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

双酚 A 和邻苯二甲酸盐暴露与胎儿生长和早产的关系

• 批准号: 8116645
• 负责人: John D. Meeker
• 金额: $ 52.42万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116645
• 关键词: 8-hydroxy-2' -deoxyguanosine; Accounting; Adverse effects; Animals; Area; Biological; Biological Factors; Birth; Birth Weight; Birth length; Boston; C-reactive protein; Chemicals; Childhood; Cholesterol; Classification; Cohort Studies; Corticotropin-Releasing Hormone; Data; Demographic Factors; Diethylhexyl Phthalate; Endocrine disruption; Environmental Exposure; Environmental Risk Factor; Enzymes; Epidemiology; Estradiol; Etiology; Exposure to; F2-Isoprostanes; Fetal Development; Fetal Growth; Funding; Future; Gamma-glutamyl transferase; General Population; Genetic Markers; Genetic Polymorphism; Genotype; Gestational Age; Health; Hormones; Human; Individual; Infant; Infant Mortality; Inflammation; Inflammatory; Interleukin-6; Life; Link; Live Birth; Low Birth Weight Infant; Maternal Exposure; Measures; Metabolism; Methods; Molecular; Mothers; Outcome; Oxidative Stress; Pathway interactions; Patients; Phase; Plastics; Population; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Pregnant Women; Premature Birth; Prevalence; Progesterone; Prostaglandins; Public Health; Research; Research Design; Research Personnel; Risk; Sampling; Self Care; Serum; Susceptibility Gene; System; Time; Tumor Necrosis Factor-alpha; Ultrasonography; Variant; adverse outcome; base; bisphenol A; case control; cohort; cost; cytokine; design; exposed human population; gene environment interaction; genotoxicity; innovation; interest; phthalates; prospective; public health relevance; urinary

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.

描述（由研究者提供）：早产是全球婴儿死亡的主要原因，也大大增加了儿童期和终生发生严重健康并发症的风险。早产以及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果的发生率增加。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%，现在占所有活产婴儿的近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大大低估。最近有初步证据表明，人类接触双酚A（BPA）和邻苯二甲酸酯，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，BPA和邻苯二甲酸酯已被证明会导致氧化应激、炎症和内分泌干扰，这些机制可能会导致胎儿生长改变和不良妊娠结局的风险增加。这一点特别令人关切，因为大多数普通人群，包括孕妇，每天都接触这类化合物。本申请旨在研究环境风险因素对700对母亲/婴儿的胎儿生长和早产的不良影响，这些母亲/婴儿是从马萨诸塞州波士顿的一项正在进行的单胎活产大规模队列研究中选出的。本研究将利用最先进的方法测量尿BPA和邻苯二甲酸酯浓度，并评估妊娠各期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）。还将探索在怀孕期间重复超声扫描的胎儿生长和胎盘功能的创新措施。该研究将利用正在进行的研究中的患者数据和生物样本，因此是一种高成本效益的研究资金使用。此外，拟议的研究将提供关于邻苯二甲酸酯和BPA代谢以及孕妇（人口中高度脆弱的部分）个体暴露易感性的新信息。该研究还将探讨BPA和邻苯二甲酸酯之间的关联是否基于创新的分类系统而不同，以根据潜在病因对早产进行分类。最后，该研究将提供邻苯二甲酸酯和BPA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的比例不断上升，这是一个重大的公共卫生挑战。全人口接触生物活性化合物双酚A和邻苯二甲酸酯的增加也是重大的公共卫生问题。该流行病学项目将使用最先进的方法和创新的研究设计，以提供对胎儿生长和早产风险产生不利影响的环境，人口统计学和生物学因素的急需信息。