Flame Retardant and Adverse Perinatal Outcome (FRAPO)

阻燃剂和不良围产期结果 (FRAPO)

• 批准号: 8724502
• 负责人: Darios Getahun
• 金额: $ 62.78万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-21 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8724502
• 关键词: Affect; Air; American; Amniotic Fluid; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Bacteria; Binding; Biological; Biological Assay; Birds; Birth; Birth Weight; Blood; Blood specimen; California; Canada; Clinical; Clothing; Code; Country; Dairy Products; Development; Discipline of obstetrics; Electronics; Endocrine Disruptors; Environment; Ethyl Ether; Exposure to; Fetal Membranes; Fetus; Fire - disasters; Fishes; Flame Retardants; Food; Furniture; Genes; Genetic Transcription; Goals; Harvest; Health; Home environment; Hormones; House Dust; Human; Human Milk; Hyperactive behavior; Hypothyroidism; Infant; Infection; Infection of amniotic sac and membranes; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Ingestion; Interleukin-1; Lead; Learning; Ligand Binding Domain; Meat Products; Memory impairment; Meningitis; North America; Organ; Outcome; Patients; Perinatal; Placenta; Plasma; Population; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Pregnant Women; Premature Birth; Prenatal care; Production; Property; Prostaglandins; Rattus; Reporting; Risk; Risk Factors; Role; Sampling; Sepsis; Site-Directed Mutagenesis; Soil; Structure of placental cotyledon; System; Thyroid Gland; Thyroid Hormone Receptor; Thyroid Hormones; Thyrotropin; Thyroxine; Time; Tissues; Umbilical cord structure; United States; Woman; animal tissue; cohort; consumer product; cytokine; fetal; human tissue; improved; meetings; offspring; phenyl ether; pollutant; public health relevance

DESCRIPTION (provided by applicant): Polybromated Diphenyl Ethers (PBDEs) are one of the most prevalent organic pollutants due to their wide- spread use during the past 40 years as flame retardants, especially in the United States and Canada. As a result, North Americans have the highest blood and breast milk concentrations of PBDEs anywhere in the world. PBDEs are present in the plasma of almost all pregnant women. They have also been isolated from the placenta, umbilical chord, amniotic fluid and fetal membranes but their effects on pregnancy outcome are unclear. PBDEs have been widely investigated as endocrine disruptors of the thyroid system due to their structural similarity with thyroxine (T4) and tri-iodothyronine (T3). Women with hypothyroidism are at increased risk for preterm birth, the foremost problem in modern obstetrics, through an unknown mechanism. Many preterm births are associated with inflammation in the placenta and fetal membranes. There is emerging evidence that thyroid hormones have anti-inflammatory properties, improving survival and reducing the production of proin- flammatory cytokines in animal models of sepsis. It is possible that inhibition of T3 and T4 bioactivity, by PBDEs increases the risk of pretem birth by favoring a pro-inflammatory environment. Our preliminary studies suggest that treatment of placental cultures with PBDE enhances the production of cytokines and prostaglandins associated with preterm birth. To determine if PBDE exposure may enhance the risk for preterm birth in women, we propose to collect blood samples from a women receiving prenatal care in southern California at each trimester of pregnancy. Samples from women who deliver preterm and 1000 randomly selected controls will be assayed for PBDE-47, the most prevalent conger detected in maternal plasma and thyroid-stimulating hormone (TSH). We hypothesize that women who deliver preterm will have increased concentrations of PBDE-47 throughout their pregnancy, especially when evidence of infection (histological chorioamnionitis) is present. Plasma PBDE-47 levels are expected to be positively correlated with plasma concentrations of TSH, suggesting reduced bioactivity of the thyroid hormones. This study will help fulfill the critical need to better understand the potential role of PBDEs, which were detectable in >90% of all pregnant women, on risk for adverse pregnancy outcomes.

描述（由申请人提供）：多溴二苯基醚（PBDES）是最普遍的有机污染物之一，因为它们在过去40年中的广泛使用作为阻燃剂，尤其是在美国和加拿大。结果，北美人的血液和母乳浓度最高，世界上任何地方的PBDES。几乎所有孕妇的血浆中都存在PBDE。它们也已从胎盘，脐带和弦，羊水和胎儿膜中分离出来，但它们对妊娠结局的影响尚不清楚。 由于PBDE与甲状腺素（T4）和三碘甲氨酸（T3）的结构相似，因此已广泛研究了甲状腺系统的内分泌干扰物。甲状腺功能减退症的妇女通过未知机制，早产的风险增加，这是现代产科中最重要的问题。许多早产与胎盘和胎儿膜的炎症有关。有新兴的证据表明，甲状腺激素具有抗炎特性，改善了存活率并减少了败血症动物模型中促炎性细胞因子的产生。抑制T3和T4可能 生物活性，PBDES通过偏爱促炎环境来增加假装出生的风险。我们的初步研究表明，使用PBDE的胎盘培养物可以增强与早产相关的细胞因子和前列腺素的产生。 为了确定PBDE暴露是否可以增加女性早产的风险，我们建议在每年怀孕的每个三个月在南加州接受产前护理的妇女那里收集血液样本。将对PBDE-47进行分析，从母体血浆和甲状腺刺激性激素（TSH）中检测到的最普遍的康格，将分析来自早产和1000个随机选择对照的女性的样本。我们假设在整个怀孕期间，提供早产的妇女的PBDE-47浓度会增加，尤其是在存在感染证据（组织学绒毛膜炎）的情况下。血浆PBDE-47水平有望与血浆浓度TSH呈正相关，表明甲状腺激素的生物活性降低。这项研究将有助于满足更好地了解PBDE的潜在作用的关键需求，PBDE在所有孕妇中> 90％的孕妇中都可以检测到的潜在作用，这在不良怀孕的风险中。