Prenatal exposure to phthalates and associations with gestational weight gain and fetal growth trajectories.

项目摘要/摘要 在怀孕期间广泛接触无处不在的内分泌干扰物，如邻苯二甲酸酯， 母亲和婴儿生命过程中的敏感期是全球关注的问题。邻苯二甲酸酯及其 代谢产物(PM)与氧化应激、激素紊乱和表观遗传有关 可能会干扰孕妇孕期体重增加(GWG)和胎儿生长模式的变化。母性 GWG和胎儿生长率很重要，因为它们影响着儿童的短期和长期健康结果 母亲和孩子。此外，妊娠结局中与怀孕有关的种族和族裔差异 随着时间的推移，环境暴露可能会导致这些问题。非西班牙裔黑人、西班牙裔和 亚洲女性的PM浓度较高，可能是因为使用了特定的个人护理产品。 尽管有几项研究评估了PM对出生体重(胎儿生长的终点)或月经的影响 在GWG中，很少有人考虑PMS与胎儿生长和GWG发生率之间的联系，以及那些 都受到方法论的限制。此外，缺乏关于关联的证据。 PMS混合物和不良健康后果之间的关系。使用来自嵌套病例对照研究的数据 种族多样化的人群(待产母亲(NuMoM2B))，特别是在健康对照中， 我们将使用复杂的统计学方法探索PMS和GWG与胎儿生长轨迹之间的关系 方法(即增长混合模型、广义估计方程和加权分位数和回归) 其中考虑了暴露和结果的多个衡量标准，并考虑了PM混合物。我们 提出以下目标：1)检查产前接触PM(和他们的 混合物)，在每个妊娠三个月测量和a)GWG和b)估计胎儿生长轨迹 在全美960名健康的孕妇中；2)评估按种族/民族和 PMS和GWG之间的胎儿性别与胎儿生长发育这将是第一次评估一种药物治疗效果的研究 无处不在的环境暴露对GWG和胎儿生长轨迹的影响。拟议研究的结果 对于确定妊娠期的关键窗口很重要，此时孕妇GWG和胎儿生长可能更 对PM的侮辱更敏感。重要的是，这将有助于设计减少邻苯二甲酸盐的干预措施。 暴露水平，告知监管产品中邻苯二甲酸盐浓度的政策，并进行教育和目标 暴露风险最大的女性。这些具体目标的实现将推动NIEHS的使命 了解无处不在的环境暴露，邻苯二甲酸盐，对显著的母体胎儿结局的影响。 拟议的培训计划将在哥伦比亚大学内实施，哥伦比亚大学是世界上最著名的大学之一 研究型大学，提供环境暴露方面的技能，包括混合物分析、母婴 健康和先进的分析方法，在优秀赞助商团队的支持下，将确保 顺利完成这项研究的目标，并为我作为一名独立的、富有成效的研究人员的职业生涯做好准备。

PROJECT SUMMARY/ABSTRACT Widespread exposure to ubiquitous endocrine disrupting chemicals, such as phthalates, during pregnancy, a sensitive period in the life course for both mother and baby, is of global concern. Phthalates and their metabolites (PMs) are associated with increased oxidative stress, hormonal disturbances and epigenetic changes that may interfere with maternal gestational weight gain (GWG) and fetal growth patterns. Maternal GWG and fetal growth rates are important as they influence both short and long-term health outcomes of the mother and baby. Further, pregnancy related racial and ethnic disparities in pregnancy outcomes have persisted over time and environmental exposures may contribute to these. Non-Hispanic Black, Hispanic and Asian women have higher concentrations of PMs likely due to the use of specific personal care products. Although several studies have evaluated PM’s effect on birthweight (the end point of fetal growth) or on periods of GWG, few have considered associations between PMs and fetal growth and GWG rates and those that have are subject to methodological limitations. In addition, there is scarcity of evidence regarding associations between mixtures of PMs and adverse health outcomes. Using data from a nested case control study in a racially diverse population (Nulliparous Mothers To Be (nuMoM2b)), and specifically among healthy controls, we will explore associations between PMs and GWG and fetal growth trajectories using sophisticated statistical methods (i.e., growth mixture models, generalized estimating equations and weighted quantile sum regression) which account for multiple measures of both exposures and outcomes, and account for PM mixtures. We propose the following aims: 1) to examine associations between prenatal exposure to PMs (and their mixtures), measured in each pregnancy trimester and a) GWG and b) estimated fetal growth trajectories among 960 healthy pregnant women across the United States; 2) to evaluate modification by race/ethnicity and fetal-sex between PMs and GWG and fetal growth. This will be the first study to evaluate the effect of a ubiquitous environmental exposure on GWG and fetal growth trajectories. Findings from the proposed study are important to identify critical windows of gestation when maternal GWG and fetal growth may be more be more sensitive to insults from PMs. Importantly, this will aid the design of interventions to reduce phthalate exposure levels, inform policies to regulate phthalate concentrations in products, and educate and target women at greatest risk of exposure. Execution of these specific aims will advance NIEHS’s mission to understand the impact of a ubiquitous environmental exposure, phthalates, on salient maternal fetal outcomes. The proposed training plan will be delivered within Columbia University, one of the world’s preeminent research universities, providing skills in environmental exposures including mixtures analysis, maternal child health and advanced analytic methods that will, with the support of an excellent sponsor team, will ensure successful completion of the study aims and prepare me to a career as an independent productive researcher.