Within-Day, Between-Day, and Between-Week Variability of Urinary Concentrations of Phenol Biomarkers in Pregnant Women

Abstract

Background: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized.

Objectives: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy.

Methods: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15±2, 24±2, and 32±1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability).

Results: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (<0.3) and 2,5-dichlorophenol the highest (ICC >0.9).

Conclusion: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. https://doi.org/10.1289/EHP1994.

Figure 1.

Urine collection, pooling procedure, and biomarker assays in all the study population ($N=8$ women) and in the nested subgroup 1 ($N=2$ women).

Figure 2.

Within-day and within-week variability – urinary concentrations of 10 phenols ($\mathrm{\mu }\mathrm{g}/\mathrm{L}$), creatinine concentration (mg/dL), and specific gravity in ${\log }_{10}\text{-scale}$ in the unpooled spot samples from subgroup 1 (2 women, $n=114$ spot samples collected over the first week of collection). Note that to facilitate visualization, each biomarker is displayed on a specific scale.

Figure 3.

Between-day (within a week) variability of pooled daily samples – urinary concentrations of 10 phenols ($\mathrm{\mu }\mathrm{g}/\mathrm{L}$), creatinine concentration (mg/dL), and specific gravity in ${\log }_{10}\text{-scale}$ in the within-woman daily pooled samples from subgroup 1 and subgroup 2 (8 women, $n=56\text{daily}\text{pools}$, one daily pool for each day of the first week of collection). Note that to facilitate visualization, each biomarker is displayed on a specific scale.

Figure 4.

Between-week variability of weekly samples – urinary concentrations of 10 phenols ($\mathrm{\mu }\mathrm{g}/\mathrm{L}$), creatinine concentration (mg/dL), and specific gravity in ${\log }_{10}\text{-scale}$ in the within-woman weekly pooled samples from subgroup 1 and subgroup 2 (8 women, $n=24\text{weekly}\text{pools}$, one weekly pool for each of the three weeks of collection). Note that to facilitate visualization, each biomarker is displayed on a specific scale.

Figure 5.

Intraclass correlation coefficients (error bars for 95% confidence intervals) for the within-day variability using the unpooled spot samples from subgroup 1 (2 women, $n=114$ spot samples collected over the first week of collection, triangle markers), the between-day variability using the within-woman daily pooled samples from subgroup 1 and subgroup 2 (8 women, $n=56\text{daily}\text{pools}$, one daily pool for each day of the first week of collection, square markers), and the between-week variability in the within-woman weekly pooled samples from subgroup 1 and subgroup 2 (8 women, $n=24\text{weekly}\text{pools}$, one weekly pool for each of the three weeks of collection, circle markers). For triclosan, we give only the confidence interval truncated to zero due to the negative estimate of between-week ICC.