Prenatal exposure to polyfluoroalkyl chemicals (PFCs) and child growth and develo

描述(申请人提供)：全氟碳化物是用作表面活性剂和表面保护的合成化学品，包括防沾污产品(如地毯和织物)，不粘物。 涂料和食品包装。全氟碳化物在环境和人体组织中普遍存在并持续存在。尽管全氟化碳在环境中存在了几十年，但在健康结果方面是相对较新的化合物，越来越多的动物和人类研究表明，它们可能是发育毒物。这项拟议研究的主要目的是调查产前PFC暴露与儿童生长发育的关系。我们将测量在妊娠早期收集的产前孕妇血浆中四种全氟化合物-全氟辛酸(PFOA)、全氟辛烷磺酸(PFOS)、全氟己烷磺酸(PFHxS)和全氟农酸(PFNA)-的水平，并评估与胎儿和婴儿体格生长、儿童肥胖和代谢结果(如血清胆固醇和胰岛素抵抗)以及神经发育(包括认知和行为)的相关性。我们将检查PFC与产前、母亲和新生儿甲状腺激素水平的关系，并探索甲状腺功能作为PFC与生长和神经发育相关的潜在途径。我们还将测量出生后7岁的子代的PFC，以探索它们对这些结果的贡献，而不是与产前暴露无关。我们将在Project Viva中调查这些目标，这是一个大型的、特征良好的纵向出生前队列，从1999年到2002年在怀孕期间招募的母亲(大约1700人存档了可用于PFC分析的早期怀孕血浆样本)及其后代(约610人存档了可用于PFC分析的出生后血液样本)，从出生到7岁。我们将使用多变量回归估计关联性，控制广泛的协变量。这将是迄今为止评估产前全氟化碳对儿童生长和发育的影响的最大规模的研究，这是第一项关于产前和出生后全氟化碳的研究。这项成本效益很高的调查将受益于使用自怀孕早期以来纵向评估的具有良好特征的人口，为这些人口收集了大量关于不利儿童发育风险因素的信息。1999-2002年期间招募孕妇恰逢PFC排放高峰期，增强了我们检测暴露影响的能力。这些结果将进一步加深我们对出生前和出生后暴露于全氟化碳对产前和幼儿期生长发育影响的理解。鉴于这些化学物质在环境和人类中的普遍存在和持久性，以及它们作为发育毒物的潜在作用，这是一个重大的公共卫生问题。

DESCRIPTION (provided by applicant): PFCs are synthetic chemicals used as surfactants and in surface protection, including stain-resistant products (e.g., carpets and fabrics), nonstick coatings, and food packaging. PFCs are ubiquitous and persistent in the environment and in human tissue. Though present in the environment for decades, PFCs are relatively new compounds of interest with respect to health outcomes and there is mounting evidence from animal and human studies suggesting that they may be developmental toxicants. The primary aim of the proposed research is to investigate the association of prenatal PFC exposure with growth and development in children. We will measure levels of four perfluorinated compounds - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) - in prenatal maternal plasma collected in early gestation and estimate associations with fetal and infant somatic growth, childhood adiposity and metabolic outcomes such as serum cholesterol and insulin resistance, and neurodevelopment, including cognition and behavior. We will examine associations of PFCs with prenatal maternal and neonatal thyroid hormone levels and explore thyroid function as an underlying pathway for PFC-related associations with growth and neurodevelopment. We will also measure postnatal PFCs in offspring at age 7 to explore their contribution to these outcomes independent of prenatal exposure. We will investigate these aims in Project Viva, a large, well-characterized longitudinal pre-birth cohort of mothers recruited 1999-2002 during pregnancy (approximately 1,700 have archived early pregnancy plasma samples available for PFC analysis) and their offspring (approximately 610 have archived postnatal blood samples available for PFC analysis) followed from birth through age 7 years. We will estimate associations using multivariable regression, controlling for a wide range of covariates. This will be the largest study to date to assess the effect of prenatal PFCs on childhood growth and development the first study to account for prenatal and postnatal PFCs. This highly cost-effective investigation will benefit from the use of a well-characterized population assessed longitudinally since early pregnancy for whom a wealth of information on risk factors for adverse child development has already been collected. Recruitment of pregnant mothers during 1999-2002 coincides with the period of peak PFC emissions, enhancing our power to detect exposure effects. Results will further our understanding of the impact of prenatal and postnatal exposure to PFCs on growth and development during the prenatal and early childhood period. This is a major public health concern given the ubiquity and persistence of these chemicals in the environment and in humans and their potential role as developmental toxicants.