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

描述(由调查人员提供)：早产是全球婴儿死亡的主要原因，也极大地增加了在儿童时期和一生中出现严重健康并发症的风险。早产和低出生体重儿是重大的公共卫生挑战，因为近几十年来这些不良出生结局的流行率不断上升。在美国，早产率自1981年以来增长了30%以上，自1990年以来增长了18%，现在占所有活产的近13%。导致早产的条件仍然不清楚，尽管环境暴露的影响一直被极少地研究。最近有初步证据表明，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品可能与早产风险增加和对胎儿发育的不利影响有关。在动物研究中，双酚A和邻苯二甲酸盐已被证明会引起氧化应激、炎症和内分泌紊乱，这可能是导致胎儿生长改变和不良妊娠结局风险增加的机制。这一点特别令人担忧，因为大多数普通人群，包括孕妇，每天都接触到这些类别的化合物。这项申请旨在研究环境风险因素对胎儿生长和早产的不利影响，从马萨诸塞州波士顿正在进行的一项大型队列研究中挑选700对母婴对胎儿生长和早产产生不利影响。这项研究将利用最先进的方法测量怀孕每三个月收集的生物样本中的尿双酚A和邻苯二甲酸盐浓度，并评估分子流行病学机制标记物(氧化应激、炎症和内分泌干扰)。还将探索在怀孕期间通过重复超声波扫描来衡量胎儿生长和胎盘功能的创新措施。这项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成本效益使用。此外，拟议的研究将提供有关邻苯二甲酸盐和双酚A代谢以及孕妇个人暴露易感性的新信息，孕妇是人口中高度脆弱的一部分。这项研究还将探索双酚A和邻苯二甲酸酯之间的联系是否基于一种创新的分类系统而不同，该系统根据潜在的病因对早产进行分类。最后，该研究将提供邻苯二甲酸盐和双酚A与感兴趣的遗传标记相互作用的数据，这些遗传标记与胎儿发育和早产风险有关。

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.