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Introduction: Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children., Methods: This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts. Associations between profiles of pregnancy (38 exposures) and childhood (84 exposures) urban and lifestyle factors, identified by clustering analysis, and respiratory health were estimated by regression models adjusted for confounders., Results: Among the 1033 included children (mean ± standard-deviation (SD) age: 8.2 ± 1.6 years old, 47% girls) the mean ± SD forced expiratory volume in 1s (FEV 1 ) and forced vital capacity (FVC) were 99 ± 13% and 101 ± 14%, respectively, and 12%, 12% and 24% reported ever-asthma, wheezing and rhinitis, respectively. Four profiles of pregnancy exposures and four profiles of childhood exposures were identified. Compared to the reference childhood exposure profile (low exposures), two exposure profiles were associated with lower levels of FEV 1 . One profile was characterized by few natural spaces in the surroundings and high exposure to the built environment and road traffic. The second profile was characterized by high exposure to meteorological factors and low levels of all other exposures and was also associated with an increased risk of ever-asthma and wheezing. A pregnancy exposure profile characterized by high exposure levels to all risk factors, but a healthy maternal lifestyle, was associated with a lower risk of wheezing and rhinitis in children, compared to the reference pregnancy profile (low exposures)., Conclusion: This comprehensive approach revealed pregnancy and childhood profiles of urban and lifestyle exposures associated with lung function and/or respiratory conditions in children. Our findings highlight the need to pursue the study of combined exposures to improve prevention strategies for multifactorial diseases such as asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aetiology of every human disease lies in a combination of genetic and environmental factors, each contributing in varying proportions. While genomics investigates the former, a comparable holistic paradigm was proposed for environmental exposures in 2005, marking the onset of exposome research. Since then, the exposome definition has broadened to include a wide array of physical, chemical, and psychosocial factors that interact with the human body and potentially alter the epigenome, the transcriptome, the proteome, and the metabolome. The chemical exposome, deeply intertwined with the metabolome, includes all small molecules originating from diet as well as pharmaceuticals, personal care and consumer products, or pollutants in air and water. The set of techniques to interrogate these exposures, primarily mass spectrometry and nuclear magnetic resonance spectroscopy, are also extensively used in metabolomics. Recent advances in untargeted metabolomics using high resolution mass spectrometry have paved the way for the development of methods able to provide in depth characterisation of both the internal chemical exposome and the endogenous metabolome simultaneously. Herein we review the available tools, databases, and workflows currently available for such work, and discuss how these can bridge the gap between the study of the metabolome and the exposome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Health effects of endocrine disrupting chemicals (EDCs) are challenging to detect in the general population. Omics technologies become increasingly common to identify early biological changes before the apparition of clinical symptoms, to explore toxic mechanisms and to increase biological plausibility of epidemiological associations. This scoping review systematically summarises the application of omics in epidemiological studies assessing EDCs-associated biological effects to identify potential gaps and priorities for future research. Ninety-eight human studies (2004-2021) were identified through database searches (PubMed, Scopus) and citation chaining and focused on phthalates (34 studies), phenols (19) and PFASs (17), while PAHs (12) and recently-used pesticides (3) were less studied. The sample sizes ranged from 10 to 12,476 (median = 159), involving non-pregnant adults (38), pregnant women (11), children/adolescents (15) or both latter populations studied together (23). Several studies included occupational workers (10) and/or highly exposed groups (11) focusing on PAHs, PFASs and pesticides, while studies on phenols and phthalates were performed in the general population only. Analysed omics layers included metabolic profiles (30, including 14 targeted analyses), miRNA (13), gene expression (11), DNA methylation (8), microbiome (5) and proteins (3). Twenty-one studies implemented targeted multi-assays focusing on clinical routine blood lipid traits, oxidative stress or hormones. Overall, DNA methylation and gene expression associations with EDCs did not overlap across studies, while some EDC-associated metabolite groups, such as carnitines, nucleotides and amino acids in untargeted metabolomic studies, and oxidative stress markers in targeted studies, were consistent across studies. Studies had common limitations such as small sample sizes, cross-sectional designs and single sampling for exposure biomonitoring. In conclusion, there is a growing body of evidence evaluating the early biological responses to exposure to EDCs. This review points to a need for larger longitudinal studies, wider coverage of exposures and biomarkers, replication studies and standardisation of research methods and reporting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to air pollution influences children's health, however, the biological mechanisms underlying these effects are not completely elucidated. We investigated the association between short- and medium-term outdoor air pollution exposure with protein profiles and their link with blood pressure in 1170 HELIX children aged 6-11 years. Different air pollutants (NO 2 , PM 10 , PM 2.5 , and PM 2.5abs ) were estimated based on residential and school addresses at three different windows of exposure (1-day, 1-week, and 1-year before clinical and molecular assessment). Thirty-six proteins, including adipokines, cytokines, or apolipoproteins, were measured in children's plasma using Luminex. Systolic and diastolic blood pressure (SBP and DBP) were measured following a standardized protocol. We performed an association study for each air pollutant at each location and time window and each outcome, adjusting for potential confounders. After correcting for multiple-testing, hepatocyte growth factor (HGF) and interleukin 8 (IL8) levels were positively associated with 1-week home exposure to some of the pollutants (NO 2 , PM 10 , or PM 2.5 ). NO 2 1-week home exposure was also related to higher SBP. The mediation study suggested that HGF could explain 19% of the short-term effect of NO 2 on blood pressure, but other study designs are needed to prove the causal directionality between HGF and blood pressure., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures., Objective: This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour., Methods: We studied 708 mother-child pairs from five European cohorts recruited in 2003-2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently., Results: LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations., Discussion: This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)