Wei Hongcheng, Zhang Xiaochen, Yang Xu, Yu Qiurun, Deng Siting, Guan Quanquan, Chen Danrong, Zhang Mingzhi, Gao Beibei, Xu Shangcheng, Xia Yankai
State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Center of Laboratory Medicine, Chongqing Prevention and Treatment Center for Occupational Diseases, Chongqing, China; Chongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning, Chongqing, China.
Environ Int. 2023 Mar;173:107814. doi: 10.1016/j.envint.2023.107814. Epub 2023 Feb 11.
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.
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 neuropsychological development.
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.
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 > 0.05). Longitudinal analyses implicated the consistent findings.
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.
农药的广泛使用导致中国普通人群普遍暴露于农药环境中。先前的研究已证明产前接触农药会产生发育性神经毒性。
我们旨在描绘孕妇血清样本中体内农药暴露水平的情况,并确定与特定领域神经心理发育相关的特定农药。
在南京市妇幼保健院开展并维持的一项前瞻性队列研究中,参与者包括710对母婴。在入组时采集孕妇的即时血样。利用一种准确、灵敏且可重复的88种农药分析方法,采用气相色谱 - 三重四极杆串联质谱法(GC-MS/MS)同时测定了49种农药。在实施严格的质量控制(QC)管理后,报告了29种农药。我们使用第三版年龄与发育进程问卷(ASQ)评估了12个月大(n = 172)和18个月大(n = 138)儿童的神经心理发育情况。采用负二项回归模型研究产前接触农药与12个月和18个月大儿童ASQ特定领域得分之间的关联。采用受限立方样条(RCS)分析和广义相加模型(GAM)来评估非线性模式。采用具有广义估计方程(GEE)的纵向模型来考虑重复观测值之间的相关性。应用加权分位数和(WQS)回归和贝叶斯核机器回归(BKMR)来检验农药混合物的联合效应。进行了多项敏感性分析以评估结果的稳健性。
我们观察到,产前接触毒死蜱与12个月大时(RR,0.96;95%CI,0.94 - 0.98;P < 0.001)和18个月大时(RR,0.96;95%CI,0.93 - 0.99;P < 0.01)ASQ沟通得分显著降低4%相关。在ASQ大运动领域,较高浓度的灭蚁灵(12个月大儿童:RR,0.96;95%CI,0.94 - 0.99,P < 0.01;18个月大儿童:RR,0.98;95%CI,0.97 - 1.00,P = 0.01)和莠去津(12个月大儿童:RR,0.97;95%CI,0.95 - 0.99,P < 0.01;18个月大儿童:RR,0.99;95%CI,0.97 - 1.00,P = 0.03)与得分降低相关。在ASQ精细运动领域,较高浓度的灭蚁灵(12个月大儿童:RR,0.98;95%CI,0.96 - 1.00,P = 0.04;18个月大儿童:RR,0.98;95%CI,0.96 - 0.99,P < 0.01)、莠去津(12个月大儿童:RR,0.97;95%CI,0.95 - 0.99,P < 0.001;18个月大儿童:RR,0.98;95%CI,0.97 - 1.00,P = 0.01)和乐杀螨(12个月大儿童:RR,0.94;95%CI,0.89 - 1.00,P = 0.04;18个月大儿童:RR,0.93;95%CI,0.88 - 0.98,P < 0.01)与得分降低相关。这些关联不受儿童性别的影响。没有证据表明农药暴露与神经发育延迟的相对风险之间存在统计学上显著的非线性关系(P > 0.05)。纵向分析得出了一致的结果。
本研究全面呈现了中国孕妇的农药暴露情况。我们发现产前接触毒死蜱、灭蚁灵、莠去津、乐杀螨与12个月和18个月大儿童特定领域的神经心理发育(即沟通、大运动和精细运动)之间存在显著的负相关。这些发现确定了具有高神经毒性风险的特定农药,并强调了对其进行优先监管的必要性。