Preconceptual Bisphenol and Phthalate Effects on Early Embryonic Development

项目摘要 纽约大学医学院、伊拉斯谟大学医学中心和纽约州卫生部 对PA-16-160的反应，建议研究产前邻苯二甲酸酯和双酚暴露 与怀孕时间、胚胎和胎儿生长以及婴儿生长的关系。内容丰富的文学作品 表明一系列不同的合成化学物质可能会影响发育的内分泌编程和 引发氧化应激，这是导致不良出生结果的主要病理生理机制。这些 包括：邻苯二甲酸盐(用于软化塑料和用作香料)；以及双酚(用于铝罐 衬里和热敏纸收据)。然而，对生命早期接触邻苯二甲酸盐和双酚的纵向研究 而且它们对人类胎儿和出生后发育的影响有限，到目前为止，很少有研究表明 没有产生一致的结论。我们建议从先入为主的三个时间点分析样本 妊娠(7周、13周和30周)在R下一代1000个父亲-母亲-婴儿三合一中，未来的， 纵向多民族出生队列研究。独特的胚胎和胎盘评估将被 分别于第7、9、11周进行重复超声检查。这些分析还将捕捉到胚胎 胎盘生长以及肝脏生长和心脏大小。拟议的研究还将利用 在1个月和12个月大时进行超声心动图和腹部超声检查，这将评估 如左室舒张末期容量、收缩末期容量、每搏量、射血分数 以及腹部脂肪和肝脏脂肪变性。圆周率(Trasande)是享誉国际的 儿童环境健康专家和拟议的研究也受益于 R下一代，包括主任(Jaddoe)，一位经验丰富的儿科和围产期流行病学家 在研究心血管疾病的早期决定因素方面有很好的记录。分析将由K. 纽约州卫生局沃兹沃斯实验室的卡南，他有很深的经验 精确测定尿液中的邻苯二甲酸盐和双酚类生物标志物。考虑到长期影响， “节俭表型”，如果发现先入为主的暴露对塑造胎儿生长和 影响分娩结局，然后指导怀孕预期，以限制之前的环境暴露 可能有怀孕的迹象。目前，这样的指导在美国是有限的，也许除了 寻求先进生殖技术的夫妇。

Project Summary NYU School of Medicine, Erasmus University Medical Center and New York State Department of Health respond to PA-16-160, proposing to study preconception and prenatal phthalate and bisphenol exposures in relationship to time to pregnancy, embryonic and fetal growth, and infant growth. A substantial literature suggests that a diverse array of synthetic chemicals may influence developmental endocrine programming and provoke oxidant stress, a major pathophysiologic mechanism underlying adverse birth outcomes. These include: phthalates (which are used to soften plastics and as scents); and bisphenols (used in aluminum can linings and thermal paper receipts). Yet, longitudinal studies of early life exposure to phthalates and bisphenols and their effects on fetal and postnatal growth in humans have been limited, and the few studies to date have not yielded consistent findings. We propose to analyze samples from preconception, three timepoints in pregnancy (7, 13 and 30 weeks) in 1000 father-mother-infant triads in Generation R Next, a prospective, longitudinal multi-ethnic birth cohort study. Unique embryonic and placental assessments will have been performed through repeated ultrasounds at 7, 9 and 11 weeks. These analyses will also capture embryonic and placental growth as well as liver growth and cardiac size. The proposed study will also leverage echocardiography and abdominal sonography performed at 1 and 12 months of age, which will assess dimensions such as left ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction and mass, as well as abdominal fat and liver steatosis. The PI (Trasande) is an internationally renowned expert in children's environmental health and the proposed study also benefits from strong support from Generation R Next, including the Director (Jaddoe), an experienced pediatric and perinatal epidemiologist with a strong record in studying early determinants of cardiovascular disease. Analyses will be performed by K. Kannan at Wadsworth Laboratories of the New York State Department of Health, who has deep experience with precise measurement of phthalate and bisphenol biomarkers in urine. Given the long-term implications of the “thrifty phenotype,” if preconceptional exposures are found to be important in shaping fetal growth and influencing birth outcomes, then guidance in anticipation of conception to limit environmental exposures before pregnancy may be indicated. Presently, such guidance is limited in the United States, save perhaps from couples seeking advanced reproductive technology.