Background

Measurements of urinary dialkyl phosphate (DAP) metabolites are often used to characterize exposures to organophosphate (OP) insecticides; however, some challenges to using urinary DAP metabolites as an exposure measure exist. OP insecticides have short biological half-lives with measurement in a single urine sample typically only reflecting recent exposure within the last few days. Because of the field staff and participant burden of longitudinal sample collection and the high cost of multiple measurements, typically only one or two urine samples have been used to evaluate OP insecticide exposure during pregnancy, which is unlikely to capture an accurate picture of prenatal exposure.

Methods

We recruited pregnant farmworker women in Chom Thong and Fang, two districts of Chiang Mai province in northern Thailand (N = 330) into the Study of Asian Women and their Offspring’s Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. We collected up to 6 serial urine samples per participant during gestation and composited the samples to represent early, mid, and late pregnancy. We measured concentrations of urinary DAP metabolites in the composited urine samples and evaluated the within- and between-participant variability of these levels. We also investigated predictors of OP insecticide exposure.

Results

DAP metabolite concentrations in serial composite samples were weakly to moderately correlated. Spearman correlations indicated that composite urine samples were more highly correlated in Fang participants than in Chom Thong participants. The within-person variances (0.064–0.65) exceeded the between-person variances for DETP, DEP, ∑DEAP, DMP, DMTP, ∑DMAP, ∑DAP. The intraclass correlations (ICCs) for the volume-based individual metabolite levels (ng/mL) ranged from 0.10 to 0.66. For ∑DEAP, ∑DMAP, and ∑DAP the ICCs were, 0.47, 0.17, 0.45 respectively. We observed significant differences between participants from Fang compared to those from Chom Thong both in demographic and exposure characteristics. Spearman correlations of composite samples from Fang participants ranged from 0.55 to 0.66 for the ∑DEAP metabolite concentrations in Fang indicating moderate correlation between pregnancy periods. The ICCs were higher for samples from Fang participants, which drove the overall ICCs.

Conclusions

Collecting multiple (∼6) urine samples during pregnancy rather than just 1 or 2 improved our ability to accurately assess exposure during the prenatal period. By compositing the samples, we were able to still obtain trimester-specific information on exposure while keeping the analytic costs and laboratory burden low. This analysis also helped to inform how to best conduct future analyses within the SAWASDEE study. We observed two different exposure profiles in participants in which the concentrations and variability in data were highly linked to the residential location of the participants.

中文翻译：

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亚洲妇女及其后代发育和环境暴露研究中有机磷农药二烷基磷酸酯代谢物的尿液浓度 (SAWASDEE)

背景

尿二烷基磷酸盐 (DAP) 代谢物的测量通常用于表征有机磷 (OP) 杀虫剂的暴露；然而，使用尿液中的 DAP 代谢物作为暴露量度存在一些挑战。OP 杀虫剂的生物半衰期很短，在单个尿液样本中进行的测量通常只能反映最近几天内的近期接触情况。由于现场工作人员和参与者纵向样本采集的负担以及多次测量的高成本，通常只使用一两个尿液样本来评估怀孕期间 OP 杀虫剂的暴露情况，这不太可能捕捉到产前暴露的准确情况。

方法

我们从 2017 年到 2019 年在泰国北部清迈省的 Chom Thong 和 Fang 两个地区招募了怀孕的农场工人妇女（N = 330）进入亚洲妇女及其后代的发展和环境暴露研究（SAWASDEE）。我们收集了多达妊娠期间每位参与者 6 份连续尿液样本，并将这些样本混合以代表妊娠早期、中期和晚期。我们测量了复合尿样中尿 DAP 代谢物的浓度，并评估了这些水平在参与者内部和参与者之间的变异性。我们还调查了 OP 杀虫剂暴露的预测因子。

结果

系列复合样品中的 DAP 代谢物浓度呈弱至中度相关。Spearman 相关性表明，复合尿液样本在 Fang 参与者中的相关性高于 Chom Thong 参与者。人内差异 (0.064–0.65) 超过了 DETP、DEP、∑DEAP、DMP、DMTP、∑DMAP、∑DAP 的人际差异。基于体积的单个代谢物水平 (ng/mL) 的类内相关性 (ICC) 范围为 0.10 至 0.66。对于 ∑DEAP、∑DMAP 和 ∑DAP，ICC 分别为 0.47、0.17、0.45。我们观察到 Fang 的参与者与 Chom Thong 的参与者在人口统计学和暴露特征方面存在显着差异。Fang 参与者的复合样本的 Spearman 相关性介于 0.55 到 0 之间。Fang 中的 ∑DEAP 代谢物浓度为 66，表明妊娠期之间存在适度相关性。来自 Fang 参与者的样本的 ICC 更高，这推动了整体 ICC。

结论

在怀孕期间收集多个 (~6) 个尿液样本，而不是仅仅收集 1 个或 2 个，提高了我们准确评估产前暴露的能力。通过合成样本，我们仍然能够获得有关暴露的三个月特定信息，同时保持较低的分析成本和实验室负担。该分析还有助于告知如何在 SAWASDEE 研究中最好地进行未来分析。我们在参与者中观察到两种不同的暴露概况，其中数据的浓度和变异性与参与者的居住地点高度相关。