RESUMEN
BACKGROUND: The global prevalence of autism spectrum disorder (ASD) is on the rise, and high levels of exposure to toxic heavy metals may be associated with this increase. Urine analysis is a noninvasive method for investigating the accumulation and excretion of heavy metals. The aim of this study was to identify ASD-associated urinary metal markers. METHODS: Overall, 70 children with ASD and 71 children with typical development (TD) were enrolled in this retrospective case-control study. In this metallomics investigation, inductively coupled plasma mass spectrometry was performed to obtain the urine profile of 27 metals. RESULTS: Children with ASD could be distinguished from children with TD based on the urine metal profile, with ASD children showing an increased urine metal Shannon diversity. A metallome-wide association analysis was used to identify seven ASD-related metals in urine, with cobalt, aluminum, selenium, and lithium significantly higher, and manganese, mercury, and titanium significantly lower in the urine of children with ASD than in children with TD. The least absolute shrinkage and selection operator (LASSO) machine learning method was used to rank the seven urine metals in terms of their effect on ASD. On the basis of these seven urine metals, we constructed a LASSO regression model for ASD classification and found an area under the receiver operating characteristic curve of 0.913. We also constructed a clinical prediction model for ASD based on the seven metals that were different in the urine of children with ASD and found that the model would be useful for the clinical prediction of ASD risk. CONCLUSIONS: The study findings suggest that altered urine metal concentrations may be an important risk factor for ASD, and we recommend further exploration of the mechanisms and clinical treatment measures for such alterations.