LIFECODES pregnancy cohort

LIFECODES是由Thomas McElrath博士在马萨诸塞州波士顿的布里格姆妇女医院进行的一项持续的预期出生队列研究。这项研究始于2006年，旨在调查与不良妊娠结局相关的环境污染物，分离其潜在的联系机制，并确定可用于预防的预测因素。在这个队列中，有几个研究项目是为了解决更具体的研究问题而存在的。在NIEHS，我们利用了这些现有的数据，并通过三种方式对其进行了补充。首先，我们与研究人员合作进行早产的病例对照研究。在这项子研究中，作为儿童健康暴露评估资源(CHEAR)计划的一项试点研究，我们分析了妊娠晚期尿样中的微量金属和代谢组学。该项目的目标是检测每一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(分娩和37周妊娠)以及早产亚型(自然和胎盘介导)；2)通过超声测量评估怀孕期间的胎儿发育；以及3)当时也测量的尿氧化应激生物标志物。此外，我们试图检查代谢组学特征作为这些关联的潜在中介。LIFECODES怀孕队列下的第二个项目是一项综合研究。基于我们的初步发现，我们汇集了LIFECODES和其他15个美国怀孕或孕前队列的数据，以更有力地调查怀孕期间邻苯二甲酸盐暴露与早产的关系。LIFECODES妊娠队列下的最后一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。在一项初步研究之后，我们从整个LIFECODES队列中随机选择了500名参与者，并通过额外选择200例小于胎龄儿(SGA)和200例大胎龄儿(LGA)来丰富队列。在该项目下，LIFECODES胎儿生长研究，我们的具体目标是：1)检查消费品化学品，包括邻苯二甲酸盐、酚、有机磷阻燃剂和杀虫剂与妊娠期间生长障碍的关系；2)提高对SGA和LGA病因的理解，特别针对炎症和氧化应激途径；以及3)在导致SGA新生儿的怀孕期间，使用一系列超声测量胎儿生长来探索生长限制的表型。 在过去的一年里，我们发表了LIFECODES胎儿生长研究的第一批论文，研究了出生时小于或大于胎龄的婴儿的胎儿生长轨迹(PMID：36027952,36241081)。我们还开始发表关于我们队列中测量的环境暴露的描述性论文，包括邻苯二甲酸盐和苯酚(PMID：37001215)。此外，在与我们在LIFECODES研究中的目标相关的主题上，我们发表了一篇统计方法论文(PMID：35909228)、一篇综述论文(PMID：35367517)、一项关于产前暴露和妊娠体重增加的调查(PMID：36841368)，并为一个财团研究尿氧化应激生物标志物与早产的关系做出了贡献(PMID：36400174)。

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. At NIEHS we have utilized this existing data and added to it in three ways. First, we collaborate with investigators on a case-control sub-study of preterm birth. Within that sub-study, 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. 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 based under the LIFECODES pregnancy cohort is a pooled study. Based on our initial findings, we pooled data from LIFECODES and 15 other US pregnancy or pre-pregnancy cohorts to more robustly investigate the relationship between phthalate exposure in pregnancy and preterm birth. The last project under the LIFECODES pregnancy cohort is an investigation of the associations between consumer product chemical exposure in pregnancy and their cumulative impact on disorders of fetal growth. Following a pilot study, we selected a random subcohort of 500 participants from among the overall LIFECODES cohort, and we enriched the cohort with additional selection of 200 cases of small-for-gestational age (SGA) births and 200 large-for-gestational age (LGA) births. Under this project, the LIFECODES Fetal Growth Study, our specific aims are to: 1) Examine associations between consumer product chemicals, including phthalates, phenols, and organophosphate flame retardants and pesticides, in relation to disorders of growth in pregnancy; 2) Improve the understanding of the etiologies of SGA and LGA, specifically targeting inflammatory and oxidative stress pathways; and 3) Within pregnancies resulting in an SGA newborn, explore phenotypes of growth restrictions using serial ultrasound measures of fetal growth. In the past year, we published the first papers from the LIFECODES Fetal Growth Study, examining trajectories of fetal growth among babies born small and large for gestational age at delivery (PMIDs: 36027952, 36241081). We also began to publish descriptive papers on the environmental exposures measured in our cohort, including phthalates and phenols (PMID: 37001215). Additionally, on topics related to our aims in the LIFECODES study, we published a statistical methods paper (PMID: 35909228), a review paper (PMID: 35367517), an investigation of prenatal exposure and gestational weight gain (PMID: 36841368), and contributed to a consortium effort to examine urinary oxidative stress biomarkers in association with preterm birth (PMID: 36400174).