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.
Source: PubMed, NCBI / U.S. National Library of Medicine
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 positivel
Abstract
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.