First trimester phthalate exposure and anogenital distance in newborns
First trimester phthalate exposure and anogenital distance in newborns
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DOI：
10.1093/humrep/deu363
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发表时间：
2015-04-01
影响因子：
6.1
通讯作者：
Redmon, J. B.
中科院分区：
文献类型：
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作者：
Swan, S. H.;Sathyanarayana, S.;Redmon, J. B.
研究问题：妊娠早期接触邻苯二甲酸盐与新生儿肛门生殖器距离 (AGD)（产前雄激素暴露的生物标志物）相关吗？总结答案：妊娠早期母体尿液样本中邻苯二甲酸二乙酯 (DEHP) 代谢物的浓度与男性新生儿的 AGD 呈负相关，但与女性新生儿的 AGD 无关。已知信息：AGD 是一种性别二态性测量方法反映产前雄激素暴露。多项动物研究表明，产前接触邻苯二甲酸盐与男性 AGD 较短有关。先前的人体研究因样本量小以及暴露时间和/或结果不精确而受到限制，报告了相互矛盾的结果。 研究设计、规模、持续时间：婴儿发育和环境研究 (TIDES) 是一项前瞻性队列研究，对象是 2010-2012 年在加利福尼亚州旧金山、明尼苏达州明尼阿波利斯、纽约州罗彻斯特和华盛顿州西雅图的产前诊所招募的孕妇。参与者接生了 787 名婴儿；本分析包含 753 名拥有完整数据的女性。 参与者/材料、环境、方法：任何年满 18 岁、能够读写英语（或加利福尼亚州西班牙语）、怀孕 13 周、怀孕未受到医学威胁且计划在研究医院分娩的女性都有资格参加。分析包括母亲提供妊娠早期尿液样本并在出生时或出生后不久接受检查的所有婴儿。检查妊娠早期尿样中邻苯二甲酸酯代谢物的比重（SpG）调整浓度与生殖器测量的关系。在男孩 (N = 366) 中，我们获得了肛门生殖器距离 (AGD)（肛门阴囊距离，或 AGD(AS) 和阴茎距离，AGD(AP)）以及阴茎宽度 (PW) 的两个测量值。在女孩 (N = 373) 中，我们测量了肛管距离 (AGD(AF)) 和肛阴距离 (AGD(AC))。我们使用多变量回归模型来调整婴儿的检查年龄、胎龄、身长体重 Z 评分、尿液收集时间、母亲年龄和研究中心。 主要结果和机会的作用：DEHP 的三种代谢物与男孩 AGD 的两项测量值均显着呈负相关。 AGD(AS) 和 (log(10)) SpG 调整的邻苯二甲酸酯浓度之间的关联（β，95% 置信区间 (CI)）为：邻苯二甲酸单 2-乙基己酯 (MEHP) 为 -1.12 (-2.16, -0.07)，邻苯二甲酸单 2-乙基己酯 (MEOHP) 为 -1.43，(-2.49, -0.38)，以及-1.28（-2.29，-0.27）对于单-2-乙基-5-羟基己基（MEHHP）。 AGD(AP) 的关联程度相似。 PW 的相关性较弱且不具有统计学显着性。没有其他邻苯二甲酸酯代谢物与男孩的任何生殖器测量相关。邻苯二甲酸盐代谢物与女孩中的任一 AGD 测量值相关。 局限性、注意原因：暴露评估基于单个妊娠早期尿液样本，这可能会导致暴露错误分类。此外，中心间的显着差异表明这种测量很难标准化。 研究结果的更广泛影响：我们的研究结果与多项啮齿动物研究和大多数规模小得多的人类研究一致。我们在此报告的数据表明，即使在目前的低水平下，环境中的 DEHP 暴露也会对男性生殖器发育产生不利影响，导致生殖道变化，从而可能影响以后的生殖健康。这些发现对公共政策具有重要影响，因为大多数孕妇都会接触这种无处不在的化学物质。
STUDY QUESTION: Is first trimester phthalate exposure associated with anogenital distance (AGD), a biomarker of prenatal androgen exposure, in newborns?SUMMARY ANSWER: Concentrations of diethylhexyl phthalate (DEHP) metabolites in first trimester maternal urine samples are inversely associated with AGD in male, but not female, newborns.WHAT IS KNOWN ALREADY: AGD is a sexually dimorphic measure reflecting prenatal androgen exposure. Prenatal phthalate exposure has been associated with shorter male AGD in multiple animal studies. Prior human studies, which have been limited by small sample size and imprecise timing of exposure and/or outcome, have reported conflicting results.STUDY DESIGN, SIZE, DURATION: The Infant Development and the Environment Study (TIDES) is a prospective cohort study of pregnant women recruited in prenatal clinics in San Francisco, CA, Minneapolis, MN, Rochester, NY and Seattle, WA in 2010-2012. Participants delivered 787 infants; 753 with complete data are included in this analysis.PARTICIPANTS/MATERIALS, SETTING, METHODS: Any woman over 18 years old who was able to read and write English (or Spanish in CA), who was,13 weeks pregnant, whose pregnancy was not medically threatened and who planned to deliver in a study hospital was eligible to participate. Analyses include all infants whose mothers provided a first trimester urine sample and who were examined at or shortly after birth. Specific gravity (SpG) adjusted concentrations of phthalate metabolites in first trimester urine samples were examined in relation to genital measurements. In boys (N = 366), we obtained two measures of anogenital distance (AGD) (anoscrotal distance, or AGD(AS) and anopenile distance, AGD(AP)) as well as penile width (PW). In girls (N = 373), we measured anofourchette distance (AGD(AF)) and anoclitoral distance (AGD(AC)). We used multivariable regression models that adjusted for the infant's age at exam, gestational age, weight-for-length Z-score, time of day of urine collection, maternal age and study center.MAIN RESULTS AND THE ROLE OF CHANCE: Three metabolites of DEHP were significantly and inversely associated with both measures of boys' AGD. Associations (beta, 95% confidence interval (CI)) between AGD(AS) and (log(10)) SpG-adjusted phthalate concentrations were: -1.12 (-2.16, -0.07) for mono-2-ethylhexyl phthalate (MEHP), -1.43, (-2.49, -0.38) for mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and -1.28 (-2.29,-0.27) for mono-2-ethyl-5-hydroxyhexyl (MEHHP). Associations were of similar magnitude for AGD(AP). Associations were weaker and not statistically significant for PW. No other phthalate metabolites were associated with any genital measurement in boys. Nophthalate metabolites were associated with either AGD measure in girls.LIMITATIONS, REASONS FOR CAUTION: Exposure assessment was based on a single first trimester urine sample, which may have introduced exposure misclassification. In addition, significant between-center differences suggest that this measurement is difficult to standardize.WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with multiple rodent studies and most human studies which were far smaller. The data we report here suggest that even at current low levels, environmental exposure to DEHP can adversely affect male genital development resulting in reproductive tract changes that may impact reproductive health later in life. These findings have important implications for public policy since most pregnant women are exposed to this ubiquitous chemical.