An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies

Abstract

Background: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions issued from biomarker-based studies when exposure assessment suffers from classicaltype 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 collecting all daily urine samples. Methods: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. Pools were prepared from either three or all daily samples. From 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.Results: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.8 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time-window (correlations, 0.6-0.7). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using one biospecimen led to an attenuation bias in the doseresponse functions of 30% (methylparaben) and 68% (bisphenol A); four and 18 samples, respectively, were required to decrease bias to 10%. Conclusion:For non-persistent 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 very little persistent chemicals like bisphenol A.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island

“…It is also important to acknowledge the potential for exposure misclassification based on OPE metabolite measurements, particularly for women who provided only one urine sample, because of possible seasonal variability in urinary concentrations of OPE metabolites, and of measurement error in infant anthropometry. Nevertheless, our data collection methods (quantifying OPE metabolites in pooled urine samples collected throughout pregnancy; using the average of two to three measurements for each anthropometric outcome) are proven techniques to minimize such potential limitations (e.g., [21,75,76]). As with all environmental epidemiology studies, residual confounding by unknown or unmeasured co-exposures that influence the outcomes of interest may be present.…”

Bisphenol A shapes children’s brain and behavior: towards an integrated neurotoxicity assessment including human data

“…Since BPA is rapidly metabolized and excreted in urine, and exposure patterns are episodic, using one spot urine sample may lead to exposure misclassification. This means that when all studies in a given field are taken together, there is a greater tendency to obtain null results, the so-called attenuation bias [6]. In other words, most of the associations observed with behavior would be systematically underestimated.…”

Association between the pregnancy exposome and fetal growth

“…These should possibly consider much larger populations and rely on repeated biospecimens collection to limit exposure measurement error for the compounds with the strongest within-subject variability. 24,56,57 From a public health perspective, lead exposure during pregnancy (at the levels encountered in the years 1999-2010, when these pregnancies occurred) may still be a health concern in the EU while the effects of pregnancy exposure to parabens warrant further investigation.…”