Project 1: Prenatal Exposure to BPA/Phthalates: Infant Physical & Behavioral

孕妇通过使用个人护理产品和塑料接触到邻苯二甲酸盐和双酚A（BPA）等干扰内分泌的化学物质。在动物模型中，邻苯二甲酸盐和BPA会导致发育异常，但人们对这些化学物质是否与人类的不良发育结果有关知之甚少。拟议的试点研究将开发新的方法来评估产前BPA或邻苯二甲酸酯暴露对出生后最初几个月内性二态性身体和行为终点的影响，并将确定对产前化学品暴露敏感的新生儿认知功能的可靠和有效措施，并预测持久的认知缺陷。拟议的初步研究的总体假设是，母亲暴露于邻苯二甲酸酯和/或BPA与其后代的不良发育结果相关。拟议项目的具体目标是：1）评估孕妇样本中邻苯二甲酸酯和BPA的暴露，2）检查产前邻苯二甲酸酯和BPA暴露与婴儿身体发育之间的关联，3）检查产前邻苯二甲酸酯和BPA暴露与婴儿认知之间的关联，和4）研究雌激素受体（ER）α和ER β的多态性是否增加对产前邻苯二甲酸酯或BPA暴露的易感性。完成拟议的工作。将从当地医院招募150名18-40岁的孕妇及其婴儿。孕妇将填写24小时产品使用日记，并提供尿液样本，用于评估总BPA和9种邻苯二甲酸酯代谢物。此外，孕妇将捐献脐带血用于测量选定的ER多态性。将在出生时评估关键的身体和认知结果，并在4.5和7.5个月大时评估认知结果。将在统计回归模型中检查暴露量和报告的产品使用之间的关系，以及母亲暴露量和婴儿身体或认知结果之间的关系。这项拟议的研究将提供关于孕妇接触邻苯二甲酸酯和BPA的性质及其婴儿发育异常风险的重要试点数据。研究结果将为将试点出生队列扩展为更大的前瞻性出生队列提供强有力的基础，并对儿童从出生到青春期进行纵向随访。

Pregnant women are exposed to endocrine disrupting chemicals such as phthalates and bisphenol A (BPA) through their use of personal care products and plastics. In animal models, phthalates and BPA cause developmental abnormalities, but littie is known about whether these chemicals are associated with adverse developmental outcomes in humans. The proposed pilot study will develop novel methods to assess the impact of prenatal BPA or phthalate exposure on sexually dimorphic physical and behavioral endpoints during the first few months of life and it will identify reliable and valid measures of cognitive function in newborns that are sensitive to prenatal chemical exposure and predictive of lasting cognitive deficits. The overall hypothesis of the proposed pilot study is that maternal exposure to phthalates and/or BPA is associated with adverse developmental outcomes in their offspring. The specific objectives of the proposed project are to: 1) assess exposure to phthalates and BPA in a sample of pregnant women, 2) examine the association between prenatal phthalate and BPA exposure and physical development in infants, 3) examine the association between prenatal phthalate and BPA exposure and cognition in infants, and 4) investigate whether polymorphisms in estrogen receptor (ER) alpha and ER beta increase susceptibility to prenatal phthalate or BPA exposure. To complete the proposed work. 150 pregnant women age 18-40 and their infants will be recruited from a local hospital. The pregnant women will complete a 24-hour product use diary and provide urine samples for assessments of total BPA and 9 phthalate metabolites. In addition, pregnant women will donate cord blood for measurement of selected ER polymorphisms. Key physical and cognitive outcomes will be assessed at birth, and cognitive outcomes will also be assessed at 4.5 and 7.5 months of age. The relationship behween measures of exposure and reported product use, and the relationship behween maternal exposures and physical or cognitive outcomes in infants will be examined in statistical regression models. The proposed study will provide important pilot data about the nature of phthalate and BPA exposure in pregnant women and the risk of developmental abnormalities in their infants. The results will provide a strong basis for expansion of the pilot birth cohort into a larger prospective birth cohort with longitudinal follow-up of the children from birth through puberty.