Flame Retardant and Adverse Perinatal Outcome (FRAPO)

描述（由申请人提供）：多溴联苯醚（PBDE）是最普遍的有机污染物之一，因为在过去40年中，它们被广泛用作阻燃剂，特别是在美国和加拿大。因此，北美人的血液和母乳中多溴二苯醚的浓度是世界上最高的。几乎所有孕妇的血浆中都含有多溴二苯醚。它们也从胎盘、脐带、羊水和胎膜中分离出来，但它们对妊娠结局的影响尚不清楚。 由于多溴联苯醚与甲状腺素（T4）和三碘甲状腺原氨酸（T3）的结构相似，因此已将其作为甲状腺系统的内分泌干扰物进行了广泛调查。患有甲状腺功能减退症的妇女通过一种未知的机制增加了早产的风险，这是现代产科的首要问题。许多早产与胎盘和胎膜炎症有关。有新的证据表明，甲状腺激素具有抗炎特性，在脓毒症动物模型中改善存活率并减少促炎细胞因子的产生。T3和T4的抑制可能 多溴联苯醚的生物活性增加了早产的风险，因为它有利于促炎环境。我们的初步研究表明，用多溴联苯醚处理胎盘培养物可增强与早产相关的细胞因子和异黄酮的产生。 为了确定多溴联苯醚暴露是否会增加妇女早产的风险，我们建议在加州南部的一名接受产前护理的妇女怀孕的每个三个月收集血液样本。从早产妇女和1000名随机选择的对照组中抽取的样本将进行PBDE-47的检测，PBDE-47是在母体血浆和促甲状腺激素（TSH）中检测到的最常见的Conger。我们推测，早产的妇女在整个怀孕期间PBDE-47的浓度会增加，特别是当存在感染（组织学绒毛膜炎）的证据时。血浆PBDE-47水平预计与血浆TSH浓度呈正相关，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多溴二苯醚对不良妊娠结果风险的潜在作用的迫切需要，多溴二苯醚在90%以上的孕妇中均可检测到。

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.