Paraquat and Parkinson’s disease: a systematic review and meta-analysis of observational studies

This investigation aimed to conduct a systematic review of the literature and meta-analysis to determine whether exposure to the herbicide paraquat was associated with the development of Parkinson’s disease (PD). Observational studies that enrolled adults exposed to paraquat with PD as the outcome of interest were searched in the PubMed, Embase, LILACS, TOXNET, and Web of Science databases up to May 2019. Two authors independently selected relevant studies, extracted data, and assessed methodological quality. The evidence certainty was assessed by the GRADE approach, which served as basis for a tentative causality assessment, supplemented by the Bradford Hill criteria when necessary. Results from nine case–control studies indicated that PD occurrence was 25% higher in participants exposed to paraquat. The only cohort investigation included demonstrated a non-significant OR of 1.08. Results from subgroup analyses also indicated higher PD frequency in participants that were exposed to paraquat for longer periods or individuals co-exposed with paraquat and any other dithiocarbamate. Data indicate apositive association between exposure to paraquat and PD occurrence, but the weight-of-evidence does not enable one to assume an indisputable cause–effect relationship between these two conditions. Better designed studies are needed to increase confidence in results. <b>Systematic Review Registration</b>: PROSPERO CRD42017069994.

本研究旨在开展系统文献回顾与荟萃分析，以明确除草剂百草枯（paraquat）暴露与帕金森病（Parkinson’s disease, PD）的发生是否存在关联。
我们于2019年5月前在PubMed、Embase、LILACS、TOXNET及Web of Science数据库中检索以百草枯暴露成年人群为研究对象、以帕金森病为关注结局的观察性研究。
由两名研究者独立完成相关文献筛选、数据提取及方法学质量评价。
采用GRADE方法（GRADE approach）对证据确定性进行评价，以此作为初步因果评估的依据，必要时辅以布拉德福德·希尔因果判断标准（Bradford Hill criteria）。
9项病例对照研究的结果显示，百草枯暴露人群的帕金森病发生风险较未暴露人群升高25%。
仅纳入的1项队列研究显示其比值比（Odds Ratio, OR）为1.08，无统计学显著性。
亚组分析结果同样表明，百草枯暴露时长较长者，或同时暴露于百草枯与其他二硫代氨基甲酸酯类物质的人群，其帕金森病发生频率更高。
现有数据显示百草枯暴露与帕金森病发生存在正相关关系，但证据强度尚不足以认定二者之间存在无可辩驳的因果关联。
未来需开展设计更严谨的研究以提升研究结果的可信度。
<b>系统评价注册信息</b>: PROSPERO CRD42017069994.