It is suggested 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.
Abstract
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.
Urinary metabolomic analysis suggests that OPs exposure and oxidative stress may be associated with metabolic changes in ADHD, particularly in energy metabolism and amino acid pathways.
Hsin-Yun Tseng, C. Lo, Boopathi Subramani et al.· Metabolomics· 0 citations
Although neurotoxic, prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) and their effects on preschoolers' autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) cotrajectories and underlying metabolic mechanisms remain unclear, we aimed to elucidate these links. Maternal urinary OPEs/PAEs were measured in 3040 dyads from the Ma'anshan Birth Cohort across three trimesters. Child ADHD/ASD symptom scale scores were assessed at ages 3, 5, and 6, and cotrajectories were identified using group-based multitrajectory modeling. Single-pollutant models revealed that bis(2-ethylhexyl) phosphate (BEHP) across pregnancy was positively associated with high-score trajectories (HST) (OR = 1.20, 95% CI: 1.06, 1.37), whereas bis(2-butoxyethyl) phosphate (BBOEP) exhibited U-shaped associations. Second-trimester diphenyl phosphate (DPHP) (OR = 1.13, 95% CI: 1.01, 1.26), BEHP (OR = 1.14, 95% CI: 1.04, 1.24), and monobutyl phthalate (OR = 1.15, 95% CI: 1.00, 1.32) were positively associated with HST. First-trimester DPHP exhibited a positive correlation with moderate-score trajectories and HST in girls, while bis(1-chloro-2-propyl) phosphate across pregnancy was inversely associated with HST in boys (psex-int < 0.05). No mixed effects were detected. BBOEP across pregnancy was negatively associated with ADHD symptoms, whereas BEHP was positively associated. BEHP, monomethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with ASD symptoms, whereas dibutyl phosphate and monoethyl phthalate were negatively associated (p < 0.05). Cord blood metabolomics identified pyrimidine, biotin, lysine, cysteine, and methionine metabolism as key mediators of OPE-induced cotrajectories, and purine metabolism mediated PAEs' effects (p < 0.05). This study highlights OPE/PAE neurotoxicity and reveals novel cord metabolomic insights.
Xing Wang, J. Tong, M. Lu et al.· Environmental Science and Te...· 0 citations
Prenatal OP exposure was not associated with autism-related traits in childhood and results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders.
Haleigh Cavalier, Heather E. Volk, A. Kivumbi et al.· JAMA pediatrics· 0 citations
BACKGROUND
Although fine particulate matter (PM2.5) has been associated with cognitive dysfunction (CD), the roles of specific PM2.5 components and potential mechanisms remain limited. This study aimed to examine the association of long-term PM2.5 and its components with CD, identify the relative importance of components in the mixture, and generate hypotheses regarding possible biological pathways.
METHODS
A total of 14,379 participants aged ≥ 60 from the Henan Rural Cohort were recruited. CD was assessed using the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS). Concentrations of PM2.5, black carbon (BC), organic matter (OM), ammonium (NH4+), sulfate (SO42-), and nitrate (NO3-) were derived from the TAP dataset. Logistic regression and weighted quantile sum (WQS) regression were applied to estimate associations of single pollutants and pollutant mixture with CD. Network toxicology and machine learning analyses were performed to explore biological pathways and prioritize candidate genes.
RESULTS
For each interquartile range (IQR) increase in PM2.5, BC, OM, NH4+, SO42-, and NO3-, the odds of CD increased by 19%-43%. BC consistently ranked as the leading contributor (weights: 86.38% to 54.31%), followed by OM (weights: 7.24% to 34.57%) across the four CD definitions. Network toxicology analysis identified 47 candidate PM2.5-CD genes, and RPL23, RPL36AL, and RPS25 were prioritized as hypothesis-generating candidate genes by the random forest model (RF).
CONCLUSION
Long-term exposure to PM2.5 and its components is associated with higher odds of CD in rural older adults. BC and OM may represent important contributors within the PM2.5 mixture. Ribosomal and mitochondrial pathways may be dysregulated in PM2.5-related neurotoxicity, but candidate genes require further validation.
Huanxiang Zhang, Ziyuan Zhang, Z. Tian et al.· Neurotoxicology· 0 citations
A growing body of evidence links gestational fine particulate matter (PM2.5) exposure to elevated childhood obesity risk, yet research on the combined impacts and respective contributions of different PM2.5 chemical constituents remains limited. This large population-based prospective study involved 339,435 mother-child pairs from Liaoning Province, China. Prenatal exposure to PM2.5 and five major chemical constituents (organic matter (OM), black carbon (BC), ammonium (NH₄⁺), nitrate (NO₃⁻), sulfate (SO₄²⁻)) was estimated using high-resolution atmospheric reanalysis data. Quantile g-computation (QGC) was used to investigate the joint associations of PM2.5 chemical constituent mixtures and the relative contribution of each constituent with childhood overweight/obesity (OwOb) risk across the first two years of life. In single-pollutant models, prenatal exposure to PM2.5 total mass (per interquartile range, odds ratio (OR) = 1.050, 95% confidence interval (CI): 1.036, 1.064) and four of the five chemical constituents (OM: OR = 1.058, 95% CI: 1.043, 1.072; NH₄⁺: OR = 1.048, 95% CI: 1.035, 1.062; NO₃⁻: OR = 1.048, 95% CI: 1.033, 1.064; and BC: OR = 1.033, 95% CI: 1.020, 1.047) were positively associated with increased risks of offspring OwOb. A one-quartile increase in the mixture of multiple PM2.5 chemical constituents was associated with increased OwOb risk (OR = 1.063, 95% CI: 1.050, 1.076), with OM (54.1%), NH₄⁺ (34.4%), and NO₃⁻ (11.5%) acting as major contributors to the overall mixture effects. These findings underscore that regulating key PM2.5 chemical constituents is a vital public health strategy to mitigate the adverse effects of prenatal air pollution on children's metabolic health.
Shuqi Wu, Sishi Liu, Huan Li et al.· Ecotoxicology and Environmen...· 0 citations
Background Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in children. The impact of environmental factors on ADHD is very important. Therefore, we analyzed and measured the correlation between the serum vitamin and microelement levels of Chinese children and the incidence rate of ADHD, hoping to provide some guidance for the prevention, diagnosis and treatment of ADHD. Methods 128 children (69 boys and 59 girls, with an average age of 9.38 ± 2.5 years) were diagnosed with ADHD. In addition, 133 healthy children were recruited as the healthy control group (HC). The levels of serum vitamins and elements were determined by liquid chromatography-mass spectrometry (LC-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Use statistical analysis to compare the differences in the content of two groups of indicators and analyze their correlation with ADHD. Results Compared with the healthy control group (HC group), children with ADHD exhibited significantly lower levels of serum vitamin A, vitamin D and vitamin D3, while the levels of lead and copper were also significantly elevated. Logistic regression analysis indicated a negative correlation between vitamin D levels and ADHD. Conclusion Children with ADHD exhibit significantly lower serum VD levels and higher Pb levels (only in boys), suggesting VD deficiency and sex-specific Pb susceptibility may be key factors associated with ADHD.
Tianzhu Chen, Jia-Xiong Yao, Yang Su et al.· Frontiers in Molecular Biosc...· 0 citations
