Lead-driven synergistic interactions in environmental metal (loid) mixtures: Systemic inflammation mediating autism spectrum disorder risk in Chinese children.

Researchers studied blood metal levels in Chinese children with autism and compared them to children without autism. They found that children with higher lead levels were much more likely to have autism - those with the highest lead levels had almost 7 times greater risk. Lead was the most important metal affecting autism risk, and inflammation in the body helped explain how lead might contribute to autism development.

This case-control study examined blood metal concentrations in 81 Chinese children with autism spectrum disorder (ASD) and 402 typically developing children. Lead exposure showed the strongest association with ASD risk, with children in the highest exposure group having nearly 7 times greater odds of ASD compared to the lowest group. Lead was identified as the primary contributor to ASD risk among eight metals tested, with evidence of synergistic interactions with cobalt. Systemic inflammation markers partially explained the relationship between lead exposure and ASD risk.

The study confirms lead as a significant environmental risk factor for ASD and suggests inflammatory pathways may mediate this association.

Findings support the importance of lead exposure prevention in early childhood. Clinicians should consider environmental lead screening for children with ASD. Results suggest systemic inflammation may be a targetable pathway in lead-related neurotoxicity, though intervention studies are needed to confirm therapeutic approaches.

Single case-control study design limits causal inference. Study conducted in Chinese population may limit generalizability to other ethnic groups. Cross-sectional design cannot establish temporal relationships between metal exposure and ASD development.

Environmental metal (loid) exposure, particularly to lead (Pb), constitutes a growing concern for potential associations with autism spectrum disorder (ASD). Current risk assessments may underestimate neurodevelopmental impacts due to co-exposure interactions, while systemic inflammation's mediating role in Pb-ASD relationships remains poorly characterized. This case-control study quantified serum concentrations of eight metal (loid)s via inductively coupled plasma mass spectrometry (ICP-MS) in 81 ASD cases and 402 typically developing (TD) Chinese children. Logistic regression demonstrated significantly elevated ASD risk with increasing Pb exposure quartiles (Q3 vs.

Q1: OR = 2.64, 95 % CI 1.42-4.89; Q4 vs. Q1: OR = 6.85, 95 % CI 3.24-14.48; P< 0.001). Restricted cubic spline analysis confirmed a positive nonlinear dose-response relationship between log-transformed Pb levels and ASD risk (P = 0.004, P< 0.001). Multi-pollutant mixture analyses identified Pb as the predominant contributor to ASD risk in both quantile g-computation (weight = 0.5099) and Bayesian kernel machine regression (PIP = 1.00) models, with evidence of significant cobalt (Co)-Pb interaction.

Mediation analyses indicated systemic inflammation indices (SIRI, SII) partially mediated the Pb-ASD association (15.8 % and 8.6 %, respectively). These findings identify Pb as a principal determinant of metal (loid)-associated ASD risk, with inflammatory pathways contributing to its neurotoxicity. The observed Co-Pb interaction warrants investigation into co-exposure neurotoxicity mechanisms.