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墨西哥早期生活环境暴露研究(ELEMENT)项目。

Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project.

机构信息

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado, USA.

Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

出版信息

BMJ Open. 2019 Aug 26;9(8):e030427. doi: 10.1136/bmjopen-2019-030427.

Abstract

PURPOSE

The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes.

PARTICIPANTS

n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico.

FINDINGS TO DATE

Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.

FUTURE PLANS

As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.

TRIAL REGISTRATION NUMBER

NCT00558623.

摘要

目的

墨西哥早期生活暴露于环境毒素(ELEMENT)项目是一项母婴妊娠和出生队列研究,最初始于 20 世纪 90 年代中期,旨在探索:(1)妊娠期间母体骨骼中铅的更大量动员是否会对胎儿和随后的后代神经发育构成风险;以及(2)妊娠和哺乳期母体补钙是否可以抑制骨铅动员,并减轻铅暴露对后代健康和发育的不利影响。通过利用精心保存的生物标本来测量其他产前暴露、DNA 储存以及对各种结果的严格测量,ELEMENT 已发展成为研究早期生活暴露和发育结果的主要资源。

参与者

1994 年至 2003 年期间,在墨西哥城的妇产医院,按顺序招募了 1643 对母婴(孕期或分娩时)。

迄今为止的发现

由于妊娠和哺乳期母体骨骼中储存的铅动员到循环中,母体骨骼(如髌骨、胫骨)是胎儿铅暴露的内源性来源,这会导致流产、低出生体重和头围较小的风险增加,并导致铅转移到母乳中。妊娠和哺乳期每天补充 1200 毫克元素钙可减少母体骨骼对铅的吸收,从而降低循环铅水平。除了围产期结果外,儿童时期铅的早期暴露与后代的神经认知缺陷、行为障碍、更高的血压和更低的体重有关。这些关系中的一些受到饮食因素、特定于铁、叶酸和脂质代谢的基因多态性以及暴露时间的影响。研究还扩展到包括已发表的关于其他有毒物质(如个人护理产品和塑料中的有毒物质[如邻苯二甲酸酯、双酚 A]、其他金属[如汞、锰、镉]、农药[有机磷酸酯]和氟化物)的研究结果;其他生物标志物(如血浆、头发和牙齿中的有毒物水平);其他结果(如性成熟、代谢综合征、龋齿);以及通过表观遗传学和代谢组学分析确定新的机制。

未来计划

随着 ELEMENT 母亲和孩子年龄的增长,我们计划:(1)继续研究围产期有毒物质暴露对青少年和年轻成人结局以及与原始 ELEMENT 母亲相关的结局(如围绝经期的代谢和骨骼健康)的长期后果;以及(2)跟踪第三代参与者(孩子的孩子),以研究宫内暴露的代际影响。

试验注册

NCT00558623。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020b/6720157/b150c5bd9c60/bmjopen-2019-030427f01.jpg

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