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

描述（研究者提供）：早产是世界范围内婴儿死亡的主要原因，并且大大增加了儿童和整个生命中发生严重健康并发症的风险。早产和低出生体重婴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发生率有所增加。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%，目前占所有活产婴儿的近13%。虽然环境暴露对早产的影响还没有得到充分的研究，但导致早产的条件仍不清楚。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，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，这一机制可能会增加改变胎儿生长和不良妊娠结局的风险。这尤其令人担忧，因为大多数普通民众，包括孕妇，每天都接触到这类化合物。本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，研究对象为700对母亲/婴儿，这些母亲/婴儿来自马萨诸塞州波士顿一项正在进行的大型活产单胎队列研究。这项研究将利用最先进的方法来测量尿液中BPA和邻苯二甲酸盐的浓度，并评估在每个怀孕三个月收集的生物样本中的分子流行病学机制途径标记（氧化应激、炎症和内分泌干扰）。胎儿生长和胎盘功能的创新措施，从反复超声扫描怀孕期间也将探讨。该研究将利用正在进行的研究中的患者数据和生物样本，因此是研究资金的高成本效益使用。此外，拟议的研究将提供关于邻苯二甲酸酯和双酚a代谢的新信息，以及孕妇的个体暴露易感性，孕妇是人口中高度脆弱的部分。该研究还将探索BPA和邻苯二甲酸酯之间的关联是否基于一种创新的分类系统，根据潜在的病因对早产进行分类。最后，该研究将提供有关邻苯二甲酸酯和双酚a与胎儿发育和早产风险相关的遗传标记相互作用的数据。

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.