Prenatal exposure to glycol ethers and motor inhibition function evaluated by functional MRI at the age of 10 to 12 years in the PELAGIE mother-child cohort

Abstract

Background: Pregnant women are ubiquitously exposed to organic solvents, such as glycol ethers. Several studies suggest potential developmental neurotoxicity following exposure to glycol ethers with a lack of clarity of possible brain mechanisms. Objectives: We investigated the association between urinary levels of glycol ethers of women during early pregnancy and motor inhibition function of their 10- to 12-year-old children by behavioral assessment and brain imaging. Methods: Exposure to glycol ethers was assessed by measuring six metabolites in urine (<19 weeks of gestation) of 73 pregnant women of the PELAGIE mother-child cohort (France). Maternal urinary levels were classified as low, medium, or high. Children underwent functional magnetic resonance imaging (fMRI) examinations during which motor inhibition function was assessed with a Go/No-Go task. Analyses were performed using linear regression for task performance and generalized linear mixed-effect models for brain activation, FWER-corrected for multiple testing at the spatial cluster level. Confounders were considered by restriction and a priori adjustment. Results: Higher maternal butoxyacetic acid (BAA) urinary concentrations were associated with poorer child performance (β = −1.1; 95% CI: −1.9, −0.2 for high vs low). There was also a trend for ethoxyacetic acid (EAA) towards poorer performance (β = −0.3; 95% CI: −0.7, 0.01). Considering inhibition demand, there were increased activity in occipital regions in association with moderate EAA (left cuneus) and moderate methoxyacetic acid (MAA) (right precuneus). When children succeeded to inhibit, high ethoxyethoxyacetic acid (EEAA) and moderate phenoxyacetic acid (PhAA) levels were associated with differential activity in frontal cortex, involved in inhibition network. Discussion: Prenatal urinary levels of two glycol ether metabolites were associated with poorer Go/No-Go task performance. Differential activations were observed in the brain motor inhibition network in relation with successful inhibition, but not with cognitive demand. Nevertheless, there is no consistence between performance indicators and cerebral activity results. Other studies are highly necessary given the ubiquity of glycol ether exposure.