Changes in molecular biomarkers of neurotoxicity in newborns following prenatal exposure to organophosphate compounds

Abstract

The rising incidence of neurodevelopmental disorders has been associated with early-life exposure to environmental factors, particularly neurotoxicants like organophosphate compounds (OPCs), which can impact brain development and function. This study examined the relationship between prenatal exposure to OPCs and molecular biomarkers of neurotoxicity in cord blood from 398 mother-child pairs in the GENEIDA birth cohort (Southeastern Spain). Urine samples were collected in the first and third trimesters and analysed for metabolites of organophosphate pesticides (dialkylphosphates, DAPs) and flame retardants (OPFRs) using LC-MS/MS. Six neurotoxicity biomarkers-brain-derived neurotrophic factor (BDNF), neurogranin (Ng), ubiquitin C-terminal hydrolase L1 (UCHL1), neurofilament heavy chain (NFH), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B)-were measured in cord blood via multiplex analysis using Luminex xMAP technology. The results showed that higher levels of DAP metabolites in maternal urine, particularly those with dimethyl groups, were associated with increased GFAP levels in cord blood. OPFR metabolites correlated with elevated GFAP and UCHL1 levels. Sex-specific effects were observed: OPFR levels were linked to higher GFAP in boys, while higher DAP metabolites, particularly those with diethyl groups, were associated with elevated BDNF in girls. Additionally, higher levels of diphenyl phosphate, an OPFR metabolite, were linked to increased S100B in boys. These findings suggest sexually dimorphic effects of prenatal OPC exposure. These findings provide preliminary evidence of developmental neurotoxicity and suggest potential biomarkers in cord blood for early detection of neurodevelopmental deficits. Further studies, including neurobehavioral evaluations and brain imaging, are needed to better understand these molecular effects.