From the Inserm, CNRS, Univ. Grenoble Alpes, Institute for Advanced Biosciences (IAB), U1209, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble, France.
Organic Analytical Toxicology Branch, Division of Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, GA.
Epidemiology. 2019 Sep;30(5):756-767. doi: 10.1097/EDE.0000000000001056.
Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void.
In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures.
Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%.
For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.
在生物标志物为基础的研究中，当暴露评估存在经典错误时，个体内生物样本混合可以从理论上减少剂量反应函数中的偏差。然而，每天收集多个尿样是很繁琐的。我们评估了个体内混合方法的经验有效性，并比较了几种避免每次采集尿样的方法。
在 16 名孕妇中，我们在数周内每天收集一次尿液样本，比较了每日、每周和个体内样本中 10 种酚类物质的浓度。我们混合了三个或所有每日样本。在一项使用这些数据的模拟研究中，我们量化了当使用每个受试者 1 到 20 个尿样来评估甲基对羟基苯甲酸酯（一种个体内变异性中等的化合物）和双酚 A（变异性高）暴露时，剂量反应函数中的偏差。
在所有时间窗口和化合物中，每日所有和仅三个样本混合的暴露估计之间的相关性均高于 0.80，除了每日时间窗口中的二苯甲酮-3 和三氯生（相关性为 0.57-0.68）。仅使用一个样本来评估妊娠暴露，相关性均低于 0.74。仅使用一个生物样本会导致剂量反应函数的衰减偏差为 29%（甲基对羟基苯甲酸酯）和 69%（双酚 A）；使用四个样本对甲基对羟基苯甲酸酯和 18 个样本对双酚 A 可将偏差降低到 10%。
对于非持久性化学物质，每天收集和混合三个样本而不是所有的每日样本，可以有效地估计一周以上的暴露情况。收集大约 20 个生物样本可以强烈限制双酚 A 等非持久性化学物质的衰减偏差。
