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Figure 2. Associations of third-trimester maternal PFAS exposure (individual and mixture) with neurodevelopmental trajectories in preschool children (33-84 months). (A) Associations between maternal serum concentrations of individual PFAS compounds (ng/mL) and neurodevelopmental trajectories in preschool-aged children, measured by neurodevelopmental scores. ORs and 95%CIs were calculated through logistic regression and GWQS regression models to compare children in the persistently low trajectory group with those in the persistently high trajectory group (n = 278). ^*P < 0.05. Two GWQS indices were created: GWQS 1 for exposure to alternative PFAS (6:2 Cl-PFESA, 8:2 Cl-PFESA, PFHxA, PFBA), and GWQS 2 for exposure to legacy PFAS (PFDoDA, PFOA, linear PFHxS, PFUnDA, PFOS, PFDA, PFNA, and PFTrDA). The GWQS indices for each group were evaluated, where a one-unit increase in the GWQS index signified a quartile increase in the PFAS mixture of each group; (B) Relative weights of individual PFAS within the mixture models in GWQS regression. Mean weights and selection frequencies were estimated from 100 bootstrap samples. Legacy PFAS GWQS model: coefficient = 0.779 (SE = 0.395, P = 0.048); Alternative PFAS GWQS model: coefficient = -0.455 (SE = 0.452, P = 0.314). The top panel shows legacy PFAS, and the bottom panel shows alternative PFAS. Larger weight indices indicate greater contributions of specific PFAS compounds to the mixture’s overall effect on neurodevelopmental trajectories. All models were controlled for maternal age, pre-pregnancy BMI, parity, maternal education, family income, maternal passive smoking before pregnancy, alcohol drinking, folic acid or vitamin supplementation during pregnancy, child sex, and gestational age. PFAS: polyfluoroalkyl substances; ORs: odds ratios; CIs: confidence intervals; GWQS: grouped weighted quantile sum; 6:2 Cl-PFESA: 6:2 chlorinated polyfluorinated ether sulfonate acid; 8:2 Cl-PFESA: 8:2 chlorinated polyfluorinated ether sulfonate acid; PFHxA: perfluoro-n-hexanoic acid; PFBA: perfluoro-n-nbutanoic acid; PFDoDA: perfluoro-n-dodecanoic acid; PFOA: perfluorooctanoic acid; PFHxS: perfluoro-1-hexane sulfonate; PFUnDA: perfluoro-n-undecanoic acid; PFOS: perfluorooctane sulfonate; PFDA: perfluoro-n-decanoic acid; PFNA: perfluoro-n-nonaoic acid; PFTrDA: perfluoro-n-tridecanoic acid; SE: standard error; BMI: body mass index; PFDA: perfluoro-n-decanoic acid.