Whole-blood lead-copper association in children with autism spectrum disorder: Implications for toxic-essential metal...

Lead (Pb) is a developmental neurotoxicant that can interfere with essential-metal regulation, whereas copper (Cu) is a tightly regulated redox-active trace element required for normal neurological function. This study investigated whether whole-blood Pb concentrations were associated with whole-blood Cu concentrations in 28 children with autism spectrum disorder (ASD), compared with 28 pediatric controls closely matched for age and with the same sex distribution. Mean whole-blood Pb concentration was 70.29 ± 31.34 µg/L in the ASD group and 47.99 ± 13.95 µg/L in controls. Pb concentrations were higher in ASD (geometric mean ratio 1.394, 95% confidence interval [CI] 1.146-1.697, p = 0.001). Within the ASD group, Pb was positively associated with Cu (Pearson r = 0.385, 95% CI 0.014-0.663, p = 0.043), with a regression slope of 1.940 µg/L Cu per 1 µg/L Pb (95% CI 0.067-3.813; R² = 0.148). After adjustment for age and sex, the Pb coefficient remained similar in magnitude (β = 1.765, 95% CI - 0.174 to 3.704, p = 0.072). The Pb-Cu correlation was not significant in controls, and there was no evidence that the Pb-Cu association differed between the ASD and control groups. The association remained directionally consistent across additional sensitivity analyses, and adjustment for Childhood Autism Rating Scale (CARS) score did not materially alter the Pb coefficient. The findings are compatible with experimental evidence on Pb-Cu interactions and Cu homeostasis but do not establish causality or ASD-specific Pb-Cu coupling. Replication in larger, prospectively characterized cohorts is required.