Background: Evidence linking chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) to preterm birth (PTB) is limited, and their relationships with the metabolome remain unexplored. Aims: Our study aimed to explore the role of the metabolome in the associations between Cl-PFESAs exposure and PTB. Methods: We conducted a nested case–control study in the Shenyang birth cohort, which included 206 spontaneous preterm birth cases and 206 full-term controls, matched for maternal age and pre-pregnancy BMI. We used conditional logistic regression models to analyze the associations between Cl-PFESAs exposure in umbilical cord blood and PTB. Moreover, the metabolomics of maternal blood (44 cases) between the preterm and control groups was analyzed using the interaction analysis. Results: We observed that a higher natural log-transformed 6:2 Cl-PFESA level was associated with greater odds of PTB in conditional multivariable-adjusted logistic regression models (OR = 1.738, 95% CI: 1.320, 2.287). The results of metabolomics pathway analysis showed that histidine metabolism pathways may modify the above risk. When stratified by histidine levels, the association between cord blood 6:2 Cl-PFESA and PTB was different. Conclusions: Intrauterine exposure to 6:2 Cl-PFESA was associated with increased PTB. Also, for the first time, our study illustrates that maternal plasma metabolite profiles may modify the associations of 6:2 Cl-PFESA with PTB. More research is needed to elucidate the mechanism underlying the reproductive toxicity of 6:2 Cl-PFESA in pregnant women following exposure.

Although particulate matter has been associated with sleep problems, the effects of PM_2.5-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 PM_2.5-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 PM_2.5-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.

Chlorinated paraffins (CPs) are emerging contaminants with potential risks to the environment and human health, but their link between fine particulate matter-bound chlorinated paraffins (PM_2.5-bound CPs) and the risk of sleep disorders has not been reported. This large-scale, population-based study included 122,965 valid questionnaires from school-aged children in the Pearl River Delta region of China. Generalized linear mixed models, restricted cubic splines, weighted quantile sum regression and Quantile g-computation models were used to evaluate the individual and combined effects of PM_2.5-bound CPs on sleep disorders. Mediation analysis assessed the potential role of body weight. Our findings showed that an interquartile range (IQR) increase in PM_2.5-bound ∑CPs was linked to a higher risk of sleep disorders, and odds ratio ranging from 1.08 to 3.20. Short-chain chlorinated paraffins (SCCPs) were identified as key contributors of CPs and might interfere with important metabolic pathways. Further analysis indicated that body weight statistically accounted for part of the observed association between exposure to CPs and sleep disorders, with the proportion mediated ranging from 3.40% to 35.67%. Stratified analyses suggested stronger associations among girls and children under 12 years. These findings support prioritizing CPs management strategies to reduce their negative impact among children and adolescents.

Widespread exposure to per- and polyfluoroalkyl substances (PFAS) is a growing public health concern, but its link to muscle damage remains largely unexplored. As PFAS exposure is associated with liver dysfunction, which is an established risk factor for muscle damage, we examined their associations and potential mediating pathways. A total of 1261 participants were recruited from Guangdong province, China, from November 2018 to August 2019 and examined for muscle mass, strength, serum PFAS levels, and biomarkers of liver function. The key results demonstrated significant positive associations between serum PFAS exposure and sarcopenia risk. Specifically, a per ln ng/mL increase in linear perfluorooctane sulfonate (PFOS), branch PFOS, and perfluorooctanoic acid (PFOA) was associated with adjusted odds ratios of 2.32 (95% CI: 1.77 to 3.00), 2.18 (95% CI: 1.67 to 2.90) and 3.01 (95% CI: 1.96 to 4.70), respectively. Analysis of PFAS mixtures via the BKMR model revealed a linear dose–response relationship of sarcopenia, with PFOS and PFOA being the primary contributor. Importantly, mediation analyses showed that liver function biomarkers served as significant mediators of the PFAS–sarcopenia association. Notably, liver synthesis function markers (albumin and globin) mediated a substantial proportion of the association, ranging from 3.48% to 82.42%, whereas liver injury markers (aspartate aminotransferase and gamma-glutamyl transferase) accounted for only 1.54% to 15.44%. This study underscores the need to be aware of the increased risk of muscle damage associated with PFAS exposure, which may primarily operate through liver function abnormalities.

Although particulate matter has been associated with sleep problems, the effects of PM_2.5-bound organophosphate esters (OPEs) on children’s sleep remain unclear. In this study, we examined the relationship between OPEs in PM_2.5 and sleep disorders in children. 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). Concentrations of OPEs were measured through school-based sampling and chemical analysis. Elastic net regression identified key OPE exposures, binomial generalized linear mixed models estimated individual OPE effects with the city as a random effect, and weighted quantile sum regression assessed the combined effects of OPE mixtures. All odds ratios indicate the change in likelihood of sleep disorders per interquartile range (IQR) increase in OPE concentrations. Although all components showed significant associations, the highest odds were observed with TDCIPP for short sleep duration (OR: 1.56–1.61), TEHP for short sleep duration (OR: 1.59–1.64), and TPHP for overall sleep disorder (OR: 1.32–1.42). Combine OPE exposure was positively associated with all childhood sleep disorders, with odds ratios ranging from 2.02 to 2.85 across various sleep outcomes. These findings highlight how OPE mixtures in PM_2.5 affect child sleep health, emphasizing the need for comprehensive analytical methods.