Aug 2026· Environmental Research· pp.
125494
· 0 citations· 89 references
Medicine
TL;DR
Prenatal TBEP exposure was associated with greater behavioral problems in early childhood, and Alter neonatal gut microbiota and related metabolic pathways may partly underlie this association.
Abstract
Organophosphate esters (OPEs) are widely used flame retardants and plasticizers. Given their structural similarity to neurotoxic organophosphorus pesticides, concerns have been raised regarding their potential developmental neurotoxicity. However, epidemiologic evidence remains limited, and the roles of gut microbial and metabolic perturbations in these associations are not well characterized. We analyzed 404 mother-child pairs from the Shanghai Maternal-Child Pairs Cohort. OPE concentrations were quantified in cord serum. Meconium samples were profiled for gut microbiota and metabolomics, and behavioral development at 2 years was assessed using the Strengths and Difficulties Questionnaire. Generalized linear models, negative-binomial hurdle regression, SHapley Additive exPlanations, high-dimensional mediation analysis, metabolome-wide association analysis, meet-in-the-middle analysis, and pathway enrichment analysis were applied. A doubling of cord serum tris(2-butoxyethyl) phosphate (TBEP) concentration was associated with a 0.09-point increase in the conduct problem score at age 2 years (95% confidence interval [CI]: 0.02, 0.16). A doubling of TBEP concentration was also associated with 7.9% higher Chao1 richness (95% CI: 2.8%, 14.1%) and 8.7% higher ACE richness (95% CI: 3.5%, 14.1%). A doubling of Chao1 and ACE richness was associated with 0.27-point (95% CI: 0.12, 0.42) and 0.31-point (95% CI: 0.15, 0.46) increases in conduct problem scores, respectively. Alpha diversity indices and Collinsella were identified as potential mediators of the TBEP-conduct problem association. Integrated metabolomic analyses further implicated five pathways, particularly catecholamine biosynthesis and tyrosine metabolism. Enrichment scores for these pathways were positively associated with Chao1, ACE, and Collinsella. Prenatal TBEP exposure was associated with greater behavioral problems in early childhood. Altered neonatal gut microbiota and related metabolic pathways may partly underlie this association.
It is revealed that maternal exposure to OPEs in e-waste recycling areas contributes to increased neonatal birth weight and length, which may elevate the risk of overweight or obesity during later growth.
Mengyuan Jin, Shenghang Wang, Shoji F. Nakayama et al.· Journal of Applied Toxicolog...· 0 citations
Evidence on the association between prenatal exposure to organophosphate ester (OPE) and small vulnerable newborn components is limited and inconsistent. This study included 3208 mother-child dyads from the Ma'anshan Birth Cohort. In the first, second, and third trimesters, urine samples were used to detect 6 OPE metabolites to reduce misclassification bias in exposure. Statistical models, including robust poisson regression and quantile g-computation model, were used to explore the associations of OPE exposure with small vulnerable newborns and their component variables and the co-exposure effects, respectively. Poisson regression analysis revealed that exposure to tris(2-chloroethyl) phosphate (TCEP) during the first trimester and diphenyl phosphate (DPHP) during the third trimester were associated with a decreased risk of small vulnerable newborns [risk ratio (RR) = 0.68, 95% confidence interval (CI): 0.49, 0.94 for TCEP; RR= 0.85, 95%CI: 0.75, 0.97 for DPHP), mirroring the results obtained from the mixture exposure analysis. This inverse relationship may inherently reflect an underlying phenomenon of prolonged gestational duration and increased birth weight. The study first explored the impact of prenatal exposure to OPEs on the entire small vulnerable newborns, suggesting that prenatal OPEs have sex- and trimester-specific effects on the risk of small vulnerable newborns. The analysis results of OPE for different small vulnerable newborn component variables also verified the complex relationship between OPE and adverse birth outcomes.
Ping Lv, Yi-fan Wang, Yongkang Liu et al.· Ecotoxicology and Environmen...· 0 citations
Prenatal exposure to OPFRs and OPPs was associated with smaller left ventricular structural measures in early childhood, mainly reflected by lower left ventricular volume and mass, with OPFRs emerging as main contributors and stronger associations among girls.
Meng Wang, Xi Zhang, Hualin Wang et al.· Environmental Pollution· 0 citations
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
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
The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored.
METHODS
We conducted a 1:1 age- and sex-matched case-control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms.
RESULTS
Participants (mean age 45.2 years, 82.3% female) had serum OCPs at 0.007-0.333 ng/mL and SPs at 0.046-0.095 ng/mL. ML algorithms identified fenpropathrin, β-BHC, cyhalothrin, α-BHC, and p,p'-DDD as the top five contributors to TC. Elevated OCPs/SPs exposure was significantly associated with increased TC risk (WQS: adjusted OR = 1.45, 95%CI = 1.34-2.24, P = 0.019; LUCID: OR = 9.33). Fenpropathrin was the primary contributor (BKMR posterior inclusion probability = 1.00; WQS weight = 67.6%). A total of 45 significant differential metabolites (DMs) were identified (VIP ≥1, P < 0.05, and qualitative level 1). LUCID revealed a distinct TC cluster characterized by upregulated S-sulfo-L-cysteine/adenosine and downregulated 2-hydroxycaprylic acid.
CONCLUSION
OCPs/SPs mixtures, driven by fenpropathrin, disrupt amino acid/nucleotide metabolism while suppressing organic acid metabolism, representing a potential TC-associated metabolic signature.
Fei Wang, Chunxiang Li, Linfang Zou et al.· Environment International· 0 citations