Long-term sequelae of early life pesticide exposure in the CHAMACOS birth cohort

摘要 萨利纳斯母亲和儿童健康评估中心（CHAMACOS） 出生队列约600主要是第一代墨西哥裔美国儿童生活在农业萨利纳斯 山谷，加州。 CHAMACOS的成立与ECHO的意图相同：检查早期 生活环境暴露与出生结果、神经发育、呼吸系统健康和肥胖。 我们有 从子宫到青春期都在跟踪孩子，现在我们建议跟踪他们到成年。 在过去的17年里，我们已经制定了有效的策略来注册，跟踪和保留学习 参与者在这个低收入的拉丁美洲人口;我们已经成功地收集了高质量的数据，所有四个 ECHO的重点端点;我们已经收集，处理，运输和存储了超过150，000种不同的 生物和环境样本;我们已经测量了100多种化学品暴露;我们已经帮助 开发和测试复杂和新颖的暴露，遗传和表观遗传实验室检测;我们有 建立了稳固的社区-大学伙伴关系，赢得了参与者和社区的信任 持份者因此，CHAMACOS可以作为ECHO的模型出生队列，其长度和宽度都很罕见 对儿童从出生到成年的评估， 提供有价值的方法、经验教训， 更大的ECHO财团的机会。此外，CHAMACOS还为 交给ECHO一个精选的高风险 一个农场工人社区的拉丁裔儿童人口 .由于60%的人超重或肥胖，我们还 提供关于代谢、心血管和肝脏疾病高风险儿童的数据。 因为 的 CHAMACOS 孩子们正在接近成年，我们 在研究成人疾病的早期起源方面有着独特的地位 并解决生命早期暴露与多种健康终点之间关系的重要差距。 我们已经报道，在子宫内的有机磷农药（OP）暴露与较差的 注意力和执行功能，智商较低，呼吸道症状，以及学龄期肺功能较差。在 在UG 3阶段，我们的目标是测试新的方法，这些方法将扩大我们对这些关系的理解， 为欧共体人道处提供先进的方法。我们建议：1）检查新研究的表观遗传 修饰，羟基甲基胞嘧啶（5-hmC）-一个潜在的强有力的候选人，了解分子 对神经发育的潜在影响机制;以及2）将近红外光谱（fNIR）应用于 功能性神经影像-功能性MRI的廉价和方便的替代品。在第三阶段，我们 建议对18岁和21岁的参与者进行随访，以评估子宫内和幼儿期的影响。 暴露于农药对：1）神经行为终点; 2）呼吸道症状和功能; 和3）体重和相关的代谢和心血管状况。这个有价值的群体有可能 为ECHO联盟增加丰富的数据、经过验证的协议和实践经验，同时也回答 关于产前和生命早期接触农药对成人健康的长期后遗症的重要问题。

ABSTRACT The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) is a longitudinal birth cohort of ~600 primarily first-generation Mexican American children living in the agricultural Salinas Valley, California. CHAMACOS was formed with the same intent as ECHO: to examine the association of early life environmental exposures with birth outcomes, neurodevelopment, respiratory health, and obesity. We have followed children from in utero through adolescence and we now propose to follow them into adulthood. Over the past 17 years, we have developed effective strategies to enroll, track, and retain study participants in this low-income Latino population; we have succeeded in collecting high quality data on all four endpoints of focus for ECHO; we have collected, processed, shipped, and stored over 150,000 varied biological and environmental samples; we have measured over 100 chemical exposures; we have helped develop and test sophisticated and novel exposure, genetic, and epigenetic laboratory assays; and we have developed a solid community-university partnership, earning the trust of participants and community stakeholders. Thus, CHAMACOS could serve as a model birth cohort for ECHO, rare in its length and breadth of assessment of children from birth to adulthood, offering valuable methodologies, lessons learned, and opportunities to the larger ECHO consortium. In addition, CHAMACOS contributes to ECHO a select, high-risk population of Latino children in a farmworker community . As 60% of this cohort is overweight or obese, we also offer data on children at high risk of metabolic, cardiovascular, and liver disease. Because the CHAMACOS children are approaching adulthood, we are uniquely positioned to examine the early origins of adult disease and address important gaps in the relationship between early life exposures and multiple health endpoints. We have reported that in utero organophosphate pesticide (OP) exposure is associated with poorer attention and executive function, lower IQ, respiratory symptoms, and poorer lung function at school-age. In the UG3 phase, we aim to test new methods that will expand our understanding of these relationships and contribute cutting-edge methodologies to ECHO. We propose to: 1) examine a newly-studied epigenetic modification, hydroxyl-methylcytosine (5-hmC) – a potentially strong candidate for understanding the molecular mechanisms underlying effects on neurodevelopment; and 2) apply near infrared spectroscopy (fNIRs) for functional neuroimaging – an inexpensive and convenient alternative to functional MRI. In the UH3 phase, we propose to follow-up participants at age 18 and 21 to assess the effects of in utero and early childhood exposure to agricultural pesticides on: 1) neurobehavioral endpoints; 2) respiratory symptoms and function; and 3) body mass and related metabolic and cardiovascular conditions. This valuable cohort has the potential to add rich data, validated protocols, and practical experience to the ECHO consortium, while also answering vital questions about the long-term sequelae of prenatal and early life exposure to pesticides on adult health.