Jordan R Kuiper1, Katie M O'Brien2, Barrett M Welch2, Emily S Barrett3, Ruby H N Nguyen4, Sheela Sathyanarayana5, Ginger L Milne6, Shanna H Swan7, Kelly K Ferguson2, Jessie P Buckley1,8. 1. From the Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. 2. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC. 3. Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute, Piscataway, NJ. 4. Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN. 5. Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, WA. 6. Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN. 7. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY. 8. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Abstract
BACKGROUND: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity. METHODS: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site. In addition to a scenario with no dilution adjustment, we applied and compared three dilution-adjustment approaches: a standard regression-based approach for creatinine, a standard approach for specific gravity (Boeniger method), and a more recently developed approach that has been applied to both (covariate-adjusted standardization method). For each scenario and dilution-adjustment method, we estimated the association between a doubling in the molar sum of DEHP (∑DEHP) and odds of preterm birth using logistic regression. RESULTS: All dilution-adjustment approaches yielded comparable associations (odds ratio [OR]) that were larger in magnitude than when we did not perform dilution adjustment. A doubling of ∑DEHP was associated with 9% greater odds of preterm birth (OR = 1.09, 95% confidence interval [CI] = 0.91, 1.30) when applying no dilution-adjustment method, whereas dilution-adjusted point estimates were higher, and similar across all scenarios and methods: 1.13-1.20 (regression-based), 1.15-1.18 (Boeniger), and 1.14-1.21 (covariate-adjusted standardization). CONCLUSIONS: In our applied example, we demonstrate that it is possible and straightforward to combine urinary biomarker data across studies when measures of dilution differ.
BACKGROUND: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity. METHODS: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site. In addition to a scenario with no dilution adjustment, we applied and compared three dilution-adjustment approaches: a standard regression-based approach for creatinine, a standard approach for specific gravity (Boeniger method), and a more recently developed approach that has been applied to both (covariate-adjusted standardization method). For each scenario and dilution-adjustment method, we estimated the association between a doubling in the molar sum of DEHP (∑DEHP) and odds of preterm birth using logistic regression. RESULTS: All dilution-adjustment approaches yielded comparable associations (odds ratio [OR]) that were larger in magnitude than when we did not perform dilution adjustment. A doubling of ∑DEHP was associated with 9% greater odds of preterm birth (OR = 1.09, 95% confidence interval [CI] = 0.91, 1.30) when applying no dilution-adjustment method, whereas dilution-adjusted point estimates were higher, and similar across all scenarios and methods: 1.13-1.20 (regression-based), 1.15-1.18 (Boeniger), and 1.14-1.21 (covariate-adjusted standardization). CONCLUSIONS: In our applied example, we demonstrate that it is possible and straightforward to combine urinary biomarker data across studies when measures of dilution differ.
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