Prenatal exposure to pesticides and domain-specific neurodevelopment at age 12 and 18 months in Nanjing, China

Background: The extensive usage of pesticides has led to a ubiquitous exposure in the Chinese general population. Previous studies have demonstrated developmental neurotoxicity associated with prenatal exposure to pesticides.Objectives: We aimed to delineate the landscape of internal pesticides exposure levels from pregnant women's blood serum samples, and to identify the specific pesticides associated with the domain-specific neuropsycho-logical development.Methods: Participants included 710 mother-child pairs in a prospective cohort study initiated and maintained in Nanjing Maternity and Child Health Care Hospital. Maternal spot blood samples were collected at enrollment. Leveraging on an accurate, sensitive and reproducible analysis method for 88 pesticides, a total of 49 pesticides were measured simultaneously using gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After implementing a strict quality control (QC) management, 29 pesticides were reported. We assessed neuropsychological development in 12-month-old (n = 172) and 18-month-old (n = 138) children using the Ages and Stages Questionnaire (ASQ), Third Edition. Negative binomial regression models were used to investigate the associations between prenatal exposure to pesticides and ASQ domain-specific scores at age 12 and 18 months. Restricted cubic spline (RCS) analysis and generalized additive models (GAMs) were fitted to evaluate non-linear patterns. Longitudinal models with generalized estimating equations (GEE) were conducted to account for correlations among repeated observations. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to examining the joint effect of the mixture of pesticides. Several sensitivity analyses were performed to assess the robustness of the results.Results: We observed that prenatal exposure to chlorpyrifos was significantly associated with a 4 % decrease in the ASQ communication scores both at age 12 months (RR, 0.96; 95 % CI, 0.94-0.98; P < 0.001) and 18 months (RR, 0.96; 95 % CI, 0.93-0.99; P < 0.01). In the ASQ gross motor domain, higher concentrations of mirex (RR, 0.96; 95 % CI, 0.94-0.99, P < 0.01 for 12-month-old children; RR, 0.98; 95 % CI, 0.97-1.00, P = 0.01 for 18-month-old children), and atrazine (RR, 0.97; 95 % CI, 0.95-0.99, P < 0.01 for 12-month-old children; RR, 0.99; 95 % CI, 0.97-1.00, P = 0.03 for 18-month-old children) were associated with decreased scores. In the ASQ fine motor domain, higher concentrations of mirex (RR, 0.98; 95 % CI, 0.96-1.00, P = 0.04 for 12-month-old children; RR, 0.98; 95 % CI, 0.96-0.99, P < 0.01 for 18-month-old children), atrazine (RR, 0.97; 95 % CI, 0.95-0.99, P < 0.001 for 12-month-old children; RR, 0.98; 95 % CI, 0.97-1.00, P = 0.01 for 18-month-old children), and dimethipin (RR, 0.94; 95 % CI, 0.89-1.00, P = 0.04 for 12-month-old children; RR, 0.93; 95 % CI, 0.88-0.98, P < 0.01 for 18-month-old children) were associated with decreased scores. The associations were not modified by child sex. There was no evidence of statistically significant nonlinear relationships between pesticides exposure and RRs of delayed neurodevelopment (P nonlinearity > 0.05). Longitudinal analyses impli-cated the consistent findings.Conclusion: This study gave an integrated picture of pesticides exposure in Chinese pregnant women. We found significant inverse associations between prenatal exposure to chlorpyrifos, mirex, atrazine, dimethipin and the domain-specific neuropsychological development (i.e. , communication, gross motor and fine motor) of children at 12 and 18 months of age. These findings identified specific pesticides with high risk of neurotoxicity, and highlighted the need for priority regulation of them.