Association between phthalates exposure and neurodevelopment of infants aged two years

Background Phthalates (PAEs), a class of endocrine disrupting chemicals (EDCs), have been linked to potential adverse effects on neurodevelopment and cognitive function of children. Therefore, it is critical to explore the effects of PAEs exposure on neurodevelopment in the earlier life stage and provide scientific evidence for making child health protection measures.

Objective This study is conducted to assess urinary PAEs levels of two-year-old toddlers, and investigate its association with neurodevelopment during early childhood.

Methods A total of 331 toddlers aged 2 years from the Sheyang Mini Birth Cohort were enrolled. A questionnaire survey was conducted to collect the socio-demographic information of the toddlers and spot urine samples were collected during the follow-up visits. Urinary concentrations of 10 PAEs metabolites were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Gesell Development Schedule (GDS) was administered to assess the neurodevelopment of children. A generalized linear regression model was employed to explore the association between PAEs exposure and infant neurodevelopment.

Results The positive rates of selected 10 urinary PAEs metabolites were between 93.05% and 100.00%. The urinary PAEs metabolites concentrations (geometric mean) were in the range of 0.25-50.13 μg·L^-1. The children's total development quotient (mean±SD) evaluated by GDS was 97.58±8.11. The urinary mono-methyl phthalate (MMP) concentration was negatively associated with the adaptive domain scores (b=-1.53, 95% CI: -2.77﹣-0.30, P=0.015), the personal-social domain scores (b=-1.58, 95% CI: -2.86﹣-0.30, P=0.015), and the total development quotient (b=-1.34, 95% CI: -2.53﹣-0.15, P=0.027). Conversely, the urinary mono-(2-ethylhexyl) phthalate (MEHP) concentration was positively associated with the motor domain scores (b=2.03, 95% CI: 0.35-3.71, P=0.018) and the total development quotient (b=1.51, 95% CI: 0.04-2.96, P=0.045). In sex-stratified analysis, the urinary concentration of MMP was negatively associated with the adaptive domain scores (b=-1.94, 95% CI: -3.81﹣-0.06, P=0.043), the personal-social domain scores (b=-2.80, 95% CI: -4.73﹣-0.87, P=0.004), and the total developmental quotient (b=-1.88, 95% CI: -3.69﹣-0.07, P=0.042) in girls, while the urinary MEHP concentration was positively associated with the motor domain scores (b=3.17, 95%CI: 1.01-5.33, P=0.004) and the total developmental quotient (b=2.15, 95%CI: 0.24-4.07, P=0.027) in boys.

Conclusion The selected 2-year-old children are extensively exposed to PAEs in the rural area of Jiangsu. Furthermore, early childhood PAEs exposure may have potential impacts on infant neurodevelopment with sex-specific effects.