Prenatal Exposure to Organophosphates and Associations with Child Growth

描述（由申请人提供）：儿童肥胖是美国主要的公共卫生问题。最近的一项基于人口的调查估计，10%的2岁以下儿童肥胖（在或超过第95百分位数的体重-卧位长度生长图表）。虽然能量摄入和能量消耗之间的不平衡肯定是体重增加的一个关键决定因素，但新出现的证据支持这样一种假设，即环境污染物暴露，特别是那些发生在生命早期的污染物暴露，可能会干扰体内平衡控制并诱发或加剧肥胖。有机磷酸盐阻燃剂（OPFR）通常添加到消费品中，以降低易燃性并满足消防安全标准。在最近对家庭、办公室和汽车灰尘的研究中，它们被高频率地检测到，这表明OPFR从产品中滤出，并且很可能广泛地暴露于人类。虽然没有对它们在一般人群中的分布进行全面评估，但我们的初步数据和几项小型研究表明，暴露是普遍存在的。我们提出的研究将是第一个评估孕妇生物样本中OPFR水平的研究，并调查与高暴露相关的个体特征，确定高暴露风险更高的亚组，并评估暴露后代中不良健康后果的可能性。动物研究提供了令人信服的证据，OPFR暴露影响生长和发育;然而，这些动物研究在多大程度上扩展到人类尚不清楚。我们的主要目标是调查产前OPFR暴露对儿童从出生到3岁生长的影响，并在此过程中填补了对OPFR影响的理解方面的一个关键空白。 关于人类健康的OPFR。我们将利用先前从妊娠感染和营养队列中收集的数据和生物标本，这是一个经过仔细评估的从出生到3岁的纵向生长指标的特征良好的队列。使用储存的孕中期尿液，我们将检查产前暴露在发育窗口，被认为是至关重要的环境化学物质，破坏生长模式和肥胖的发展。确定产前OPFR暴露与生命早期生长改变之间的联系可能会对公共卫生产生重大影响，因为即使是体重状况的微小变化也与长期不良健康有关。这些数据是迫切需要的，因为随着其他阻燃化合物的逐步淘汰或禁止，预计OPFR的使用将增加。

DESCRIPTION (provided by applicant): Obesity among children is a major public health concern in the United States. A recent population-based survey estimated that 10% of children under age 2 are obese (at or above the 95th percentile of the weight-for-recumbent-length growth charts). Although imbalance between energy intake and energy expenditure is certainly a key determinant of weight gain, emerging evidence supports the hypothesis that environmental contaminant exposures, particularly those occurring in early-life, may interfere with homeostatic control and induce or exacerbate obesity. Organophosphate flame retardants (OPFRs) are commonly added to consumer products to reduce flammability and to meet fire safety standards. They have been detected with high frequency in recent studies of home, office, and automobile dust, suggesting that OPFRs leach from products and that widespread human exposure is likely. Although no comprehensive assessment of their distribution in the general population has been undertaken, our preliminary data and several small studies indicate that exposures are ubiquitous. Our proposed research will be the first to assess levels of OPFRs in biological samples from pregnant women and investigate individual characteristics associated with high exposure, identify subgroups at greater risk of high exposure, and assess the potential for adverse health outcomes among exposed offspring. Animal studies provide compelling evidence that OPFR exposures impact growth and development; however, the extent to which these animal studies extend to human populations is unclear. Our primary objective is to investigate the impacts of prenatal OPFR exposure on children's growth from birth through age 3, and in doing so, to fill a critical gap in the understanding of the impacts of OPFRs on human health. We will capitalize on previously collected data and biospecimens from the Pregnancy Infection and Nutrition cohort, a well- characterized cohort with carefully assessed longitudinal measures of growth from birth through age 3. Using stored second trimester urines, we will examine prenatal exposure during the developmental window that is thought to be critically relevant for environmental chemicals that disrupt growth patterning and the development of adiposity. Identifying a link between prenatal OPFR exposure and altered growth in early life could have a substantial public health impact given that even small changes in weight status have been associated with long-term adverse health. Such data is critically needed as use of OPFRs is predicted to increase as other flame retardant compounds are phased-out or banned.