Evaluation of Polyphenol Intake in Pregnant Women from South-Eastern Spain and the Effect on Anthropometric Measures at Birth and Gestational Age.

During pregnancy, controlling nutrition is crucial for the health of both mother and foetus. While polyphenols have positive health effects, some studies show harmful outcomes during pregnancy. This study evaluated polyphenol intake in a cohort of mother-child pairs and examined its effects on foetal anthropometric parameters. Polyphenol intake was assessed using food frequency questionnaires (FFQs) and 24-h dietary recalls, and analysed with the Phenol-Explorer database. Gestational age and birth measurements were retrieved from medical records. Statistical analyses validated dietary records and assessed polyphenol impact using multivariate generalised linear models. The study found that mean gestational age was 39.6 weeks, with a mean birth weight of 3.33 kg. Mean total polyphenol intake by FFQ was 2231 mg/day, slightly higher than 24-h recall data. Flavonoids and phenolic acids constituted 52% and 37% of intake, respectively, with fruits and legumes as primary sources. This study highlights the use of FFQs to estimate polyphenol intake. Furthermore, the study found associations between polyphenol consumption and anthropometric parameters at birth, with the effects varying depending on the type of polyphenol. However, a more precise evaluation of individual polyphenol intake is necessary to determine whether the effects they produce during pregnancy may be harmful or beneficial for foetal growth.

Association between exposure to organophosphate pesticides and cytokine levels in a population of flower workers in Mexico.

The ability of organophosphate pesticides to disturb immune function has been demonstrated by in vivo and in vitro studies, but evidence of such effects on humans remains scarce. To assess the association between organophosphate pesticides exposure and cytokine levels in Mexican flower workers, a cross-sectional study was carried out. A questionnaire was provided to 121 male flower workers, and urine and blood samples were collected. Using gas chromatography, urinary concentrations of dialkylphosphate metabolites were determined. The serum cytokine levels, IL-4, IL-5, IL-6, IL-8, and IL-10, were measured using multiplex analysis, and levels of INF-γ and TNF-α by ELISA. We found that a higher dialkylphosphate concentration decreased the pro-inflammatory cytokines INF-γ (ß = -0.63; 95 % CI: -1.22, -0.05), TNF-α (ß= -1.18; 95 % CI: -2.38, 0.02), and IL-6 (ß= -0.59; 95 % CI: -1.29, 0.12), and increased IL-10 (ß=0.56; 95 % CI: 0.02, 1.09), the main anti-inflammatory cytokine, suggesting an imbalance of the immune response in flower workers.

A Th2-type immune response and low-grade systemic inflammatory reaction as potential immunotoxic effects in intensive agriculture farmers exposed to pesticides.

Pesticides are chemicals widely used in agriculture to keep crops healthy and prevent them from being destroyed by pests, thus contributing to a sustainable food and feed production. However, long-term exposure to these compounds may be harmful to human health as they can affect the function of various organs systems, including the immune system. There is growing evidence that pesticides may increase the risk of developing immune-based diseases and inflammation. This study assessed whether greenhouse farmers occupationally exposed to pesticides presented alterations in immunoregulatory proteins, used as surrogate biomarkers of immune function. The study population consisted of 175 greenhouse workers occupationally exposed to pesticides and 91 non-exposed controls. Serum levels of 27 cytokines, chemokines and growth factors were measured using a magnetic bead-based immunoassay in a subpopulation of 111 greenhouse workers and 79 non-exposed controls. Since analytical determinations were performed in two periods of the same crop season with different use of pesticides (period of high and low pesticide exposure), linear mixed models for repeated measures were used to optimize statistical inference. The increase in IL-13, IL-4 and IL-6 observed in greenhouse workers compared to controls, and in the period of high exposure to pesticides relative to that of low exposure, suggest an altered Th1/Th2 balance towards the Th2 response. This finding points to a type-2 inflammation commonly presented as allergic inflammation, which has often been reported in farm-workers and in which pesticide exposure is considered a risk factor. Furthermore, the increase in IL-1ß and VEGF, mediators of inflammation and angiogenesis, may suggest a low-grade systemic inflammation that might underlie chronic pathological conditions linked to pesticide exposure.

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.

Pesticide use patterns and their association with cytokine levels in Mexican flower workers.

OBJECTIVE: Occupational exposure to pesticides is a known risk for disrupting cellular immune response in flower workers due to their use of multiple chemical products, poor work conditions, and inadequate protection. Recently, the analysis of pesticide use patterns has emerged as an alternative to studying exposure to mixtures of these products. This study aimed to evaluate the association between exposure to different patterns of pesticide use and the cytokine profile of flower workers in the State of Mexico and Morelos, Mexico. METHODS: A cross-sectional study was carried out on a population of 108 flower workers. Serum levels of IL-4, IL-5, IL-6, IL-8, IL-10 cytokines were analyzed by means of multiplex analysis, and TNF-α and IFN-γ using an ELISA test. Pesticide use patterns were generated by principal components analysis. RESULTS: The analysis revealed that certain patterns of pesticide use, combining insecticides and fungicides, were associated with higher levels of pro-inflammatory cytokines, particularly IL-6 and IFN-γ. CONCLUSION: These findings indicate that pesticides may possess immunotoxic properties, contributing to increased inflammatory response. However, further comprehensive epidemiological studies are needed to establish a causal relationship.

Renal tubular dysfunction in greenhouse farmers exposed to pesticides unveiled by a panel of molecular biomarkers of kidney injury.

Growing evidence suggests that chronic exposure to pesticides may cause adverse effects on the health of the exposed population leading to organ-specific toxicity, including kidney damage. Traditional markers used to assess renal function (glomerular filtration rate (GFR), and serum creatinine and cystatin C -Cys-C-) are inadequate to evaluate a potential subclinical renal impairment linked to occupational exposure to pesticides, since levels above the upper limit of normal only occur when renal damage is very extensive. The use of more sensitive biomarkers is therefore needed. This study investigated novel urinary biomarkers of kidney function (microalbuminuria, osteopontin (OPN), trefoil factor 3 (TFF3), ß-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL), and Cys-C), together with the aforementioned traditional serum biomarkers, to assess potential kidney damage in farmers exposed to pesticides in an intensive agriculture setting. The study population consisted of 175 greenhouse workers and 91 healthy control subjects from Almeria (Southeastern Spain), a major hub of greenhouse agriculture. Data were collected at two different time-points of the same crop season: a period with greater pesticide use (high exposure period) and another with lower pesticide use (low exposure period). Significantly higher urinary levels of OPN and TFF3 were found in greenhouse workers than in controls, and in the high pesticide exposure period compared to that of low exposure. These changes suggest a subclinical tubular damage linked to pesticide exposure. In contrast, microalbuminuria, GFR, serum creatinine and Cys-C failed to be associated with pesticide exposure, suggesting that glomerular function was spared. Increased OPN and TFF3 levels over time may suggest a gradual progression from tubular dysfunction to chronic kidney disease in the exposed population.

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy - Study design and characteristics of participants.

BACKGROUND: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. METHODS: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. RESULTS: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and <50% of Greek, Cypriot and Icelandic women reported that they had consumed big oily fish. Relevant to non-dietary exposure sources, most participants (>90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. CONCLUSIONS: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.

Effect of prenatal exposure to organophosphates and pyrethroid pesticides on neonatal anthropometric measures and gestational age.

Several studies have examined the association between prenatal exposure to organophosphate and pyrethroid pesticides and their impact on foetal growth and newborn anthropometry; however, the available evidence is limited and inconclusive. This study examined whether prenatal organophosphate and pyrethroid pesticide exposure was associated with anthropometric measures at birth (weight, length, head circumference), ponderal index, gestational age, and prematurity in 537 mother-child pairs. These were randomly selected from the 800 pairs participating in the prospective birth cohort GENEIDA (Genetics, early life environmental exposures and infant development in Andalusia). Six non-specific organophosphate metabolites (dialkylphosphates, DAPs), one metabolite relatively specific to chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy) and a common metabolite to several pyrethroids (3-phenoxybenzoic acid, 3-PBA) were measured in maternal urine from the 1st and 3rd pregnancy trimesters. Information on anthropometric measures at birth, gestational age and prematurity was retrieved from medical records. The sum on a molar basis of DAPs with methyl (Æ©DMs) and ethyl (Æ©DEs) moieties and the sum of the 6 DAPs metabolites (Æ©DAPs) was calculated for both trimesters of pregnancy. High urinary levels of dimethyl phosphate (DMP) during the 3rd trimester were associated with a decrease in birth weight (ß = -0.24; 95% CI: 0.41; -0.06) and birth length (ß = -0.20; 95% CI: 0.41; 0.02). Likewise, ΣDMs during 3rd trimester were near-significantly associated with decreased birth weight (ß = -0.18; 95% CI: 0.37; 0.01). In turn, increased urinary TCPy during 1st trimester was associated with a decreased head circumference (ß = -0.31; 95% CI: 0.57; -0.06). Finally, an increase in 3-PBA in the 1st trimester was associated with a decreased gestational age (ß = -0.36 95% CI: 0.65-0.08), whereas increased 3-PBA at 1st and 3rd trimester was associated with prematurity. These results indicate that prenatal exposure to organophosphate and pyrethroid insecticides could affect normal foetal growth, shorten gestational age and alter anthropometric measures at birth.

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge.

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.

A step towards harmonising human biomonitoring study setup on European level: Materials provided and lessons learnt in HBM4EU.

Internal exposure of the human body to potentially harmful chemical substances can be assessed by Human Biomonitoring (HBM). HBM can be used to generate conclusive data that may provide an overview of exposure levels in entire or specific population groups. This knowledge can promote the understanding of potential risks of the substances of interest or help monitoring the success of regulatory measures taken on the political level. Study planning and design are key elements of any epidemiologic study to generate reliable data. In the field of HBM, this has been done using differing approaches on various levels of population coverage so far. Comparison and combined usage of the resulting data would contribute to understanding exposure and its factors on a larger scale, however, the differences between studies make this a challenging and somewhat limited endeavour. This article presents templates for documents that are required to set up an HBM study, thus facilitating the generation of harmonised HBM data as a step towards standardisation of HBM in Europe. They are designed to be modular and adaptable to the specific needs of a single study while emphasising minimum requirements to ensure comparability. It further elaborates on the challenges encountered during the process of creating these documents during the runtime of the European Joint Programme HBM4EU in a multi-national expert team and draws up lessons learnt in the context of knowledge management.

[Climate change and vector-borne diseases. From knowledge to action]. / Cambio climático y enfermedades transmitidas por vectores. Convertir el conocimiento en acción.

Andalusia is particularly sensitive to climate change, not only because of extreme weather events, but also because of the impact on the population dynamics of vectors, pathogens, reservoirs and hosts, which has led to a change in the epidemiological patterns of vector-borne diseases. In order to achieve an integrated vector management for disease control, public action is necessary. This study describes the design of the initial phase of a strategy for knowledge translation about climate change and vector-borne diseases to the public, using transdisciplinary co-creation and the World Café participatory method with three discussion rounds to address strategies for three age groups (adults, adolescents and schoolchildren). The aim is to drive knowledge into action and for this purpose the underlying messages for action (strategic and instrumental) have been identified, as well as the formats of the knowledge products and the potential implementers of the strategies.

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health.

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

The questionnaire design process in the European Human Biomonitoring Initiative (HBM4EU).

BACKGROUND: Designing questionnaires is a key point of epidemiological studies assessing human exposure to chemicals. The lack of validated questionnaires can lead to the use of previously developed and sub-optimally adapted questionnaires, which may result in information biases that affect the study's validity. On this ground, a multidisciplinary group of researchers developed a series of tools to support data collection within the HBM4EU initiative. The objective of this paper is to share the process of developing HBM4EU questionnaires, as well as to provide researchers with harmonized procedures that could help them to design future questionnaires to assess environmental exposures. METHODS: In the frame of the work package on survey design and fieldwork of the HBM4EU, researchers carried out procedures necessary for the development of quality questionnaires and related data collection tools. These procedures consisted of a systematic search to identify questionnaires used in previous human biomonitoring (HBM) studies, as well as the development of a checklist and evaluation sheet to assess the questionnaires identified. The results of these evaluations were taken into consideration for the development of the final questionnaires. RESULTS: The main points covered by each of the sections included in HBM4EU questionnaires are described and discussed in detail. Additional tools developed for data collection in the HBM4EU (e.g. non-responder questionnaire, satisfaction questionnaire, matrix-specific questionnaire) are also addressed. Special attention is paid to the limitations faced and hurdles overcome during the process of questionnaire development. CONCLUSIONS: Designing questionnaires for use in HBM studies requires substantial effort by a multidisciplinary team to guarantee that the quality of the information collected meets the study's objectives. The process of questionnaire development described herein will contribute to improve the harmonization of HBM studies within the social and environmental context of the EU countries.

Validity and Reproducibility of a Food Frequency Questionnaire to Assess Nutrients Intake of Pregnant Women in the South-East of Spain.

Proper nutrition during pregnancy is pivotal to maintain good health for the child and the mother. This study evaluates the reproducibility and validity of a food frequency questionnaire (FFQ) designed to assess nutrient intake during pregnancy in the GENEIDA (Genetics, Early life Environmental Exposures and Infant Development in Andalusia) prospective birth cohort study. In addition, the nutrient intake was estimated and then compared with European guidelines and other studies. Diet information was collected from 690 pregnant women using a FFQ administered at two periods of pregnancy (used for the reproducibility study) and 24-h dietary recall (for the validity study). Statistical approaches included Spearman's correlation coefficient and percentage agreement, classifying women into the same or adjacent quintiles to assess reproducibility, and limits of agreement (LoA) to evaluate validity. In the study of reproducibility, significant correlations for nutrients adjusted for total energy had an average of 0.417. Moreover, the percentage of subjects classified in the same quintile for nutrient intakes were above 66%. In the validation study, the significant correlation for nutrients adjusted for total energy had an average of 0.272. Nevertheless, the percentage of results in the LoA was above 94%. Our results were similar to other studies suggesting that the FFQ used is a valid tool of collect dietary intakes for South-East Spanish pregnant women.

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism and Infant's Anthropometry at Birth.

Identification of causal factors that influence fetal growth and anthropometry at birth is of great importance as they provide information about increased risk of disease throughout life. The association between maternal genetic polymorphism MTHFR(677)C>T and anthropometry at birth has been widely studied because of its key role in the one-carbon cycle. MTHFR(677) CT and TT genotypes have been associated with a greater risk of low birth weight, especially in case of deficient intake of folic acid during pregnancy. This study aimed to analyze the association between the maternal MTHFR(677)C>T genetic polymorphism and anthropometry at birth in a population with adequate folate consumption. We included 694 mother-newborn pairs from a prospective population-based birth cohort in Spain, in the Genetics, Early life enviroNmental Exposures and Infant Development in Andalusia (GENEIDA) project. Women were genotyped for MTHFR(677)C>T SNP by Q-PCR using TaqMan© probes. Relevant maternal and newborn information was obtained from structured questionnaires and medical records. Results showed that maternal MTHFR(677)C>T genotype was associated with newborn anthropometry. Genotypes CT or CT/TT showed statistically significant associations with increased or decreased risk of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) based on weight and height, depending on the newborn's sex, as well as with SGA in premature neonates. The relationships between this maternal genotype and anthropometry at birth remained despite an adequate maternal folate intake.

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides.

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase -ALP- and γ-glutamyl transferase -GGT-), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (-OTC-), Arginase-1 -ARG1- and glutathione S-transferase alpha -GSTα-) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO2, CO, PM2.5, PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es.

Childhood chromium exposure and neuropsychological development in children living in two polluted areas in southern Spain.

This study aimed to assess the association between exposure to chromium and neuropsychological development among children. A cross-sectional study was conducted with 393 children aged 6-11 years old randomly selected from State-funded schools in two provinces in Southern Spain (Almeria and Huelva), in 2010 and 2012. Chromium levels in urine and hair samples were analyzed by inductively coupled plasma mass spectrometry with an octopole reaction system. Neuropsychological development was evaluated using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and three computerized tests from the Behavioural Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariable linear regression models adjusted for potential confounders, including heavy metals, were applied to examine the association between chromium levels and neuropsychological outcomes. A 10-fold increase in urine chromium levels was associated with a decrease of 5.99 points on the WISC-IV Full-Scale IQ (95% CI: 11.98 to -0.02). Likewise, a 10-fold increase in urine chromium levels in boys was associated with a decrease of 0.03 points in the percentage of omissions (95% CI: 0.0 to 0.05) in the SAT, with an increase of 68.35 points in latency (95% CI: 6.60 to 130.12) in the RTT, and with an increase in the number of trials with latencies > 1000 ms (ß = 37.92; 95% CI: 2.73 to 73.12) in the RTT. An inverse significant association was detected between chromium levels in hair and latency in the SAT in boys (ß = -50.53; 95% CI: 86.86 to -14.22) and girls (ß = -55.95; 95% CI: 78.93 to -32.97). Excluding trials with latencies >1000 ms in the RTT increased latency scores by 29.36 points in boys (95% CI: 0.17 to 58.57), and 39.91 points in girls (95% CI: 21.25 to 58.59). This study is the first to show the detrimental effects of postnatal chromium exposure on neuropsychological development in school-aged children.

Biomonitoring of common organophosphate metabolites in hair and urine of children from an agricultural community.

Levels of dialkylphosphate (DAP) metabolites were measured in hair and urine of children that lived close to intensively farmed areas of Almeria (Southeast Spain). The levels were used as proxies for exposure of these children to organophosphate pesticides (OPs). Determinants of exposure to DAPs were also examined. Urine and hair samples were collected from 222 children aged 3-11 years and information on lifestyle and dietary habits was collected from questionnaires administered to mothers. Urinary DAPs were analyzed by ultra-high performance liquid-chromatography coupled to triple-quadrupole tandem mass-spectrometry (UHPLC-QqQ-MS/MS) and hair DAPs by gas-chromatography coupled to mass spectrometry (GC-MS). Detection rates ranged from 21.8% for diethylphosphate (DEP) and diethylthiophosphate (DETP) to 35.9% for dimethylphosphate (DMP) in urine; and from 42.3% for DETP to 92.8% for DMP in hair. Diethyldithiophosphate (DEDTP) was detected in 0.5% of urine samples (one child), and in 26.6% of children's hair samples. A lack of correlation was observed for individual DAP metabolites and ΣDAPs between urine and hair samples, except for DEDTP. Urinary DAP levels of our child population were lower than those reported for children from other countries, including NHANES 1999-2000 data. The main determinants of hair DAP levels were age, sex, vegetable intake, parental exposure to pesticides at work, time spent playing indoors, monthly income and father's education level. Conversely, none of the predictors studied was significantly associated with urinary DAPs except age. Overall, hair has advantages over urine as it is easier to collect, handle and store, and allows for assessment of cumulative exposure to OPs, thus providing a greater insight for human biomonitoring.