Prenatal thallium exposure, cord plasma metabolome, and child neurodevelopment: A prospective birth cohort study

Maternal exposure to thallium may cause fetotoxicity in offspring. However, epidemiological studies on the neurodevelopmental toxicity associated with early-life thallium exposure are limited, and the underlying mechanisms remain ambiguous. Based on a prospective longitudinal birth cohort study in Wuhan, China (n = 1036), we quantified maternal thallium concentrations in spot urine samples collected during late pregnancy. Metabolomics analyses were performed on cord blood plasma samples collected at birth. Offspring neurodevelopment, characterized by mental developmental index (MDI) and psychomotor developmental index (PDI), was assessed at 2 years of age. Maternal thallium levels, modeled as either continuous or categorical variables, demonstrated significant inverse associations with children's MDI and PDI scores. Each unit increase in thallium was linked to a 2.66-point decrease (95 % CI: -4.02, -1.30) in MDI scores and a 1.79-point decrease (95 % CI: -2.92, -0.65) in PDI scores. The inverse relationships were further confirmed across tertiles of thallium exposure, and linear dose-response associations were observed. Metabolomics analysis revealed that perturbations in multiple amino acid and lipid metabolism, involving differential metabolites and related pathways such as 4-hydroxyproline, 5-hydroxylysine, and fatty acids, exerted significant mediating effects on the observed inverse associations. Our study provides novel evidence linking maternal thallium exposure to adverse offspring neurodevelopment and highlights metabolic disturbances as important underlying biological mechanisms for this association.