Bisphenol A and Phthalate Exposure in Relation to Fetal Growth and Preterm Birth

描述（由研究者提供）：早产是全世界婴儿死亡的主要原因，也大大增加了儿童期和一生中出现严重健康并发症的风险。由于近几十年来这些不良出生结果的发生率不断增加，早产以及低出生体重婴儿已成为重大的公共卫生挑战。在美国，早产率自 1981 年以来增加了 30% 以上，自 1990 年以来增加了 18%，目前占所有活产婴儿的近 13%。尽管环境暴露的影响尚未得到充分研究，但导致早产的条件仍不清楚。最近的初步证据表明，人类接触双酚 A (BPA) 和邻苯二甲酸盐、塑料、个人护理产品和其他消费品中使用的化学物质可能会增加早产风险并对胎儿发育产生不利影响。在动物研究中，BPA 和邻苯二甲酸盐已被证明会引起氧化应激、炎症和内分泌干扰，这种机制可能会增加胎儿生长改变和不良妊娠结局的风险。这是特别值得关注的，因为大多数普通人群，包括孕妇，每天都会接触这些类别的化合物。本申请旨在研究对胎儿生长和早产产生不利影响的环境风险因素，研究对象是从马萨诸塞州波士顿正在进行的一项针对活产单胎的大型队列研究中选出的 700 对母婴。该研究将利用最先进的方法测量尿液中 BPA 和邻苯二甲酸盐的浓度，并评估怀孕每个三个月期间收集的生物样本中的分子流行病学机制途径标志物（氧化应激、炎症和内分泌干扰）。还将探索通过怀孕期间重复超声扫描来测量胎儿生长和胎盘功能的创新方法。该研究将利用正在进行的研究中的患者数据和生物样本，因此是对研究资金的高度成本效益的利用。此外，拟议的研究还将提供有关邻苯二甲酸盐和 BPA 代谢以及孕妇（人群中高度脆弱的群体）的个体暴露敏感性的新信息。该研究还将基于创新的分类系统，根据潜在病因对早产进行分类，探讨 BPA 和邻苯二甲酸盐之间的关联是否有所不同。最后，该研究将提供邻苯二甲酸盐和 BPA 与与胎儿发育和早产风险相关的遗传标记物相互作用的数据。 公共卫生相关性：美国早产和低出生体重婴儿率的上升构成了重大的公共卫生挑战。人群对生物活性化合物双酚 A 和邻苯二甲酸盐的接触增加也是一个重大的公共卫生问题。该流行病学项目将采用最先进的方法和创新的研究设计，提供急需的有关环境、人口和生物因素的信息，这些因素会对胎儿生长和早产风险产生不利影响。

DESCRIPTION (provided by investigator): Preterm birth is the leading cause of infant mortality worldwide, and also greatly increases the risk of developing serious health complications in childhood and throughout life. Preterm birth, as well as low birth weight infants, are significant public health challenges due to the increased prevalence in these adverse birth outcomes in recent decades. In the US, rates of preterm birth have increased over 30 percent since 1981 and 18 percent since 1990, and now accounts for nearly 13 percent of all live births. Conditions that contribute to preterm birth remain unclear, though the influence of environmental exposures has been immensely understudied. There is recent preliminary evidence that human exposure to bisphenol A (BPA) and phthalates, chemicals used in plastics, personal care products, and other consumer goods may be associated with increased risk of preterm birth and adverse effects on fetal development. In animal studies, BPA and phthalates have been shown to cause oxidative stress, inflammation, and endocrine disruption, mechanism that may contribute to increased risk of altered fetal growth and adverse pregnancy outcomes. This is of particular concern since most of the general population, including pregnant women, are exposed to these classes of compounds on a daily basis. This application proposes to study environmental risk factors for adverse effects on fetal growth and preterm birth among 700 mother/infant pairs selected from a large ongoing cohort study of live born singletons in Boston, MA. The study will utilize state-of-the-art methods for measuring urinary BPA and phthalate concentrations, and for assessing molecular epidemiologic mechanistic pathway markers (oxidative stress, inflammation and endocrine disruption), in biological samples collected during each trimester of pregnancy. Innovative measures of fetal growth and placental function from repeated ultrasound scans during pregnancy will also be explored. The study will utilize patient data and biological samples from an ongoing study and is thus a highly cost-efficient use of research funds. In addition, the proposed study will provide new information on phthalate and BPA metabolism and individual exposure susceptibility among pregnant women, a highly vulnerable segment of the population. The study will also explore whether associations between BPA and phthalates differs based on an innovative classification system to disaggregate preterm births according to underlying etiology. Finally, the study will provide data on the interaction of phthalates and BPA with genetic markers of interest in relation to fetal development and risk of preterm birth. PUBLIC HEALTH RELEVANCE: The rising rates of preterm birth and low birth weight infants in the U.S. represents a significant public health challenge. Increased population-wide exposures to the biologically active compounds bisphenol A and phthalates are also of great public health concern. This epidemiological project will use state-of-the-art methods and an innovative study design to provide much needed information on environmental, demographic, and biological factors that contribute to adverse effects on fetal growth and preterm birth risk.