孕期邻苯二甲酸酯和酚类暴露与婴儿内分泌敏感结局：MIREC 研究。
Prenatal exposure to phthalates and phenols and infant endocrine-sensitive outcomes: The MIREC study.
机构信息
Population Studies Division, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Population Studies Division, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada; Clinical Research Unit, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
出版信息
Environ Int. 2018 Nov;120:572-583. doi: 10.1016/j.envint.2018.08.034. Epub 2018 Sep 6.
BACKGROUND
Anogenital distance (AGD) and the second to fourth finger (2D:4D) digit ratio may be early markers of in utero androgen exposure for the infant. Phthalates and phenols have been identified as endocrine disrupting chemicals.
OBJECTIVES
To study the association between prenatal exposure to phthalates, bisphenol A (BPA) and triclosan (TCS) and AGD and the 2D:4D digit ratios.
METHODS
Single spot urine samples were collected in the first trimester from the MIREC Study and analyzed for phthalates and phenols. Anogenital distance (n = 394) at birth and 2D:4D digit ratios (n = 420) at 6 months were measured in male and female infants. Associations between maternal concentrations of phenols and phthalate metabolites and these outcomes were estimated using multiple linear regression models.
RESULTS
In females, the anoclitoris distance (ACD) was negatively associated with mono-benzyl phthalate (MBzP) (β = -1.24; 95% CI -1.91, -0.57) and positively associated with mono-ethyl phthalate (MEP) (β = 0.65; 95% CI 0.12, 1.18) (masculinizing). In males, anopenile distance (APD) was positively associated with mono-n-butyl phthalate (MnBP) (β = 1.17; 95% CI 0.02, 2.32) and the molar sum of low molecular weight phthalates (ΣLMW). Female 2D:4D of the right hand was positively associated with MnBP and negatively with total BPA (masculinizing).
CONCLUSIONS
Significant associations were only observed for the long AGD metrics. Positive associations were observed between MnBP or LMW phthalates and APD in males. In females, prenatal MEP was associated with a masculinizing effect on ACD, while MBzP was associated with a feminizing effect. No significant associations were observed between prenatal phenols and AGD. Given the paucity of research on digit ratios and prenatal chemical exposures, it is difficult to say whether this metric will be a useful marker of prenatal androgen or anti-androgen exposure. Given the large number of associations examined, the statistical associations observed may have been due to Type 1 error. The inconsistencies in results between studies suggest that this issue is yet to be resolved.
背景
肛殖距（AGD）和第二到第四指（2D:4D）的比值可能是婴儿宫内雄激素暴露的早期标志物。已鉴定出邻苯二甲酸酯和酚类物质为内分泌干扰化学物质。
目的
研究产前暴露于邻苯二甲酸酯、双酚 A（BPA）和三氯生（TCS）与 AGD 和 2D:4D 比值之间的关系。
方法
从 MIRCEL 研究中收集了第一孕期的单次尿液样本，并对其进行了邻苯二甲酸酯和酚类物质的分析。在男性和女性婴儿出生时测量了肛殖距（n=394），在 6 个月时测量了 2D:4D 比值（n=420）。使用多元线性回归模型估计母体酚类和邻苯二甲酸酯代谢物浓度与这些结果之间的关系。
结果
在女性中，阴蒂距离（ACD）与单苄基邻苯二甲酸酯（MBzP）呈负相关（β=-1.24；95%置信区间-1.91，-0.57），与单乙基邻苯二甲酸酯（MEP）呈正相关（β=0.65；95%置信区间 0.12，1.18）（男性化）。在男性中，阴茎距离（APD）与单正丁基邻苯二甲酸酯（MnBP）和低分子量邻苯二甲酸酯（ΣLMW）的总和呈正相关。女性右手 2D:4D 与 MnBP 呈正相关，与总 BPA 呈负相关（男性化）。
结论
仅观察到长 AGD 指标的显著关联。在男性中，MnBP 或低分子量邻苯二甲酸酯与 APD 之间存在正相关。在女性中，产前 MEP 与 ACD 的男性化效应相关，而 MBzP 与女性化效应相关。产前酚类物质与 AGD 之间无显著关联。鉴于关于数字比率和产前化学暴露的研究较少，因此尚不清楚该指标是否会成为产前雄激素或抗雄激素暴露的有用标志物。鉴于所检查的关联数量众多，观察到的统计学关联可能是由于第一类错误所致。研究之间的结果不一致表明，该问题尚未得到解决。
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