Neurodevelopmental exposome: The effect of in utero co-exposure to heavy metals and phthalates on child neurodevelopment

In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure metals and phthalates, metabolic pathways deregulation, clinically observed phenotypes of neurodevelopmental disorders such as problems linguistic, motor development cognitive capacity. Children (n = 148) tested at first second year their life using Bayley Scales Infant Toddler Development, Third Edition (Bayley-III). Their mothers had exposed phthalates during pregnancy, according biomonitoring results from previously performed studies. Untargeted analysis biobanked samples was combination high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) nuclear magnetic resonance (NMR). Most perturbed heavy related tricarboxylic acid cycle (TCA cycle) oxidative phosphorylation, indicating possibility disruption mitochondrial respiration. Overproduction reactive oxygen species (ROS); presence glutathione peroxidase 3 (GPx3) pregnancy 1 (GPx1) umbilical cord linked verbal problems. Another finding study is that real life, adverse outcomes occur environmental social factors, all them acting synergistically towards deployment phenotype. Finally, two-steps process (exposure outcomes) able (a) provide associations are not evident directly associating exposure (b) provides additional insides mechanisms disease.