chromatography coupled to Quadrupole Time of Flight Mass Spectrometry (LC-Q-TOF-MS). The targeted mycotoxins were: enniatin A, B, A1, and B1, beauvericine, aflatoxin B1, B2, G1 and G2, and ochratoxin A. Several extraction procedures such as liquid-liquid extraction, dilute and shoot, and QuEChERS were assessed. Finally, a modified simple QuEChERS extraction method was selected. Creatinine adjustment and matrix-matched calibration curves are required. The limit of detection and limit of quantification values ranged from 0.1 to 1.5 and from 0.3 to 5 ng/mL, respectively. Recoveries achieved were higher than 65% for all mycotoxins. Later, the method was applied to 100 samples of women's urine to confirm the applicability and determine their internal exposure. The untargeted mycotoxins most found were trichothecenes, zearalenones, and ochratoxins.

Household income, fetal size and birth weight: an analysis of eight populations.

BACKGROUND: The age at onset of the association between poverty and poor health is not understood. Our hypothesis was that individuals from highest household income (HI), compared to those with lowest HI, will have increased fetal size in the second and third trimester and birth. METHODS: Second and third trimester fetal ultrasound measurements and birth measurements were obtained from eight cohorts. Results were analysed in cross-sectional two-stage individual patient data (IPD) analyses and also a longitudinal one-stage IPD analysis. RESULTS: The eight cohorts included 21 714 individuals. In the two-stage (cross-sectional) IPD analysis, individuals from the highest HI category compared with those from the lowest HI category had larger head size at birth (mean difference 0.22 z score (0.07, 0.36)), in the third trimester (0.25 (0.16, 0.33)) and second trimester (0.11 (0.02, 0.19)). Weight was higher at birth in the highest HI category. In the one-stage (longitudinal) IPD analysis which included data from six cohorts (n=11 062), head size was larger (mean difference 0.13 (0.03, 0.23)) for individuals in the highest HI compared with lowest category, and this difference became greater between the second trimester and birth. Similarly, in the one-stage IPD, weight was heavier in second highest HI category compared with the lowest (mean difference 0.10 (0 .00, 0.20)) and the difference widened as pregnancy progressed. Length was not linked to HI category in the longitudinal model. CONCLUSIONS: The association between HI, an index of poverty, and fetal size is already present in the second trimester.

Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network.

BACKGROUND: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. OBJECTIVE: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. METHODS: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. RESULTS: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. CONCLUSION: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort.

BACKGROUND: Prenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. OBJECTIVES: To explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. MATERIALS AND METHODS: Study subjects were 807 mother-child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). RESULTS: The geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) µg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. ß [CI95%] = -1.37 [-2.33, -0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. DISCUSSION: An inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

Advancing tools for human early lifecourse exposome research and translation (ATHLETE): Project overview.

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE's results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward.

Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study.

BACKGROUND: The prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts. METHODS: We studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10-15, >15-20, >20-25 years, and overall, 5-25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ≥LLN, and FVC z-score

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4.

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 µg/L and 0.97 µg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (pint < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (pint < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (pint < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.

Urinary arsenic species and methylation efficiency during pregnancy: Concentrations and associated factors in Spanish pregnant women.

BACKGROUND: Arsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. OBJECTIVES: To describe the urinary concentrations of the different As species and evaluate the methylation efficiency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. METHODS: Participants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003-2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Sociodemographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. RESULTS: Median urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 µg/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., ß [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). DISCUSSION: Certain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.

Exposure to mercury among 9-year-old children and neurobehavioural function.

Mercury (Hg) is an environmental neurotoxicant whose main route of exposure in humans is the consumption of seafood. The aim of this study was to explore the relationship between Hg exposure at 9 years old and behaviour assessed at 9 and 11 years old. Study subjects were mother-child pairs participating in the INMA (Environment and Childhood) Project in Valencia (Spain). Total Hg (THg) was measured in hair samples from the children at 9 years old. Behaviour and emotions were assessed at 9 (n = 472) years and 11 (n = 385) years of age using the Child Behaviour Checklist test (CBCL) and the Conners Parents Rating Scale-Revised: Short Form (CPRS-R:S). Furthermore, the attention function was assessed by the Attention Network Test at 11 years old. Socio-demographic, lifestyle and dietary information was collected through questionnaires during pregnancy and childhood. Polymorphism in BDNF, APOE and GSTP1 were genotyped in cord blood DNA. Multivariable negative binomial regression models were built in order to study the association between THg concentrations and the scores obtained by the children at 9 and 11 years old. Effect modification by sex and genetic polymorphisms was assessed. The association between Hg levels and CBCL scores was positive (worse neurobehavioural development) for the CBCL internalizing and total problem scales (Incidence Rate Ratio [95% confidence interval] = 1.07 [1.01, 1.13] and 1.05 [0.99, 1.11], respectively). The association between Hg and the externalizing and total problems CBCL scales and the Attention Deficit Hyperactivity Disorder (ADHD) index of the CPRS-R:S was different according to sex, with boys obtaining worse scores with increasing Hg, compared to girls. Statistically significant interactions were also observed for genetic polymorphisms affecting the association between early exposure to Hg and both CBCL and CPRS-R:S scores. In conclusion, postnatal Hg exposure is associated with poorer neurobehavioural development in 9- and 11-year-old children. Sex and the presence of certain genetic polymorphisms modified this association.

Urban environment during early-life and blood pressure in young children.

BACKGROUND: The urban environment is characterised by many exposures that may influence hypertension development from early life onwards, but there is no systematic evaluation of their impact on child blood pressure (BP). METHODS: Systolic and diastolic blood pressure were measured in 4,279 children aged 4-5 years from a multi-centre European cohort (France, Greece, Spain, and UK). Urban environment exposures were estimated during pregnancy and childhood, including air pollution, built environment, natural spaces, traffic, noise, meteorology, and socioeconomic deprivation index. Single- and multiple-exposure linear regression models and a cluster analysis were carried out. RESULTS: In multiple exposure models, higher child BP, in particular diastolic BP, was observed in association with higher exposure to air pollution, noise and ambient temperature during pregnancy, and with higher exposure to air pollution and higher building density during childhood (e.g., mean change [95% confidence interval] for an interquartile range increase in prenatal NO2 = 0.7 mmHg[0.3;1.2]). Lower BP was observed in association with higher temperature and better street connectivity during childhood (e.g., temperature = -1.1[-1.6;-0.6]). Some of these associations were not robust in the sensitivity analyses. Mother-child pairs were grouped into six urban environment exposure clusters. Compared to the cluster representing the least harmful urban environment, the two clusters representing the most harmful environment (high in air pollution, traffic, noise, and low in green space) were both associated with higher diastolic BP (1.3[0.1;2.6] and 1.5[0.5;2.5]). CONCLUSION: This first large systematic study suggests that living in a harmful urban environment may impact BP regulation in children. These findings reinforce the importance of designing cities that promote healthy environments to reduce long-term risk of hypertension and other cardiovascular diseases.