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Fangbiao Tao

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Jul 2026

Sex- and Trimester-Specific Associations of Prenatal Co-Exposure to Organophosphate Esters and Phthalates with Preschoolers' Trajectories of Co-Occurring ADHD and ASD Symptoms: Cord Blood Metabolomic Study in the Ma'anshan Birth Cohort.

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. · 0 citations
Open access Aug 2026

Small vulnerable newborns and prenatal exposure to organophosphate esters: Insights from the Ma'anshan Birth Cohort.

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. · 0 citations