OBJECTIVE:To assess secular trend in age at menarche spanning nearly eight decades and to explore variations in these patterns according to selected sociodemographic and anthropometric determinants in the Valencian Community, Spain. MATERIALS AND METHODS:This population-based study included 417 260 participants born between 1931 and 2008. First, secular trend in age at menarche were assessed using time-series models across 5-year birth cohorts for the overall population. Then, 5-year birth cohorts were combined into two groups based on the data availability for the determinant analyses: an earlier-born group (1941-1975), whose age at menarche was reported retrospectively in adulthood, and a later-born group (1991-2005), whose age at menarche was collected during childhood and/or adolescence. Bayesian linear regression models were fitted for each group, adjusting for 5-year birth cohort and continent of birth in all models, and additionally for educational level in the earlier-born group and body mass index (BMI) in the later-born group. RESULTS:Mean age at menarche decreased by 1.9 years, from 13.1 to 11.1, between the 1931-1935 and 2006-2008 birth cohorts, with a steeper decline after 1975. Compared with European-born participants, those born in South/Central America (β [95% CI]: 0.33 [0.30, 0.36] years) and Africa (0.52 [0.45, 0.58] years) experienced later menarche in the earlier-born group, whereas those born in South/Central America experienced earlier menarche in the later-born group (-0.18 [-0.28, -0.09] years). In the later-born group, lower BMI was associated with later menarche (0.96 [0.74, 1.18] years) whereas higher BMI with earlier onset (-0.53 [-0.57, -0.48] years). CONCLUSION:There was a marked decline in age at menarche in the Valencian Community. Factors associated with age at menarche included continent of birth (with cohort-specific effects) and BMI.

Background: Menarche is a critical developmental milestone, with earlier onset associated with adverse long-term health consequences. Despite a reported global decline in age at menarche over the last century, this trend and its determinants remain insufficiently studied in Spain. Objective: To assess secular trends in age at menarche and its determinants in the Valencian Community, Spain. Methods: This population-based study included 417,260 participants born between 1931 and 2008. First, secular trends in age at menarche were assessed using time-series models across 5-year birth cohorts for the overall population. Then, participants were categorized as either women (born 1931-1985) or girls (born 1990-2008), and Bayesian linear regression models were fitted for each group, adjusting for birth cohort and continent of birth in all models, and additionally for educational level in women and body mass index (BMI) in girls. Results: Mean age at menarche decreased by 1.9 years, from 13.1 to 11.1, between the 1931-1935 and 2006-2008 birth cohorts, with a steeper decline after 1975. Compared to Europeans, women born in South/Central America (β[95% CI]: 0.33[0.30, 0.36] years) and Africa (0.52[0.45, 0.58] years) experienced later menarche, while girls from South/Central America experienced earlier onset (-0.18[-0.28, -0.09] years). In girls, lower BMI was associated with later menarche (0.96[0.74, 1.18] years) and higher BMI with earlier onset (-0.53[-0.57, -0.48] years). Conclusion: There was a marked decline in age at menarche in the Valencian Community, with no evidence of leveling off. Key determinants included continent of birth (with cohort-specific effects) and BMI. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This article received funding from multiple sources. European Union funding was provided through the ATHLETE project (Grant Agreement No. 874583) under the Horizon 2020 programme, and the JAPreventNCD project (Grant Agreement No. 101128023), co-funded by the EU4Health Programme 2021-2027. Additional funding was provided by Spanish institutions, including the Ministry of Science, Innovation and Universities (Grant CNS2023-145286, funded by MICIU/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR); the Spanish Association Against Cancer (MICROVAGIPAP: IDEAS19098LOPE); the CIBER of Epidemiology and Public Health (PAPILONGO: ESP21PI03); the General Council of Official Nursing Associations of Spain (PAPISEX: inv\_cge\_2022_04); the Foundation for the Promotion of Health and Biomedical Research of the Valencian Region (PAPILONG: UGP-20-242); the Regional Ministry of Innovation, Universities, Science and Digital Society of the Generalitat Valenciana (MENTABIOTA: AICO/2021/182 and CIAICO/2023/184); and the Fundacio La Marato (202414). In addition, this article was supported by funding for research positions from the Carlos III Health Institute (Miguel Servet-FEDER: CP11/00178, MSII16/00051, CP20/0006, and Sara Borrell: CD23/00090, all co-funded by the European Union), as well as the Regional Ministry of Innovation, Universities, Science and Digital Society (Investigo contracts: INVEST/2022/310 and CIACIF/2022/268). The latter corresponds to a grant from the Programme for the Promotion of Scientific Research, Technological Development and Innovation in the Valencian Community, supporting the recruitment of predoctoral research staff and eligibility for co-financing by the European Social Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All study protocols, including two secondary population-based registries and two datasets collected by the research team, were approved by the Directorate of Public Health and the Higher Centre for Research in Public Health (DGSP-CSISP) Ethics Committee from Valencia (references numbers: 20180112/03; 20190329/3; 20190301/09/1; and 20210604/10/01). Secondary data were provided anonymized, while investigator-collected data were anonymized prior to analysis following written informed consent from participants or legal guardians (for minors). All procedures were conducted in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data from population-based registries (Valencian Breast Cancer Screening Program and the Ambulatory Care Information System of the Valencian Health Agency) are not publicly available due to ethical and legal restrictions related to the use of sensitive health data, and access is restricted. Data from the INMA and PAPILONG cohort studies are available upon request to the corresponding author and in accordance with the applicable data access procedures and ethical approvals. The INMA cohort data are subject to the INMA collaboration policy (https://www.proyectoinma.org/en/inma-project/inma-collaborationpolicy/).

Puberty relies on a hormone-regulated cascade of events initiated in fetal life and might be disrupted by prenatal exposure to endocrine-disrupting chemicals (EDCs), with alterations manifesting during pubertal development. However, studies addressing prenatal exposure to multiple EDCs remain scarce. This study explores the associations between prenatal exposure to 33 EDCs and early sex maturation in 386 Spanish mother-child pairs (girls: 49%; recruitment: 2003-2005). We measured seven organochlorine compounds (OCs) and four perfluoroalkyl substances (PFAS) in maternal blood, and seven phenols and 15 phthalates in maternal urine. Pubertal development was assessed at age 9 using Tanner staging for genital development (GD), breast development (BD), and pubic hair development (PH) alongside salivary sex hormones. Sex-specific analyses included single-chemical (robust Poisson/linear regression) and mixture (principal components/Bayesian kernel machine regression) analyses. In single-chemical models, higher prenatal p,p'-DDE and p,p'-DDT concentrations were associated with delayed BD and GD, respectively, while PCB-180 and parabens (ETPA, BUPA) were associated with earlier BD, and phthalates were associated with earlier PH (girls: MEHP, MEHHP, MEOHP, and MECPP; boys: MEP and MnBP). For sex hormones, β-HCH (both sexes), p,p'-DDE, PCB-180, PFOS (boys), and p,p'-DDT, OH-MPHP (girls) were positively associated with testosterone, and HCB was positively associated with estradiol (boys). Conversely, BUPA, OH-MPHP (boys), and BPA (girls) were inversely associated with testosterone. In chemical mixture models, the first component of OCs was positively associated with male testosterone, but the results of other mixture analyses were unclear. Overall, prenatal exposure to some EDCs may impair fetal programming of puberty, yet the impact of chemical mixtures remains uncertain.

Systemic inflammation during pregnancy is associated with adverse health outcomes for both mother and child. C-reactive protein (CRP) is a widely used biomarker of inflammation, and its levels may be influenced by environmental factors. This study examined the association between 26 components of the external urban exposome-including air pollutants, land use, and access to green and blue spaces-and CRP concentrations in 1547 pregnant women from the INMA birth cohort in Spain (Gipuzkoa, Sabadell, and Valencia). Environmental exposures during the first trimester were assessed using GIS-based indicators and land-use regression models, and were grouped into low, moderate, and high exposome clusters using hierarchical clustering on principal components. Associations between exposome clusters and CRP were evaluated using multivariable linear regression models and meta-analyses, adjusting for maternal and lifestyle covariates. No significant associations were found between exposome clusters and CRP levels. However, specific air pollutants-fine particulate matter (PM2.5: 1.08% increase per unit; 95% CI: 1.02-1.15) and nitrogen oxides (NOx: 1.03%; 95% CI: 1.00-1.06)-were positively associated with CRP. No associations were observed for green space indicators or other built environment variables. CRP concentrations also varied by region, with the highest levels observed in Valencia (3.2 ± 4.6 mg/dL). These findings suggest that while overall urban exposome profiles may not predict systemic inflammation, individual air pollutants such as PM2.5 and NOx are key contributors. Targeting these exposures in maternal health strategies may help mitigate inflammation-related risks during pregnancy, supporting the need for more detailed and component-specific exposome assessments.

This study aimed to evaluate the association between prenatal exposure to inorganic arsenic (iAs) and maternal and offspring thyroid hormone levels, assessed during pregnancy and at 15 years of age. We also evaluated the role of genetic polymorphisms in the DIO1 and DIO2 genes in this associationThe study population comprised pregnant women-offspring pair participants in the INMA project in Spain. Free thyroxine (FT4), total triiodothyronine (TT3) and thyroid-stimulating hormone (TSH) were measured in serum samples collected during the first trimester and at 15 years of age. iAs and its metabolites (DMA, MMA) were measured in urine samples collected during the first trimester. The sum of iAs and its metabolites (SumAs) and the iAs methylation efficiency (%iAs, %DMA, %MMA) were calculated. Covariates were obtained through questionnaires. Two SNPs in the DIO1 (rs2235544) and DIO2 (rs12885300) genes were genotyped in maternal and offspring DNA. The association between maternal As exposure and thyroid hormone levels measured at both time points (n=981 and n=330) was evaluated using multivariable linear regression models. Interaction terms were included in the models in order to evaluate effect modification.A lower methylation efficiency of maternal iAs (denoted as higher %MMA) was directly associated with maternal FT4, and maternal SumAs concentrations were directly associated with adolescent TSH levels. Additionally, these associations seemed to be modified by two SNPs in the DIO1 and DIO2 genes. Our results suggest that prenatal exposure to iAs could disrupt thyroid function during both pregnancy and adolescence, and that deiodinase enzymes may play a role.

The rapid urbanisation of many countries has raised important questions about how neighbourhood characteristics affect wellbeing, particularly during adolescence, a period of vulnerability to mental health conditions. This study investigated how population density, neighbourhood deprivation, green space availability and residential greenness are related to psychological wellbeing in adolescence, as well as the role of perceived social support and autonomy in this relationship. Using data from 970 participants aged 9–17 years in the INMA (Infancia y Medio Ambiente) cohort in Spain, collected between 2016 and 2022, we applied a set of linear mixed effects models to examine these associations, and also explored potential differences by age, sex and family affluence. The results showed an association between higher residential greenness and better psychological wellbeing in older adolescents (15–17 years). This association was partially mediated by greater family support and feelings of autonomy. In addition, there was an association between higher population density and worse psychological wellbeing in older adolescents. No significant associations were found between neighbourhood deprivation, green space availability and psychological wellbeing. Finally, the relationships reported in this study were not modified by family affluence. These findings suggest that neighbourhood residential greenness could contribute to feelings of family support and autonomy, which contribute to important aspects of psychosocial adaptation during adolescence.

BACKGROUND:To assess the prenatal, early postnatal and adolescent factors associated with overweight/obesity (OwO) and other cardiometabolic risk factors at age 15. METHODS:Longitudinal study based on 241 participants from the INMA-Valencia cohort. Z-scores of body mass index (zBMI), waist circumference (zWC), and waist-to-height ratio (WHtR), systolic and diastolic BP (zSBP and zDBP) were evaluated at ages 4, 7, 9, 11 and 15. A cardiometabolic risk score was calculated. Covariates were collected at pregnancy, birth, and age 15. RESULTS:At age 4, 30.7% presented overweight/obesity (zBMI > 1 SD), increasing to 46.1% at age 9, and decreasing to 29.3% at age 15 (29.3%). The proportion of high/excess central adiposity was lower than overweight/obesity at all ages. Adjusted models showed that pre-pregnancy obesity was positively associated with all cardiometabolic outcomes, except zSBP (i.e. β [95% CI]: 0.77 [0.25, 1.29] for zBMI, and 2.31 [0.94, 3.69] for CMR score). Smoking during pregnancy was directly related to zSBP and zBMI. Adolescent physical activity was inversely associated with WHtR, zFM, zWC, zDBP and cardiometabolic risk scores (β -0.65 [95% CI -0.95, -0.36]). Cereal intake and processed meat consumption were positively related to WHtR, zBMI and zWC. CONCLUSION:Early modifiable factors impact adolescent cardiometabolic health. This information could improve preventive interventions and policies from very early. IMPACT:This longitudinal study shows how sociodemographic, clinical, and lifestyle factors influence adolescents' cardiometabolic health from very early stages of life until adolescence. Maternal characteristics, such as pre-gestational obesity or tobacco consumption during pregnancy, were directly associated with cardiometabolic risk factors in adolescence, such as BMI, percentage of fat mass, and diastolic blood pressure. Adolescents' intake of cereals, and processed meats, and consumption of less than five dairy meals, were positively related to an increase in cardiometabolic risk factors. Findings from this longitudinal study provide valuable insights for designing early-life interventions in prevention, health promotion, and adolescent health management.

Background/Objectives: To analyze the prevalence and risk factors associated with the onset of urinary incontinence (UI) in primiparous non-menopausal women with no personal history of pregestational UI, as well as its impact on quality of life. Methods: An ambispective observational cohort study was conducted among primiparous women between 5 and 10 years after childbirth. Sociodemographic and health characteristics were analyzed, along with the presence of UI using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Results: Of the 425 women analyzed, 228 (53.6%) presented UI. After adjusting for confounding factors, women who delivered by cesarean section showed a lower risk of developing UI (aOR = 0.52; 95% CI: 0.32-0.85; p = 0.009). Conversely, a family history of UI (mother or sister) (aOR = 2.03; 95% CI: 1.25-3.32; p = 0.004) and the presence of medical history (chronic diseases/comorbidities) were associated with a higher risk of UI (aOR = 1.58; 95% CI: 1.02-2.45; p = 0.040). Regarding quality of life, 25.88% of participants responded affirmatively to the specific interview question on UI, whereas 58.65% presented some degree of UI when assessed with the ICIQ-UI-SF. This discrepancy likely corresponds to mild-to-moderate cases. Conclusions: In primiparous, non-menopausal women without prior incontinence, the occurrence of UI in subsequent years following childbirth is associated with vaginal delivery, family history of UI, and the presence of chronic diseases or comorbidities. Evidence-based strategies for detection and prevention should be further developed and implemented.

Background Children growing up in disadvantaged socioeconomic circumstances (SECs) have an increased risk of asthma. Objective To increase our understanding of the pathways to inequalities in asthma and potential targets for intervention by (1) examining how the social patterning of asthma and its early-life risk factors varies across countries and (2) quantifying the mediation of observed inequalities by early-life risk factors. Methods We used data for 107,884 mother-child dyads from 7 European birth cohorts across 6 countries. Maternal education was the primary exposure measure of early-life SECs. The outcome was current asthma in childhood (3-12 years). Inequalities were examined using multivariable regression and random effects meta-analysis. The mediating effects of early-life risk factors (maternal smoking during pregnancy, adverse birth outcomes, and breastfeeding duration) were examined using counterfactual mediation analysis. Results In meta-analysis, children of mothers with low/medium versus high education had a 17% (95% confidence interval: 8%-27%, I2 = 21.6%) increased risk of asthma. Cohort-specific risk ratios ranged between 1.07 (0.97-1.18, Danish National Birth Cohort, Denmark) and 1.61 (1.08-2.40, study on the pre- & early postnatal determinants of child health & development, France). The early-life risk factors were similarly socially patterned, but with greater heterogeneity across cohorts (I2 range = 66.2%-95.3%). The mediation analysis suggested that these factors play a relevant role in mediating observed inequalities (proportion mediated range: 0.08-0.72). Conclusions There was a consistent tendency for children from disadvantaged SECs to be at greater risk of asthma in the European cohorts examined. Our results suggest that early-life risk factors partially mediate these disparities and, therefore, that public health interventions in the perinatal period may help to address inequalities in asthma.

Context 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. Objective 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 the United States 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 particulate matter (PM)2.5 and higher odds of suboptimal vitamin D levels (ie, 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. Conclusion 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.

Human exposure to mycotoxins is a global concern since several mycotoxins, such as enniatins and aflatoxins, have shown carcinogenic and neurotoxic effects, and the toxicologic mechanisms of most of them still need to be clarified. This study aims to investigate the metabolic pathways affected by mycotoxin exposure by evaluating metabolite alterations in urine. The participants were 540 women from the Spanish Childhood and Environment Project (INMA). For metabolite identification, a dilute and shoot extraction, followed by HPLC-Q-TOF-MS identification analysis, was performed. Data were processed using Agilent Mass Hunter Workstation with the METLIN database, Agilent Mass Profiler Professional 10.0, and Metaboanalyst 6.0. Over 2000 metabolites were obtained in each sample after feature extraction, and the most significant metabolites (p-value ≤ 0.05, fold change ≥ 2.0) were considered for pathway analysis. Enrichment analysis and topology showed that the most significantly affected pathway was the biosynthesis of unsaturated fatty acids (adjusted p-value = 0.007), with four metabolomic hits associated: linoleic acid, octadecanoic acid/stearic acid, an arachidonic acid metabolite, and (9Z)-octadecenoic acid/oleic acid. Other related pathways (unadjusted p-value ≤ 0.1) included fatty acid biosynthesis, glycerophospholipid metabolism, and ether lipid metabolism. The present study highlights the importance of metabolomics in increasing knowledge of the toxicity mechanisms and health effects of mycotoxins, especially emerging ones.

RATIONALE Atopic diseases are commonly present in childhood. We aimed to create a novel collaborative library of individual-level participant data for research on atopic diseases from birth through adolescence, and to demonstrate its prevalences and general high-risk groups. METHODS We harmonized and standardized individual-level data of 202,475 children from 14 European and Australian pregnancy and birth cohorts participating in the EU CHILD Cohort Network. Sex, geographic region, parental history of atopic diseases, physician-diagnosed current wheezing, asthma and eczema were primarily determined by parental-reported questionnaires, and physician-diagnosed inhalant allergy by parental-reported questionnaires and/or measurement of allergic sensitization by skin prick or allergen-specific Immunoglobulin E testing. Lung function measures were obtained by spirometry and converted into an age, sex, and ethnicity-adjusted obstructive lung function phenotype (FEV1/FVC < lower limited of normal). Statistical one-stage meta-analyses were performed through the shared federated R-based platform DataSHIELD. RESULTS Across cohorts, mean prevalences of eczema and wheezing were highest in infancy (<1y) or at preschool age (1-4y) after which they gradually declined into adolescence (≥12y)(21% to 5.2% and 23% to 16%, respectively), while those of inhalant allergy and asthma were reversely present (4.9% to 18% and 6.2% to 12%, respectively)(Figure 1). The prevalence of obstructive lung function remained consistent from school age (5-11y) through adolescence (5.5% to 5.9%). Compared to girls, boys had a higher prevalence of wheezing in infancy, at preschool age and at school age (27% vs. 19%; 26% vs. 21%; 19% vs. 16%, respectively), asthma in adolescence (13% vs. 10%), eczema at school age (14% vs. 13%), and inhalant allergy in adolescence (20% vs. 15%)(p-values <0.05 for meta-analyzed χ2 test for differences in prevalences). All atopic diseases from birth until adulthood were evenly present among children from Northern European/Western European/Australian and Southern European regions. Children with a family history of atopic diseases more often had wheezing in infancy and at preschool age, asthma in adolescence, eczema at school age and in adolescence, and inhalant allergy in adolescence than those without a family history of atopic diseases (p-values <0.05). CONCLUSION Prevalences of atopic diseases vary from birth through adolescence and are more commonly present among boys and children with a family history of atopic diseases. The novel developed collaborative library of individual-level participant data could be used as a resource for meta-analyses on the early origins of atopic diseases (https://data-catalogue.molgeniscloud.org/catalogue/ssr-catalogue/EUChildNetwork).

Whether greenspace affects lung function is unclear. We explored associations between the level of greenness or presence of urban green space near the home with lung function measures taken repeatedly during childhood and adolescence in five European birth cohorts. Lung function was measured by spirometry between six and 22 years (2-3 times), and 9,206 participants from BAMSE (Sweden), GINI/LISA South and GINI/LISA North (Germany), PIAMA (The Netherlands) and INMA (Spain) contributed at least one lung function measurement. The mean Normalized Difference Vegetation Index (NDVI) in a 300 m buffer and presence of urban green space within a 300 m buffer (yes/no) were estimated at the home address at the time of each spirometry measurement. Cohort-specific associations were assessed using adjusted linear mixed models and combined in a random-effects meta-analysis. Residential greenness was not associated with forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or FEV1/FVC in the meta-analysis (2.3 ml [-3.2, 7.9], 6.2 ml [-3.4, 15.7] and -0.1 [-0.3, 0.1] per 0.1 increase in NDVI, respectively), nor was having a nearby urban green space (-8.6 ml [-22.3, 5.0], -7.6 ml [-24.7, 9.4] and 0.0 [-0.4, 0.3], respectively). Heterogeneity was low to moderate (I2 = 0 -39 %). Asthma, atopy, air pollution, sex, socioeconomic status and urbanization did not modify the null associations. Using repeated data from five large independent European birth cohorts, we did not find associations between vegetation levels around the home or the presence of an urban green space and lung function levels during childhood and adolescence.

Since its emergence, the COVID-19 pandemic has profoundly and extensively affected global health and society. Numerous studies have focused on detecting SARS-CoV-2 in air samples collected in healthcare indoor spaces, but few have analysed its presence in air samples from other public community spaces. In addition, limited studies have surveyed indoor spaces where it was not known if individuals with COVID-19 were present or had been present at the time of sampling. This study aimed to determine the SARS-CoV-2 genetic load in aerosol samples collected in public community indoor environments where prior knowledge of the presence of infected individuals with COVID-19 cases is not available at the time of sampling. Air samples (N = 497) were collected from healthcare settings, elderly care homes, and educational settings in the Valencian Community, Spain. RNA was extracted and the N1, N2, and E gene fragments of SARS-CoV-2 were quantified using RT-qPCR. SARS-CoV-2 RNA was detected in 8.9 % of air samples. The highest positivity rates were observed in hospitals (16.2 %), elderly care homes (15.3 %), and primary care centres (12.7 %). Concentration of the N1 gene in positive samples ranged 4.3–504 gc/m3 (n = 10), 6.2–77 gc/m3 (n = 8) and 5.1–14 gc/m3 (n = 7), respectively. The genes N2 and E were less frequently detected and generally reported lower concentrations. The frequency of detection of SARS-CoV-2 in aerosols increased at the same time that the population COVID-19 cumulative incidence increased.

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.

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 (β = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (β = 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 (β = -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.