Background Ambient air pollution, particularly black carbon (BC), is associated with adverse pregnancy outcomes, but the molecular pathways linking in utero particle exposure to fetal programming remain incompletely understood. We examined whether cord-blood BC particle burden relates to small extracellular vesicle (sEV)-associated microRNA (miRNA) profiles and enriched developmental pathways. Methods Cord blood was collected from newborns in the Born in Bradford's Better Start (BiBBS) cohort. Plasma sEVs were isolated and miRNA was profiled by small RNA sequencing. BC particle load in whole cord blood was quantified by femtosecond pulsed-laser microscopy. After quality control and complete-case restriction, 68 newborns were included in the analysis. Candidate miRNAs were prioritised using elastic-net regression, and associations with log10-transformed BC particle burden were estimated using linear mixed-effects models with covariate adjustment and Benjamini---Hochberg false discovery rate (BH-FDR) control. Results Five of the ten candidate miRNAs were associated with BC at BH-FDR ≤0.10: hsa-miR-25-3p and hsa-miR-433-3p (positive associations) and hsa-miR-518a-3p, hsa-miR-519a-3p/519b-3p, and hsa-miR-520g-3p/520h (negative associations). Three of the five negatively associated miRNAs belong to the placenta-specific chromosome 19 miRNA cluster (C19MC). All five signals were robust in 100 × 20% holdout resampling. Validated target pathway analysis revealed enrichment for developmental and specifically neurodevelopmental processes, including axon guidance and neurotrophin signaling. Conclusions These findings link cord-blood BC particle burden to a placenta-linked C19MC miRNA signature in newborn sEVs and developmental pathway enrichment, providing molecular evidence consistent with particle-associated fetal programming at birth.

BACKGROUND:Growing evidence indicates that early brain development is particularly vulnerable to environmental influences, with early-life air pollution exposure linked to attention problems, anxiety, and depression. In this study, we examined associations of early-life air pollution exposure with eye-tracking-derived measures of cognitive workload and emotion-related attentional bias in school-aged children, while also assessing whether recent exposure was associated with these outcomes. METHODS:This prospective cohort study was conducted within the ongoing ENVIRONAGE birth cohort, which has enrolled over 2400 mother-child pairs. The present study included 196 children aged 9-11 years who had reached the eligible age for follow-up and completed eye-tracking paradigms assessing cognitive workload and subconscious attention bias between September 2021 and November 2023. Residential black carbon (BC), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) exposures were estimated using a high-resolution spatiotemporal modelling framework based on fixed-site monitoring data, land-use/land-cover information, and dispersion modelling. Associations between predefined exposure windows and eye-tracking outcomes were first assessed using multiple linear regression models, followed by Bayesian kernel machine regression distributed lag models (BKMR-DLM) to evaluate multi-pollutant and multi-window exposure-response patterns. FINDINGS:Higher recent residential air pollution exposure was most consistently associated with saccadic outcomes. After correction for multiple testing, an interquartile range (IQR) increase in last-month BC and NO2 exposure was associated with lower saccade velocity (BC: -10.97°/s; 95% CI -18.67, -3.26; NO2: -10.81°/s; 95% CI -18.13, -3.49), and last-month NO2 and PM2.5 exposure were associated with fewer saccades. Early-life exposure windows also showed associations mainly with saccade velocity, including first-trimester BC and PM2.5, whole-pregnancy PM2.5, and first-1000-days BC exposure. Associations with pupil diameter, fixation count, urinary BC, and emotion-related attention-bias outcomes did not remain statistically significant after correction for multiple testing. INTERPRETATION:Using objective eye-tracking outcomes within a prospective birth cohort, our findings suggest that residential air pollution exposure is associated with subtle oculomotor differences in school-aged children, particularly patterns consistent with increased cognitive workload. Emotion-related attention-bias findings were exploratory after correction for multiple testing. FUNDING:Special Research Fund (BOF), Flemish Scientific Research Fund (FWO), Methusalem, and Horizon Europe project MISTRAL.

Background: Micro- and nano-plastics (MNPs) are pervasive environmental contaminants that accumulate in various tissues, including the placenta. Experimental and clinical studies suggest potential cytotoxic, oxidative, and inflammatory effects that may lead to placental dysfunction and adverse obstetric outcomes. However, high-quality evidence on the clinical relevance of MNPs exposure during pregnancy remains scarce, underscoring the need for systematic evaluation of their impact on maternal and fetal health. Methods: The databases PubMed, ScienceDirect, CENTRAL, Embase, MDPI and Google Scholar were searched for studies published up to September 2025 investigating the relationship between MNPs and obstetric outcomes. Results: Twelve studies were included in this review, with half employing an observational design in human subjects and the other half using experimental studies in murine models. Although the available evidence is limited, there are studies reporting the association between MNPs exposure and premature birth, low birth weight, intrauterine growth restriction, and miscarriage. The most prevalent polymer detected was polyethylene, and the most commonly used MNPs detection techniques were Raman microspectroscopy, digital microscopy, Fourier Transform Infrared, and Pyrolysis gas chromatography-mass spectrometry. Conclusions: This systematic review summarizes current limited insights on the potential effects of MNPs on obstetric outcomes, highlighting possible associations with low gestational age, low birth weight, intrauterine growth restriction, and miscarriage. Findings do not allow causal inference due to heterogeneity in study design, exposure assessment, contamination control, and analytical methodologies.

Human exposure to currently used pesticides (CUPs) is widespread, with children being especially vulnerable to possible adverse health effects. Assessing exposure and related risks in children is therefore essential. In this study, 6 parent compounds and 9 metabolites of a subset of CUPs were analyzed in 327 urine samples from children (4-12 years) in the ENVIRONAGE cohort, as part of the characterization of their chemical exposome. Among the targeted compounds, 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA) and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA) were detected in > 50 % of samples, with 3-PBA showing the highest median level (0.33 ng/mL, interquartile range (IQR): 0.18-0.61 ng/mL). These metabolites reflect exposure to chlorpyrifos and pyrethroids, while other biomarkers showed low detection frequencies. The low detection frequencies might partly reflect a limited suitability of included biomarkers rather than absence of exposure. TCPY concentrations (median: 0.16 ng/mL, IQR: 0.07-0.27 ng/mL) were lower than previously reported studies, possibly reflecting the ban on chlorpyrifos in the European Union. Questionnaires on demographics, lifestyle, and dietary habits were used to identify possible exposure determinants. Risk assessment was performed by calculating estimated daily intakes (EDIs), risk characterization ratios (RCRs), and hazard indices (HI) applying a worst-case scenario; assuming metabolites were formed due to exposure to the most toxic parent compound. Time spent cycling was positively associated with levels of 3-PBA and trans-DCCA, while sampling season was identified as a significant variable for trans-DCCA, with the highest concentrations in autumn. Juice consumption was positively associated with TCPY concentrations. All risk characterization ratios for single compounds were below 1, while for two children, the HI for combined exposure to pyrethroids exceeded 1. The current study demonstrates that Belgian children are exposed to chlorpyrifos and pyrethroid pesticides, with most exposures falling within ranges considered safe under the assumed conditions.

Importance:Blood pressure (BP) is a crucial modifiable risk factor associated with cardiovascular disease in adulthood. The modifiable impact of BP may begin from birth and operate across the whole life span. However, no up-to-date studies have tracked BP from birth onward. Objective:To explore BP trajectory in childhood and evaluate whether the risk of hypertension later in childhood is associated with BP at birth and in early childhood. Design, Setting, and Participants:This cohort study evaluated data from the Belgian ENVIRONAGE birth cohort study with longitudinal follow-up visits in children aged 4 to 6 years (first follow-up [FU1]) and aged 9 to 11 years (second follow-up [FU2]). The study was initiated February 2, 2010, and data were collected and analyzed until August 30, 2024. Exposure:Childhood blood pressure. Main Outcomes and Measures:The main outcomes were incidences of elevated BP and hypertension at the last follow-up (FU1 or FU2). Tracking was assessed using change in mean arterial pressure (MAP) percentiles between 2 visits. Elevated BP and hypertension at childhood were standardized for age, sex, and height following the 2017 American Academy of Pediatrics guideline. Analyses were performed using multivariable-adjusted linear, mixed, and Cox proportional hazards regression models. Results:The study included 500 healthy children (mean [SD] gestational age, 39.2 [1.6] weeks; 266 girls [53.2%]), with 445 having 2 BP measurements and 55 having 3 BP measurements. From birth to FU1, mean (SD) systolic BP (SBP), diastolic BP (DBP), and MAP tracked from 67.3 (8.8) mm Hg, 40.5 (8.3) mm Hg, and (8.2) mm Hg, respectively, to 100.2 (8.5) mm Hg, 57.5 (9.1) mm Hg, and 74.6 (7.8) mm Hg, respectively. At FU2, mean (SD) SBP, DBP, and MAP tracked to 107.7 (9.5) mm Hg, 65.1 (6.4) mm Hg, and 82.1 (6.7) mm Hg, respectively. Per 1-SD increase in initial BP at birth or age 4 to 6 years, for all children in the combined dataset, BP at the last follow-up increased by 2.66 mm Hg (95% CI, 1.65-3.67 mm Hg) for SBP, 1.37 mm Hg (95% CI, 0.28-2.46 mm Hg) for DBP, and 1.97 mm Hg (95% CI, 0.85-3.10 mm Hg) for MAP. In the fully adjusted models, for each 1-SD increase in the initial MAP, the hazard ratios of elevated BP and hypertension were 2.84 (95% CI, 1.50-5.38) and 3.75 (95% CI, 1.79-7.86), respectively. Conclusions and Relevance:This prospective cohort study found that BP tracked consistently from birth through childhood. Higher BP levels at birth and early childhood were associated with an increased risk of elevated BP and hypertension later in childhood. These findings highlight the importance of monitoring and managing BP from birth as a potential strategy to reduce cardiovascular risk later in life.

BACKGROUND:Cholesterol at birth influences development and long-term health, but its environmental and biological determinants remain understudied. METHODS:This study investigates associations between the prenatal exposome and cord blood lipid profiles in 1,732 mother-child pairs from the Belgian ENVIRONAGE cohort. An exposome-wide association study, a deletion/substitution/addition variable selection, and multi-exposure regressions were applied to assess 90 external exposures in relation to cord blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and low-density lipoprotein cholesterol (LDL-C). Partial correlations were used to assess relations between 14 internal exposures and cholesterol levels. Mediation of identified internal exposures was tested via an imputation-based approach. RESULTS:Greater sunshine duration and higher atmospheric pressure during pregnancy were inversely associated with TC. Exposure to black carbon, presence of a heating tank in the household, maternal smoking, and primiparity were associated with lower HDL-C, while folic acid supplementation was associated with higher HDL-C. Primiparity was also associated with higher non-HDL-C, and sunshine exposure with lower non-HDL-C. Several biomarkers, including ferritin, thyroid hormones, and inflammatory markers, were correlated with lipid profiles. Homocysteine mediated the effect of atmospheric pressure on TC. Triiodothyronine (fT3), insulin, estradiol, and IL-6 mediated the effect of smoking on HDL-C. fT3 mediated the effect of folic acid on HDL-C, while insulin mediated the effect of primiparity on HDL-C. These findings reveal complex interactions between prenatal environmental exposures, internal biomarkers, and newborn lipid profiles, underscoring the importance of early-life exposome research for preventive health strategies.

Air pollution has been implicated in various adverse health effects, including neurodevelopmental and neurodegenerative impairments. However, the long-term impact of early-life ultrafine particle (UFP) exposure on the brain remains poorly understood. Using a sequential exposure mouse model, we investigated how early-life ultrafine carbonaceous particles (UFPC) exposure programs neurobehavioural and molecular vulnerability upon adult re-exposure. Wild-type C57BL/6J mice were exposed to either HEPA-filtered air or UFPC during the prenatal (gestational days 8-9 and 16-17) and/or postnatal periods (postnatal days 4-7 and 10-13), followed by a 4-day re-exposure in adulthood (postnatal days 142-145). Behavioural assessments revealed hippocampus-dependent spatial memory deficits and anxiolytic-like behaviour following cumulative exposure. Brain proteomic analysis identified reduced protein levels of key modulators of synaptic signalling and neurovascular homeostasis (Erbb4 and Ddah1), accompanied by gene-specific promoter methylation changes and shortened telomere length, indicating persistent epigenetic reprogramming and accelerated cellular aging. We validated the epigenetic sensitivity of ERBB4 to prenatal air pollution in human cord blood from the ENVIRONAGE birth cohort. The integrative design, encompassing behavioural phenotyping and molecular profiling, offers a comprehensive systems-level perspective on the neurobiological effects of UFPC. Our findings suggest that developmental UFPC exposure induces increased susceptibility to re-exposure on behavioural, epigenetic, and proteomic outcomes. This work provides evidence for UFP as a potentially critical environmental determinant of brain health throughout life.

AIMS:Early-life environment is crucial for foetal programming and later-life development. Exposure to particulate air pollution during gestation may increase the risk of cardiovascular diseases (CVD) later in life. We investigated the association between exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or less) during gestation and pulse wave velocity (PWV) in children. METHODS AND RESULTS:In the prospective ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort (Belgium), mother-child pairs were recruited at birth, and 244 children between 9 and 11 years were followed up. Arterial stiffness was assessed using carotid-femoral PWV via the Vicorder® (Skidmore Medical, Bristol, UK). A high-resolution spatiotemporal model was used to model daily prenatal and postnatal PM2.5 exposure levels. Associations between prenatal PM2.5 exposures and PWV were tested using linear regression models followed by fitting weekly prenatal exposures to distributed lag non-linear models (DLNM). Among the 244 children [132 girls (54.1%); mean (S) age, 10.2 (0.8) years], a 5 μg/m3 increment in prenatal PM2.5 exposure during trimester two was significantly associated with a 0.09 m/sec higher PWV (95% CI, 0.01 to 0.17; P = 0.03). Accounting for entire childhood PM2.5 exposure, PM2.5 exposure during trimester two remained a predictor of PWV (0.08 m/sec, 95% CI: -0.0006 to 0.16; P = 0.05). CONCLUSION:PWV is an independent predictor of future CVD and all-cause mortality in the general population. Therefore, associations of air pollution exposure during gestation with childhood PWV highlight the potential long-term consequences on the child's cardiovascular system from early life onwards.

Ribosomal DNA copy number (rDNAcn) and DNA methylation are important modulators of the human genome, both studied in relation to overall cellular function, biological ageing, and disease development. Despite the overlapping roles, their relationship remains poorly understood, especially in the early stages of life, characterized by rapid growth and high cellular demands. Even though previous studies have associated rDNA methylation with cancer and ageing, no study to date has examined the interplay between rDNAcn and whole-genome DNA methylation. In an epigenome-wide association study of 45S rDNAcn variation in 194 newborns, we show strong positive associations between rDNAcn and single DNA methylated CpGs, measured with the Illumina EPIC array. Out of the 122 Bonferroni-significant CpGs, 63.5% were also Bonferroni-significant in a replication cohort of 167 newborns, in which a second EWAS was conducted using DNA methylation data from the Illumina 450K array. The identified CpGs were dispersed over the autosomes and were not functionally related to the rDNA-forming nucleolar-associated domains. The top CpGs were annotated to genes (GFI1, USP46, ABHD14B, CHL1, CGREF1) that are functionally linked to cancer and cellular proliferation. In downstream analyses, the 122 rDNAcn-related CpGs revealed 31 differentially methylated regions and 253 nominally significant correlations with cord blood gene transcripts in an eQTM analysis. Pathway enrichment analyses showed an overrepresentation of the following pathways: 'RNA Polymerase III transcription' (R-HSA-76071, R-HSA-76046, R-HSA-74158, R-HSA-749476, R-HSA-73780, R-HSA-73980, R-HSA-76066, R-HSA-76061, hsa03020), ‘cytosolic sensors of pathogen-associated DNA’ (R-HSA-1834949), ‘RNA polymerase II transcribes snRNA genes’ (R-HSA-6807505), and 'translation initiation' (R-HSA-72613, R-HSA-72737). Our findings reveal a close link between rDNAcn variation and DNA methylation in early life. Disruptions in this interplay may influence cellular functions critical for early development, potentially shaping health and disease trajectories later in life.

BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, and paternal quitting before pregnancy). METHODS: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data for maternal SHS and smoking during pregnancy. Primary analyses used Illumina450 K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] < 0.05) at 8,862 CpGs on the 450 K (n = 8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (MED13L) was associated with former paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n = 3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking, and paternal smoking.

Prenatal exposure to ambient air pollution, particularly black carbon (BC), has been linked to adverse pregnancy outcomes and life-long neurodevelopmental disorders. Yet the mechanism by which inhaled nanoparticles cross the placenta and reach fetal tissues is unclear. Here we show that black carbon (BC) is detectable in association with small extracellular vesicles (sEVs) in fetal circulation and in tissue-enriched sEV subsets. Using label-free two-photon microscopy, we visualised BC associated with individual sEVs isolated from cord-blood plasma of 20 mother-infant pairs. BC-sEV association occurred in 27 % of total cord-blood sEVs, 54 % of placental alkaline-phosphatase-positive (PLAP+) placental vesicles and 68 % of fetal-brain-derived (Contactin-2+) vesicles. Among BC-positive fetal-brain sEVs, >90 % of the vesicle fluorescence co-localised with BC, demonstrating extensive pollutant loading. These findings provide evidence that BC can be detected in association with sEV-enriched preparations in fetal circulation, consistent with a possible role for sEV-associated carriage following transplacental particle transfer, though the dominant transport mechanism remains unestablished.

Exposure to per- and poly-fluoroalkyl substances is associated with adverse health outcomes and may generate substantial healthcare and societal costs. This concept study presents an interdisciplinary framework that links epidemiological evidence, health economic modeling, and legal analysis to estimate the health-related costs of PFAS pollution and explore compensation under the polluter pays principle. The framework combines systematic evidence synthesis, pooled effect estimates, and population attributable fractions to quantify the disease burden attributable to PFAS exposure. These estimates are integrated into cost-of-illness analyses to assess preventive and curative healthcare costs, productivity losses, and wider societal impacts. Legal analysis, including hypothetical cases and existing compensation fund mechanisms, is used to examine how quantified health-related costs can inform liability and compensation approaches. By connecting scientific evidence, economic valuation, and legal reasoning, the framework supports evidence-informed policymaking and adaptable compensation mechanisms as knowledge on PFAS-related health effects develops.

Background: Childhood obesity and mental health problems are major public health concerns worldwide. Early-life exposure to green spaces has been shown to promote physical activity, reduce obesity risk, and improve cognitive and emotional development. Schoolyards offer a unique opportunity to promote health, as children spend a large proportion of their time at school. Methods: This quasi-experimental protocol study investigates the effects of transforming gray schoolyards into biodiverse green spaces on children’s health and well-being. Four primary schools in Limburg (Belgium and The Netherlands) were recruited: two intervention schools and two control schools. Children aged 7–12 years were enrolled, with baseline data collected in November 2021 and follow-up measurements scheduled every six months until November 2023. Outcomes include body mass index (BMI) z-score (primary outcome), waist circumference, diet, cognitive performance, psychological well-being, biodiversity knowledge, and physical activity. Data will be analyzed using linear mixed models, and cost-effectiveness analyses will be performed. Expected Results: Improvements in BMI z-scores, cognitive functioning, dietary behavior, and psychological well-being are expected among children in green schoolyards compared to those in control schools. Increased biodiversity awareness and reduced exposure to black carbon are also anticipated. Conclusions: This study is designed to provide evidence on the health impacts of greener schoolyards and contribute to strategies for promoting child development through environmental interventions.

The intestinal microbiome is essential for gastrointestinal and overall health, yet its response to air pollution in children remains underexplored. In a study involving 412 young children from the ENVIRONAGE cohort, stool samples were analysed via Illumina Miseq sequencing to assess microbiome alpha diversity (observed richness, species evenness, and Shannon diversity) and composition. Exposure to previous year particulate air pollution (black carbon, PM2.5, coarse PM, and PM10) was modeled using high-resolution spatial-temporal interpolation models. Multiple linear regression models were adjusted for a priori selected covariables and stratified by sex. Furthermore, we performed a differential relative abundance analysis at family and genus level, while accounting for the same covariables. Statistically significant effect modification by sex was apparent for several intestinal alpha diversity indices and air pollutants. In boys, we observed negative associations between particulate air pollution exposure and intestinal microbiome richness (estimates ranging from -5.55 to -9.06 per interquartile range (IQR) increase in particulate air pollution exposure) and Shannon diversity (estimates ranging from -0.058 to -0.095 per IQR increase). Differently, in girls non-significant positive associations were observed with species evenness (estimates ranging from 0.019 to 0.020 per IQR increase) and Shannon diversity (estimate 0.065 per IQR increase in black carbon). After multiple testing correction, we reported several bacterial families and genera (Streptococcaceae, Clostridiales Incertae Sedis XIII, Coriobacteriaceae, Streptococcus, and Paraprevotella) to be oppositely associated with particulate air pollution exposure in boys and girls. Our findings show a sex-dependent association between particulate air pollution exposure and intestinal microbiome composition, highlighting boys as potentially more vulnerable to diversity loss associated with childhood exposure to particulate pollution.

To fully comprehend host-microorganism interactions, it is crucial to understand the composition and diversity of the microbiome, as well as the factors that shape these characteristics. We investigated microbiome variation using the freshwater planarian Schmidtea mediterranea, an invertebrate model in regeneration biology and (eco-)toxicology, by exposing the organisms to various controlled conditions. The microbiome composition exhibited high variability, with most of the bacteria belonging to the Betaproteobacteria. Among the diverse microbial communities, a few genera, such as Curvibacter, were consistently present, but exhibited significant alterations in response to changing conditions. The relative abundance of Curvibacter fluctuated during the regeneration process, initially increasing before returning to a composition similar to the beginning situation. After applying external stress, the relative abundance of Curvibacter and other genera decreased. Variation over time, between different origin laboratories and between individuals, showed that additional, yet to-be-identified, factors of variation are present. Taking all results together, our study provides a solid basis for future research focusing on bacterial functionality in planarians and other invertebrates.

BACKGROUND:Fine particulate matter (<2.5 μm, PM2.5), and its subcomponent ultrafine carbonaceous particles (UFP), have been shown to cause adverse health effects, including respiratory and cardiovascular disease, and decline in kidney function. Previous research demonstrated the presence of these particles in the kidney, yet potential effects on kidney tissue remain elusive. METHODS:We exposed wild-type C57BL/6J mice to either HEPA-filtered air or clean ultrafine carbonaceous particles (UFPC, 450 μg/m3) during the prenatal (gestational day 8-9 + 16-17) and/or postnatal (PND 4-7 + 10-13) phase, with an additional re-exposure on PND 142-145 of the exposed animals, and harvested kidney tissue on PND 181-182. Large-scale histomorphometry (pathomics) was utilized to quantify the effects of exposure to UFPC on kidney tissue morphology. Here, we quantified an average (SD) of 205 (56) arteries, 113 (15) glomeruli, and 6966 (887) tubules in each group. Differences between exposure groups were assessed using the Kruskal-Wallis tests. UFPC were detected using non-incandescent white light generation under femtosecond-pulsed illumination. Correlations between measured UFPC and morphometric features were evaluated with Pearson's correlation coefficient. RESULTS:Compared to the sham group, the pre- and postnatally exposed group had significantly smaller cortical and larger medullary areas (p < 0.05). The postnatally exposed group had more glomeruli in comparison to the sham group (p < 0.01). The prenatally exposed group showed lower tubular area and altered tubular shapes, with reduced circularity and solidity (p < 0.02). The prenatally exposed and pre- and postnatally exposed groups showed higher percentages of the interstitial area (p < 0.05). Correlation analysis revealed positive associations between UFPC exposure and tubular morphometric features, while negative correlations were found with interstitial area percentage; no significant correlations were noted for glomerular or arteriolar features. CONCLUSIONS:This study shows the impact of UFPC exposure on kidney morphology with altered overall cortical and medullary areas and altered tubular and interstitial structures. These structural alterations may potentially increase kidney vulnerability to injury, underscoring the need for further studies to assess the long-term impact of environmental pollutants on kidney health.

Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length. This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated. After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways. Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.

Greenspace can promote health via diverse pathways. A common approach to assessing greenspace exposure is to estimate vegetation availability within buffers surrounding locations where people reside or spend time. However, no clear framework for informed buffer selection exists, and choices made show considerable heterogeneity, impeding evidence synthesis and causal inference. In this Personal View conducted by an interdisciplinary panel of experts, we aimed to establish a framework for informed buffer selection for epidemiological studies on greenspace. We began by reviewing available approaches for the selection of buffer types, which range from single fixed-location approaches to high-resolution mobility-based activity-space approaches, as well as different buffer sizes. We then summarised the determinants of buffer type and size selection including health outcomes and underlying mechanisms, study population, contextual factors, and data characteristics. Finally, based on these determinants, we developed recommendations for future research. Buffer type and size selection should be hypothesis driven, reflecting presumed greenspace-health mechanisms. Buffer selection should target activity-based approaches where feasible, and multiple buffer sizes should be tested. Overall, the assessment of greenspace exposure should shift from ad-hoc approaches to personalised, multiscale, and context-specific methods. We call for standardising and reporting the rationale for buffer selection to minimise bias and enhance comparability and evidence synthesis across studies.

Background: The Baby-Friendly Hospital Initiative (BFHI) promotes, protects, and supports optimal breastfeeding through facility-based strategies. While prior studies have examined individual BFHI components in specific contexts, global evidence on its overall impact remains limited. This systematic review and meta-analysis aimed to evaluate the BFHI’s effectiveness in improving early initiation and exclusive breastfeeding practices worldwide. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and Google for English-language studies. Eligible studies included randomized controlled trials (RCTs), cluster RCTs, and quasi-experimental designs assessing BFHI’s effect on breastfeeding outcomes. Random-effects meta-analysis models were used to estimate the pooled effects with 95% confidence intervals (CI). Heterogeneity was assessed using I2 statistics and p-values. Study quality was appraised using the GRADE approach. Results: Thirty studies met the inclusion criteria. The BFHI was associated with increased early initiation of breastfeeding (pooled RR 1.43; 95% CI: 1.12–1.81; I2 = 97.1%). Positive associations were also observed for exclusive breastfeeding at four months (RR 1.18, 95% CI: 1.08–1.29; I2 = 61.7%) and at six months (RR 1.56, 95% CI: 1.14–2.14; I2 = 82.8%). Substantial heterogeneity reflected variability in study design, BFHI implementation fidelity, and context. Conclusions: Our findings suggest that the BFHI is effective in improving breastfeeding practices globally. However, study variability and partial implementation may limit the generalizability of results. High-quality RCTs assessing full BFHI implementation are needed to strengthen evidence and guide global maternal–child health policy.