The Infant Development and the Environmental Study (TIDES)

描述（由研究者提供）：环境化学物质可能导致男性生殖障碍的增加，这在工业国家已经被注意到。虽然这方面的讨论大多围绕着环境雌激素展开，但抗雄激素，尤其是邻苯二甲酸盐，已经证明了男性生殖功能受损与环境因素之间最引人注目的联系。在啮齿类动物中，邻苯二甲酸二乙基己酯（DEHP）和邻苯二甲酸二丁酯（DBP）引起一系列男性生殖道疾病，称为“邻苯二甲酸酯综合征”。肛门生殖器距离（AGD），即肛门到生殖器的距离，是该综合征的一个决定性标志，该综合征还包括睾丸大小小和睾丸下降不完全。我们发现产前尿液中DEHP和DBP代谢物浓度较高与男婴较短的AGD有关。DEHP代谢物也与阴茎宽度（PW）和不完全睾丸下降呈负相关。妊娠队列：婴儿发育与环境研究（TIDES）的主要目的是检查男婴生殖器标志与产前DEHP和DBP暴露的关系。为了实现这一目标，我们将从四个中心（西雅图，WA，明尼阿波利斯，MN，旧金山，CA和罗切斯特，NY）招募1000名怀孕前三个月的妇女，并在每个三个月存储所有妇女的尿液样本。我们将检测生育男性的女性妊娠早期尿液样本中的DEHP和DBP代谢物浓度，并储存女性分娩的尿液以供未来研究。我们将测量50%的男性母亲每个孕期尿液样本中的代谢物浓度，以估计整个孕期代谢物的变异性。出生队列：TIDES的第二个目的是获得基于人群的男性新生儿AGD、PW、睾丸体积（TV）和睾丸位置（TL）的标准，特别是出生体重和胎龄。我们将使用精确的方法和测量方法检查1000名新生儿（包括500名怀孕队列成员所生的男性和500名新生儿托儿所男孩的额外样本），这些方法和测量方法在临床中心标准化，具有严格的质量控制程序。随访队列：为了检查出生测量的稳定性，我们将在怀孕队列中女性所生的男性6个月和12个月时重复出生检查。我们还将试点新的方法，通过相机和超声波获得的标准化数字图像进行肛门生殖器区域的形态测量。结果：本研究将为测量AGD、PW和TL（可能还有TV）提供标准方法，并在不同人群的男性婴儿样本中获得这些生殖器标志的规范，这可能适合在儿科实践中使用。我们正在研究的邻苯二甲酸酯代谢物与雄激素敏感指标之间的关联可能在公共卫生政策中发挥重要作用，因为这些暴露无处不在，而且在胎儿发育过程中适当的雄激素刺激具有临床重要性。公共卫生相关性：本研究将提供测量人群中四种雄激素敏感指标的标准方法；肛门生殖器距离，阴茎宽度，睾丸体积和睾丸位置。我们将为这些生殖器官制定年龄和体重调整标准

DESCRIPTION (provided by investigator): Environmental chemicals may contribute to increases in male reproductive disorders that have been noted in industrial nations. While much of this discussion has revolved around environmental estrogens, the most compelling links between impaired male reproductive function and environmental agents have been demonstrated for anti-androgens, and phthalates, in particular. In rodents, diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) induce a spectrum of male genital tract disorders termed the "phthalate syndrome". Anogenital distance (AGD), the distance from anus to genitals, is a defining marker of this syndrome, which also includes small testes size and incomplete testicular descent. We found higher concentrations of metabolites of DEHP and DBP in prenatal urine to be associated with shorter AGD in male infants. DEHP metabolites were also negatively correlated with penile width (PW) and incomplete testicular descent. Pregnancy cohort: A primary aim of The Infant Development and Environment Study (TIDES) is to examine genital landmarks in male infants in relation to prenatal DEHP and DBP exposure. To address this aim, we will recruit 1,000 women in the first trimester of pregnancy from four centers (Seattle, WA, Minneapolis, MN, San Francisco, CA and Rochester, NY) and store a urine sample in each trimester from all women. We will examine DEHP and DBP metabolite concentrations in first trimester urine samples in women who give birth to males, and store urine from female births for future study. We will measure metabolite concentration in urine samples from each trimester for 50 per cent of mothers of males to estimate metabolite variability across pregnancy. Birth cohort: The second aim of TIDES is to obtain population-based norms for AGD, PW, testicular volume (TV) and testicular location (TL) in male newborns, specific for birthweight and gestational age. We will examine 1,000 newborn males (including 500 males born to members of the pregnancy cohort and an additional sample of 500 boys from the newborn nursery) using precise methods and measures standardized across clinical centers with strict quality control procedures. Follow-up cohort: To examine the stability of birth measurements, we will repeat the birth exam at 6 and 12 months in males born to women in the pregnancy cohort. We will also pilot novel methods for conducting morphometry of the anogenital region from standardized digital images obtained by camera and ultrasound. Consequences: This research will provide standard methods for easily measuring AGD, PW, and TL (and perhaps TV) and norms for these genital landmarks obtained in a diverse, population-based, sample of male infants, which may be suitable for use in pediatric practice. Associations between phthalate metabolites and the androgen-sensitive measures we are examining could play an important role in public health policy given the ubiquitous nature of these exposures and the clinical importance of appropriate androgen stimulation during fetal development. PUBLIC HEALTH RELEVANCE: This research will provide standard methods measuring four androgen-sensitive measures in human populations; anogenital distance, penile width, testicular volume and testicular location. We will develop age and weight adjusted norms for these genital landmarks in a diverse population-based sample of male infants, which may then be suitable for use in pediatric practice. The study will also examine patterns of associations among metabolites of DEHP and DBP and these measures, which, if significant, could play an important role in public health policy given the ubiquitous nature of these exposures and the clinical importance of appropriate androgen stimulation during fetal development.