Background

Exposome studies are challenged by exposure misclassification for non-persistent chemicals, whose temporal variability contributes to bias in dose-response functions.

Objectives

We evaluated the variability of urinary concentrations of 24 non-persistent chemicals: 10 phthalate metabolites, 7 phenols, 6 organophosphate (OP) pesticide metabolites, and cotinine, between weeks from different pregnancy trimesters in pregnant women, and between days and between seasons in children.

Methods

154 pregnant women and 152 children from six European countries were enrolled in 2014–2015. Pregnant women provided three urine samples over a day (morning, midday, and night), for one week in the 2nd and 3rd pregnancy trimesters. Children provided two urines a day (morning and night), over two one-week periods, six months apart. We pooled all samples for a given subject that were collected within a week. In children, we also made four daily pools (combining morning and night voids) during the last four days of the first follow-up week. Pools were analyzed for all 24 metabolites of interest. We calculated intraclass-correlation coefficients (ICC) and estimated the number of pools needed to obtain an ICC above 0.80.

Results

All phthalate metabolites and phenols were detected in >90% of pools whereas certain OP pesticide metabolites and cotinine were detected in <43% of pools. We observed fair (ICC = 0.40–0.59) to good (0.60–0.74) between-day reliability of the pools of two samples in children for all chemicals. Reliability was poor (<0.40) to fair between trimesters in pregnant women and between seasons in children. For most chemicals, three daily pools of two urines each (for weekly exposure windows) and four weekly pools of 15–20 urines each would be necessary to obtain an ICC above 0.80.

Conclusions

This quantification of the variability of biomarker measurements of many non-persistent chemicals during several time windows shows that for many of these compounds a few dozen samples are required to accurately assess exposure over periods encompassing several trimesters or months.

中文翻译：

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孕妇和学龄儿童尿中非持久性化学物质的浓度变化

背景

非持久性化学品的暴露分类错误挑战了暴露研究，因为非持久性化学品的时间变化会导致剂量反应功能出现偏差。

目标

我们评估了孕妇不同妊娠三个星期之间，儿童日间和季节之间24种非持久性化学品的尿液浓度的变异性：10种邻苯二甲酸酯代谢物，7种酚，6种有机磷酸酯（OP）农药代谢物和可替宁。 。

方法

2014-2015年，来自六个欧洲国家的154名孕妇和152名儿童入选。孕妇在妊娠的第2和第3个月的一天（早晨，中午和晚上）提供了三个尿液样本，为期一周。孩子们每天（早上和晚上）提供两个尿液，间隔两个月（一周），间隔六个月。我们汇总了一周内收集的给定主题的所有样本。在儿童中，我们在第一个随访周的最后四天也做了四个每日游泳池（结合了早晨和夜晚的虚空）。分析所有24种目标代谢物的库。我们计算了类内相关系数（ICC），并估算了获得高于0.80的ICC所需的池数。

结果

在> 90％的样品池中检测到所有邻苯二甲酸酯代谢物和酚，而在<43％的样品池中检测到某些OP农药代谢物和可替宁。我们观察到儿童中所有化学品的两个样本池的日间可靠性（ICC = 0.40–0.59）至良好（0.60–0.74）。孕妇的妊娠中期和儿童的季节之间的可靠性差（<0.40），尚可。对于大多数化学药品而言，要获得高于0.80的ICC，将需要三个每天两次的尿液池（每个星期用于暴露窗口）和四个每周一次的15-20尿液池。

结论

在几个时间窗口内对许多非持久性化学物质的生物标志物测量值的变异性的量化表明，对于这些化合物中的许多化合物，需要几十个样品才能准确评估在过去三个月或几个月内的暴露水平。