Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.

Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.
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解释围着床期样本中的尿液稀释:对肌酐调整和样本合并的影响。

DOI:
10.1038/s41370-020-0227-1
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发表时间:
2021-03
影响因子:
4.5
通讯作者:
Jukic AMZ
Jukic AMZ
中科院分区:
医学3区
文献类型:
--
作者:
Rosen Vollmar AK;Johnson CH;Weinberg CR;Deziel NC;Baird DD;Wilcox AJ;Jukic AMZ

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本研究探讨了用于评估环境暴露的围着床样本中尿液稀释的关键问题。妊娠早期可能影响肌酐排泄,当使用肌酐调整时,这可能会影响生物标志物的测量和解释。我们比较了妊娠3-6周植入前和植入后不久的肌酐水平。使用145名怀孕妇女的数据和尿液样本,我们使用线性混合模型来估计怀孕对肌酐浓度的影响。我们还研究了当使用汇总的、个人样本而不是平均个人调整结果时,肌酐调整是否有偏差。为此,我们将2,655例每日尿雌激素代谢物和相关肌酐测量值分组到762个数学构建的样本池中,并使用加权kappa系数和t检验将平均个体测量值与合并测量值进行比较。尿肌酐浓度从植入前到植入后平均下降14% (95% CI: - 19%, - 11%)。虽然基于两种肌酐调整方法的结果之间存在很强的相关性,但与平均单独调整样本相比,基于合并样本的调整引入了对分析物的3% (95% CI: 2%, 4%)的低估。在比较植入前和植入后的暴露测量时,植入后肌酐下降可能会导致生物监测结果的误差。虽然合并肌酐调整低估了调整后的分析物浓度,但合并评估和平均个人调整评估之间的偏差很小,一致性很好。
This study examines critical issues in accounting for urinary dilution in peri-implantation samples used to assess environmental exposures. Early pregnancy could impact creatinine excretion, which could bias biomarker measurement and interpretation when creatinine adjustment is used. We compared creatinine levels pre-implantation with levels soon after implantation at 3–6 weeks gestation. Using data and urine specimens from 145 women who conceived, we used linear mixed models to estimate the effect of pregnancy on creatinine concentrations. We also studied whether creatinine adjustment is biased when using pooled, within-person samples rather than averaging individually-adjusted results. For this, we grouped 2,655 daily urinary estrogen metabolite and associated creatinine measures into 762 mathematically-constructed sample pools, and compared averaged individual measures with pooled measures using weighted kappa coefficients and t-tests. Urinary creatinine concentration declined an average of 14% (95% CI: −19%, −11%) from pre- to post-implantation. While there was strong correlation between results based on the two creatinine adjustment methods, adjustment based on pooled specimens introduced a small 3% (95% CI: 2%, 4%) underestimation of the analyte compared to averaging individually-adjusted samples. Post-implantation creatinine declines could introduce errors in biomonitoring results when comparing exposure measures from pre- and post-implantation. Though pooled creatinine adjustment underestimated adjusted analyte concentrations, the bias was small and agreement excellent between pooled and averaged individually-adjusted assessments.
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