LIFECODES pregnancy cohort

LIFECODES是一项由托马斯麦克尔拉特博士在马萨诸塞州波士顿布里格姆妇女医院进行的持续前瞻性出生队列研究。该研究始于2006年，旨在调查与不良妊娠结局相关的环境污染物，分离其相关机制，并确定可用于预防的预测因子。在这一群体中，有几个研究项目是为了解决更具体的研究问题。开发了双酚A和邻苯二甲酸酯暴露与胎儿生长和早产的关系（R 01 ES 018872; PI John Meeker），以研究对胎儿生长和早产产生不良影响的环境风险因素。该研究测量了2006-2008年LIFECODES队列招募的早产病例和对照组的尿邻苯二甲酸酯代谢物以及炎症、氧化应激和内分泌干扰的生物标志物。主要研究目的是评估母体邻苯二甲酸酯暴露与BPA暴露之间的关系，在妊娠期间每例受试者最多4次访视时测量BPA暴露与早产以及胎儿生长之间的关系，通过重复超声测量进行评估。此外，该研究试图探索这些关联的生物学机制，并确定暴露的易感性窗口。 在NIEHS，我们已经利用了这些现有的数据，并以多种方式对其进行了补充。首先，作为儿童健康暴露评估资源（CHEARS）计划的一项试点研究，我们分析了上述早产病例对照研究参与者妊娠晚期尿液标本中的尿微量金属和代谢组学。本项目的目的是检查每种微量金属以及金属混合物与以下方面的关系：1）总体早产（分娩<37周妊娠）以及早产亚型（自发性和胎盘介导的）; 2）妊娠期超声测量评估的胎儿生长; 3）在该时间点测量的尿液氧化应激生物标志物。此外，我们试图检查代谢组学概况作为这些协会的潜在介质。LIFECODES研究的第二个项目是调查怀孕期间消费品化学品暴露与其对胎儿生长障碍的累积影响之间的关系。 去年的进展 于2020财政年度，我们在LIFECODES出生队列下的两个项目均取得重大进展。首先，关于妊娠期金属暴露的研究，我们发表了关于尿微量金属混合物与氧化应激生物标志物、炎症生物标志物和胎儿生长结果之间关系的研究结果（3篇单独的论文）。对于第二个项目，经过外部审查，我们收到了分支资金，用于全面研究。这项研究的规划工作正在进行中。我们还发表了一篇来自试点数据的论文，证明了血浆类花生酸与胎儿生长结果之间的相关性（出版中）。

LIFECODES is an ongoing prospective birth cohort conducted at Brigham and Womens Hospital in Boston, MA by Dr. Thomas McElrath. Begun in 2006, this study aims to investigate environmental contaminants associated with adverse pregnancy outcomes, isolate mechanisms underlying their associations, and identify predictors that can be used for prevention. Within this cohort there are several research projects which exist to address more specific research questions. Bisphenol A and Phthalate Exposure in Relation to Fetal Growth and Preterm Birth (R01ES018872; PI John Meeker) was developed to study environmental risk factors for adverse effects on fetal growth and preterm birth. The study measured urinary phthalate metabolites as well as biomarkers of inflammation, oxidative stress, and endocrine disruption of cases of preterm birth as well as controls from the LIFECODES cohort recruitment from 2006-2008. The primary research objectives were to assess the relationship between maternal exposure to phthalates and BPA exposure measured at up to four visits per subject during pregnancy in relation to preterm birth as well as fetal growth, as assessed by repeated ultrasound measures. Additionally, the study sought to explore biological mechanisms underlying these associations and identify windows of susceptibility to exposure. At NIEHS we have utilized this existing data and added to it in several ways. First, as a pilot study in the Childrens Health Exposure Assessment Resource (CHEAR) program, we analyzed urinary trace metals as well as metabolomics in urine specimens from the 3rd trimester of pregnancy from the participants of the preterm birth case-control study described above. The objectives of this project were to examine each individual trace metals as well as metal mixtures in relation to: 1) overall preterm birth (delivery <37 weeks gestation) as well as preterm birth subtypes (spontaneous and placentally mediated); 2) fetal growth as assessed by ultrasound measures in pregnancy; and 3) urinary oxidative stress biomarkers that were also measured at that time point. Additionally, we sought to examine metabolomics profiles as potential mediators of these associations. The second project under the LIFECODES study is an investigation of the association between consumer product chemical exposure in pregnancy and their cumulative impact on disorders of fetal growth. Last years progress In FY 2020 we made substantial progress in both projects under the LIFECODES birth cohort. First, in regard to the study of metals exposure in pregnancy, we published findings on the associations between urinary trace metals mixtures and oxidative stress biomarkers, inflammation biomarkers, and fetal growth outcomes (3 separate papers). For the second project, we received branch funding, following external review, for the full study. Planning for this study is now underway. We additionally published one paper from the pilot data, demonstrating associations between plasma eicosanoids and fetal growth outcomes (in press).