Associations of exposure to bisphenol A and its substitutes with neurodevelopmental outcomes among infants at 12 months of age: A cross-sectional study

Bisphenol A (BPA) exposure has been linked to adverse childhood neurodevelopment, but little is known about whether BPA substitutes exposures are also related to childhood neurodevelopment.To investigate the associations of exposure to BPA and its substitutes with infant neurodevelopment at 12 months.A total of 420 infants at 12 months were included from the Laizhou Wan (Bay) Birth Cohort in Shandong, China. Urinary concentrations of BPA and its substitutes including bisphenol S (BPS), bisphenol B (BPB), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol P (BPP) and bisphenol Z (BPZ) were measured. Developmental quotient (DQ) scores based on the Gesell Development Schedules (GDS) were used to evaluate infant neurodevelopment. The multivariable linear regression and weighted quantile sum (WQS) regression were applied to estimate the associations of exposure to individual bisphenols and their mixtures with DQ scores, respectively. Sex-stratified analyses were also performed.BPA was detected in most infants (89.05%) and had the highest median concentration (0.709 ng/mL) among all bisphenols. BPA substitutes except BPZ were ubiquitous in infants' urine samples (>70%), and BPS showed the highest median concentration (0.064 ng/mL) followed by BPAP (0.036 ng/mL), BPAF (0.028 ng/mL), BPP (0.015 ng/mL) and BPB (0.013 ng/mL). In multivariable linear regression, only BPAF exposure was inversely associated with social DQ scores among all infants (β = -0.334; 95% CI: -0.650, -0.019). After sex stratification, this inverse association was significant in girls (β = -0.605; 95% CI: -1.030, -0.180). Besides, BPA exposure was negatively related to gross motor DQ scores in boys (β = -1.061; 95% CI: -2.078, -0.045). WQS analyses confirmed these results.Our study suggests that bisphenol exposure during infancy may be associated with poor infant neurodevelopment, and BPAF as a commonly used BPA substitute contributing the most to this adverse association deserves more attention.