Pesticide Exposure and Cerebral Palsy

 描述(申请人提供)：脑性瘫痪(CP)是指一组永久性和非进行性的运动和姿势障碍，是儿童最常见的发育性神经运动障碍，每1000名新生儿中约有2-3人受到影响。超过50%的CP儿童不能独立行走，必须使用助行器或轮椅等辅助设备。头部创伤或出生时窒息是脑瘫的已知原因，但通常不知道的是，这些因素在所有脑瘫病例中出现的比例不到10%。因此，大多数病例的病因仍不清楚，发现其他可预防的CP危险因素很重要。我们最近发现，在丹麦国家出生队列中，产前暴露于全氟化化学品，即潜在的内分泌干扰物的持久性有机污染物，与CP风险的增加呈剂量依赖关系。许多农药化合物具有发育神经毒性和/或内分泌干扰特性，据我们所知，到目前为止还没有发表的研究探讨早期接触农药的可能影响和CP的风险。我们提出的研究是新颖的，将是迄今为止最大的基于人群的脑瘫和杀虫剂研究。我们将使用加州发展服务部(DDS)到2010年的记录来识别1995-2007年出生并被诊断为加州CP的儿童。我们预计将识别约10,000例CP病例，并将从加州出生证明中为每个CP病例随机选择1：10匹配的对照。每个孩子孕前、怀孕期间和/或第一年的环境农药暴露估计将使用我们之前开发的地理信息系统(GIS)模型进行估计，该模型将出生证明上报告的分娩时居住地址与加州农药使用报告(PUR)系统联系起来。PUR系统包含自1974年以来加州所有农业农药应用的类型、日期和地点的信息。我们的地理信息系统模型使用PUR和土地使用地图，是同类系统中最复杂的系统，允许使用记录进行具体和详细的农药暴露评估，从而避免回忆偏差，并检查怀孕期间(三个月或怀孕几个月)的特定脆弱时期。加州农业活动的多样性、使用的大量和种类的杀虫剂使我们能够检查特定的杀虫剂及其组合。这个项目将增加我们对环境毒素在胎儿大脑发育中所起作用的了解，并将促进对脑瘫病因学的科学见解。我们的最终目标是改进对这些严重的神经发育障碍的初级预防策略，这些严重的神经发育障碍对患者和照顾者的生活质量产生终身影响，并成为巨大的公共卫生负担。这一试点项目的结果对于未来可能使用生物标记物方法和积极数据收集来检验环境假说的应用也将是至关重要的。

 DESCRIPTION (provided by applicant): Cerebral palsy (CP) refers to a group of permanent and non-progressive movement and posture disorders, which are the most common developmental neuro-motor disabilities of childhood affecting about 2-3 per 1000 births. More than 50% of children with CP cannot walk independently and have to use assistive devices such as walkers or wheelchairs. Head trauma or asphyxia during birth are known causes of CP, but what is generally not known is that these factors are present in less than 10% of all CP cases. Thus, the etiology of the majority of cases remains unexplained and it is important to discover additional preventable CP risk factors. We recently found that prenatal exposure to perfluorinated chemicals, persistent organic pollutants that are potential endocrine disruptors, are associated with increased CP risk in a dose-dependent manner in the Danish National Birth Cohort. Many pesticide compounds have developmental neurotoxic effects and/or endocrine disrupting properties, and to our knowledge no published study to date has examined the possible effects of early life pesticide exposure and the risk of CP. Our proposed study is novel and will be the largest population-based study of cerebral palsy and pesticides to date. We will use records from the California Department of Developmental Services (DDS) up to 2010 to identify children that were born 1995-2007 and diagnosed with CP in California. We expect to identify ~10,000 CP cases and will randomly select 1:10 matched controls from the California birth certificates for each CP case. Ambient pesticide exposure estimates pre-pregnancy, during pregnancy and/or first year of life for each child will be estimated using a Geographic Information System (GIS) model we previously developed that links residential addresses at delivery as reported on birth certificates to the California Pesticide Use Reporting (PUR) system. The PUR system contains information on the type, date, and location of all agricultural pesticide applications since 1974 in California. Our GIS model using PUR and land-use maps is the most sophisticated system of its kind and allows specific and detailed pesticide exposure assessment using records which avoids recall bias and to examine specific vulnerable periods in pregnancy (trimesters or months of pregnancy). The diversity of agricultural activities, large amounts and variety of pesticides used in California allow us to examine specific pesticides and their combinations. This project will increase our knowledge of the role environmental toxins play in fetal brain development and will advance scientific insights into CP disease etiology. Our ultimate goal is to improve primary prevention strategies for these severe neurodevelopmental disorders that have lifelong impacts on the quality of life of the patients and caregivers and are great public health burden. The results from this pilot project will also be critical for future applications to examine environmental hypotheses possibly using biomarkers approaches and active data collection.