The Infant Development and the Environmental Study (TIDES)

描述（由研究者提供）：环境中的化学物质可能导致工业化国家男性生殖疾病的增加。虽然大部分讨论都围绕着环境雌激素，但男性生殖功能受损与环境因素之间最令人信服的联系已被证明是抗雄激素，特别是邻苯二甲酸酯。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）可诱导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），从肛门到生殖器的距离，是这种综合征的定义标志，它还包括小睾丸大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AGD较短相关。DEHP代谢产物也与阴茎宽度（PW）和睾丸下降不完全呈负相关。妊娠队列：婴儿发育和环境研究（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（华盛顿州西雅图、明尼苏达州明尼阿波利斯、加利福尼亚州旧金山弗朗西斯科和纽约州罗切斯特）招募1,000名妊娠前三个月的女性，并储存所有女性每个三个月的尿液样本。我们将检测产下男性的女性的妊娠早期尿液样本中DEHP和DBP代谢物的浓度，并储存来自女性分娩的尿液以供将来研究。我们将测量50%的男性母亲在每个三个月的尿液样本中的代谢物浓度，以估计整个怀孕期间的代谢物变异性。出生队列：TIDES的第二个目的是获得男性新生儿的AGD、PW、睾丸体积（TV）和睾丸位置（TL）的基于人群的标准，具体针对出生体重和胎龄。我们将使用临床中心标准化的精确方法和测量方法以及严格的质量控制程序检查1，000名新生男性（包括妊娠队列成员所生的500名男性和新生儿保育室的500名男孩的额外样本）。随访队列：为了检查出生测量的稳定性，我们将在妊娠队列中的女性所生的男性中在6个月和12个月时重复出生检查。我们还将试点新的方法进行形态测量的肛门生殖器区域从标准化的数字图像获得的相机和超声。后果：这项研究将提供标准的方法，易于测量AGD，PW和TL（也许TV）和规范，这些生殖器标志获得了一个多样化的，基于人口的，样本的男婴，这可能是适合在儿科实践中使用。邻苯二甲酸酯代谢物和雄激素敏感性指标之间的关联，我们正在研究可能在公共卫生政策中发挥重要作用，因为这些暴露的普遍性和在胎儿发育过程中适当的雄激素刺激的临床重要性。 公共卫生相关性：这项研究将提供测量人类人群中四种雄激素敏感性指标的标准方法;肛门生殖器距离，阴茎宽度，睾丸体积和睾丸位置。我们将制定这些生殖器的年龄和体重调整标准， 在一个不同的人口为基础的样本的男性婴儿的标志，然后可能适用于儿科实践。该研究还将检查DEHP和DBP代谢物与这些措施之间的关联模式，如果这些措施具有重要意义，则可以在公共卫生政策中发挥重要作用，因为这些暴露的普遍性以及在胎儿发育期间适当雄激素刺激的临床重要性。

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.