Research into the developmental origins of, and lifecourse influences on, health and disease has a significant gap: infections. Clinical and subclinical infections are nearly universal in early life and can induce structural and functional changes in developing organ systems with life-long consequences. Emerging evidence links common childhood infections—such as Epstein–Barr virus, Cytomegalovirus and Helicobacter pylori—to so-called non-communicable diseases ranging from respiratory to neurodevelopmental and cardiometabolic diseases. Identifying infectious determinants of non-communicable diseases offers substantial opportunities for prevention and early intervention. We describe a newly developed infectious data resource within the EU Child Cohort Network, designed to enable triangulation of evidence on the impact of early life infections on children’s health and long-term trajectories of disease. The network established in 2017, currently brings together 37 pregnancy and childhood cohorts from 16 predominantly European countries and follows over 300,000 children and their families from pregnancy through childhood and, in many cohorts, into adulthood. Cohorts include a comprehensive set of harmonized variables covering health and disease phenotypes (cardiometabolic, respiratory, and mental) that are also well-established early indicators of later-life non-communicable disease risk. Building upon this, we present here the extensive infections data available in the cohorts ranging from questionnaires and registries to serological measurements for more than 20 pathogens. Harmonizing and integrating infection data within the EU Child Cohort Network supports a shift from viewing infections solely as causes of acute disease towards recognising them as integral components of the early-life exposome and potential determinants of lifelong health trajectories.

Background & aims: The human gut microbiota plays a key role in health. Factors shaping its composition and diversity have been widely studied during infancy and adulthood, but far less in adolescence, despite this being a key developmental stage. We examined the potential associations between the gut microbiota of adolescents and 82 variables measured from pregnancy to adolescence. Methods: In this cross-sectional study, stool samples were collected from 366 adolescents (age range: 13-16 years) from two INMA cohorts (Spain), while a range of variables, including diet, lifestyle, sociodemographic factors, health status, antibiotic use, vaccination, COVID-19, anthropometrics, and pubertal development, were collected from pregnancy to adolescence. The gut microbiota was characterized using 16S rRNA gene sequencing and assessed using α- and β-diversity indices and abundances of individual taxa. Associations were evaluated using linear models and permutational multivariate analysis of variance (PERMANOVA). Results: Vegetable intake during pregnancy was positively associated with α-diversity, as well as with general composition and the abundance of four genera (inversely with Dialister , Lachnoclostridium and Agathobacter , and positively with Phascolarctobacterium ). Legume intake was also inversely associated with Desulfovibrionaceae and Sutterella . During adolescence, cereal and pasta intake was positively associated with α-diversity, as well as with general composition and inversely associated with Bacteroides , whereas fish and seafood intake was inversely associated with α-diversity. Relevant non-dietary variables measured during pregnancy and at birth, such as biological sex, parental social class, and maternal education, and during adolescence, such as antibiotic use, body mass index, and pubertal status, were also associated with general composition of the gut microbiota and different taxa in either direction. Conclusions: Diet during pregnancy and adolescence, together with some anthropometric, clinical, and biological factors, appeared to play an important role in shaping the composition and diversity of the gut microbiota in this population of adolescents.

Despite the availability of vaccinations and screenings, cervical cancer (CC) remains a major global health challenge. Understanding the factors influencing adherence to CC prevention strategies is essential, particularly among overlooked groups such as middle-aged and/or underprivileged women. For this purpose, a cross sectional study was conducted in a population comprising 379 women (aged 37 to 64 years, recruitment: 2019 to 2023) from Valencia (Spain), representing diverse socioeconomic profiles, including female sex workers (FSWs; n = 46). Data were analysed using multivariate logistic regression models. Overall, 88.65% of participants adhered to CCS recommendations and 22.16% reported past-year condom use, compared with 86.96% and 76.09%, respectively, among FSWs. In the overall population, CCS adherence was significantly associated with higher education and marginally associated with a history of candidiasis, non-condom contraceptive use in the past year, and having more children and sexual partners. Higher condom use was associated with lower alcohol consumption, being single, non-Spanish origin, not being postmenopausal, use of vaginal health products, and not previous recurrent urinary tract infections. Marginally significant positive associations were also observed for the absence of chronic disease and a history of sexually transmitted infections. Among FSWs, earlier menarche age and lower gravidity were marginally associated with higher CCS adherence, while older age at entry into prostitution and earlier sexual debut were associated with condom use, the latter marginally significant. Overall, our findings highlight the importance of further research into underprivileged groups such as midlife women across socioeconomic strata. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This article received funding for projects from the European Union: ATHLETE (EU874583), funded under the European Union Horizon 2020 programme, and JAPreventNCD (GA101128023), co funded by the European Union under the EU4Health Programme 2021 2027; the Ministry of Science, Innovation and Universities (Grant CNS2023145286 funded by MICIU/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR); the Spanish Association Against Cancer (MICROVAGIPAP: IDEAS19098LOPE); CIBER of Epidemiology and Public Health (PAPILONGO: ESP21PI03); the General Council of Official Nursing Associations of Spain (PAPISEX: inv\_cge\_2022\_04 and inv\_cge\_2024\_14); the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (PAPILONG: UGP20242); and the Regional Ministry of Innovation, Universities, Science and Digital Society, Generalitat Valenciana (MENTABIOTA: AICO/2021/182 and CIAICO/2023/184). This work also received funding for research positions from the Carlos III Health Institute (Miguel Servet FEDER: CP20/0006 and Sara Borrell: CD23/00090, both co funded by the European Union); the Spanish Ministry of Universities (Margarita Salas Grant: MS21133); and the Regional Ministry of Innovation, Universities, Science and Digital Society (Investigo contracts: INVEST/2022/310 and INVEST/2023/219; and CIACIF/2022/268). The latter is 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 eligible 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: Ethics Committee for Research of the General Directorate of Public Health and the Higher Centre for Research in Public Health, Valencia, Spain gave ethical approval for this work (reference numbers: 20190301/09, 20190301/09/2, 20210604/10/02) 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 The data supporting the findings of this study are available upon request.

The consumption of ultra-processed foods (UPF) has been associated with adverse health effects. The predictors of consumption, particularly in high-intake groups like children and adolescents, are scarcely understood. We evaluated UPF consumption and associated factors among male and female Spanish children aged 8–12 years participating in the INMA birth cohort. We cross-sectionally analyzed data from 1565 mother–child pairs at age 8 and 314 pairs at age 12. Children’s diets were assessed using validated food frequency questionnaires. UPF consumption was defined using the NOVA classification and categorized into tertiles. The associations between maternal-child characteristics and children’s UPF consumption were analyzed using multinomial logistic regression to estimate relative risk ratios (RRR) and 95

BACKGROUND:Food allergy (FA) arises from a complex interplay between an individual's genetic predisposition and environmental factors, and its prevalence is increasing. Genome-wide association studies to date have been hindered by small sample sizes and varying FA definitions. OBJECTIVE:We sought to identify novel FA risk loci by conducting a genome-wide association study meta-analysis in children and adults by using a multiphenotype approach to ensure a good trade-off between sufficient sample size and valid FA definitions. METHODS:Analyses were conducted separately in children and adults on the basis of the following FA phenotypes: self-report, doctor diagnosis, food-specific sensitization, and doctor diagnosis plus food-specific sensitization. A meta-analysis was performed of genome-wide association studies from up to 16 cohorts of people of European ancestry including 229,426 adults and 14,234 children. Models were adjusted for sex, age, principal components, and, if applicable, further study-specific confounders. Sensitivity models were additionally adjusted for hay fever. Replication was conducted in additional external cohorts and a validation in oral food challenge-defined FA cases. RESULTS:Thirty-seven single nucleotide polymorphisms met suggestive significance (P < 1 × 10-6), with two reaching genome-wide significance: rs116936231 (FGL1) in adult doctor-diagnosed FA plus food-specific sensitization phenotype (stable after additional hay fever adjustment) and rs8022829 (AKAP6-NPAS3), which was significant only in the hay fever-adjusted model in adults. However, neither variant was validated. Further, we identified 3 single nucleotide polymorphisms previously reported for FA and atopic disease. CONCLUSION:This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies.

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.

Abstract Background Mercury is ubiquitous in the environment. Substantial levels of its organic form, methylmercury, pose a risk to fetal neurodevelopment through the maternal diet. Conversely, nutrients such as the polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) promote neurodevelopment. We aimed to elucidate the neuroprotective role of PUFA signaling against prenatal methylmercury exposure in a Mediterranean fish-consuming area, addressing a critical gap in understanding nutritional modulation of neurotoxicity. Methods Associations between levels of oxidized PUFA metabolites (oxylipins) in placental tissue (N = 12) or cord blood plasma (N = 39) and postnatal neurodevelopment in children were evaluated at two levels of prenatal mercury exposure. Low and moderate exposure groups were defined by total mercury concentrations in whole cord blood of 1.4–6.6 µg/L and 20–66 µg/L, respectively. Oxylipins were measured using liquid chromatography ­ mass spectrometry. Neurodevelopment was assessed at 14 months and 5 years using Bayley and McCarthy scales, respectively. Oxylipins were also analyzed in mouse brain tissue after treatment with a soluble epoxide hydrolase inhibitor to increase AA epoxide levels. Results Under low mercury exposure, EPA-, DHA- and AA-derived placental oxylipins showed positive Spearman correlations with 14-month scores. In cord blood plasma, AA epoxides correlated positively with cognitive parameters at both ages under moderate exposure. Multivariate linear regression revealed positive associations between anti-inflammatory AA-derived epoxides and neurodevelopmental scores across tissues and ages, and between a DHA oxylipin in cord blood plasma and 14-month scores. No neurodevelopmental delays were observed in the moderate exposure group compared to the low exposure group. Oxylipin levels exhibited a more anti-inflammatory profile in samples from the moderate exposure group. Additionally, the brain oxylipin profile of mice treated with an AA epoxide enhancer indicated reduced inflammation. Conclusions PUFA signaling dynamics revealed potential protective pathways against methylmercury-induced neurodevelopmental toxicity. Differential oxylipin modulation, together with the absence of neurodevelopmental delays, underscores the importance of a maternal diet rich in anti-inflammatory PUFAs for children at risk of cognitive impairment due to prenatal methylmercury exposure.

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.

Prenatal cadmium (Cd) exposure may impair placental function and disrupt biological processes relevant to foetal neurodevelopment, including oxidative stress and metal homeostasis, but epidemiological evidence linking Cd to childhood behavioural and emotional problems remains inconsistent. We examined whether prenatal Cd exposure was associated with behavioural and emotional symptoms from early childhood to pre-adolescence in the Spanish INMA birth cohort. We included 1270 mother-child pairs from Valencia, Sabadell, and Gipuzkoa. Cd and creatinine were measured in maternal urine collected in the first and third trimesters of pregnancy, and average prenatal Cd exposure was analysed. Behavioural and emotional outcomes were assessed at ages 4-5, 7-8, 9, and 11 years using the ADHD-DSM-IV, Strengths and Difficulties Questionnaire, and Conners' Parent Rating Scales-Revised. Associations were estimated using multivariable negative binomial and mixed-effects models, with additional analyses for trimester-specific exposure, non-linearity, and effect modification by selected single nucleotide polymorphisms. Prenatal Cd exposure was not associated with any behavioural or emotional outcome across childhood. Results were also null when exposure was analysed separately for the first and third trimesters. In contrast, male sex and maternal smoking during pregnancy were consistently associated with poorer behavioural scores, whereas higher parental education and parity were generally associated with lower symptom levels. Interaction analyses indicated greater susceptibility among children whose mothers carried the MT1DP rs8044719 GT + TT genotype. In this population-based cohort, prenatal Cd exposure was not associated with behavioural or emotional problems across childhood. The findings nevertheless suggest that genetic susceptibility may contribute to interindividual differences in Cd-related neurodevelopmental vulnerability.

Background/Objectives: This study aimed to examine the association between leukocyte telomere length (TL) measured at ages 4 and 8 and emotional and behavioral problems at age 8. We also explored whether changes in leukocyte TL between ages 4 and 8 were associated with outcomes. Methods: Data were obtained from a population-based birth cohort and included 647 children with TL at age 4 and emotional and behavioral assessments at age 8, 673 with TL and outcomes at age 8, and 315 with TL measured at both ages. TL was determined using quantitative PCR on blood samples and converted into z-scores for analysis. Emotional and behavioral problems—including internalizing, externalizing, and total difficulties—were assessed using the Strengths and Difficulties Questionnaire. Regression models were conducted using zero-inflated and negative binomial, adjusting for sociodemographic and lifestyle covariates. Results: No statistically significant associations were observed between leukocyte TL at ages 4 or 8, or TL changes over this period, and emotional and behavioral outcomes at age 8. Conclusions: Although no significant associations were found, further longitudinal research is warranted to clarify the role of TL as a potential psychobiomarker of emotional and behavioral disorders in childhood.

We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.

BACKGROUND:Early-life mercury (Hg) exposure has been associated with adverse cardiometabolic health effects, though the evidence remains inconclusive. This study aims to evaluate the association between prenatal and postnatal Hg exposure and cardiometabolic risk factors in 15-year-old adolescents, considering the influence of sex, fish consumption, omega-3 polyunsaturated fatty acids (n-3 PUFAs) intake, and an obesity-related polygenic risk score (PRS). METHODS:Participants comprised 243 mother-adolescent pairs from the Spanish INMA (Childhood and Environment) cohorts. Total Hg (THg) levels were analyzed at birth and ages 4, 9, and 15 years in different matrices (cord blood, blood, and hair). At age 15, waist-to-height ratio (WHtR), fat mass percentage (%FM), systolic and diastolic blood pressure (SBP, DBP), serum alanine aminotransferase (ALT), and cardiometabolic risk (CMR) score were assessed. Sociodemographic, lifestyle, and genetic data were collected. Associations between THg levels and outcomes were analyzed using multivariable linear regression, with interaction terms to assess effect modification. RESULTS:Cord blood THg was marginally and directly associated with SBP (β [95 %CI: 0.08 [-0.01, 0.17]), with stronger associations observed among boys. THg at age 9 was marginally and inversely associated with %FM and CMR score (-0.15 [-0.32, 0.01] and -0.45 [-0.95, 0.06], respectively). A U-shape association was found between blood THg at age 15 and SBP z-scores, with a cut-off at 2.8 (95 %CI: 1.28, 4.06) μg/L. Sex and the amount of fish and n-3 PUFA consumed influenced this association in an outcome-dependent manner. No other associations were detected with the other CMR outcomes evaluated. CONCLUSION:The results of this longitudinal study suggest that both pre- and postnatal THg exposure have a relationship on SBP in adolescents. Sex appears to modify these associations.

Evidence on the link between physical activity (PA) and telomere length (TL) in childhood is scarce and inconsistent. This study examined the association between extracurricular PA at age 4 and changes in TL ranking from 4 to 8 years. Longitudinal data from 547 children in the INMA birth cohort study (ages 4–8) were analyzed. Parent-reported extracurricular PA at age 4 was used to calculate metabolic equivalents (METs) in hours per day and categorized into tertiles (low, middle, and high). Leukocyte TL was measured at ages 4 and 8 using qPCR, with the primary outcome being the percentage change in TL ranking between ages 4 and 8. Multiple robust regression models were used for the main analyses. Children in the highest tertile of extracurricular PA (11.9–31.0 METs h/day) showed a significant 2.25

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.

Mercury (Hg), particularly methylmercury (MeHg), is a widespread environmental toxicant linked to early-life cardiometabolic risk. This study examined associations between pre- and postnatal total blood mercury (THg) exposure and cardiometabolic outcomes in children, exploring telomere length (TL) as a potential mediator and polymorphisms in the TERT and CLPTM1L genes as effect modifiers. The analysis included 1,301 mother-child pairs from six European cohorts in the HELIX project. THg was measured in maternal and child blood to assess prenatal and postnatal exposure. Cardiometabolic outcomes, including BMI, waist circumference, blood pressure, lipid profile, insulin, and a metabolic syndrome (MetS) risk score, were evaluated in children aged 6-12. TL was measured by quantitative PCR, and polymorphisms in TERT and CLPTM1L were assessed by genome-wide genotyping. Models adjusted for sociodemographic and lifestyle variables, with sensitivity analyses including other environmental contaminants (PCBs, DDE, As, Cd, Pb, Se). Prenatal THg exposure was positively associated with insulin levels, waist circumference, systolic blood pressure, and MetS risk score. Postnatal THg exposure was negatively associated with waist circumference, diastolic blood pressure and hypertension prevalence. TL was inversely associated with adiposity and blood pressure but showed minimal mediation, with only a marginal effect on BMI. TERT polymorphisms, particularly rs33954691 and rs2853669, significantly modified the association between THg and cardiometabolic outcomes. These results identify the prenatal period as a particularly vulnerable window for MeHg toxicity on cardiometabolic risk factors. These associations were largely independent of TL, though genetic variants in TERT altered susceptibility. Future research should explore additional biological pathways beyond telomere dynamics.

The present study analysed the exposure to 20 metals in the urine of 604 children aged 6–11 years in the Valencia region of Spain, together with socio-demographic and dietary factors. It focused on seven essential metals (Co, Cu, Mn, Mo, Se, Zn and V) and 13 toxic metals (Al, Sb, As, Ba, Be, Cd, Cs, Pb, Ni, Pt, Th, Tl and U). Risk assessments were performed for three essential metals (Se, Mo, Zn) and five toxic metals (Al, Ba, Cd, USAs, Tl) based on established benchmarks. All essential metals except Co (91