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

CHAMACOS出生队列中早期农药暴露的长期后遗症

BRENDA ESKENAZI (2016-09-21 to 2021-03-31) $999,969

Project ID: UH3ES030631 (NIEHS)

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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.

萨利纳斯母亲和儿童健康评估中心（CHAMACOS）是一个纵向出生队列，约有600名居住在加利福尼亚州萨利纳斯山谷的第一代墨西哥裔美国儿童。 CHAMACOS的成立与ECHO的目的相同：研究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的关系。我们跟踪了从子宫到青春期的儿童，我们现在建议他们跟进他们进入成年期。在过去17年中，我们制定了有效的策略来招募，跟踪和留住这些低收入拉丁裔人口的研究参与者;我们成功地收集了ECHO所有四个重点的高质量数据;我们收集，加工，运输和储存了超过150,000种不同的生物和环境样品;我们测量了100多种化学品暴露;我们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分析;我们已经建立了牢固的社区 - 大学合作伙伴关系，赢得了参与者和社区利益相关者的信任。因此，CHAMACOS可以作为ECHO的模范出生队列，在从出生到成年的儿童的评估范围和广度上很少见，为更大的ECHO联盟提供了宝贵的方法，经验教训和机会。此外，CHAMACOS为ECHO在农场工作者社区中为拉丁裔儿童选择的高风险人群做出了贡献。由于该队列的60％超重或肥胖，我们还提供有代谢，心血管和肝脏疾病高风险儿童的数据。由于CHAMACOS儿童正在接近成年期，我们处于独特的位置，可以检查成人疾病的早期起源，并解决早期生活暴露与多种健康终点之间关系中的重要差距。我们已经报道，子宫内有机磷农药（OP）暴露与学龄期较差的注意力和执行功能，较低的智商，呼吸系统症状和较差的肺功能相关。在UG3阶段，我们的目标是测试新方法，以扩展我们对这些关系的理解，并为ECHO提供前沿方法。我们建议：1）检查新研究的表观遗传修饰，羟甲基胞嘧啶（5-hmC）？一个潜在的强有力的候选人，了解影响神经发育的分子机制; 2）应用近红外光谱（fNIRs）进行功能性神经影像学检查？功能性MRI的便宜和方便的替代品。在UH3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园接触农业杀虫剂对以下方面的影响：1）神经行为终点; 2）呼吸道症状和功能; 3）体重和相关的代谢和心血管疾病。这一有价值的队列有可能为ECHO联盟增加丰富的数据，经过验证的协议和实践经验，同时还回答关于成人健康中产前和早期接触杀虫剂的长期后遗症的重要问题。