The Infant Development and the Environmental Study (TIDES)

描述(由研究人员提供)：工业化国家已经注意到，环境化学物质可能会导致男性生殖障碍的增加。虽然大部分讨论都是围绕环境雌激素展开的，但男性生殖功能受损与环境因素之间最有说服力的联系已经被证明是抗雄激素，尤其是邻苯二甲酸酯。在啮齿动物中，邻苯二甲酸二乙基己酯(DEHP)和邻苯二甲酸二丁酯(DBP)会引起一系列男性生殖道疾病，称为“邻苯二甲酸盐综合征”。肛门生殖距离(AGD)，即从肛门到生殖器的距离，是这种综合征的一个决定性标志，它还包括睾丸体积小和睾丸不完全下降。我们发现，产前尿中DEHP和DBP代谢产物浓度较高与男婴AGD较短有关。DEHP代谢产物与阴茎宽度(PW)和睾丸不全下降呈负相关。妊娠队列：婴儿发育和环境研究(DEDS)的一个主要目标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，华盛顿州，明尼阿波利斯，明尼苏达州，旧金山，加利福尼亚州和纽约州罗切斯特)招募1,000名怀孕前三个月的女性，并存储每个三个月所有女性的尿样。我们将检测生育男性的女性早期妊娠尿样中DEHP和DBP代谢物的浓度，并储存女性出生的尿液以备将来研究。我们将测量50%男性母亲在每三个月的尿样中的代谢物浓度，以评估代谢物在怀孕期间的变异性。出生队列：DEDS的第二个目标是获得男性新生儿AGD、PW、睾丸体积(TV)和睾丸位置(TL)的基于人群的正常值，具体用于出生体重和胎龄。我们将使用精确的方法和措施，通过严格的质量控制程序，通过临床中心标准化的方法和措施，检查1000名新生儿男性(包括500名妊娠队列成员所生的男性和从新生儿托儿所额外抽取的500名男孩)。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的女性所生的男性6个月和12个月时重复出生检查。我们还将试验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形态测量的新方法。结果：这项研究将提供容易测量AGD、PW和TL(可能还有TV)的标准方法，以及从不同的、以人群为基础的男性婴儿样本中获得的这些生殖器标志的标准，这可能适合用于儿科实践。邻苯二甲酸盐代谢产物与我们正在研究的雄激素敏感措施之间的联系可能在公共卫生政策中发挥重要作用，因为这些暴露的无处不在的性质，以及在胎儿发育期间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项雄激素敏感指标的标准方法：肛门距离、阴茎宽度、睾丸体积和睾丸位置。我们将为这些生殖器制定年龄和体重调整的标准 在以人群为基础的不同男婴样本中，这可能是一个里程碑，然后可能适合用于儿科实践。这项研究还将研究DEHP和DBP代谢物之间的关联模式以及这些措施，如果有意义，这些措施可能在公共卫生政策中发挥重要作用，因为这些暴露的无处不在的性质，以及在胎儿发育期间适当的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.