The association between childhood exposure to PM2.5-bound organophosphate esters (OPEs) and attention deficit hyperactivity disorder (ADHD) remains poorly understood. In this large population-based study of 131,412 children aged 6-18 years attending schools in the Pearl River Delta, China, we collected ambient fine particulate matter (PM2.5) samples from schools to quantify OPEs levels, and screened for ADHD symptoms using parent-reported ADHD/Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅳ) Scales. We employed elastic net regression for variable selection, generalized linear mixed models (GLMMs) for association estimates, and weighted quantile sum regression to evaluate mixture effects. Odds ratios (ORs) are expressed as the change in odds of ADHD symptoms per interquartile range (IQR) increase in OPE levels. Elevated PM2.5-bound OPE exposure was associated with higher odds of ADHD symptoms in children, especially for triphenyl phosphate (TPHP) (OR = 1.75, 95% CI: 1.70-1.79), tris(2-ethylhexyl) phosphate (TEHP) (OR = 1.73, 95% CI: 1.69-1.77), tris(1,3-dichloroisopropyl) phosphate (TDCIPP) (OR = 1.71, 95% CI: 1.67-1.75), and tris(3,4-dimethylphenyl) phosphate (T34DMPP) (OR = 1.45, 95% CI: 1.41-1.49). Similar associations were observed across different ADHD subtypes. Stratified analyses indicated heterogeneous associations across age, sex, and breastfeeding subgroups, with no consistent pattern of effect modification across all OPE exposures. These findings suggest that inhalation of OPE mixtures may be associated with adverse neurodevelopmental outcomes in children, highlighting a potential developmental window of susceptibility and raising public health concerns about airborne contaminants.

Per and polyfluoroalkyl substances (PFAS) and their alternatives are recognized environmental hepatotoxins, yet their combined effects with metals on liver health in human populations remain underexplored. This study measured serum levels of 13 PFAS (including legacy and emerging alternatives such as Cl-PFESAs) and plasma levels of 25 metals, and evaluated their individual and joint associations with five liver function biomarkers (ALT, AST, ALP, GGT, and DBIL) among 1,263 adults in Guangzhou, China. Generalized additive models (GAMs) revealed that most individual pollutants were positively associated with liver function biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and direct bilirubin (DBIL). Advanced Bayesian kernel machine regression (A-BKMR) analyses, employed to assess the joint associations of these complex mixtures, further demonstrated significant positive associations between the overall mixture of PFAS, alternatives, and metals and these biomarkers. Crucially, PFOS and PFHpS among the PFAS, alongside Pb, Cd, Tl, Zn, and Fe among the metals, were identified as the primary contributors to the observed mixture effect. These findings provide additional epidemiological evidence that co-exposure to PFAS (including emerging alternatives) and metals is adversely associated with liver health, highlighting the importance of assessing complex environmental mixtures. Further population-based studies are warranted, including studies measuring metals in matrices other than plasma, to validate these associations and elucidate underlying biological pathways.

Insulin and insulin-like growth factor 1 (IGF1) play key roles in fetal growth and development. However, their roles in the association between fetal growth and perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure remain unclear. In this study, the levels of 34 PFAS, IGF1, and insulin were measured in 258 paired mother-infant serum samples collected from a nested case-control study in Maoming city. Isomeric perfluorooctanesulfonate (PFOS) exposure significantly increased the preterm birth or low birth weight (PTB/LBW) risk, and the odds ratios for ∑2m, 3+4+5m, iso, and branched PFOS were 1.50, 1.72, 1.61, and 1.77, respectively. Cord IGF1 could explain 15.4, 13.4, 9.7, and 11.9% of these associations, respectively. Additionally, cord IGF1 mediated 12.3 to 44.6% of the associations between PFOS isomers, perfluorooctanoate acid (PFOA), and its alternative (perfluorobutanoic acid: PFBA) with a fetal growth index. For instance, cord IGF1 contributed 42.0% (95% Cl: 0.8, 140.0%), 42.7% (95% Cl: 13.0, 110.0%), and 43.0% (95% Cl: 8.4, 130.0%) to the associations between z-scores of birth weight and branched PFOS, PFOA, and PFBA, respectively. These findings suggest that cord IGF1 plays a mediating role in the associations between PFAS exposure and fetal growth.

China has invested heavily in air pollution control in recent years, yet comprehensive assessments of the associated health economic benefits remain limited. Prior research on the health economic benefits of air pollution control has mainly focused on mortality outcomes and PM2.5, which may substantially underestimates the true benefits of clean air policies. This study aims to evaluate the health economic benefits and losses associated with air pollution control by incorporating multiple health outcomes, population groups and air pollutants. We integrate daily mortality, hospital admission and outpatient visits and air pollutant (nitrogen dioxide, ozone [O3] and fine particulate matter) data from 18 cities from 2015 to 2022 to assess the health economic benefits. A generalized additive model was used to estimate concentration-response relationships. Health economic benefits were calculated based on the value of statistical life (VSL) and direct medical costs. Between 2015 and 2022, controlling PM2.5 and NO2 yielded significant health economic benefits across all health outcomes. Air pollution control generated significant health economic benefits across multiple outcomes in Guangdong Province. The total health economic benefits associated with PM2.5 and NO2 were 10,305.35 and 1017.00 million CNY, respectively. In contrast, O3 control yielded negative net benefits across all outcomes. Between 2015 and 2022, the multi-outcome health benefits of controlling PM2.5 exceeded mortality-only estimates by 31.79%, respectively For PM2.5 control, the elderly accounted for over 85% of the mortality-related benefits. These findings highlight the need for coordinated PM2.5-O3 control, the integration of multi-outcome evaluations into policy design, and targeted protection for vulnerable populations particularly the elderly.

Fine particulate matter (PM2.5) serves as a significant carrier of toxic heavy metals and poses potential health risks, particularly for children in school environments. However, limited studies have systematically compared school settings across cities with differing industrial profiles, resulting in a critical gap in understanding spatial variations in exposure risks. This study characterized the concentrations, seasonal variability, sources, and inhalation health risks of five PM2.5-bound metals, namely Cu, Cd, Ni, Pb, and Zn, in schools from two contrasting cities in Guangdong Province, China: Guangzhou and Maoming. PM2.5 samples were collected from 20 schools during summer and winter of 2018 and analyzed by inductively coupled plasma mass spectrometry. Pollution status, assessed using the geoaccumulation index (Igeo) and enrichment factor (EF), indicated that PM2.5-bound metals in both Guangzhou and Maoming were predominantly of anthropogenic origin, with Cu and Cd exhibiting the highest enrichment and contamination levels, whereas Ni and Pb were largely associated with natural background sources and Zn reflected mixed origins. Principal component analysis (PCA) was used to identify dominant sources of heavy metals and support source apportionment. The noncarcinogenic and carcinogenic risks were assessed for children and adults. Across both cities, Cu (471.19) showed the highest mean concentrations, followed by Zn, Pb, Ni, and Cd, with winter values generally exceeding summer values. Guangzhou exhibited stronger anthropogenic enrichment than Maoming, particularly for Cu (27.72) and Cd (27.32), indicating greater influence from traffic, industrial combustion, and urban emissions. Correlation analysis suggested common and seasonally enhanced sources in winter. Health risk assessment showed that all hazard quotients and carcinogenic risk values were below accepted thresholds, indicating low immediate inhalation risk. However, children experienced higher exposure than adults, and Pb (4.85E-03) and Cu (3.27E-03) contributed most to noncarcinogenic risk, while Cd (7.30E-06) and Ni (2.21E-06) posed the main carcinogenic concern. Overall, the results highlight the need for continued source control in school environments, with special attention to nonexhaust traffic emissions and industrial combustion.

While perfluorooctane sulfonate (PFOS) has been epidemiologically associated with ocular disorders, its direct specific role in retinal disease and the underlying molecular mechanisms are still not well understood. We initially examined serum PFAS levels in relation to retinal diseases among 777 participants (666 controls vs. 111 cases) from the Isomer of C8 Health Project in China. Then, C57BL/6 mice were orally gavaged with PFOS at doses of 0.8, 8, and 80 μg/kg/day for 90 days in vivo. The retinal ganglion cell line (RGC-5) was also exposed to PFOS at concentrations of 0, 1, 10, and 100 μM for 24 h in vitro. Epidemiological analysis showed a significant positive association between serum PFOS levels and the risk of retinal disease (OR = 1.46, 95%CI: 1.20, 1.80). In mice, exposure to PFOS caused progressive retinal thinning, retinal ganglion cell (RGC) loss, and retinal inflammation. In RGC-5 cells, PFOS activated Caspase-8, which led to cleavage of both GSDMD and GSDME, thereby inducing pyroptosis. Blocking Caspase-8 significantly reduced pyroptotic cell death involving GSDMD or GSDME. This study identifies PFOS as a new environmental trigger for retinal diseases through Caspase-8-mediated dual cleavage of GSDMD and GSDME. Our findings connect human exposure data with mechanistic toxicology and highlight the Caspase-8-gasdermin axis as a potential therapeutic target for PFOS related retinal disease.

Studies have shown polycyclic aromatic hydrocarbons (PAHs) exposure was related to reduced lung function. Existing studies mainly focused on the metabolites of several specific components with high detection rates in urine while internal exposure levels of other PAHs priority pollutant were rarely reported. Studies conducted in general population from China were limited and their findings were not completely consistent. Although the half-lives of PAHs are only approximately 6-35h, parent PAHs can still be detected in blood samples. Therefore, we recruited 1232 community residents from Guangzhou, China. We measured the concentration of 18 parent PAHs in their serum samples and performed pulmonary function tests on our participants. We included 15 components with a detection rate higher than 70 % in subsequent analysis and selected forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and the ratio of FEV1 to FVC (FEV1/FVC) as outcomes. We observed significant associations between serum PAHs and lower lung function parameters in generalized linear models (GLMs) and weighted quantile sum regression (WQS) models. Compared with the lowest quartile (Q1) of serum fluorene concentration, higher quartiles of concentrations were associated with a decrease of FEV1/FVC of -1.35 [95 % CI, (-2.55, -0.14)] in Q2, -2.21 [95 % CI, (-3.42, -0.99)] in Q3 and -1.57 [95 % CI, (-2.78, -0.36)] in Q4. Similarly, higher quartiles of PAHs mixture were associated with a decrease in FEV1 of -56.00 [95 % CI, (-108.92, -3.08)] and in FEV1/FVC of -1.60 [95 % CI, (-2.56, -0.64)]. Sensitivity analysis indicated that our results were robust.

Previous studies have reported associations between exposure to persistent organic pollutants (POPs) and childhood obesity. However, the role of chlorinated paraffins (CPs), an emerging class of POPs, in childhood obesity remains underexplored. To assess the associations, a total of 131,370 school-aged children and adolescents from 105 primary and middle schools in the Pearl River Delta region of southern China were included in this study. PM2.5 samples were collected and the PM2.5-bound CPs were detected. Age- and sex-specific BMI z-scores were calculated based on the World Health Organization growth standards. Overweight and obesity were defined according to Chinese screening criteria for children and adolescents. Generalized linear mixed-effects models (GLMMs) were used to evaluate the associations between PM2.5-bound CPs and BMI z-scores as well as weight status. The Quantile G-Computation model was employed to assess the combined effects of CPs mixture. Interaction analyses were conducted to assess potential effect modifications by covariates. We found each interquartile range (IQR) increase in ∑CPs was associated with higher BMI z-scores (β: 0.03; 95% CI: 0.02, 0.04) and increased risks of overweight (OR: 1.44; 95% CI: 1.41, 1.47) and obesity (OR: 1.50; 95% CI: 1.46, 1.53). Similarly, positive associations were also observed in SCCPs, MCCPs and LCCPs. QG-Comp analysis indicated SCCPs accounted for the highest contribution to the overall mixture effect, followed by MCCPs and LCCPs. No significant sex- or age-specific differences in the associations between CPs exposure and overweight/obesity risk were found in the interaction analyses. Our findings provide epidemiological evidence linking CPs to obesity and contribute to their health risk assessment.

IntroductionEmerging studies indicate exposure to heavy metals is linked with uric acid levels and hyperuricemia risk. However, the combined effects of heavy metals and the underlying mechanisms remain poorly characterized.MethodsIn this community-based cross-sectional study, plasma concentrations of 20 heavy metals and serum uric acid were measured in 1,312 adults in China. Triglyceride-glucose (TyG) index, a biomarker of insulin resistance, was also calculated. Generalized linear regression model, bayesian kernel machine regression, weighted quantile sum, and quantile G-computation were used to explore the associations between single or co-exposure to heavy metals and serum uric acid levels (SUA), as well as hyperuricemia (HUA). We also explored the mediating role of TyG in these associations. And then, benchmark dose lower bound (BMDL) of selenium (Se) was calculated using benchmark dose model.ResultsIn the single pollutant model, Se was positively associated with SUA (β = 0.18, 95% CI: 0.04, 0.32) and HUA (OR = 1.51, 95% CI: 1.08, 2.11). Three multi-pollutant models all revealed positive associations between metal mixtures and SUA as well as HUA, with Se being the primary contributor. Furthermore, TyG significantly mediated the associations of Se with SUA and HUA, with the mediated proportions of 47.85% and 34.72%, respectively. BMDL of Se was 118.70–233.12 μg/d based on HUA.DiscussionIn conclusion, metal mixtures had positive associations with SUA and HUA. Insulin resistance might be a crucial mediated pathway between Se and outcomes. Our estimated point of departure (POD) for Se was lower than those recommended by other studies.

Exposure to legacy per- and polyfluoroalkyl substance (PFAS) has been positively associated with impaired kidney function; however, evidence regarding PFAS isomers and emerging PFAS, as well as the underlying mechanisms, remains limited. PFAS isomers were defined as linear and branched structural forms of the same compound; legacy PFAS as historically produced compounds (e.g., PFOS and PFHxS); and emerging PFAS as newer replacement chemicals, including 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA). This study integrated epidemiological analyses and animal experiments to examine associations between PFAS exposure, systemic inflammation, and kidney function. In the epidemiological analysis, both legacy and emerging PFAS were associated with reduced estimated glomerular filtration rate (eGFR), and mediation analysis indicated that systemic inflammation partially explained these associations. For example, each one-unit increase in log-transformed 6:2 Cl-PFESA concentration was associated with lower eGFR (β = -1.56; 95 % CI: -2.37 to -0.74), with white blood cell count mediating 7.91 % of the Cl-PFESA-eGFR association. Isomer-specific effects were observed: linear PFOS and PFHxS showed stronger associations with inflammatory markers than their branched counterparts, while eGFR did not differ by isomer. Weighted quantile sum regression identified 6:2 Cl-PFESA as the largest contributor to reduced eGFR within the PFAS mixture (weight = 0.321). In mice, Cl-PFESA exposure resulted in increases in serum creatinine compared with the control group (2.70-fold in the 400 μg/L group; P < 0.01). Tumor necrosis factor-α was strongly correlated with serum creatinine (r = 0.949; P < 0.01) and mediated 58.41 % of the Cl-PFESA-creatinine association.

The longitudinal relationship between per- and polyfluoroalkyl substances (PFAS) exposure and dysglycemia in adults is not well understood. This study aimed to investigate this association in a prospective cohort of 741 adults (2015-2020). Serum concentrations of nine PFAS congeners were measured, and FBG levels were assessed annually. Linear mixed models (LMM) assessed individual PFAS associations with FBG changes, while quantile g-computation (qg-comp) and advanced bayesian kernel machine regression (A-BKMR) evaluated mixture effects. A Group-based trajectory model (GBTM) identified four FBG trajectories: normal-low, normal, at-risk for high-FBG, and persistent-increasing. Multinomial logistic regression, qg-comp and A-BKMR were further applied to estimate the associations between PFAS exposure and FBG trajectories. LMM, qg-comp and A-BKMR analyses indicated positive associations between PFAS exposure and longitudinal FBG levels. Longitudinal analysis indicated that perfluorooctane sulfonate (PFOS) and perfluoro-n-tridecanoic acid (PFTrDA) were associated with increases in FBG from 2015 to 2020. In multinomial logistic regression, two PFAS congeners PFOS and PFTrDA were associated with a higher probability of belonging to the persistent-increasing trajectory group. In the longitudinal qg-comp and A-BKMR models, higher PFAS mixture concentrations were associated with increased odds of belonging to the persistent-increasing trajectory group, compared with the normal-low trajectory. Higher PFAS mixture concentrations were also significantly associated with prediabetes (HR = 2.09, 95% CI: 1.03-4.23). PFTrDA and PFOS emerged as potential key contributors to the observed associations. Overall, these findings suggest that PFAS exposure may contribute to persistently increasing FBG levels in adults.

BACKGROUND:Hypertension affects 27.5% of Chinese adults, yet remains poorly controlled. Light at Night (LAN) is an emerging environmental factor potentially linked to hypertension, but evidence from developing countries is limited. METHODS:This retrospective cohort study included 8308 hypertension-free adults from the Future Longitudinal Observational Research in Adults (FLORA) project (2012 baseline). Outdoor LAN exposure was assessed annually using VIIRS-DNB satellite data at 500m × 500m range based on each participant's residential address, with time-varying exposure levels updated according to follow-up residence changes. Participants underwent annual physical examinations over 9.22 years (mean follow-up). Time-varying Cox proportional hazards regression models were used to assess the association between outdoor LAN exposure and the risk of incident hypertension and hypertension subtype. Subgroup analyses were conducted to identify vulnerable populations. Bootstrap models (1000 resamplings) were performed to explore the extent to which body mass index (BMI), fasting blood glucose (FBG) and triglycerides (TG) could account for the LAN-hypertension association. RESULTS:Compared with the lowest LAN quintile (Q1), participants in Q2-Q5 had significantly increased hypertension and hypertension subtype. For hypertension, the hazard ratios (HRs) from Q2 to Q5 were 1.14 (95%CI: 1.01, 1.29), 1.16 (95%CI: 1.03, 1.35), 1.19 (95%CI: 1.05, 1.35), and 1.23 (95%CI: 1.09, 1.40), respectively. BMI, FBG, and TG partially explained the association between outdoor LAN exposure and hypertension in exploratory analyses, accounting for 10.32% (95%CI: 6.69%, 16.09%), 4.81% (95%CI: 2.15%, 7.80%), and 1.71% (95%CI: 0.57%, 2.97%) of the total effect, respectively. CONCLUSIONS:This cohort study provides longitudinal evidence that higher residential ambient light at night exposure is associated with an increased risk of hypertension in adults from a developing country. Abnormal metabolism represented by high BMI, FBG, and TG levels may partially serve as a potential explanation that needs further research.

Although particulate matter has been associated with sleep problems, the effects of PM2.5-bound organophosphate esters (OPEs) on children's sleep remain unclear. OPEs have neurotoxic and endocrine-disrupting effects that may disrupt sleep-wake regulation during neurodevelopment, supporting biological plausibility for sleep impacts. In this study, we quantified the individual and mixture effects of PM2.5-bound OPEs on the sleep disorder domain. This cross-sectional study included 110,169 children aged 6-18 years from primary and secondary schools in the Pearl River Delta (PRD), China. Sleep disorders were evaluated using the validated Sleep Disturbance Scale for Children (SDSC). Elastic net and mixed effect models identified specific OPE-sleep associations, while weighted quantile sum regression evaluated mixture effects. All odds ratios indicate a change in the likelihood of sleep disorders per interquartile range (IQR) increase in OPE concentrations. The strongest individual associations were observed for TDCIPP with short sleep duration (OR = 1.56-1.61; moderate association), TEHP with short sleep duration (OR = 1.59-1.64; moderate association), and TPHP with overall sleep disorder (OR = 1.32-1.42; modest association). Combined OPE exposure was positively associated with all sleep disorder domains (ORs = 2.02-2.85; moderate-to-large associations). These results indicate that inhaling PM2.5-bound OPE mixtures could negatively impact children's sleep health. This emphasizes a critical developmental period and highlights the importance of public health concerns related to emerging airborne contaminants.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants associated with neurodevelopmental toxicity. However, the combined effects of PFAS subclasses and the modifying role of endogenous hormones remain poorly understood. Using data from the Maoming birth cohort (n = 543), we longitudinally assessed associations between prenatal exposure to perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) and developmental delay in children aged 3-60 months, employing generalized linear mixed models for individual PFAS and grouped weighted quantile sum regression for effects of PFAS mixtures. We further examined the effect modification by cord blood estradiol and progesterone, classified via latent profile analysis, and conducted molecular docking to explore potential receptor interactions. Both individual compounds [e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid (PFOS)] and PFCA mixtures were associated with increased odds of developmental delay, particularly in total-ASQ, communication, and motor domains. These associations were significantly modified by latent profiles of cord blood hormones. For example, in the low-hormone profile, perfluorodecanoic acid was associated with fine motor delay (Odds ratio [OR] = 2.04; 95% CI: 1.18, 3.49), whereas linear-PFOS was associated with gross motor delay (OR = 4.76; 95% CI: 1.96, 11.54) in the high-hormone profile. Molecular docking indicated that most PFCAs have a preferential binding affinity for the ligand-binding domains of estradiol and progesterone receptors, supporting the biological plausibility of the observed hormonal effect modification. Our findings demonstrate that the association between prenatal PFAS exposure and neurodevelopment is subclass-specific and critically shaped by the in utero hormonal environment.

Dioxin-like polychlorinated biphenyls (DL-PCBs) are persistent environmental pollutants known to induce oxidative stress and inflammation, which may accelerate telomere shortening and affect neurodevelopment. We hypothesized that DL-PCB exposure contributes to cognitive deficits in children by accelerating telomere attrition, which in turn impairs brain function. We analyzed serum DL-PCB levels, leukocyte telomere length (LTL), and cognitive performance in 1756 primary school children (aged 7–10 years) from Shenyang, China. Twelve DL-PCB congeners were measured, and cognitive outcomes were assessed using a standardized test battery, including the n-back task (Two-Back and Three-Back) and the Attentional Network Test (ANT). LTL was quantified via qRT-PCR. Linear mixed models, mixture analyses (Quartile g-computation analysis (g-comp), Generalized Weighted Quantile Sum regression (gWQS), Bayesian Kernel Machine Regression (BKMR) ), and mediation analysis were applied, adjusting for relevant covariates. Serum concentrations of PCB77, PCB126, and PCB189 were significantly associated with shorter LTL after Bonferroni correction (β = −0.041 for PCB189 per IQR increase, adjusted p = 0.001). PCB81 and PCB189 showed robust negative associations with superior working memory (Three-Back task; adjusted p < 0.05), while basic working memory (Two-Back) exhibited no significant associations. Inattentiveness (HRT-SE) was negatively associated with PCB157, PCB167, PCB169, and PCB189 in crude models, but these associations were attenuated after correction. Mixture analyses confirmed that DL-PCB mixtures were strongly associated with shorter LTL (g-comp β = −0.104, p < 0.001; gWQS β = −0.055, p < 0.001), as well as poorer superior working memory and inattentiveness. Mediation analysis revealed that LTL explained approximately 5–10

The Follow-up Longitudinal Observational study on Risk factors and Health in Adults (FLORA) is a prospective cohort established in Guangzhou, China, in 2008 to investigate the impact of rapid urbanization, environmental transitions, and macrosocial changes on non-communicable diseases (NCDs) in working-age and older adults. The cohort comprises 7,855 participants aged 19–83 years at baseline, drawn from the city’s annual mandatory health examination system for civil servants. Followup integrates passive annual electronic health record linkage with active questionnaire surveys, covering a period that spans three major pandemics (H1N1, H7N9, COVID-19) and key national environmental policies. FLORA also includes a biobank for future mechanistic research. The cohort provides a unique platform to examine how macrolevel societal transformations interact with individual-level risk factors in shaping NCD trajectories in a dynamic megacity setting.

Evidence from multicenter studies in Chinese populations on prenatal per- and polyfluoroalkyl substance (PFAS) exposure and preterm birth (PTB), and related metabolic mechanisms, remains limited. We conducted a multicenter case-control study including 1990 mother-infant pairs from northern, northwestern, and southern China (2015-2021) to examine associations between umbilical cord serum PFAS levels and PTB risk. In a subcohort (n = 134), maternal venous blood was analyzed using untargeted metabolomics. Higher levels of most PFAS were associated with an increased PTB risk. Pentacosafluorotridecanoic acid (PFTrDA) showed the strongest association, with a 51% higher PTB risk per interquartile range increase (OR = 1.51; 95% CI: 1.29-1.76), and elevated risks for moderate PTB (OR = 1.66; 95% CI: 1.22-2.25) and late PTB (OR = 1.45; 95% CI: 1.21-1.74). PFAS mixture analyses indicated a positive joint effect (OR = 1.03; 95% CI: 1.01-1.06 per decile increase). Metabolomics identified PFTrDA as the PFAS linked to the most metabolic perturbations (four metabolites). Glycodeoxycholic acid (GDCA) was consistently associated with PFAS exposure and mediated 21-44% of associations between selected PFAS and PTB, suggesting disruptions in bile acid and lipid metabolism.

Pakistan has the highest child diarrhoea mortality in South Asia, but the impact of household air pollution from polluting cooking fuels remains understudied. This study explores the association between exposure to such fuels and the odds of diarrhoea in children under five, using PDHS 2017-18 data. Diarrhoea prevalence was based on maternal self-reports of episodes in the past two weeks. Household air pollution exposure was measured using the household's primary cooking fuel. Multivariable logistic regression models were applied, adjusting for socioeconomic, child, maternal, nutritional, and water, sanitation, and hygiene factors. Among 11,947 children included, diarrhoea was reported in 2107 (17.6%). In the fully adjusted model, exposure to polluting cooking fuels was associated with higher odds of diarrhoea (OR: 1.13, 95% CI: 1.03-1.25, P-value = 0.013). Fuel-specific analysis showed that children in households using animal dung had the highest odds of diarrhoea (OR: 1.41, 95% CI: 1.06-1.84, P-value = 0.015). Subgroup analyses showed the strongest association among infants under 1 year, children with stunting, and those born to uneducated mothers. This study found that cooking with solid fuels increases childhood diarrhoea in Pakistan. Transitioning to clean fuels is crucial for public health in Pakistan and similar countries to reduce this burden.